The Role of Inflammatory Mediators in the Pathogenesis of Otitis Media and Sequelae

Steven K. Juhn,정민교,Mark D. Hoffman,Brian R. Drew,Diego A. Preciado,Nicholas J. Sausen,Timothy T.K. Jung,Bo Hyung Kim,박상유,Jizhen Lin,Frank G. Ondrey,David R. Mains,Tina Huang 대한이비인후과학회 2008 Clinical and Experimental Otorhinolaryngology Vol.1 No.3

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.

Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer

Sundar, R,Huang, K K,Qamra, A,Kim, K -M,Kim, S T,Kang, W K,Tan, A L K,Lee, J,Tan, P Oxford University Press 2019 Annals of oncology Vol.30 No.3

<P><B>Abstract</B></P><P><B>Background</B></P><P>Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer.</P><P><B>Patients and methods</B></P><P>Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (<I>N </I>=<I> </I>24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString<SUP>®</SUP> (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (<I>N </I>=<I> </I>37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival.</P><P><B>Results</B></P><P>In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (AP<SUB>high</SUB>), and this was used to define the AP<SUB>high</SUB> tertile of the second cohort (13 AP<SUB>high</SUB> of 37). AP<SUB>high</SUB> tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, <I>P </I>=<I> </I>0.03). Median progression-free survival was lower in the AP<SUB>high</SUB> group (55 versus 180 days, <I>P </I>=<I> </I>0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival [hazard ratio 0.29, 95% confidence interval 0.099–0.85, <I>P </I>=<I> </I>0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response.</P><P><B>Conclusion</B></P><P>A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy.</P><P><B>Trial Registration</B></P><P>ClinicalTrials.gov Identifier: NCT#02589496</P>

Optical Characterization of Zn0.95-xBe0.05MnxSe Mixed Crystals

H. P. Hsu,T. W. Chang,Y. S. Huang,F. Firszt,S. Legowski,H. Meczynsk,A. Marasek,K. Strza lkowski,K. K. Tiong,M. Munoz 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.53 No.1

Temperature-dependent photoluminescence (PL), contactless electrore ectance (CER) and surface photovoltage spectroscopy (SPS) characterizations of two Zn0.95-xBe0.05MnxSe mixed crystals with Mn contents x=0.05 and 0.20 grown by using the modified high-pressure Bridgman method has been carried out in the temperature range of 15-300 K. A typical PL spectrum at low temperature consists of a free exciton line, an edge emission due to recombenation of shallow donor-acceptor pairs and Mn2+-related intra-ionnic emissions. Te near band edge transition energies are determined lines in the PL spectra correspond quite well to the energies of the fundamental trasitions determinde from CER and SPS data. The parameters that descrbe the temperature dependence of the trasition energy of the fundamental band-edge excton are evaluated and discussed. Temperature-dependent photoluminescence (PL), contactless electrore ectance (CER) and surface photovoltage spectroscopy (SPS) characterizations of two Zn0.95-xBe0.05MnxSe mixed crystals with Mn contents x=0.05 and 0.20 grown by using the modified high-pressure Bridgman method has been carried out in the temperature range of 15-300 K. A typical PL spectrum at low temperature consists of a free exciton line, an edge emission due to recombenation of shallow donor-acceptor pairs and Mn2+-related intra-ionnic emissions. Te near band edge transition energies are determined lines in the PL spectra correspond quite well to the energies of the fundamental trasitions determinde from CER and SPS data. The parameters that descrbe the temperature dependence of the trasition energy of the fundamental band-edge excton are evaluated and discussed.

Photoluminescence and Electromodulation Spectroscopy Characterization of Zn0.93Mg0.07Se and Zn0.81Be0.04Mg0.15Se Mixed Crystals

H. P. Hsu,D. O. Dumcenco,C. T. Huang,Y. S. Huang,F. Firszt,S. Legowski,H. Meczynsk,K. Strza lkowski,A. Marasek,K. K. Tiong 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.53 No.1

A detailed optical characterization of zinc-blende-type Zn0.93Mg0.07Se and Zn0.81Be0.04Mg0.15Se mixed-crystal samples grown by using the modified high pressure Bridgman method has been carried out via photoluminescence (PL), contactless electrore ectance (CER) and photore ectance (PR) in the temperature range of 15 to 400 K. PL spectra at low temperatures consist of an exciton line, a broader emission band due to recombination of donor-acceptor pairs and a broad band related to recombination through deep-level defects. Interband transitions, originating from the band edge and spin-orbit splitting critical points, have been observed in the CER/PR spectra. The optical properties of these two mixed crystals are compared and the results indicate the superior quality of the Be-incorporated mixed quaternary crystals. The peak positions of the excitonic emission lines in the PL spectra correspond quite well to the energies of the fundamental transitions obtained by means of electromodulation data. The parameters that describe the temperature dependence of the fundamental and spin split-off band gaps and the broadening function of the band-edge excitons are evaluated and discussed. A detailed optical characterization of zinc-blende-type Zn0.93Mg0.07Se and Zn0.81Be0.04Mg0.15Se mixed-crystal samples grown by using the modified high pressure Bridgman method has been carried out via photoluminescence (PL), contactless electrore ectance (CER) and photore ectance (PR) in the temperature range of 15 to 400 K. PL spectra at low temperatures consist of an exciton line, a broader emission band due to recombination of donor-acceptor pairs and a broad band related to recombination through deep-level defects. Interband transitions, originating from the band edge and spin-orbit splitting critical points, have been observed in the CER/PR spectra. The optical properties of these two mixed crystals are compared and the results indicate the superior quality of the Be-incorporated mixed quaternary crystals. The peak positions of the excitonic emission lines in the PL spectra correspond quite well to the energies of the fundamental transitions obtained by means of electromodulation data. The parameters that describe the temperature dependence of the fundamental and spin split-off band gaps and the broadening function of the band-edge excitons are evaluated and discussed.

IDENTIFICATION CAMPAIGN OF SUPERNOVA REMNANT CANDIDATES IN THE MILKY WAY. I.<i>CHANDRA</i>OBSERVATION OF G308.3-1.4

Hui, C. Y.,Seo, K. A.,Huang, R. H. H.,Trepl, L.,Woo, Y. J.,Lu, T.-N.,Kong, A. K. H.,Walter, F. M. IOP Publishing 2012 The Astrophysical journal Vol.750 No.1

<P>ROSAT all-sky survey data have provided another window in which to search for supernova remnants (SNRs). In re-examining this data archive, a list of unidentified extended X-ray objects have been suggested as promising SNR candidates. However, most of these targets have not yet been fully explored by state-of-the-art X-ray observatories. To select a pilot target for a long-term identification campaign, we observed the brightest candidate, G308.3-1.4, with the Chandra X-ray Observatory. An incomplete shell-like X-ray structure that is well correlated with the radio shell emission at 843 MHz has been revealed. The X-ray spectrum suggests the presence of a shock-heated plasma. All these evidences confirm G308.3-1.4 as an SNR. The brightest X-ray point source detected in this field of view is also the one located closest to the geometrical center of G308.3-1.4, which has a soft spectrum. The intriguing temporal variability and the identification of the optical/infrared counterpart rule out the possibility of an isolated neutron star. On the other hand, the spectral energy distribution from the K-s band to the R band suggests a late-type star. Together with a putative periodicity of similar to 1.4 hr, the interesting excesses in the V and B bands and in H alpha suggest that this source is a promising candidate for a compact binary that survived a supernova explosion.</P>

Magnetic Properties and Microstructure of Cr₉₀Ru₁₀/Fe₅₅Pt₄₅ Bilayer Thin Film

K. T. Huang,H. W. Chang,An-Cheng Sun,P. C. Kuo,C. T. Lee,S. C. Chen,Jen-Hwa Hsu 한국자기학회 2007 한국자기학회 학술연구발표회 논문개요집 Vol.- No.-

Tabletop laser-driven gamma-ray source with nanostructured double-layer target

Huang, T W,Kim, C M,Zhou, C T,Ryu, C M,Nakajima, K,Ruan, S C,Nam, C H IOP 2018 Plasma physics and controlled fusion Vol.60 No.11

<P>Laser-driven gamma-ray source potentially offers a compact, cost-effective, ultra-short, and ultra-bright alternative to conventional gamma-ray sources based on large-scale particle accelerators. Based on the laser-driven approach, we use multidimensional particle-in-cell simulations to demonstrate that a nanostructured double-layer target, which consists of a nanostructured foam coated on top of a metal substrate, can absorb laser energy into high-energy electrons in the nanostructured foam, and then efficiently convert it into copious gamma photons via the nonlinear Compton scattering process enabled by the solid-density substrate, which acts as a plasma mirror to reflect the laser pulse. The effects of different nanostructures in the foam target and the oblique laser incidence are presented. It is shown that the conversion efficiency of gamma photons increases when the size of nanoparticles decreases or the filling factor of nanoparticles increases in nanostructured foam target, but decreases when the laser incidence angle increases. At realistic conditions with nanostructured foam and non-normal incidence, the double-layer target still exhibits an unprecedentedly high conversion efficiency in high-energy gamma-ray production due to the laser reflection by the plasma mirror, which can be two and even three orders of magnitude higher than that of the single-layer target without the substrate using currently available lasers with intensity of 10<SUP>21</SUP> <img ALIGN='MIDDLE' ALT='${\rm{W}}/{\mathrm{cm}}^{2}$' SRC='http://ej.iop.org/images/0741-3335/60/11/115006/ppcfaadbebieqn1.gif'/>.</P>

Fracture in Strain Gradient Elasticity

Hwang, K . C .,Cuo, T . F .,Huang, Y .,Chen, J . Y . 대한금속재료학회(대한금속학회) 1998 METALS AND MATERIALS International Vol.4 No.4

Recent experiments have shown that the microscale material behavior is very different from that of bulk materials, and displays strong size effects when the characteristic length associated with the deformation is on the order of microns. Conventional continuum theories, however, can not predict this size dependence because they do not have an intrinsic length in their constitutive models. A new continuum theory, namely the strain gradient theory, has been proposed to investigate the deformation of solids at the microscale. For materials undergoing plastic deformation, the basis of strain gradient theory is the dislocation theory in materials science, and strain gradient plasticity has agreed remarkably well with experiments. For elastic materials with microstructures, it has also been established that the material behavior can be represented by an elastic strain gradient theory. A general approach to investigate fracture of materials with strain gradient effects i;; established. Both the near-tip asymptotic fields and the elastic full-field solutions are obtained in closed form. Due to stain gradient effects, stresses ahead of a crack tip are significantly higher than those in the classical K field. The plastic zone size surrounding a crack tip is estimated by elastic near-tip fields, as well as by the Dugdale model. It is established that the plastic zone is, in general, much more round and larger than that estimated from the classical K field.

East Asian GRB Follow-up Network (EAFON)

Y. Urata,K.Y. Huang,W.H. Ip,P.H. Kuo,Y.S Lee,Y. Qiu,J. Wei,J. Deng,W. Zheng,M. Zhai,M. Tashiro,K. Abe,K. Onda,T. Tamagawa,K. Ioka,M. Kuwahara,F. Usui 한국천문학회 2006 天文學會報 Vol.31 No.1

DISCOVERY OF AN UNIDENTIFIED <i>FERMI</i> OBJECT AS A BLACK WIDOW-LIKE MILLISECOND PULSAR

Kong, A. K. H.,Huang, R. H. H.,Cheng, K. S.,Takata, J.,Yatsu, Y.,Cheung, C. C.,Donato, D.,Lin, L. C. C.,Kataoka, J.,Takahashi, Y.,Maeda, K.,Hui, C. Y.,Tam, P. H. T. IOP Publishing 2012 ASTROPHYSICAL JOURNAL LETTERS - Vol.747 No.1

<P>The Fermi gamma-ray Space Telescope has revolutionized our knowledge of the gamma-ray pulsar population, leading to the discovery of almost 100 gamma-ray pulsars and dozens of gamma-ray millisecond pulsars (MSPs). Although the outer-gap model predicts different sites of emission for the radio and gamma-ray pulsars, until now all of the known gamma-ray MSPs have been visible in the radio. Here we report the discovery of a 'radio-quiet' gamma-ray-emitting MSP candidate by using Fermi, Chandra, Swift, and optical observations. The X-ray and gamma-ray properties of the source are consistent with known gamma-ray pulsars. We also found a 4.63 hr orbital period in optical and X-ray data. We suggest that the source is a black widow-like MSP with a similar to 0.1 M-circle dot late-type companion star. Based on the profile of the optical and X-ray light curves, the companion star is believed to be heated by the pulsar while the X-ray emissions originate from pulsar magnetosphere and/or from intrabinary shock. No radio detection of the source has been reported yet, and although no gamma-ray/radio pulsation has been found we estimate that the spin period of the MSP is similar to 3-5 ms based on the inferred gamma-ray luminosity.</P>