Electron Spin for Classical Information Processing: A Brief Survey of Spin-Based Logic Devices, Gates and Circuits

In electronics, information has been traditionally stored, processed and communicated using an electron's charge. This paradigm is increasingly turning out to be energy-inefficient, because movement of charge within an information-processing device invariably causes current flow and an associated dissipation. Replacing charge with the "spin" of an electron to encode information may eliminate much of this dissipation and lead to more energy-efficient "green electronics". This realization has spurred significant research in spintronic devices and circuits where spin either directly acts as the physical variable for hosting information or augments the role of charge. In this review article, we discuss and elucidate some of these ideas, and highlight their strengths and weaknesses. Many of them can potentially reduce energy dissipation significantly, but unfortunately are error-prone and unreliable. Moreover, there are serious obstacles to their technological implementation that may be difficult to overcome in the near term. This review addresses three constructs: (1) single devices or binary switches that can be constituents of Boolean logic gates for digital information processing, (2) complete gates that are capable of performing specific Boolean logic operations, and (3) combinational circuits or architectures (equivalent to many gates working in unison) that are capable of performing universal computation.Comment: Topical Revie

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Annexin V assay.

<p>Apoptotic effect of flavone A at a concentration of 40 μM, on the more differentiated pancreatic Panc28 and colon CaCo 2 cancer cells (Fig 1A and 1B), as determined by Annexin V assay (green channel) six hours after treatment. Dapi (blue channel) is used to locate the nuclei of the cells. Cells treated with vehicle only (DMSO at a final concentration of 0.27%) served as a control. Activation of apoptosis on the poorly differentiated pancreatic MIA PaCa and colon HCT116 cancer cells (Figs 1C and 1D) by flavone B at a concentration of 40 μM, as determined by Annexin V assay (green channel) six hours after treatment. Control conditions are the same as described above and Dapi was used to locate nuclei.</p

Analysis of downstream effector BAD after treatment with flavone A and flavone B.

<p>A and B: Detection of the loss of phosphorylation of BAD by immunoblot of total SDS extracts. Better differentiated Panc 28 and CaCo 2 cells were treated with 40μM of flavone A (+A), and poorly differentiated MIA PaCa and HCT116 cells with flavone B (+B), or DMSO (-) the dissolution vehicle. After lysis and SDS-PAGE, membranes were probed with an antibody specific to BAD phosphorylated at serine 112 or the unphosphorylated protein. The membranes were reprobed for actin as a loading control. The results shown are representative of three independent experiments. C and D: For quantification (graphs) the band densities from the treated/untreated conditions identified by (+) or (-), were normalized and calculated as percentages of the value for the untreated cells (100%), and shown averages ± standard deviations from three independent experiments (*p<0.05). E and F: Detection of phosphorylated BAD at serine 112 (red channel), after treatment of Panc 28 cells with flavone A and MIA PaCa cells with flavone B by immunofluorescence. Dapi (blue channel) was used to locate the nuclei.</p

Comparison of the effect of flavone A and flavone B on proliferative, and survival pathways.

<p>A and B: Detection of the activated and unphosphorylated forms of ERK, c-JUN, S6, AKT by immunoblot of total SDS extracts. Better differentiated Panc28 and CaCo 2 cells were treated with 40μM of flavone A (+A), and poorly differentiated MIA PaCa and HCT116 cells with flavone B (+B), or DMSO (-) the dissolution vehicle. After lysis and SDS-PAGE, membranes were probed with the indicated antibody. The membranes were reprobed for actin as a loading control, and a representative image is provided. The results shown are representative of three independent experiments. C and D: For quantification (graphs) the band densities from the treated/untreated conditions identified by (+) or (-), were normalized and calculated as percentages of the value for the untreated cells (100%), and shown averages ± standard deviations from three independent experiments (*p<0.05). E and F: Detection of phosphorylated ERK after treatment of CaCo 2 cells with flavone A and HCT116 cells with flavone B by immunofluorescence.</p

Analysis of caspase 9 after treatment with flavone A.

<p>Detection of activated caspase 9 by immunoblot of SDS extracts of A. CaCo 2 and B. Panc 28 cells 1.5, 3, 6, 9 and 12 hours (lanes 2–6) after treatment with flavone A or vehicle (DMSO) for the control (C, lane 1) and SDS-PAGE. The membranes were probed with an antibody capable of detecting both the procaspase (47 kDa) and the large fragments resultant after activation (37 and 35 kDa). The membranes were reprobed for actin or tubulin as a loading control. The results shown are representative of three independent experiments. The membranes were reprobed for actin or tubulin as a loading control. The results shown are representative of three independent experiments.</p

Annexin V-FITC and propidium iodide flow cytometry.

<p>A. Apoptosis was detected using Annexin V-FITC and propidium iodide in Panc 28 cells treated with 40 μM flavone A, 9 hours after treatment. B. Detection of apoptosis in HCT 116 cells treated with 40 μM flavone B, 9 hours after treatment. C. Bar graph representation of apoptosis in Panc 28 and HCT 116 cells treated with flavone A and B respectively. D-E. Cell cycle determination using propidium iodide in Panc 28 cells treated 40 μM flavone A. F-G. Cell cycle determination in HCT 116 cells treated with 40 μM flavone B.</p

Analysis of c-JUN phosphorylation of threonines 91/93 and caspase 8 after treatment with 40 μM flavone B.

<p>A and B. Immunofluorescence of treated cells show expression of phospho-c-JUN (T91/T93) in SKBR3 cells (green channel) but not on HCT116 cells. Dapi (blue channel) was used to localize the nuclei. C. Immunoblot of phospho-c-JUN (T91/T93) using SDS extracts of poorly differentiated HCT116 cells treated with 40μM of flavone B (+B), or the dissolution vehicle DMSO (-). SDS lysates from SKBR3 cells treated with 10μM tamoxifen (+) were used as a positive control. After SDS-PAGE, nitrocellulose membranes were probed with an antibody specific to this phosphorylated form. D. Detection of caspase 8 by immunoblot of SDS lysates of HCT116 cells 1.5, 3, 6, 9 and 12 hours (lanes 2–6) after treatment with flavone B or vehicle (DMSO) for the control (C, lane 1) and SDS-PAGE. The membranes were probed with an antibody capable of detecting both the procaspase (54/55 kDa) and the fragments resultant after activation (43 and 18 kDa). The membranes were reprobed for actin or tubulin as a loading control. The results shown are representative of three independent experiments.</p