Radiating dipoles in photonic crystals

The radiation dynamics of a dipole antenna embedded in a Photonic Crystal are modeled by an initially excited harmonic oscillator coupled to a non--Markovian bath of harmonic oscillators representing the colored electromagnetic vacuum within the crystal. Realistic coupling constants based on the natural modes of the Photonic Crystal, i.e., Bloch waves and their associated dispersion relation, are derived. For simple model systems, well-known results such as decay times and emission spectra are reproduced. This approach enables direct incorporation of realistic band structure computations into studies of radiative emission from atoms and molecules within photonic crystals. We therefore provide a predictive and interpretative tool for experiments in both the microwave and optical regimes.Comment: Phys. Rev. E, accepte

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

Lasers in Orthodontics - A Review

Understanding the various uses of lasers ,is simply to accept, the cutting edge of present day orthodontics .From the daily orthodontic procedure of surface preparation, bonding, debonding till the adjunctive procedures of frenectomy, canine exposure, gingivectomy can be done with lasers. Record maintenance, cast analysis in 3D, holography, spectroscopy, welding, scanning and many more are done with lasers. Future of painless & faster dentistry, in an orthodontics practice, can all be achieved, to the one that understands the use of lasers in the field of orthodontics. Lasers are our tools of tomorrow, only if we are ready with the knowledge of it today

ASC-AD Penetration Modeling FY05 Status Report

Sandia currently lacks a high fidelity method for predicting loads on and subsequent structural response of earth penetrating weapons. This project seeks to test, debug, improve and validate methodologies for modeling earth penetration. Results of this project will allow us to optimize and certify designs for the B61-11, Robust Nuclear Earth Penetrator (RNEP), PEN-X and future nuclear and conventional penetrator systems. Since this is an ASC Advanced Deployment project the primary goal of the work is to test, debug, verify and validate new Sierra (and Nevada) tools. Also, since this project is part of the V&V program within ASC, uncertainty quantification (UQ), optimization using DAKOTA [1] and sensitivity analysis are an integral part of the work. This project evaluates, verifies and validates new constitutive models, penetration methodologies and Sierra/Nevada codes. In FY05 the project focused mostly on PRESTO [2] using the Spherical Cavity Expansion (SCE) [3,4] and PRESTO Lagrangian analysis with a preformed hole (Pen-X) methodologies. Modeling penetration tests using PRESTO with a pilot hole was also attempted to evaluate constitutive models. Future years work would include the Alegra/SHISM [5] and AlegrdEP (Earth Penetration) methodologies when they are ready for validation testing. Constitutive models such as Soil-and-Foam, the Sandia Geomodel [6], and the K&C Concrete model [7] were also tested and evaluated. This report is submitted to satisfy annual documentation requirements for the ASC Advanced Deployment program. This report summarizes FY05 work performed in the Penetration Mechanical Response (ASC-APPS) and Penetration Mechanics (ASC-V&V) projects. A single report is written to document the two projects because of the significant amount of technical overlap

Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer

PURPOSE: To evaluate noninvasive molecular imaging methods as correlative biomarkers of therapeutic efficacy of cetuximab in human colorectal cancer cell line xenografts grown in athymic nude mice. The correlation between molecular imaging and immunohistochemical analysis to quantify epidermal growth factor (EGF) binding, apoptosis, and proliferation was evaluated in treated and untreated tumor-bearing cohorts. EXPERIMENTAL DESIGN: Optical imaging probes targeting EGF receptor (EGFR) expression (NIR800-EGF) and apoptosis (NIR700-Annexin V) were synthesized and evaluated in vitro and in vivo. Proliferation was assessed by 3′-[(18)F]fluoro-3′-deoxythymidine ([(18)F] FLT) positron emission tomography. Assessment of inhibition of EGFR signaling by cetuximab was accomplished by concomitant imaging of NIR800-EGF, NIR700-Annexin V, and [(18)F] FLT in cetuximab-sensitive (DiFi) and insensitive (HCT-116) human colorectal cancer cell line xenografts. Imaging results were validated by measurement of tumor size and immunohistochemical analysis of total and phosphorylated EGFR, caspase-3, and Ki-67 immediately following in vivo imaging. RESULTS: NIR800-EGF accumulation in tumors reflected relative EGFR expression and EGFR occupancy by cetuximab. NIR700-Annexin V accumulation correlated with cetuximab-induced apoptosis as assessed by immunohistochemical staining of caspase-3. No significant difference in tumor proliferation was noted between treated and untreated animals by [(18)F] FLT positron emission tomography or Ki-67 immunohistochemistry. CONCLUSIONS: Molecular imaging can accurately assess EGF binding, proliferation, and apoptosis in human colorectal cancer xenografts. These imaging approaches may prove useful for serial, noninvasive monitoring of the biological effects of EGFR inhibition in preclinical studies. It is anticipated that these assays can be adapted for clinical use

Multi-omic characterization reveals a distinct molecular landscape in young-onset pancreatic cancer

PurposeUsing a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between young-onset pancreatic cancer (YOPC; <50-yrs.) and average-onset pancreatic cancer (AOPC; ≥70-yrs.) patients. MethodsWe analyzed matched whole-transcriptome and DNA sequencing data from 2430 patient samples (YOPC, n=292; AOPC, n=2138) from the Caris Life Sciences database (Phoenix, AZ). Immune deconvolution was performed using the quanTIseq pipeline. Overall survival (OS) data was obtained from insurance claims (n=4928); Kaplan-Meier estimates were calculated for age-and molecularly-defined cohorts. Significance was determined as FDR-corrected P -values ( Q )<0.05. ResultsYOPC patients had higher proportions of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H), BRCA2 -mutant, and PALB2 -mutant tumors compared with AOPC patients, but fewer SMAD4-, RNF43-, CDKN2A- , and SF3B1- mutant tumors. Notably, YOPC patients demonstrated significantly lower incidence of KRAS mutations compared with AOPC patients (81.3% vs. 90.9%; Q =0.004). In the KRAS- wildtype subset (n=227), YOPC tumors demonstrated fewer TP53 mutations and were more likely driven by NRG1 and MET fusions, while BRAF fusions were exclusively observed in AOPC patients. Immune deconvolution revealed significant enrichment of natural killer (NK) cells, CD8 + T cells, monocytes, and M2 macrophages in YOPC patients relative to AOPC patients, which corresponded with lower rates of HLA-DPA1 homozygosity. There was an association with improved OS in YOPC patients compared with AOPC patients with KRAS -wildtype tumors (median 16.2 [YOPC- KRAS WT ] vs. 10.6 [AOPC- KRAS WT ] months; P =0.008) but not KRAS -mutant tumors ( P =0.084). ConclusionIn this large, real-world multi-omic characterization of age-stratified molecular differences in PDAC, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications

Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer

PURPOSE Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between patients with young-onset pancreatic cancer (YOPC; younger than 50 years) and patients with average-onset pancreatic cancer (AOPC; 70 years and older). METHODS We analyzed matched whole-transcriptome and DNA sequencing data from 2,430 patient samples (YOPC, n = 292; AOPC, n = 2,138) from the Caris Life Sciences database (Phoenix, AZ). Immune deconvolution was performed using the quanTIseq pipeline. Overall survival (OS) data were obtained from insurance claims (n = 4,928); Kaplan-Meier estimates were calculated for age- and molecularly defined cohorts. Significance was determined as FDR-corrected P values ( Q) < .05. RESULTS Patients with YOPC had higher proportions of mismatch repair–deficient/microsatellite instability-high, BRCA2-mutant, and PALB2-mutant tumors compared with patients with AOPC, but fewer SMAD4-, RNF43-, CDKN2A-, and SF3B1-mutant tumors. Notably, patients with YOPC demonstrated significantly lower incidence of KRAS mutations compared with patients with AOPC (81.3% v 90.9%; Q = .004). In the KRAS wild-type subset (n = 227), YOPC tumors demonstrated fewer TP53 mutations and were more likely driven by NRG1 and MET fusions, whereas BRAF fusions were exclusively observed in patients with AOPC. Immune deconvolution revealed significant enrichment of natural killer cells, CD8 + T cells, monocytes, and M2 macrophages in patients with YOPC relative to patients with AOPC, which corresponded with lower rates of HLA-DPA1 homozygosity. There was an association with improved OS in patients with YOPC compared with patients with AOPC with KRAS wild-type tumors (median, 16.2 [YOPC- KRAS WT ] v 10.6 [AOPC- KRAS WT ] months; P = .008) but not KRAS-mutant tumors ( P = .084). CONCLUSION In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications. Distinct molecular landscape of #YoungOnset #PancreaticCancer #pancsm using @carisls data from @DrJashDatta #DattaLab @IOgobuiro #CARISPOA & #CPC (in @JCOPO_ASCO)—the parentheses are optional since it will be coming from this handle

Multiomic characterization to reveal a distinct molecular landscape in young-onset pancreatic cancer

594 Background: Young-onset pancreatic cancer (YOPC; < 50 years at diagnosis) has been associated with male preponderance, extensive smoking history, and a trend towards improved survival compared with average-onset pancreatic cancer (AOPC; ≥70 years). However, the genomic and transcriptomic correlates underlying these clinical differences are incompletely understood. Using a large matched genomic-transcriptomic next-generation sequencing (NGS) dataset, we sought to characterize the distinct molecular landscape associated with YOPC compared with AOPC. Methods: A total of 2430 pancreatic ductal adenocarcinoma NGS samples (YOPC n = 292; AOPC n = 2138) with matched whole-transcriptome (NovaSeq) and DNA (NextSeq, 592-gene or NovaSeq, whole-exome) sequencing data were analyzed (Caris Life Sciences, Phoenix, AZ). Immune deconvolution was performed using the QuantiSeq pipeline. Limited clinical data precluded stage- and treatment-stratified comparisons between cohorts. Overall survival (OS) was obtained from insurance claims, and Kaplan-Meier estimates were calculated for age- and molecularly-defined cohorts. Significance was determined as FDR-corrected P-values (Q) < 0.05. Results: Of 2430 PDAC patients undergoing NGS, YOPC patients (median age 46 years) were more likely to be male (65% vs. 52%; P < 0.001) and current smokers (32% vs. 11%; P = 0.02) compared with AOPC patients (median age 75 years). YOPC patients had higher proportions of mismatch repair-deficient (MMR)/MSI-H (2.8% vs. 0.8%, P = 0.001), BRCA2-mutant (4.7% vs 2.1%, P = 0.009), and PALB2-mutant (1.4% vs 0.5%, P = 0.04) tumors compared with AOPC patients, while tumors in AOPC patients had more frequent SMAD4 (20.1% vs. 14.7%, P = 0.03), RNF43 (6.3% vs. 2.5%, P = 0.012), CDKN2A (24.8% vs. 19.2%, P = 0.04), and SF3B1 (2.7% vs. 0.7%, P = 0.04) mutations. YOPC patients also demonstrated lower HLA-DPA1 homozygosity (55.2% vs. 64.1%, Q < 0.05) vs. AOPC patients. Notably, YOPC patients demonstrated significantly lower incidence of KRAS-mutant (81.3% vs. 90.9%, Q < 0.01) tumors compared with AOPC patients. In the KRAS-wildtype subset (n = 225), YOPC tumors were more likely to be driven by NRG1 and MET fusions, while BRAF fusions were exclusively observed in AOPC patients. Computationally inferred immune deconvolution revealed enrichment of NK cell (Q = 0.04) and M2 macrophages (Q = 0.01) populations in YOPC tumors. There was an association with improved OS in YOPC patients with KRAS-wildtype (median 22.4 [YOPC- KRAS WT ] vs. 15.1 [AOPC- KRAS WT ] months, P = 0.02) but not KRAS-mutant (P = 0.28), tumors compared with AOPC patients. Conclusions: In this large real-world multi-omic characterization of age-stratified molecular differences in PDAC, YOPC is associated with a distinct molecular landscape compared with AOPC. These data reveal molecular features of YOPC with prognostic and therapeutic implications