diagnosis-neoplasia-barretts-esophagus-using-vital-dye-enhanced

Diagnosis of Neoplasia in Barrett&#8217;s Esophagus using Vital-dye Enhanced Fluorescence Imaging

The ability to differentiate benign metaplasia in Barrett&#8217;s Esophagus (BE) from neoplasia in vivo remains difficult as both tissue types can be flat ...

Icahn School of Medicine at Mount Sinai

In this paper, we report a novel optokinetic nystagmus (OKN), which was evoked by stationary gratings presented intermittently. OKN eye movements were accurately measured by the electromagnetic scleral search-coil technique. For the luminance stimuli, alternating OKN was elicited when the interstimulus interval (ISI) ranged from 33 to 83 ms duration and the ISI luminance approximated to the mean luminance of the stimulus grating; for chromatic (red/green) stimuli, the OKN could be evoked in non-isoluminant condition and vanished in the isoluminant condition. It is a plausible explanation that the present OKN, intermittent display-of-gratings-induced OKN (IDG-OKN), might be related to the temporal impulse response of the luminance channel in vision.

Alternating optokinetic nystagmus (OKN) induced by intermittent display of stationary gratings.

N5-Carboxyaminoimidazole ribonucleotide mutase (N5-CAIR mutase or PurE) from Escherichia coli catalyzes the reversible interconversion of N5-CAIR to carboxyaminoimidazole ribonucleotide (CAIR) with direct CO2 transfer. Site-directed mutagenesis, a pH-rate profile, DFT calculations, and X-ray crystallography together provide new insight into the mechanism of this unusual transformation. These studies suggest that a conserved, protonated histidine (His45) plays an essential role in catalysis. The importance of proton transfers is supported by DFT calculations on CAIR and N5-CAIR analogues in which the ribose 5'-phosphate is replaced with a methyl group. The calculations suggest that the nonaromatic tautomer of CAIR (isoCAIR) is only 3.1 kcal/mol higher in energy than its aromatic counterpart, implicating this species as a potential intermediate in the PurE-catalyzed reaction. A structure of wild-type PurE cocrystallized with 4-nitroaminoimidazole ribonucleotide (NO2-AIR, a CAIR analogue) and structures of H45N and H45Q PurEs soaked with CAIR have been determined and provide the first insight into the binding of an intact PurE substrate. A comparison of 19 available structures of PurE and PurE mutants in apo and nucleotide-bound forms reveals a common, buried carboxylate or CO2 binding site for CAIR and N5-CAIR in a hydrophobic pocket in which the carboxylate or CO2 interacts with backbone amides. This work has led to a mechanistic proposal in which the carboxylate orients the substrate for proton transfer from His45 to N5-CAIR to form an enzyme-bound aminoimidazole ribonucleotide (AIR) and CO2 intermediate. Subsequent movement of the aminoimidazole moiety of AIR reorients it for addition of CO2 at C4 to generate isoCAIR. His45 is now in a position to remove a C4 proton to produce CAIR.

N5-CAIR mutase: role of a CO2 binding site and substrate movement in catalysis.

&#x6563;&#x4E71; &#xFF08;SERS&#xFF09; &#x57FA;&#x677F;&#x5927;&#x9762;&#x7A4D;&#x306E;&#x8868;&#x9762;&#x5897;&#x5F37;&#x30E9;&#x30DE;&#x30F3;&#x6563;&#x4E71;&#x306B;&#x3088;&#x308B;&#x30D5;&#x30A7;&#x30E0;&#x30C8;&#x30E2;&#x30EB; &#x30EC;&#x30D9;&#x30EB; &#x30C8;&#x30EC;&#x30FC;&#x30B9;&#x691C;&#x51FA; &#xFF08;10 (9) &#x5206;&#x5B50;&#xFF09; &#x306E;&#x6539;&#x5584;&#x6CD5;&#x3092;&#x63D0;&#x6848;&#x3057;&#x307E;&#x3059;&#x3002;&#x591A;&#x5149;&#x5B50;&#x52B1;&#x8D77;&#x9732;&#x51FA;&#x5546;&#x696D;&#x30D5;&#x30A9;&#x30C8;&#x30EC;&#x30B8;&#x30B9;&#x30C8;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x3001;&#x7269;&#x7406;&#x7684;&#x306B;&#x5229;&#x7528;&#x53EF;&#x80FD;&#x306A;&#x5206;&#x5B50;&#x5438;&#x7740;&#x30B5;&#x30A4;&#x30C8;&#x306E;&#x307F;&#x306E;&#x96FB;&#x78C1;&#x300C;&#x30DB;&#x30C3;&#x30C8; &#x30B9;&#x30DD;&#x30C3;&#x30C8;&#x300D;&#x57FA;&#x677F;&#x4E0A;&#x3092;&#x5236;&#x9650;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x306F;&#x3001;&#x30B5;&#x30A4;&#x30C8;&#x3078;&#x306E;&#x540C;&#x6642;&#x5438;&#x7740;&#x30B5;&#x30A4;&#x30C8;&#x306E;&#x81E8;&#x6642; SERS &#x5897;&#x5F37;&#x3059;&#x308B;&#x8A31;&#x53EF;&#x3001;&#x5F31;&#x3044; SERS &#x5897;&#x5F37;&#x5438;&#x7740;&#x304B;&#x3089;&#x5206;&#x5B50;&#x3092;&#x9632;&#x304E;&#x307E;&#x3059;&#x3002;&#x30D9;&#x30F3;&#x30BC;&#x30F3;&#x30C1; &#x30AA;&#x30FC;&#x30EB;&#x5206;&#x5B50;&#x306E;&#x30E9;&#x30F3;&#x30C0;&#x30E0;&#x306B;&#x5438;&#x7740;&#x30B5;&#x30D6;&#x30E2;&#x30CE;&#x30EC;&#x30A4;&#x30E4;&#x30FC;&#x7528;&#x6563;&#x4E71;&#x65AD;&#x9762;&#x52A0;&#x5DE5;&#x30B5;&#x30F3;&#x30D7;&#x30EB;&#x306E;&#x5E73;&#x5747;&#x30E9;&#x30DE;&#x30F3;&#x672A;&#x51E6;&#x7406; sers &#x306E; 27 &#x500D;&#x306E;&#x5927;&#x304D;&#x3055;&#x3067;&#x3059;&#x3002;

&#x591A;&#x5149;&#x5B50;&#x30EA;&#x30BD;&#x30B0;&#x30E9;&#x30D5;&#x30A3;&#x30FC;&#x306B;&#x3088;&#x308B;&#x8868;&#x9762;&#x5897;&#x5F37;&#x30E9;&#x30DE;&#x30F3;&#x6563;&#x4E71;&#x30DB;&#x30C3;&#x30C8; &#x30B9;&#x30DD;&#x30C3;&#x30C8;&#x3092;&#x5206;&#x96E2;&#x3057;&#x307E;&#x3059;&#x3002;

&#x6211;&#x4EEC;&#x76EE;&#x524D;&#x65B9;&#x6CD5;&#x6539;&#x8FDB; femtomole &#x7EA7;&#x522B;&#x8DDF;&#x8E2A;&#x68C0;&#x6D4B; (10(9) &#x5206;&#x5B50;) &#x4F7F;&#x7528;&#x5927;&#x9762;&#x79EF;&#x8868;&#x9762;&#x589E;&#x5F3A;&#x62C9;&#x66FC;&#x6563;&#x5C04; (SERS) &#x886C;&#x5E95;&#x3002;&#x6211;&#x4EEC;&#x4F7F;&#x7528;&#x591A;&#x5149;&#x5B50;&#x8BF1;&#x5BFC;&#x63A5;&#x89E6;&#x5546;&#x4E1A;&#x7684;&#x5149;&#x81F4;&#x6297;&#x8680;&#x5242;&#xFF0C;&#x7269;&#x7406;&#x4E0A;&#x9650;&#x5236;&#x53EF;&#x7528;&#x7684;&#x5206;&#x5B50;&#x5438;&#x9644;&#x7F51;&#x7AD9;&#x5230;&#x53EA;&#x6709;&#x7535;&#x78C1;&quot;&#x70ED;&#x70B9;&quot;&#x5730;&#x533A;&#x7684;&#x57FA;&#x677F;&#x4E0A;&#x3002;&#x6B64;&#x8FC7;&#x7A0B;&#x53EF;&#x9632;&#x6B62;&#x5206;&#x5B50;&#x5438;&#x9644;&#x5230;&#x5F31; SERS &#x589E;&#x5F3A;&#xFF0C;&#x540C;&#x65F6;&#x5141;&#x8BB8;&#x5438;&#x9644;&#x5230;&#x975E;&#x540C;&#x5BFB;&#x5E38;&#x7684;&#x8868;&#x9762;&#x589E;&#x5F3A;&#x62C9;&#x66FC;&#x589E;&#x5F3A;&#x7AD9;&#x70B9;&#x7684;&#x7AD9;&#x70B9;&#x3002;Benzenethiol &#x5206;&#x5B50;&#x968F;&#x673A;&#x5438;&#x9644;&#x5C40;&#x57DF;&#x5E73;&#x5747;&#x62C9;&#x66FC;&#x6563;&#x5C04;&#x622A;&#x9762;&#x52A0;&#x5DE5;&#x6837;&#x54C1;&#x7684;&#x662F;&#x672A;&#x52A0;&#x5DE5;&#x7684;&#x8868;&#x9762;&#x589E;&#x5F3A;&#x62C9;&#x66FC;&#x57FA;&#x5E95;&#x7684; 27 &#x500D;&#x3002;

&#x9694;&#x79BB;&#x7684;&#x8868;&#x9762;&#x589E;&#x5F3A;&#x62C9;&#x66FC;&#x6563;&#x5C04;&#x70ED;&#x70B9;&#x4F7F;&#x7528;&#x591A;&#x5149;&#x5B50;&#x5149;&#x523B;&#x6280;&#x672F;&#x3002;

We present a method for improving femtomole-level trace detection (10(9) molecules) using large-area surface-enhanced Raman scattering (SERS) substrates. Using multiphoton-induced exposure of a commercial photoresist, we physically limit the available molecular adsorption sites to only the electromagnetic "hot spots" on the substrate. This process prevents molecules from adsorbing to sites of weak SERS enhancement, while permitting adsorption to sites of extraordinary SERS enhancement. For a randomly adsorbed submonolayer of benzenethiol molecules the average Raman scattering cross section of the processed sample is 27 times larger than that of an unprocessed SERS substrate.

Isolating surface-enhanced Raman scattering hot spots using multiphoton lithography.

Nous pr&eacute;sentons une m&eacute;thode pour am&eacute;liorer la d&eacute;tection de trace au niveau femtomole (10 9 mol&eacute;cules) &agrave; l&#39;aide de Raman exalt&eacute;e de surface de grande surface de substrats de diffusion (SERS). &Agrave; l&#39;aide de multiphoton induite par l&#39;exposition d&#39;une photor&eacute;sine commerciale, nous limitons physiquement les sites d&#39;adsorption mol&eacute;culaire disponible pour seulement l&#39;&eacute;lectromagn&eacute;tiques &laquo; points chauds &raquo; sur le substrat. Ce processus emp&ecirc;che les mol&eacute;cules d&#39;adsorber aux sites de faible am&eacute;lioration de SERS, tout en permettant l&#39;adsorption sur les sites de l&#39;extraordinaire am&eacute;lioration de SERS. Pour une diffractions adsorb&eacute;e de mani&egrave;re al&eacute;atoire des mol&eacute;cules benz&egrave;nethiol la moyenne Raman scattering coupe transversale de l&#39;&eacute;chantillon trait&eacute; est 27 fois plus grande que celle d&#39;un substrat SERS non transform&eacute;.

Isolement exalt&eacute;e de surface Raman scattering points chauds &agrave; l&#39;aide de la lithographie multiphoton.

Wir pr&auml;sentieren eine Methode zur Verbesserung der Femtomole-Ebene-Ablaufverfolgung-Erkennung (Neubewerber Molek&uuml;le) mit gro&szlig;fl&auml;chigen Surface enhanced Raman-Streuung (SERS) Substrate. Mit Multiphoton-induzierte Exposition von einem kommerziellen Fotolack, begrenzen wir physisch den verf&uuml;gbaren Molekulare Adsorption-Websites, um nur die elektromagnetische &quot;Hot Spots&quot; auf dem Substrat. Dadurch wird verhindert, dass Molek&uuml;le adsorbierenden auf Seiten der schwachen SERS-Verbesserung, w&auml;hrend sch&ouml;nem Adsorption an den Seiten von au&szlig;ergew&ouml;hnlichen SERS-Verbesserung. F&uuml;r eine nach dem Zufallsprinzip adsorbierten Submonolayer Benzenethiol Molek&uuml;le ist die durchschnittliche Raman-Streuung Querschnitt der verarbeiteten Probe 27 mal gr&ouml;&szlig;er als die von einem unverarbeiteten SERS-Substrat.

Surface enhanced Raman-Streuung Hot-Spots mit multiphoton-Lithografie zu isolieren.

Vi presentiamo un metodo per migliorare il rilevamento traccia a livello femtomole (arrecavano molecole) utilizzando la grande area superficie-enhanced Raman substrati scattering (SERS). Utilizzando l&#39;esposizione multiphoton-indotta di un photoresist commerciale, limitiamo fisicamente i siti di adsorbimento molecolare disponibili a solo l&#39;elettromagnetica &quot;hot spot&quot; sul substrato. Questo processo impedisce molecole di adsorbente per siti di debole enhancement SERS, pur consentendo di adsorbimento a siti di straordinaria valorizzazione SERS. Per un submonolayer casualmente adsorbita di molecole benzenethiol media Raman scattering la sezione trasversale del campione trasformato &egrave; 27 volte maggiore di quello di un substrato SERS non trasformato.

Isolare la superficie-enhanced Raman scattering hot spot utilizzando multifotonica litografia.

&#xC0B0;&#xB780; (SERS) &#xAE30;&#xD310; femtomole &#xC218;&#xC900; &#xCD94;&#xC801; &#xD0D0;&#xC9C0; (10(9) &#xBD84;&#xC790;) &#xD070; &#xC601;&#xC5ED; &#xD45C;&#xBA74; &#xAC15;&#xD654; &#xB77C;&#xB9CC; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xAC1C;&#xC120; &#xD558;&#xB294; &#xBC29;&#xBC95;&#xC744; &#xC18C;&#xAC1C; &#xD569;&#xB2C8;&#xB2E4;. &#xAC8C; &#xC720;&#xB3C4; &#xB178;&#xCD9C; &#xC0C1;&#xC5C5; &#xB808;&#xC9C0;&#xC2A4;&#xD2B8;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC;, &#xBB3C;&#xB9AC;&#xC801;&#xC73C;&#xB85C;&#xB294; &#xC804;&#xC790;&#xAE30; &quot;&#xD56B; &#xC2A4;&#xD3EC;&#xD2B8;&quot; &#xAE30;&#xD310;&#xC5D0; &#xC0AC;&#xC6A9;&#xD560; &#xC218; &#xC788;&#xB294; &#xBD84;&#xC790; &#xD761;&#xCC29; &#xC0AC;&#xC774;&#xD2B8; &#xC81C;&#xD55C;. &#xC774; &#xC774;&#xB807;&#xAC8C; &#xD2B9;&#xBCC4; &#xD55C; SERS &#xD5A5;&#xC0C1;&#xC758; &#xC0AC;&#xC774;&#xD2B8;&#xB85C; &#xD761;&#xCC29;&#xC744; &#xD5C8;&#xC6A9; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC57D;&#xD55C; SERS &#xD5A5;&#xC0C1;&#xC758; &#xC0AC;&#xC774;&#xD2B8; adsorbing&#xC5D0;&#xC11C; &#xBD84;&#xC790;&#xB97C; &#xBC29;&#xC9C0; &#xD569;&#xB2C8;&#xB2E4;. Benzenethiol &#xBD84;&#xC790;&#xC758; &#xD761;&#xCC29;&#xB41C; &#xC784;&#xC758;&#xB85C; submonolayer&#xC5D0; &#xB300; &#xD55C; &#xD6A1;&#xB2E8;&#xBA74; &#xAC00;&#xACF5;&#xB41C; &#xC0D8;&#xD50C;&#xC758; &#xBE44; &#xC0B0; &#xD3C9;&#xADE0; &#xB77C;&#xB9CC; &#xCC98;&#xB9AC; &#xB418;&#xC9C0; &#xC54A;&#xC740; &#xAD00;&#xB828; &#xAE30;&#xD310; &#xBCF4;&#xB2E4; 27 &#xBC30; &#xD070;.

&#xD45C;&#xBA74; &#xAC15;&#xD654; &#xB77C;&#xB9CC; &#xC0B0;&#xB780; &#xD56B;&#xC2A4;&#xD31F; multiphoton &#xB9AC;&#xC18C; &#xADF8;&#xB798;&#xD53C;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xACA9;&#xB9AC; &#xD569;&#xB2C8;&#xB2E4;.

Se presentan un m&eacute;todo para mejorar la detecci&oacute;n de trazas de nivel femtomole (mol&eacute;culas de 10 (9)) con gran superficie surface enhanced Raman sustratos de dispersi&oacute;n (SERS). Usando multifot&oacute;n inducida por la exposici&oacute;n de un comercial photoresist, limitamos f&iacute;sicamente los sitios de adsorci&oacute;n molecular disponible a s&oacute;lo los electromagn&eacute;ticos &quot;puntos calientes&quot; en el substrato. Este proceso impide que las mol&eacute;culas adsorbentes a sitios de realce de SERS d&eacute;bil, permitiendo la adsorci&oacute;n a sitios de realce de SERS extraordinario. Para una submonolayer al azar fijado por adsorci&oacute;n de mol&eacute;culas benzenethiol el promedio Raman dispersi&oacute;n transversal de la muestra procesada es 27 veces m&aacute;s grande que la de un sustrato SERS sin procesar.

Aislamiento surface enhanced Raman scattering puntos calientes mediante litograf&iacute;a multifot&oacute;n.

The response rate has been frequently used as the primary endpoint of phase II cancer clinical trials. It may not be an appropriate endpoint when a new treatment is not expected to produce any tumour shrinkage. When a large database for a historical control is available, the direct comparison of survival curves between a new treatment and the historical control may be made in phase II cancer clinical trials. In this paper, a one-sample log-rank test is introduced for the design and analysis of phase II cancer clinical trials with time-to-event endpoints. Corrections to the one-sample log-rank test are also derived based on the Edgeworth expansion. Simulations showed that the original one-sample log-rank test may be preferred if strictly controlling for type I error is important or when the sample size of a phase II trial is as large as 50, and a corrected one-sample log-rank test is used if the sample size of a phase II trial is small. A data set from a clinical trial conducted by the NCIC Clinical Trials Group is used to illustrate the proposed procedures.

Paul Peng

Department of Gastroenterology

Icahn School of Medicine at Mount Sinai

Diagnosis of Neoplasia in Barrett’s Esophagus using Vital-dye Enhanced Fluorescence Imaging

Paul Peng

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Gastroenterology

Icahn School of Medicine at Mount Sinai

Diagnosis of Neoplasia in Barrett’s Esophagus using Vital-dye Enhanced Fluorescence Imaging

Department of Gastroenterology