Timothy J. Fawcett

GaN resistive hydrogen gas sensors

GaN epilayers grown by organometallic vapor phase epitaxy have been used to fabricate resistive gas sensors with a pair of planar ohmic contacts. Detectible sensitivity to H2 gas for a wide range of gas mixtures in an Ar ambient has been realized; the lowest concentration tested is ∼0.1% H2 (in Ar), well below the lower combustion limit in air. No saturation of the signal is observed up to 100% H2 flow. Real-time response to H2 shows a clear and sharp response with no memory effects during the ramping cycles of H2 concentration. The change in current at a fixed voltage to hydrogen was found to change with sensor geometry. This appears to be consistent with a surface-adsorption-induced change of conductivity; a detailed picture of the gas sensing mechanism requires further systematic studies.

Wide-range (0.33%–100%) 3C–SiC resistive hydrogen gas sensor development

Silicon carbide (SiC) resistive hydrogen gas sensors have been fabricated and tested. NiCr planar ohmic contacts were deposited on both a 4μm 3C–SiC epitaxial film grown on n-type Si(001) and directly on Si to form the resistive sensor structures. Detection at concentrations as low as 0.33% and as high as 100% (H2 in Ar) was observed with the 3C–SiC sensor while the Si sensor saturated at 40%. The 3C–SiC sensors show a remarkable range of sensitivity without any saturation effects typically seen in other solid-state hydrogen gas sensors. Under a constant 2V bias, these sensors demonstrated an increase in current up to 17mA upon exposure to pure H2. Preliminary experiments aimed at determining the gas sensing mechanism of these devices have been conducted and are also reported.

Thermal detection mechanism of SiC based hydrogen resistive gas sensors

Silicon carbide (SiC) resistive hydrogen gas sensors have been fabricated and tested. Planar NiCr contacts were deposited on a thin 3C-SiC epitaxial film grown on thin Si wafers bonded to polycryst ...

Hydrogen Gas Sensors using 3C-SiC/Si Epitaxial Layers

A hydrogen gas sensor consisting of planar electrical NiCr contacts formed on the surface of a 3C-SiC epitaxial layer grown on Si(001) has been fabricated and tested. The n-type, 4 μm thick 3C-SiC epi layer was grown under low-pressure conditions with an approximate doping density of 10 cm. This sensor demonstrates a two-fold repeatable improvement in stability and sensitivity in comparison to an n-type Si sensor of the same type also fabricated and tested under the same conditions. Both the 3C-SiC/Si and Si sensors operated up to 250 oC; however, the 3C-SiC/Si sensor was able to detect hydrogen at concentrations far exceeding that of the Si sensor. The 3CSiC/Si device detected hydrogen at concentrations ranging from 0.333% to 100% in Ar while the Si sensor could only detect hydrogen at concentrations ranging from 2% to 100% in Ar. Based on this preliminary data, it has been shown that 3C-SiC/Si hydrogen sensors of this type have a larger dynamic range and higher sensitivity to hydrogen than Si sensors, thus allowing for harsh environmental applications.

Lung tumor exome files with T-cell receptor recombinations: a mouse model of T-cell infiltrates reflecting mutation burdens

Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis. Results indicated that exomes representing lung adenomas reveal significantly more TcR recombinations than do exomes from lung adenocarcinomas; and that exome files representing high mutation adenomas, arising from chemical mutagens, have more TcR recombinations than do exome files from low mutation adenomas arising from an activating Kras mutation. The latter results were also consistent with a similar analysis performed on human lung adenocarcinoma exomes. The mouse and human results for obtaining TcR recombination reads from tumor specimen exomes are consistent with human tumor biology results indicating that adenomas and high mutation cancers are sites of high immune activity. The results indicate hitherto unappreciated opportunities for the use of tumor specimen exome files, particularly from experimental animal models, to study the connection between the adenoma stage of tumorigenesis, or high cancer mutation rates, and high level lymphocyte infiltrates.

Cytoskeleton and ECM tumor mutant peptides: Increased protease sensitivities and potential consequences for the HLA class I, mutant epitope reservoir

Cytoskeleton and extracellular matrix‐related proteins (CECMPs) represent the most common class of cancer mutants, owing to the large size of their coding regions and the randomness of mutagenesis. We used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to proteases relevant to melanoma and on the binding affinities for HLA class I. CECMP peptides with AA substitutions overwhelmingly reflect increased sensitivity to proteases implicated in melanoma development (MME, CTSS, MMP2, CTSD, CTSL) in comparison to the wild‐type peptide sequences. Furthermore, peptides with AA substitutions representing increased peptide protease sensitivity also represented relatively high binding affinities for HLA class I allelic variants. These analyses raise the question of whether increased protease sensitivity, of mutant cancer peptides represents a significant increase in the availability of cancer mutant, HLA class I epitopes and a hitherto unappreciated aspect of cancer cell immunogenicity, particularly in the case of melanoma?

T-cell receptor-β V and J usage, in combination with particular HLA class I and class II alleles, correlates with cancer survival patterns

Class I and class II HLA proteins, respectively, have been associated with subsets of V(D)J usage resulting from recombination of the T-cell receptor (TCR) genes. Additionally, particular HLA alleles, in combination with dominant TCR V(D)J recombinations, have been associated with several autoimmune diseases. The recovery of TCR recombination reads from tumor specimen exome files has allowed rapid and extensive assessments of V(D)J usage, likely for cancer resident T-cells, across relatively large cancer datasets. The results from this approach, in this report, have permitted an extensive alignment of TCR-β VDJ usage and HLA class I and II alleles. Results indicate the correlation of both better and worse cancer survival rates with particular TCR-β, V and J usage-HLA allele combinations, with differences in median survival times ranging from 7 to 130 months, depending on the cancer and the specific TCR-β V and J usage/HLA class allele combination.

Impedance spectroscopy as an indicator for successful in vivo electric field mediated gene delivery in a murine model

In vivo gene electro transfer technology has been very successful both in animal models and in clinical trials over the past 20years. However, variable transfection efficiencies can produce inconsistent outcomes. This can be due to differences in tissue architecture and/or chemical composition which may effectively create unique biological environments from subject to subject that may respond differently to the identical electric pulses. This study investigates the integration of impedance spectroscopy into the gene electro transfer process to measure murine skin impedance spectra before, during (after pulse delivery), and after gene electro transfer pulse application to determine if changes in impedance correlate with reporter gene expression. Both post-treatment impedance spectra and gene expression were dependent upon the applied electric field strength. These results indicate that alterations in tissue impedance produced by the applied electric field represent an excellent parameter to predict degrees of transfection and gene expression. These results could ultimately be used to alter pulsing parameters in order to optimize delivery/expression.

Germline cytoskeletal and extra-cellular matrix-related single nucleotide variations associated with distinct cancer survival rates

BACKGROUND Human mutagenesis has a large stochastic component. Thus, large coding regions, especially cytoskeletal and extra-cellular matrix protein (CECMP) coding regions are particularly vulnerable to mutations. Recent results have verified a high level of somatic mutations in the CECMP coding regions in the cancer genome atlas (TCGA), and a relatively common occurrence of germline, deleterious mutations in the TCGA breast cancer dataset. METHODS The objective of this study was to determine the correlations of CECMP coding region, germline nucleotide variations with both overall survival (OS) and disease-free survival (DFS). TCGA, tumor and blood variant calling files (VCFs) were intersected to identify germline SNVs. SNVs were then annotated to determine potential consequences for amino acid (AA) residue biochemistry. RESULTS Germline SNVs were matched against somatic tumor SNVs (i.e., tumor mutations) over twenty TCGA datasets to identify 23 germline-somatic matched, deleterious AA substitutions in coding regions for FLG, TTN, MUC4, and MUC17. CONCLUSIONS The germline-somatic matched SNVs, in particular for MUC4, extensively implicated in cancer development, represented highly, statistically significant effects on OS and DFS survival rates. The above results contribute to the establishment of what is potentially a new class of inherited cancer-facilitating genes, namely dominant negative tumor suppressor proteins.

Overlap of the cancer genome atlas and the immune epitope database

Mutant peptides resulting from cancer drivers or passenger mutations are expected to have the potential to serve as a basis for cancer vaccines. However, a number of parameters regulate vaccine-associated immunogenicity, including the suitability of a peptide for binding to an antigen-presenting molecule or antibody. In order to obtain a basic indication of the prospect of human cancer epitope identification via current database development strategies, an overlap of the mutant Homo sapiens epitopes listed on the Immune Epitope Database (IEDB) and the mutant peptides indicated by The Cancer Genome Atlas (TCGA) somatic mutation database was obtained. No putative TCGA mutant peptides were detected among the 8,890 14–18 amino acid (AA) IEDB peptides available. In total, 3 IEDB mutant epitopes that encompassed a TCGA mutant AA position, but did not overlap the exact position of the TCGA mutant AA, were detected. The results of the present analysis confirm that verification of certain aspects of cancer epitope function can be obtained via the continued and systematic expansion of databases representing human protein epitopes. However, the analysis also indicates that there is relatively limited systematic information available regarding antigen-presenting molecule epitopes and cancer-related mutant peptides.