Design aspects of dual gate GaAs nanowire FET for room temperature charge qubit operation: A study on diameter and gate engineering

The current work explores a geometrically engineered dual gate GaAs nanowire FET with state of the art miniaturized dimensions for high performance charge qubit operation at room temperature. Relevant gate voltages in such device can create two voltage tunable quantum dots (VTQDs) underneath the gates, as well as can manipulate their eigenstate detuning and the inter-dot coupling to generate superposition, whereas a small drain bias may cause its collapse leading to qubit read out. Such qubit operations, i.e., Initialization, Manipulation, and Measurement, are theoretically modeled in the present work by developing a second quantization filed operator based Schrodinger-Poisson self-consistent framework coupled to non-equilibrium Greens function formalism. The study shows that the Bloch sphere coverage can be discretized along polar and azimuthal directions by reducing the nanowire diameter and increasing the inter-dot separation respectively, that can be utilized for selective information encoding. The theoretically obtained stability diagrams suggest that downscaled nanowire diameter and increased gate separation sharpen the bonding and anti-bonding states with reduced anticrossing leading to a gradual transformation of the hyperbolic current mapping into a pair of straight lines. However, the dephasing time in the proposed GaAs VTQD-based qubit may be significantly improved by scaling down both the nanowire diameter and gate separation. Therefore, the present study suggests an optimization window for geometrical engineering of a dual gate nanowire FET qubit to achieve superior qubit performance. Most importantly, such device is compatible with the mainstream CMOS technology and can be utilized for large scale implementation by little modification of the state of the art fabrication processes

Quantification of 5-methylcytosine, 5-hydroxymethylcytosine and 5-carboxylcytosine from the blood of cancer patients by an Enzyme-based Immunoassay

BACKGROUND: Genome-wide aberrations of the classic epigenetic modification 5-methylcytosine (5mC), considered the hallmark of gene silencing, has been implicated to play a pivotal role in mediating carcinogenic transformation of healthy cells. Recently, three epigenetic marks derived from enzymatic oxidization of 5mC namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), have been discovered in the mammalian genome. Growing evidence suggests that these novel bases possess unique regulatory functions and may play critical roles in carcinogenesis. METHODS: To provide a quantitative basis for these rare epigenetic marks, we have designed a biotin-avidin mediated enzyme-based immunoassay (EIA) and evaluated its performance in genomic DNA isolated from blood of patients diagnosed with metastatic forms of lung, pancreatic and bladder cancer, as well as healthy controls. The proposed EIA incorporates spatially optimized biotinylated antibody and a high degree of horseradish-peroxidase (HRP) labeled streptavidin, facilitating signal amplification and sensitive detection. RESULTS: We report that the percentages of 5mC, 5hmC and 5caC present in the genomic DNA of blood in healthy controls as 1.025±0.081, 0.023±0.006 and 0.001±0.0002, respectively. We observed a significant (p<0.05) decrease in the mean global percentage of 5hmC in blood of patients with malignant lung cancer (0.013±0.003%) in comparison to healthy controls. CONCLUSION: The precise biological roles of these epigenetic modifications in cancers are still unknown but in the past two years it has become evident that the global 5hmC content is drastically reduced in a variety of cancers. To the best of our knowledge, this is the first report of decreased 5hmC content in the blood of metastatic lung cancer patients and the clinical utility of this observation needs to be further validated in larger sample datasets

Chronic inflammation in polycystic ovary syndrome: A case–control study using multiple markers

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and elevated risk of cardiovascular disease and diabetes. Chronic inflammation has been observed in PCOS in several studies but there is also opposing evidence and a dearth of research in Indians. Objective: To estimate chronic inflammation in PCOS and find its relationship with appropriate anthropometric and biochemical parameters. Materials and Methods: Chronic inflammation was assessed in 30 women with PCOS (Group A) and 30 healthy controls (Group B) with highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), and platelet microparticles (PMP). In group A, the relationship of chronic inflammation with insulin resistance, waist hip ratio (WHR) serum testosterone, and serum glutamate pyruvate transaminase (SGPT) were examined. Results: In group A, the hsCRP, TNFα, and PMP were significantly elevated compared to group B. However, IL-6 level was similar between the groups. In group A, PMP showed a significant positive correlation with waist-hip ratio and serum testosterone. IL-6 showed a significant positive correlation with insulin sensitivity and significant negative correlation with insulin resistance and serum glutamate pyruvate transaminase. Conclusion: PCOS is associated with chronic inflammation and PMP correlates positively with central adiposity and biochemical hyperandrogenism in women with PCOS. Key words: Polycystic ovary syndrome, Inflammation, C-reactive protein, Interleukin-6, Tumor necrosis factor, Microparticles

Increased toll-like receptor-2 expression on nonclassic CD16⁺monocytes from patients with inflammatory stage of eales' disease

Purpose.: To identify the distribution, differential Toll-like receptor (TLR) expression, and functional contribution of monocyte subpopulations in the inflammatory stage of Eales' disease (ED). Methods.: Peripheral blood mononuclear cells were isolated from nine patients during the inflammatory stage of ED and nine age- and sex-matched healthy controls. The expression of CD14, CD16, TLR-2, and TLR-4 on monocytes was measured by flow cytometry. The CD14+, CD16−, and CD16+ monocyte populations were sorted on the basis of magnetic-activated cell-sorting methodology, and levels of cytokines were measured by ELISA. Results.: In ED patients, the number of circulating monocytes was significantly expanded compared with that in controls (P = 0.01), with a marked increase in the nonclassic CD16+ subset, which showed an activated phenotype in patients that correlated with levels of serum proinflammatory cytokines and clinical progression. A higher expression of cell surface TLR-2 (P = 0.02), but not TLR-4, was found in monocytes of patients with ED. Furthermore, TLR-2 was expressed at higher levels on CD16+ monocytes than on CD16− monocytes in patients, whereas no significant variation was found in TLR-4 expression on different monocyte subsets. Peptidoglycan-induced TNF-α expression correlated with TLR-2 expression in monocytes isolated from controls (r = 0.85, P = 0.0061), but not in monocytes isolated from ED patients (r = 0.553, P = 0.1328). Conclusions.: These results indicate that in the pathogenesis of ED, TLR activation and increased numbers of nonclassic CD16+ monocytes are crucial regulators, along with the secretion of proinflammatory cytokines that perpetuate the inflammatory process in the retina

A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells

Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations

Epigenomic landscape of 5-hydroxymethylcytosine and implications in cancer

The addition of a methyl group (-CH3) at the C-5 position of the pyrimidine ring of cytosine nucleotide in DNA serves as an epigenetic signaling tool employed by cells to turn off gene expression. This epigenetic modification also known as 5-methylcytosine, 5mC, plays a critical role in numerous cellular processes including genomic imprinting, cellular differentiation and preservation of genomic stability. Aberrant 5mC patterns like hypermethylation of tumor suppressor genes and hypomethylation of oncogenes are traditional hallmarks of cancer and a testament to the role of epigenetics in oncogenesis. Recently, three other epigenetic derivatives of 5mC (enzymatically mediated by Ten-eleven-translocation dioxygenase; TET) namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) have been discovered. The biological significance of these novel DNA modifications is still unclear but it has been hypothesized that these novel derivatives serve as intermediates in the DNA demethylation pathway and confer unique transcriptional potential to genes. Understanding how these novel epigenetic marks are interpreted at discrete loci in cancers has been the goal of my doctoral study and can be broadly classified into the following domains. (i) Mapping the Epigenetic Landscape (5mC and 5hmC) of myeloid differentiation in human leukemia cells using Next Generation Sequencing (NGS) followed by exhaustive bioinformatics analysis. For the very first time, we have defined the differentiation dependent changes in the methylated and hydroxymethylated regions across the genome in the context of (a) promoters, (b) gene bodies and (c) intergenic regions. Additionally, we have correlated the changes of the methylome with the changing transcriptional profile upon HL-60 differentiation to comprehensively characterize the epigenetic landscape during myeloid differentiation. (ii) Development of a sensitive technique for the quantification of these rare epigenetic marks that constitute less than 0.05% of the genome. We have developed an enhanced Immunoassay based platform to precisely quantitate the global levels of 5mC, 5hmC, 5fC and 5caC and have evaluated its performance in genomic DNA isolated from blood of patients diagnosed with metastatic forms of lung, pancreatic and bladder cancer. We have reported a decrease in the mean level of 5hmC by 56.37% (p-value \u3c 0.05) in blood of malignant lung cancer patients in comparison to levels in healthy controls and the clinical utility of this observation is being currently explored (iii) Elucidating a novel insight into the therapeutic activity of Decitabine (DAC), recently FDA-approved epigenetic drug in myeloid malignancies. Though the hypomethylating effect of DAC is attributed to the depletion of DNA-methyltransferase-1 (DNMT1), the nature of the genomic loci susceptible to DAC-induced demethylation is poorly understood. We show that DAC induces demethylation in HL60 with a paradoxical increase in 5hmC, 5fC and 5caC. Using a multi-compartmental model of DNA methylation, we propose that the observed increase in 5hmC following DAC treatment is caused by the partial selectivity of the TET dioxygenase enzymes for hemi-methylated CpG dinucleotides, whose abundance is increased during drug induced inhibition of the DNMT1-mediated maintenance methylation

Probing site-exclusive binding of aqueous QDs and their organelle-dependent dynamics in live cells by single molecule spectroscopy

Understanding the biophysical and chemical interactions of nanoprobes and their fate upon entering live cells is critical for developing fundamental insights related to intracellular diagnostics, drug delivery and targeting. In this article we report herein a single molecule analysis procedure to quantitate site-specific exclusive membrane binding of N-acetyl-L-cysteine (NAC)-capped cadmium telluride (CdTe) quantum dots (QDs) in A-427 lung carcinoma cells (k(eq) = 0.075 +/- 0.011 nM(-1)), its relative intracellular distribution and dynamics using fluorescence correlation spectroscopy (FCS) combined with scanning confocal fluorescence lifetime imaging (FLIM). In particular, we demonstrate that the binding efficacy of QDs to the cell membrane is directly related to their size and the targeting of QDs to specific membrane sites is exclusive. We also show that QDs are efficiently internalized by endocytosis and enclosed within the endosome and organelle-dependent diffusion dynamics can be monitored in live cells