Acousto-Optic Filter Device Using Proton-Exchanged Waveguides

This thesis describes an investigation of the acoustic and optical properties of waveguides fabricated by proton-exchange from dilute melts. Initially a narrow-band acousto-optic filter, based on the Integrated Optical Spectrum Analyser, is investigated. The device is proposed to detect and separate two acoustic frequencies and it was envisaged that the angular separation of the acoustically diffracted optical beams could be performed within a channel waveguide structure. However, analysis has indicated the impracticality of the device when operational requirements are considered. The dilute melt proton-exchange process for waveguide fabrication on LiNbO3 substrates is characterised. The waveguides have step-index profiles and are stable immediately after exchange. The waveguide depth increases as a t function of exchange time, so a temperature dependent diffusion coefficient can be assigned and this coefficient fits an Arrhenius law. In comparison with pure melt proton-exchange waveguides, dilute melt waveguides exhibit less in-plane scattering and Rutherford Back-Scattering Spectrometry (RBS) measurements indicate a significantly lower level of latice disorder. Close agreement is found between optical measurements of waveguide depth (assuming a step-index profile) and RBS data for a range of melt dilutions, thus supporting the step-index model as an appropriate profile for the refractive index. Multi-mode waveguides are fabricated on Y-cut LiNbO3 substrates without surface damage, though short post annealing is necessary to relieve induced strain. Planar optical waveguides are fabricated on X-cut and Z-cut LiTaO3 substrates from dilute melts without the need for prolonged post annealing. High quality waveguides with low in-plane scattering levels are produced. The refractive index change is similar to that achieved with titanium indiffused LiNbO3 and RBS measurements indicate a region of lattice disorder similar to that observed with LiNbO3. A line-focus-beam Scanning Acoustic Microscope is used to investigate the acoustical properties of dilute melt proton-exchanged LiNbO3 waveguides. Substantial changes (as much as 5%) in the surface acoustic wave (SAW) propagation velocity due to proton-exchange are observed on all three major-axis crystal cuts, with both increases and decreases in velocity occurring, depending on propagation direction. Changes in acoustic attenuation are also observed. A simple model is used to calculate the 'true' velocity change for a proton-exchange region without the infulence of a virgin LiNbO3 base and the acoustic anisotropy exhibited by the X-and Y-cut LiNbO3 appears greater than that of virgin LiNbO3. A theoretical analysis based on the quasi-static approximation is used to determine the overlap integral between the acoustic and optical waves in proton-exchange waveguides. The overlap integral falls with variations in index profile from step-index to graded-index and the domination of the acousto-optic interaction by the electro-optic effect is emphasized. The analysis indicates that shallow (~3mum) step-index waveguides are required for maximum interaction efficiency and that prolonged annealing results in reduced interaction efficiencies. Acousto-optic devices are fabricated on dilute melt proton-exchanged LiNbO3 and LiTaO3 waveguides using simple, non-optimal, electrode structures. For 7. 5 minutes exchange in 0.5% dilute melt on X-cut LiNbO3 at 22

Projection of Indian summer monsoon climate in 2041–2060 by multiregional and global climate models

Using the results from three global climate models (GCMs) and seven regional climate models (RCMs), summer monsoon climate changes during 2041–2060 over Indian Peninsula are projected based on the Intergovernmental Panel on Climate Change A1B emission scenario. For the control climate of 1981–2000, most nested RCMs can improve the temporal-spatial distributions of temperature and precipitation over Indian Peninsula compared to the driving GCM of European Centre/Hamburg Fifth Generation (ECHAM5). Most nested RCMs produce advanced monsoon onset for control climate, which is similar to the result of driving GCM of ECHAM5. For future climate widespread summer warming is projected over Indian Peninsula by all climate models, with the Multi-RCMs ensemble mean (MME) temperature increasing of 1°C to 2.5°C and the maximum warming center located in northern Indian Peninsula. The disagreement in precipitation changes projected by RCMs indicates that the surface climate change on regional scale is not only dominated by the large-scale forcing which is provided by driving GCM but also sensitive to RCM\u27 internal physics. Overall, wetter condition is shown in MME with significant increase of monsoon rainfall over southern India, with intermodel spread ranging from −8.9% to 14.8%. Driven by same GCM, most RCMs project advanced monsoon onset while delayed onset is found in two Regional Climate Model (RegCM3) projections, indicating uncertainty can be expected in the Indian Summer Monsoon onset. All climate models except Conformal-Cubic Atmospheric Model with equal resolution (referred as CCAMP) and two RegCM3 models project stronger summer monsoon during 2041–2060

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The impact of emotional intelligence in health care professionals on caring behaviour towards patients in clinical and long-term care settings: Findings from an integrative review

Background: Over recent years there has been criticism within the United Kingdom’s health service regarding a lack of care and compassion, resulting in adverse outcomes for patients. The impact of emotional intelligence in staff on patient health care outcomes has been recently highlighted. Many recruiters now assess emotional intelligence as part of their selection process for health care staff. However, it has been argued that the importance of emotional intelligence in health care has been overestimated. Objectives: To explore relationships between emotional intelligence in health care professionals, and caring behaviour. To further explore any additional factors related to emotional intelligence that may impact upon caring behaviour. Design: An integrative review design was used. Data sources: Psychinfo, Medline, CINAHL Plus, Social Sciences Citation Index, Science Citation Index, and Scopus were searched for studies from 1995 to April 2017. Review methods: Studies providing quantitative or qualitative exploration of how any healthcare professionals’ emotional intelligence is linked to caring in healthcare settings were selected. Results: Twenty two studies fulfilled the inclusion criteria. Three main types of health care professional were identified: nurses, nurse leaders, and physicians. Results indicated that the emotional intelligence of nurses was related to both physical and emotional caring, but emotional intelligence may be less relevant for nurse leaders and physicians. Age, experience, burnout, and job satisfaction may also be relevant factors for both caring and emotional intelligence. Conclusions: This review provides evidence that developing emotional intelligence in nurses may positively impact upon certain caring behaviours, and that there may be differences within groups that warrant further investigation. Understanding more about which aspects of emotional intelligence are most relevant for intervention is important, and directions for further large scale research have been identified

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies