Demonstration of a Bias Tunable Quantum Dots-in-a-well Focal Plane Array

Infrared detectors based on quantum wells and quantum dots have attracted a lot of attention in the past few years. Our previous research has reported on the development of the first generation of quantum dots-in-a-well (DWELL) focal plane arrays, which are based on InAs quantum dots embedded in an InGaAs well having GaAs barriers. This focal plane array has successfully generated a two-color imagery in the mid-wave infrared (i.e. 3–5 μm) and the long-wave infrared (i.e. 8–12 μm) at a fixed bias voltage. Recently, the DWELL device has been further modified by embedding InAs quantum dots in InGaAs and GaAs double wells with AlGaAs barriers, leading to a less strained InAs/InGaAs/GaAs/AlGaAs heterostructure. This is expected to improve the operating temperature while maintaining a low dark current level. This paper examines 320 × 256 double DWELL based focal plane arrays that have been fabricated and hybridized with an Indigo 9705 read-out integrated circuit using Indium-bump (flip-chip) technology. The spectral tunability is quantified by examining images and determining the transmittance ratio (equivalent to the photocurrent ratio) between mid-wave and long-way infrared filter targets. Calculations were performed for a bias range from 0.3 to 1.0 V. The results demonstrate that the mid-wave transmittance dominates at these low bias voltages, and the transmittance ratio continuously varies over different applied biases. Additionally, radiometric characterization, including array uniformity and measured noise equivalent temperature difference for the double DWELL devices is computed and compared to the same results from the original first generation DWELL. Finally, higher temperature operation is explored. Overall, the double DWELL devices had lower noise equivalent temperature difference and higher uniformity, and worked at higher temperature (70 K and 80 K) than the first generation DWELL device

The Nature of SN 1961V

The nature of SN 1961V has been uncertain. Its peculiar optical light curve and slow expansion velocity are similar to those of super-outbursts of luminous blue variables (LBVs), but its nonthermal radio spectral index and declining radio luminosity are consistent with decades-old supernovae (SNe). We have obtained Hubble Space Telescope STIS images and spectra of the stars in the vicinity of SN 1961V, and find Object 7 identified by Filippenko et al. to be the closest to the optical and radio positions of SN 1961V. Object 7 is the only point source detected in our STIS spectra and only its H-alpha emission is detected; it cannot be the SN or its remnant because of the absence of forbidden lines. While the H-alpha line profile of Object 7 is remarkably similar to that of eta Car, the blue color (similar to an A2Ib supergiant) and lack of appreciable variability are unlike known post-outburst LBVs. We have also obtained Very Long Baseline Array (VLBA) observations of SN 1961V at 18 cm. The non-detection of SN 1961V places a lower limit on the size of the radio-emitting region, 7.6 mas or 0.34 pc, which implies an average expansion velocity in excess of 4,400 km/s, much higher than the optical expansion velocity measured in 1961. We conclude the following: (1) A SN occurred in the vicinity of SN 1961V a few decades ago. (2) If the SN 1961V light maximum originates from a giant eruption of a massive star, Object 7 is the most probable candidate for the survivor, but its blue color and lack of significant variability are different from a post-outburst eta Car. (3) The radio SN and Object 7 could be physically associated with each other through a binary system. (4) Object 7 needs to be monitored to determine its nature and relationship to SN 1961V.Comment: 16 pages, 3 figures, accepted by the Astronomical Journal for the 2004 May issu

International cancer microbiome consortium consensus statement on the role of the human microbiome in carcinogenesis

Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer

Radiosensitivity in breast cancer assessed by the Comet and micronucleus assays

Spontaneous and radiation-induced genetic instability of peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=50) was examined using the single-cell gel electrophoresis (Comet) assay and a modified G2 micronucleus (MN) test. Cells from apparently healthy donors (n=16) and from cancer patients (n=9) with an adverse early skin reaction to radiotherapy (RT) served as references. Nonirradiated cells from the three tested groups exhibited similar baseline levels of DNA fragmentation assessed by the Comet assay. Likewise, the Comet analysis of in vitro irradiated (5 Gy) cells did not reveal any significant differences among the three groups with respect to the initial and residual DNA fragmentation, as well as the DNA repair kinetics. The G2 MN test showed that cells from cancer patients with an adverse skin reaction to RT displayed increased frequencies of both spontaneous and radiation-induced MN compared to healthy control or the group of unselected BC patients. Two patients from the latter group developed an increased early skin reaction to RT, which was associated with an increased initial DNA fragmentation in vitro only in one of them. Cells from the other BC patient exhibited a striking slope in the dose–response curve detected by the G2 MN test. We also found that previous RT strongly increased both spontaneous and in vitro radiation-induced MN levels, and to a lesser extent, the radiation-induced DNA damage assessed by the Comet assay. These data suggest that clinical radiation may provoke genetic instability and/or induce persistent DNA damage in normal cells of cancer patients, thus leading to increased levels of MN induction and DNA fragmentation after irradiation in vitro. Therefore, care has to be taken when blood samples collected postradiotherapeutically are used to assess the radiosensitivity of cancer patients

Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression

Author Summary Genetic variants on chromosome 9p21 have been associated with several important diseases including coronary artery disease, diabetes, and multiple cancers. Most of the risk variants in this region do not alter any protein sequence and are therefore likely to act by influencing the expression of nearby genes. We investigated whether chromosome 9p21 variants are correlated with expression of the three nearest genes ( CDKN2A , CDKN2B , and ANRIL ) which might mediate the association with disease. Using two different techniques to study effects on expression in blood from two separate populations of healthy volunteers, we show that variants associated with disease are all correlated with ANRIL expression, but associations with the other two genes are weaker and less consistent. Multiple genetic variants are independently associated with expression of all three genes. Although total expression levels of CDKN2A , CDKN2B , and ANRIL are positively correlated, individual genetic variants influence ANRIL and CDKN2B expression in opposite directions, suggesting a possible role of ANRIL in CDKN2B regulation. Our study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior