Plasmon assisted photonic crystal quantum dot sensors

We report Quantum Dot Infrared Detectors (QDIP) where light coupling to the self assembled quantum dots is achieved through plasmons occurring at the metal-semiconductor interface. The detector structure consists of an asymmetric InAs/InGaAs/GaAs dots-in-a-well (DWELL) structure and a thick layer of GaAs sandwiched between two highly doped n-GaAs contact layers, grown on a semi-insulating GaAs substrate. The aperture of the detector is covered with a thin metallic layer which along with the dielectric layer confines light in the vertical direction. Sub-wavelength two-dimensional periodic patterns etched in the metallic layer covering the aperture of the detector and the active region creates a micro-cavity that concentrate light in the active region leading to intersubband transitions between states in the dot and the ones in the well. The sidewalls of the detector were also covered with metal to ensure that there is no leakage of light into the active region other than through the metal covered aperture. An enhanced spectral response when compared to the normal DWELL detector is obtained despite the absence of any aperture in the detector. The spectral response measurements show that the Long Wave InfraRed (LWIR) region is enhanced when compared to the Mid Wave InfraRed (MWIR) region. This may be due to coupling of light into the active region by plasmons that are excited at the metal-semiconductor interface. The patterned metal-dielectric layers act as an optical resonator thereby enhancing the coupling efficiency of light into the active region at the specified frequency. The concept of plasmon-assisted coupling is in principle technology agnostic and can be easily integrated into present day infrared sensors

Plasmon assisted photonic crystal quantum dot sensors

We report Quantum Dot Infrared Detectors (QDIP) where light coupling to the self assembled quantum dots is achieved through plasmons occurring at the metal-semiconductor interface. The detector structure consists of an asymmetric InAs/InGaAs/GaAs dots-in-a-well (DWELL) structure and a thick layer of GaAs sandwiched between two highly doped n-GaAs contact layers, grown on a semi-insulating GaAs substrate. The aperture of the detector is covered with a thin metallic layer which along with the dielectric layer confines light in the vertical direction. Sub-wavelength two-dimensional periodic patterns etched in the metallic layer covering the aperture of the detector and the active region creates a micro-cavity that concentrate light in the active region leading to intersubband transitions between states in the dot and the ones in the well. The sidewalls of the detector were also covered with metal to ensure that there is no leakage of light into the active region other than through the metal covered aperture. An enhanced spectral response when compared to the normal DWELL detector is obtained despite the absence of any aperture in the detector. The spectral response measurements show that the Long Wave InfraRed (LWIR) region is enhanced when compared to the Mid Wave InfraRed (MWIR) region. This may be due to coupling of light into the active region by plasmons that are excited at the metal-semiconductor interface. The patterned metal-dielectric layers act as an optical resonator thereby enhancing the coupling efficiency of light into the active region at the specified frequency. The concept of plasmon-assisted coupling is in principle technology agnostic and can be easily integrated into present day infrared sensors

A Multi-Institutional Phase II Trial of Preoperative Full-Dose Gemcitabine and Concurrent Radiation for Patients With Potentially Resectable Pancreatic Carcinoma

We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41411/1/10434_2006_Article_9435.pd

Novel post-synthetic generation, isomeric resolution, and characterization of Fapy-dG within oligodeoxynucleotides: differential anomeric impacts on DNA duplex properties

Accumulation of damaged guanine nucleobases within genomic DNA, including the imidazole ring opened N6-(2-Deoxy-α,β-D-erythro-pentafuranosyl)-2,6-diamino-4-hydroxy-5-formylamidopyrimidine (Fapy-dG), is associated with progression of age-related diseases and cancer. To evaluate the impact of this mutagenic lesion on DNA structure and energetics, we have developed a novel synthetic strategy to incorporate cognate Fapy-dG site-specifically within any oligodeoxynucleotide sequence. The scheme involves the synthesis of an oligonucleotide precursor containing a 5-nitropyrimidine moiety at the desired lesion site via standard solid-phase procedures. Following deprotection and isolation, the Fapy-dG lesion is generated by catalytic hydrogenation and subsequent formylation. NMR assignment of the Fapy-dG lesion (X) embedded within a TXT trimer reveals the presence of rotameric and anomeric species. The latter have been characterized by synthesizing the tridecamer oligodeoxynucleotide d(GCGTACXCATGCG) harboring Fapy-dG as the central residue and developing a protocol to resolve the isomeric components. Hybridization of the chromatographically isolated fractions with their complementary d(CGCATGCGTACGC) counterpart yields two Fapy-dG·C duplexes that are differentially destabilized relative to the canonical G·C parent. The resultant duplexes exhibit distinct thermal and thermodynamic profiles that are characteristic of α- and β-anomers, the former more destabilizing than the latter. These anomer-specific impacts are discussed in terms of differential repair enzyme recognition, processing and translesion synthesis

DNA adducts of aristolochic acid II: total synthesis and site-specific mutagenesis studies in mammalian cells

Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species. Ingestion of these acids either in the form of herbal remedies or as contaminated wheat flour causes a dose-dependent chronic kidney failure characterized by renal tubulointerstitial fibrosis. In ∼50% of these cases, the condition is accompanied by an upper urinary tract malignancy. The disease is now termed aristolochic acid nephropathy (AAN). AA-I is largely responsible for the nephrotoxicity while both AA-I and AA-II are genotoxic. DNA adducts derived from AA-I and AA-II have been isolated from renal tissues of patients suffering from AAN. We describe the total synthesis, de novo, of the dA and dG adducts derived from AA-II, their incorporation site-specifically into DNA oligomers and the splicing of these modified oligomers into a plasmid construct followed by transfection into mouse embryonic fibroblasts. Analysis of the plasmid progeny revealed that both adducts blocked replication but were still partly processed by DNA polymerase(s). Although the majority of coding events involved insertion of correct nucleotides, substantial misincorporation of bases also was noted. The dA adduct is significantly more mutagenic than the dG adduct; both adducts give rise, almost exclusively, to misincorporation of dA, which leads to AL-II-dA→T and AL-II-dG→T transversions

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Visual Representations as an Aid to Concept Generation

This paper describes our initial efforts to develop a 3D visualization tool that is part of an overall effort to create a Concept Generator, an automated conceptual design tool, to aid a designer during the early stages of the design process. The use of CAD software has diversified into various disciplines that have made use of simulation and software modeling tools for reasons that range from improving accuracy in design, reduction in lead times, and simple visualizations. The impacts of CAD software have been beneficial in industry and education. Described in this paper is the use of low-memory VRML models to represent components. These low memory models have been created to achieve several goals that complement the overall objectives of the concept generator. One key goal is that the concept generator be accessible via the web, thus the need for low-memory and low-data models. Additionally, as the concept generator is intended for usage during early conceptual design, the 3D visualization tool allows the creation of models upon which basic manipulations can be performed so that a designer can get an initial feel of the structure that his product is going to take. Our research has enabled us to create a basic visualization tool which, while similar in nature to most other CAD software tools, is unique, in that it represents the link, as a visual interface, between a formulated concept and the designer. The paper presents the research problem, an overview of the architecture of the software tool and some preliminary results on visual representations as an aid to concept generation