<i>SPITZER</i>AND HEINRICH HERTZ TELESCOPE OBSERVATIONS OF STARLESS CORES: MASSES AND ENVIRONMENTS

Stutz, Amelia M.,Rieke, George H.,Bieging, John H.,Balog, Zoltan,Heitsch, Fabian,Kang, Miju,Peters, William L.,Shirley, Yancy L.,Werner, Michael W. IOP Publishing 2009 The Astrophysical journal Vol.707 No.1

<P>We present Spitzer observations of a sample of 12 starless cores selected to have prominent 24 mu m shadows. The Spitzer images show 8 mu m and 24 mu m shadows and in some cases 70 mu m shadows; these spatially resolved absorption features trace the densest regions of the cores. We have carried out a (CO)-C-12 (2-1) and (CO)-C-13 (2-1) mapping survey of these cores with the Heinrich Hertz Telescope (HHT). We use the shadow features to derive optical depth maps. We derive molecular masses for the cores and the surrounding environment; we find that the 24 mu m shadow masses are always greater than or equal to the molecular masses derived in the same region, a discrepancy likely caused by CO freezeout onto dust grains. We combine this sample with two additional cores that we studied previously to bring the total sample to 14 cores. Using a simple Jeans mass criterion, we find that similar to 2/3 of the cores selected to have prominent 24 mu m shadows are collapsing or near collapse, a result that is supported by millimeter line observations. Of this subset at least half have indications of 70 mu m shadows. All cores observed to produce absorption features at 70 mu m are close to collapse. We conclude that 24 mu m shadows, and even more so the 70 mu m ones, are useful markers of cloud cores that are approaching collapse.</P>

Practice of causal inference with the propensity of being zero or one: assessing the effect of arbitrary cutoffs of propensity scores

Kang, Joseph,Chan, Wendy,Kim, Mi-Ok,Steiner, Peter M. The Korean Statistical Society 2016 Communications for statistical applications and me Vol.23 No.1

Causal inference methodologies have been developed for the past decade to estimate the unconfounded effect of an exposure under several key assumptions. These assumptions include, but are not limited to, the stable unit treatment value assumption, the strong ignorability of treatment assignment assumption, and the assumption that propensity scores be bounded away from zero and one (the positivity assumption). Of these assumptions, the first two have received much attention in the literature. Yet the positivity assumption has been recently discussed in only a few papers. Propensity scores of zero or one are indicative of deterministic exposure so that causal effects cannot be defined for these subjects. Therefore, these subjects need to be removed because no comparable comparison groups can be found for such subjects. In this paper, using currently available causal inference methods, we evaluate the effect of arbitrary cutoffs in the distribution of propensity scores and the impact of those decisions on bias and efficiency. We propose a tree-based method that performs well in terms of bias reduction when the definition of positivity is based on a single confounder. This tree-based method can be easily implemented using the statistical software program, R. R code for the studies is available online.

Fibrin-Targeted and H₂O₂-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels

Kang, Changsun,Gwon, Sian,Song, ChulGyu,Kang, Peter M.,Park, Seong-Cheol,Jeon, Jongho,Hwang, Do Won,Lee, Dongwon American Chemical Society 2017 ACS NANO Vol.11 No.6

<P>A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nano medicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (H2O2), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis. FTIAN inhibited the generation of H2O2 and suppressed the expression of tumor necrosis factor-alpha (TNF-alpha) and soluble CD40 ligand (sCD40L) in activated platelets, demonstrating its intrinsic antioxidant, anti-inflammatory, and antiplatelet activity. In a mouse model of ferric chloride (FeCl3)-induced carotid thrombosis, FTIAN specifically targeted the obstructive thrombus and significantly enhanced the fluorescence/photoacoustic signal. When loaded with the antiplatelet drug tirofiban, FTIAN remarkably suppressed thrombus formation. Given its thrombus-specific imaging along with excellent therapeutic activities, FTIAN offers tremendous translational potential as a nanotheranostic agent for obstructive thrombosis.</P>

Apoptosis in Cardiovascular Diseases:Mechanism and Clinical Implications

김남호,Peter M. Kang 대한심장학회 2010 Korean Circulation Journal Vol.40 No.7

Apoptosis is a tightly regulated, cell deletion process that plays an important role in various cardiovascular diseases, such as myocardial infarction, reperfusion injury, and heart failure. Since cardiomyocyte loss is the most important determinant of patient morbidity and mortality, fully understanding the regulatory mechanisms of apoptotic signaling is crucial. In fact, the inhibition of cardiac apoptosis holds promise as an effective therapeutic strategy for cardiovascular diseases. Caspase, a critical enzyme in the induction and execution of apoptosis, has been the main potential target for achieving anti-apoptotic therapy. Studies suggest, however, that a caspase-independent pathway may also play an important role in cardiac apoptosis, although the mechanism and potential significance of caspase-independent apoptosis in the heart remain poorly understood. Herein we discuss the role of apoptosis in various cardiovascular diseases, provide an update on current knowledge about the molecular mechanisms that govern apoptosis, and discuss the clinical implications of anti-apoptotic therapies.

Halogenation of simplies resiniferatoxin TRPV1 agonists showed enhanced actagonism to capsaicin

YOON Hyejin,KANG Dong wook,CHO Yong Sung,BLUMBERG Peter M,LEE Jeewoo 大韓藥學會 2012 大韓藥學會 總會 및 學術大會 Vol.2012 No.1

Acoustic emission analysis of the compressive deformation of iron foams and their biocompatibility study

Park, Hyeji,Hong, Kicheol,Kang, Jin Soo,Um, Teakyung,Knapek, Michal,Miná,rik, Peter,Sung, Yung-Eun,Má,this, Kristiá,n,Yamamoto, Akiko,Kim, Hyun-Kyung,Choe, Heeman Elsevier 2019 Materials Science and Engineering C Vol.97 No.-

<P><B>Abstract</B></P> <P>We synthesized Fe foams using water suspensions of micrometric Fe<SUB>2</SUB>O<SUB>3</SUB> powder by reducing and sintering the sublimated Fe oxide green body to Fe under 5% H<SUB>2</SUB>/Ar gas. The resultant Fe foam showed aligned lamellar macropores replicating the ice dendrites. The compressive behavior and deformation mechanism of the synthesized Fe foam were studied using an acoustic emission (AE) method, with which we detected sudden localized structural changes in the Fe foam material. The evolution of the deformation mechanism was elucidated using the adaptive sequential <I>k</I>-means (ASK) algorithm; specifically, the plastic deformation of the cell struts was followed by localized cell collapse, which eventually led to fracturing of the cell walls. For potential biomedical applications, the corrosion and biocompatibility characteristics of the two synthesized Fe foams with different porosities (50% vs. 44%) were examined and compared. Despite its larger porosity, the superior corrosion behavior of the Fe foam with 50% porosity can be attributed to its larger pore size and smaller microscopic surface area. Based on the cytotoxicity tests for the extracts of the foams, the Fe foam with 44% porosity showed better cytocompatibility than that with 50% porosity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Iron foam synthesized from water suspension of Fe<SUB>2</SUB>O<SUB>3</SUB> powder under 5% H<SUB>2</SUB>/Ar gas. </LI> <LI> Compressive deformation mechanism of iron foam is analyzed using an acoustic emission. </LI> <LI> Not porosity but pore size is a dominant factor for corrosion behavior of iron foams. </LI> <LI> Concentration released Fe<SUP>n+</SUP> controls cytotoxicity of iron foam extracts. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination

Olmos-Serrano, J.,Kang, H.,Tyler, William A.,Silbereis, John C.,Cheng, F.,Zhu, Y.,Pletikos, M.,Jankovic-Rapan, L.,Cramer, Nathan P.,Galdzicki, Z.,Goodliffe, J.,Peters, A.,Sethares, C.,Delalle, I.,Gold Cell Press 2016 Neuron Vol.89 No.6

Trisomy 21, or Down syndrome (DS), is the most common genetic cause of developmental delay and intellectual disability. To gain insight into the underlying molecular and cellular pathogenesis, we conducted a multi-region transcriptome analysis of DS and euploid control brains spanning from mid-fetal development to adulthood. We found genome-wide alterations in the expression of a large number of genes, many of which exhibited temporal and spatial specificity and were associated with distinct biological processes. In particular, we uncovered co-dysregulation of genes associated with oligodendrocyte differentiation and myelination that were validated via cross-species comparison to Ts65Dn trisomy mice. Furthermore, we show that hypomyelination present in Ts65Dn mice is in part due to cell-autonomous effects of trisomy on oligodendrocyte differentiation and results in slower neocortical action potential transmission. Together, these results identify defects in white matter development and function in DS, and they provide a transcriptional framework for further investigating DS neuropathogenesis.

Preparation and Characterization of Valsartan-Loaded Polyoxalate Microspheres: In vitro Release Profiles

이정근,유석철,김아람,이동원,Peter M. Kang,육순홍,Paul M. Vanhoutte,강길선 한국고분자학회 2013 Macromolecular Research Vol.21 No.5

Valsartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has a high bioavailability. Hydrophobic polyoxalate has been suggested for use in biodegradable medical devices such as absorbable sutures and controlled release applications. In this study, we developed valsartan-loaded polyoxalate microspheres by varying the polyoxalate molecular weight, surfactant content, and initial drug loading rate. The morphology of the valsartanloaded polyoxalate microspheres was evaluated by scanning electron microscopy and the hydrolysis kinetics of polyoxalate were investigated. The influences regarding the preparation parameters were evaluated with respect to the release of valsartan. The results demonstrated that the release behavior can be effectively controlled by the preparation conditions.

A Gene Regulatory Network for Root Epidermis Cell Differentiation in Arabidopsis

Bruex, Angela,Kainkaryam, Raghunandan M.,Wieckowski, Yana,Kang, Yeon Hee,Bernhardt, Christine,Xia, Yang,Zheng, Xiaohua,Wang, Jean Y.,Lee, Myeong Min,Benfey, Philip,Woolf, Peter J.,Schiefelbein, John Public Library of Science 2012 PLoS genetics Vol.8 No.1

<▼1><P>The root epidermis of Arabidopsis provides an exceptional model for studying the molecular basis of cell fate and differentiation. To obtain a systems-level view of root epidermal cell differentiation, we used a genome-wide transcriptome approach to define and organize a large set of genes into a transcriptional regulatory network. Using cell fate mutants that produce only one of the two epidermal cell types, together with fluorescence-activated cell-sorting to preferentially analyze the root epidermis transcriptome, we identified 1,582 genes differentially expressed in the root-hair or non-hair cell types, including a set of 208 “core” root epidermal genes. The organization of the core genes into a network was accomplished by using 17 distinct root epidermis mutants and 2 hormone treatments to perturb the system and assess the effects on each gene's transcript accumulation. In addition, temporal gene expression information from a developmental time series dataset and predicted gene associations derived from a Bayesian modeling approach were used to aid the positioning of genes within the network. Further, a detailed functional analysis of likely bHLH regulatory genes within the network, including <I>MYC1</I>, <I>bHLH54</I>, <I>bHLH66</I>, and <I>bHLH82</I>, showed that three distinct subfamilies of bHLH proteins participate in root epidermis development in a stage-specific manner. The integration of genetic, genomic, and computational analyses provides a new view of the composition, architecture, and logic of the root epidermal transcriptional network, and it demonstrates the utility of a comprehensive systems approach for dissecting a complex regulatory network.</P></▼1><▼2><P><B>Author Summary</B></P><P>A current challenge in the field of developmental biology is to define the composition and organization of gene networks that direct the pattern and differentiation of cells, tissues, and organs. In this study, we address this problem using Arabidopsis root epidermis development, a relatively simple model for studies of cell pattern formation and differentiation in plants. We used a tissue-specific cell sorting approach to define more than 1,500 genes whose transcripts differentially accumulate in the developing root epidermis. A series of transcriptome analyses were performed with 17 root epidermal mutants and 2 plant hormone treatments to dissect the regulatory relationships between 208 core genes. In addition, gene expression information from a developmental time series dataset was used to organize genes temporally. The results provide insight into the composition, organization, and logic of a developmental gene regulatory network. Furthermore, this work demonstrates the utility of an integrated analysis in gene regulatory network construction using genetic, genomic, and computational approaches.</P></▼2>

Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies.

Lee, Jin Hee,Lee, Yoonji,Ryu, HyungChul,Kang, Dong Wook,Lee, Jeewoo,Lazar, Jozsef,Pearce, Larry V,Pavlyukovets, Vladimir A,Blumberg, Peter M,Choi, Sun ESCOM ; Kluwer Academic Publishers 2011 Journal of computer-aided molecular design Vol.25 No.4

<P>The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rat TRPV1 (rTRPV1). We experimentally evaluated by mutational analysis the contribution of residues of rTRPV1 contributing to ligand binding by the prototypical TRPV1 agonists, capsaicin and resiniferatoxin (RTX). We then performed docking analysis using our homology model. The docking results with capsaicin and RTX showed that our homology model was reliable, affording good agreement with our mutation data. Additionally, the binding mode of a simplified RTX (sRTX) ligand as predicted by the modeling agreed well with those of capsaicin and RTX, accounting for the high binding affinity of the sRTX ligand for TRPV1. Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands.</P>