Remote capacitive sensing in two-dimension quantum-dot arrays

We investigate gate-defined quantum dots in silicon on insulator nanowire field-effect transistors fabricated using a foundry-compatible fully-depleted silicon-on-insulator (FD-SOI) process. A series of split gates wrapped over the silicon nanowire naturally produces a $2\times n$ bilinear array of quantum dots along a single nanowire. We begin by studying the capacitive coupling of quantum dots within such a 2$\times$2 array, and then show how such couplings can be extended across two parallel silicon nanowires coupled together by shared, electrically isolated, 'floating' electrodes. With one quantum dot operating as a single-electron-box sensor, the floating gate serves to enhance the charge sensitivity range, enabling it to detect charge state transitions in a separate silicon nanowire. By comparing measurements from multiple devices we illustrate the impact of the floating gate by quantifying both the charge sensitivity decay as a function of dot-sensor separation and configuration within the dual-nanowire structure.Comment: 9 pages, 3 figures, 35 cites and supplementar

A Silicon Surface Code Architecture Resilient Against Leakage Errors

Spin qubits in silicon quantum dots are one of the most promising building blocks for large scale quantum computers thanks to their high qubit density and compatibility with the existing semiconductor technologies. High fidelity single-qubit gates exceeding the threshold of error correction codes like the surface code have been demonstrated, while two-qubit gates have reached 98\% fidelity and are improving rapidly. However, there are other types of error --- such as charge leakage and propagation --- that may occur in quantum dot arrays and which cannot be corrected by quantum error correction codes, making them potentially damaging even when their probability is small. We propose a surface code architecture for silicon quantum dot spin qubits that is robust against leakage errors by incorporating multi-electron mediator dots. Charge leakage in the qubit dots is transferred to the mediator dots via charge relaxation processes and then removed using charge reservoirs attached to the mediators. A stabiliser-check cycle, optimised for our hardware, then removes the correlations between the residual physical errors. Through simulations we obtain the surface code threshold for the charge leakage errors and show that in our architecture the damage due to charge leakage errors is reduced to a similar level to that of the usual depolarising gate noise. Spin leakage errors in our architecture are constrained to only ancilla qubits and can be removed during quantum error correction via reinitialisations of ancillae, which ensure the robustness of our architecture against spin leakage as well. Our use of an elongated mediator dots creates spaces throughout the quantum dot array for charge reservoirs, measuring devices and control gates, providing the scalability in the design

The Supreme Court\u27s First One Hundred Charter of Rights Decisions: A Statistical Analysis

This study presents a descriptive statistical analysis of the Supreme Court of Canada\u27s first one hundred Charter of Rights decisions (1982-1989). Charter appeals now constitute one-quarter of the Court\u27s annual caseload. The Court has abandoned the judicial self-restraint that shaped its pre-Charter civil liberties jurisprudence. It has upheld rights claimants in 35 percent of its decisions and declared nineteen statutes void. Seventy-five percent of the Court\u27s Charter work dealt with legal rights and criminal justice, but more provincial statutes were declared invalid than federal. After an initial period of consensus, the Court divided into identifiable voting blocs, with wide discrepancies between different Judges\u27 support for Charter claims. In three respects-composition of docket, success rate, and nullification of statutes- the Canadian Supreme Court closely resembled its American counterpart

The Supreme Court\u27s First One Hundred Charter of Rights Decisions: A Statistical Analysis

This study presents a descriptive statistical analysis of the Supreme Court of Canada\u27s first one hundred Charter of Rights decisions (1982-1989). Charter appeals now constitute one-quarter of the Court\u27s annual caseload. The Court has abandoned the judicial self-restraint that shaped its pre-Charter civil liberties jurisprudence. It has upheld rights claimants in 35 percent of its decisions and declared nineteen statutes void. Seventy-five percent of the Court\u27s Charter work dealt with legal rights and criminal justice, but more provincial statutes were declared invalid than federal. After an initial period of consensus, the Court divided into identifiable voting blocs, with wide discrepancies between different Judges\u27 support for Charter claims. In three respects-composition of docket, success rate, and nullification of statutes- the Canadian Supreme Court closely resembled its American counterpart

Kepler-445, Kepler-446 And The Occurrence Of Compact Multiples Orbiting Mid-M Dwarf Stars

We confirm and characterize the exoplanetary systems Kepler-445 and Kepler-446: two mid-M dwarf stars, each with multiple, small, short-period transiting planets. Kepler-445 is a metal-rich ([ Fe/H] = + 0.25 0.10) M4 dwarf with three transiting planets, and Kepler-446 is a metal-poor ([ Fe/H] = -0.30 0.10) M4 dwarf also with three transiting planets. Kepler-445c is similar toGJ 1214b: both in planetary radius and the properties of the host star. The Kepler-446 system is similar to the Kepler-42 system: both are metal-poor with large galactic space velocities and three short-period, likely rocky transiting planets that were initially assigned erroneously large planet-to-star radius ratios. We independently determined stellar parameters from spectroscopy and searched for and fitted the transit light curves for the planets, imposing a strict prior on stellar density in order to remove correlations between the fitted impact parameter and planet-to-star radius ratio for short-duration transits. Combining Kepler-445, Kepler-446, and Kepler-42, and isolating all mid-M dwarf stars observed by Kepler with the precision necessary to detect similar systems, we calculate that 21+ 7 -5 % of mid-M dwarf stars host compact multiples ( multiple planets with periods of less than 10 days) for a wide range of metallicities. We suggest that the inferred planet masses for these systems support highly efficient accretion of protoplanetary disk metals by mid-M dwarf protoplanets.NSF DGE1144152, AST-1005313NASA NAS5-26555NASA Office of Space Science NNX13AC07GAstronom

ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a KrasG12D/p53R172H mouse PDAC model, was associated with reduced survival. Conditional ROCK1 or ROCK2 activation promoted invasive growth of mouse PDAC cells into three‐dimensional collagen matrices by increasing matrix remodeling activities. RNA sequencing revealed a coordinated program of ROCK‐induced genes that facilitate extracellular matrix remodeling, with greatest fold‐changes for matrix metalloproteinases (MMPs) Mmp10 and Mmp13. MMP inhibition not only decreased collagen degradation and invasion, but also reduced proliferation in three‐dimensional contexts. Treatment of KrasG12D/p53R172H PDAC mice with a ROCK inhibitor prolonged survival, which was associated with increased tumor‐associated collagen. These findings reveal an ancillary role for increased ROCK signaling in pancreatic cancer progression to promote extracellular matrix remodeling that facilitates proliferation and invasive tumor growth

The genetics, structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease

The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved. Here we discuss what is known about their structure and function and highlight some of the knowledge gaps that affect development of drugs targeting these enzymes

A Nanoparticle-Based Combination Chemotherapy Delivery System for Enhanced Tumor Killing by Dynamic Rewiring of Signaling Pathways

Exposure to the EGFR (epidermal growth factor receptor) inhibitor erlotinib promotes the dynamic rewiring of apoptotic pathways, which sensitizes cells within a specific period to subsequent exposure to the DNA-damaging agent doxorubicin. A critical challenge for translating this therapeutic network rewiring into clinical practice is the design of optimal drug delivery systems. We report the generation of a nanoparticle delivery vehicle that contained more than one therapeutic agent and produced a controlled sequence of drug release. Liposomes, representing the first clinically approved nanomedicine systems, are well-characterized, simple, and versatile platforms for the manufacture of functional and tunable drug carriers. Using the hydrophobic and hydrophilic compartments of liposomes, we effectively incorporated both hydrophobic (erlotinib) and hydrophilic (doxorubicin) small molecules, through which we achieved the desired time sequence of drug release. We also coated the liposomes with folate to facilitate targeting to cancer cells. When compared to the time-staggered application of individual drugs, staggered release from tumor-targeted single liposomal particles enhanced dynamic rewiring of apoptotic signaling pathways, resulting in improved tumor cell killing in culture and tumor shrinkage in animal models.National Institutes of Health (U.S.) (NIH and Center for Cancer Nanotechnology Excellence, grant no. P30-CA14051)National Institutes of Health (U.S.) (NIH and Center for Cancer Nanotechnology Excellence, grant no. U54-CA151884)National Institutes of Health (U.S.) (NIH and Center for Cancer Nanotechnology Excellence, grant no. U54-CA112967)National Institutes of Health (U.S.) (NIH and Center for Cancer Nanotechnology Excellence, grant no. R01-ES015339)National Institutes of Health (U.S.) (NIH and Center for Cancer Nanotechnology Excellence, grant no. R21-ES020466)Breast Cancer Alliance (Exceptional Project Grant)National Science Foundation (U.S.) (Graduate Research Fellowship)National Health and Medical Research Council (Australia) (CJ Martin Fellowship)National Institutes of Health (U.S.) (Kirschstein NRSA 1F32EB017614-01)Natural Sciences and Engineering Research Council of Canada (post-doctoral fellowship)Kathy and Curt Marble Cancer Research FundDavid H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute Frontier Research Program