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COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF

Proper embryonic and postnatal skeletal development require coordination of myriad complex molecular mechanisms. Disruption of these processes, through genetic mutation, contributes to variation in skeletal development. We developed a high-throughput N-ethyl-N-nitrosourea (ENU)-induced saturation mutagenesis skeletal screening approach in mice to identify genes required for proper skeletal development. Here, we report initial results from live-animal X-ray and dual-energy X-ray absorptiometry (DXA) imaging of 27,607 G3 mice from 806 pedigrees, testing the effects of 32,198 coding/splicing mutations in 13,020 genes. A total of 39.7% of all autosomal genes were severely damaged or destroyed by mutations tested twice or more in the homozygous state. Results from our study demonstrate the feasibility of in vivo mutagenesis to identify mouse models of skeletal disease. Furthermore, our study demonstrates how ENU mutagenesis provides opportunities to create and characterize putative hypomorphic mutations in developmentally essential genes. Finally, we present a viable mouse model and case report of recessive skeletal disease caused by mutations in FAM20B. Results from this study, including engineered mouse models, are made publicly available via the online Mutagenetix database. © 2021 American Society for Bone and Mineral Research (ASBMR).

International audience; Significance: The vast majority of autoimmune diseases are polygenic, and causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this missing heritability include rare meaningful variants, rare copy number variations or deletions, epistasis, epigenetics, disease heterogeneity, and rare or infrequent variants that segregate within individual families (even within monozygotic twins). Here we demonstrate that experimental models of spontaneous autoimmune diseases may be invaluable tools to map rare germline variants impacting disease susceptibility traits. We identified a variant of the dual-specificity phosphatase 10 encoding gene that accelerates disease in an autoimmune type 1 diabetes model, the nonobese diabetic mouse.Abstract: Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation–phenotype association. At this time, CE has evaluated putative mutation–phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

Here we report the isolation by selective breeding of two sublines of Non-Obese Diabetic (NOD) mice exhibiting a significant difference in the incidence of autoimmune type 1 diabetes (T1D). Whole genome sequencing of the NOD/NckH (high T1D incidence) and NOD/NckL (low T1D incidence) revealed the presence of a limited number of variants specific to each subline. Treating the age of T1D onset as a quantitative trait and using automated meiotic mapping (AMM), enhanced susceptibility in the NOD/NckH subline was unambiguously attributed to a recessive allele of Dusp10 which encodes a dual specificity phosphatase. The causative effect of the mutation was verified with a high level of confidence by targeting Dusp10 with CRISPR/Cas9 in NOD/NckL mice: in these animals a higher incidence of diabetes was observed. Expression of wild-type Dusp10 correlated with higher levels of surface PD-L1 in the islets of NOD/NckL mice.

Neutral silicon vacancy (SiV^{0}) centers in diamond are promising candidates for quantum networks because of their excellent optical properties and long spin coherence times. However, spin-dependent fluorescence in such defects has been elusive due to poor understanding of the excited state fine structure and limited off-resonant spin polarization. Here we report the realization of optically detected magnetic resonance and coherent control of SiV^{0} centers at cryogenic temperatures, enabled by efficient optical spin polarization via previously unreported higher-lying excited states. We assign these states as bound exciton states using group theory and density functional theory. These bound exciton states enable new control schemes for SiV^{0} as well as other emerging defect systems.

When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

A behind the scenes look at ILM's visual effects work on "Star Wars: The Rise of Skywalker."The featured work was created by ILM's visual effects crews in San Francisco, Singapore, Vancouver, London, and Sydney.

Retinal disease and loss of vision can result from any disruption of the complex pathways controlling retinal development and homeostasis. Forward genetics provides an excellent tool to find, in an unbiased manner, genes that are essential to these processes. Using N -ethyl- N -nitrosourea mutagenesis in mice in combination with a screening protocol using optical coherence tomography (OCT) and automated meiotic mapping, we identified 11 mutations presumably causative of retinal phenotypes in genes previously known to be essential for retinal integrity. In addition, we found multiple statistically significant gene-phenotype associations that have not been reported previously and decided to target one of these genes, Sfxn3 (encoding sideroflexin-3), using CRISPR/Cas9 technology. We demonstrate, using OCT, light microscopy, and electroretinography, that two Sfxn3 −/− mouse lines developed progressive and severe outer retinal degeneration. Electron microscopy showed thinning of the retinal pigment epithelium and disruption of the external limiting membrane. Using single-cell RNA sequencing of retinal cells isolated from C57BL/6J mice, we demonstrate that Sfxn3 is expressed in several bipolar cell subtypes, retinal ganglion cells, and some amacrine cell subtypes but not significantly in Müller cells or photoreceptors. In situ hybridization confirmed these findings. Furthermore, pathway analysis suggests that Sfxn3 may be associated with synaptic homeostasis. Importantly, electron microscopy analysis showed disruption of synapses and synaptic ribbons in the outer plexiform layer of Sfxn3 −/− mice. Our work describes a previously unknown requirement for Sfxn3 in retinal function.

Er3+ ions in crystals are promising for quantum networks. We demonstrate ion implantation of Er3+ into TiO2, a potential low-noise host material, with narrow optical and spin linewidths and high implantation yield.

Atomic and atom-like defects in the solid-state are widely explored for quantum computers, networks and sensors. Rare earth ions are an attractive class of atomic defects that feature narrow spin and optical transitions that are isolated from the host crystal, allowing incorporation into a wide range of materials. However, the realization of long electronic spin coherence times is hampered by magnetic noise from abundant nuclear spins in the most widely studied host crystals. Here, we demonstrate that Er$^{3+}$ ions can be introduced via ion implantation into TiO$_2$, a host crystal that has not been studied extensively for rare earth ions and has a low natural abundance of nuclear spins. We observe efficient incorporation of the implanted Er$^{3+}$ into the Ti$^{4+}$ site (40% yield), and measure narrow inhomogeneous spin and optical linewidths (20 and 460 MHz, respectively) that are comparable to bulk-doped crystalline hosts for Er$^{3+}$. This work demonstrates that ion implantation is a viable path to studying rare earth ions in new hosts, and is a significant step towards realizing individually addressed rare earth ions with long spin coherence times for quantum technologies.

We characterize a fluxonium qubit consisting of a Josephson junction inductively shunted with a NbTiN nanowire superinductance. We explain the measured energy spectrum by means of a multimode theory accounting for the distributed nature of the superinductance and the effect of the circuit nonlinearity to all orders in the Josephson potential. Using multiphoton Raman spectroscopy, we address multiple fluxonium transitions, observe multilevel Autler-Townes splitting and measure an excited state lifetime of ${T}_{1}=20\text{ }\text{ }\ensuremath{\mu}\mathrm{s}$. By measuring ${T}_{1}$ at different magnetic flux values, we find a crossover in the lifetime limiting mechanism from capacitive to inductive losses.

Coherence times of electron spins bound to phosphorus donors have been measured, using a standard Hahn echo technique, to be up to 20 ms in isotopically pure silicon with [P]$ = 10^{14}$ cm$^{-3}$ and at temperatures $\leq 4 $K. Although such times are exceptionally long for electron spins in the solid state, they are nevertheless limited by donor electron spin-spin interactions. Suppressing such interactions requires even lower donor concentrations, which lie below the detection limit for typical electron spin resonance (ESR) spectrometers. Here we describe an alternative method for phosphorus donor ESR detection, exploiting the spin-to-charge conversion provided by the optical donor bound exciton transition. We characterise the method and its dependence on laser power and use it to measure a coherence time of $T_2 = 130 $ms for one of the purest silicon samples grown to-date ([P]$ = 5\times 10^{11} $cm$^{-3}$). We then benchmark this result using an alternative application of the donor bound exciton transition: optically polarising the donor spins before using conventional ESR detection at 1.7~K for a sample with [P]$ = 4\times10^{12} $cm$^{-3}$, and measuring in this case a $T_2$ of 350 ms.

We have developed a method to probe the temperature of surface state electrons (SSE) above a superfluid Helium-4 surface using the Seebeck effect. In contrast to previously used SSE thermometry, this technique does not require detailed knowledge of the non-linear mobility. We demonstrate the use of this method by measuring energy relaxation of SSE at 1.6 K in a microchannel device with $0.6\:\mu\mbox{m}$ deep helium. In this regime, both vapor atom scattering and 2-ripplon scattering contribute to energy relaxation to which we compare our measurements. We conclude that this technique provides a reliable measure of electron temperature while requiring a less detailed understanding of the electron interactions with the environment than previously utilized thermometry techniques.

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1β (IL-1β) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.

We describe sensitive magnetometry using lumped-element resonators fabricated from a superconducting thin film of NbTiN. Taking advantage of the large kinetic inductance of the superconductor, we demonstrate a continuous resonance frequency shift of $27$ MHz for a change in magnetic field of $1.8~\mu$T within a perpendicular background field of 60 mT. By using phase-sensitive readout of microwaves transmitted through the sensors, we measure phase shifts in real time with a sensitivity of $1$ degree/nT. We present measurements of the noise spectral density of the sensors, and find their field sensitivity is at least within one to two orders of magnitude of superconducting quantum interference devices operating with zero background field. Our superconducting kinetic inductance field-frequency sensors enable real-time magnetometry in the presence of moderate perpendicular background fields up to at least 0.2 T. Applications for our sensors include the stabilization of magnetic fields in long coherence electron spin resonance measurements and quantum computation., Comment: 5 pages, 4 figures with 2-page supplementary material

We report transport measurements of electrons on helium in a microchannel device where the channels are 200 nm deep and 3 $\mu$m wide. The channels are fabricated above amorphous metallic Ta$_{40}$W$_{40}$Si$_{20}$, which has surface roughness below 1 nm and minimal variations in work function across the surface due to the absence of polycrystalline grains. We are able to set the electron density in the channels using a ground plane. We estimate a mobility of 300 cm$^2$/V$\cdot$s and electron densities as high as 2.56$\times$10$^9$ cm$^{-2}$. We demonstrate control of the transport using a barrier which enables pinchoff at a central microchannel connecting two reservoirs. The conductance through the central microchannel is measured to be 10 nS for an electron density of 1.58$\times$10$^9$ cm$^{-2}$. Our work extends transport measurements of surface electrons to thin helium films in microchannel devices above metallic substrates., Comment: 4 pages, 4 figures

One of the biggest challenges impeding the progress of Metal-Oxide-Silicon (MOS) quantum dot devices is the presence of disorder at the Si/SiO$_2$ interface which interferes with controllably confining single and few electrons. In this work we have engineered a low-disorder MOS quantum double-dot device with critical electron densities, i.e. the lowest electron density required to support a conducting pathway, approaching critical electron densities reported in high quality Si/SiGe devices and commensurate with the lowest critical densities reported in any MOS device. Utilizing a nearby charge sensor, we show that the device can be tuned to the single-electron regime where charging energies of $\approx$8 meV are measured in both dots, consistent with the lithographic size of the dot. Probing a wide voltage range with our quantum dots and charge sensor, we detect three distinct electron traps, corresponding to a defect density consistent with the ensemble measured critical density. Low frequency charge noise measurements at 300 mK indicate a 1/$f$ noise spectrum of 3.4 $\mu$eV/Hz$^{1/2}$ at 1 Hz and magnetospectroscopy measurements yield a valley splitting of 110$\pm$26 $\mu$eV. This work demonstrates that reproducible MOS spin qubits are feasible and represents a platform for scaling to larger qubit systems in MOS., Comment: 16 pages, 5 figures

In this work, we demonstrate the use of frequency-tunable superconducting NbTiN coplanar waveguide microresonators for multi-frequency pulsed electron spin resonance (ESR) experiments. By applying a bias current to the center pin, the resonance frequency ($\sim$7.6 GHz) can be continuously tuned by as much as 95 MHz in 270 ns without a change in the quality factor of 3000 at 2K. We demonstrate the ESR performance of our resonators by measuring donor spin ensembles in silicon and show that adiabatic pulses can be used to overcome magnetic field inhomogeneities and microwave power limitations due to the applied bias current. We take advantage of the rapid tunability of these resonators to manipulate both phosphorus and arsenic spins in a single pulse sequence, demonstrating pulsed double electron-electron resonance (DEER). Our NbTiN resonator design is useful for multi-frequency pulsed ESR and should also have applications in experiments where spin ensembles are used as quantum memories., 5 pages, 4 figures

We achieve the strong coupling regime between an ensemble of phosphorus donor spins in a highly enriched $^{28}$Si crystal and a 3D dielectric resonator. Spins were polarized beyond Boltzmann equilibrium using spin selective optical excitation of the no-phonon bound exciton transition resulting in $N$ = $3.6\cdot10^{13}$ unpaired spins in the ensemble. We observed a normal mode splitting of the spin ensemble-cavity polariton resonances of 2$g\sqrt{N}$ = 580 kHz (where each spin is coupled with strength $g$) in a cavity with a quality factor of 75,000 ($\gamma \ll \kappa \approx$ 60 kHz where $\gamma$ and $\kappa$ are the spin dephasing and cavity loss rates, respectively). The spin ensemble has a long dephasing time (T$_2^*$ = 9 $\mu$s) providing a wide window for viewing the dynamics of the coupled spin ensemble-cavity system. The free induction decay shows up to a dozen collapses and revivals revealing a coherent exchange of excitations between the superradiant state of the spin ensemble and the cavity at the rate $g\sqrt{N}$. The ensemble is found to evolve as a single large pseudospin according to the Tavis-Cummings model due to minimal inhomogeneous broadening and uniform spin-cavity coupling. We demonstrate independent control of the total spin and the initial Z-projection of the psuedospin using optical excitation and microwave manipulation respectively. We vary the microwave excitation power to rotate the pseudospin on the Bloch sphere and observe a long delay in the onset of the superradiant emission as the pseudospin approaches full inversion. This delay is accompanied by an abrupt $\pi$ phase shift in the peusdospin microwave emission. The scaling of this delay with the initial angle and the sudden phase shift are explained by the Tavis-Cummings model., Comment: 9 pages, 7 figures

Computational inference of mutation effects is necessary for genetic studies in which many mutations must be considered as etiologic candidates. Programs such as PolyPhen-2 predict the relative severity of damage caused by missense mutations, but not the actual probability that a mutation will reduce/eliminate protein function. Based on genotype and phenotype data for 116,330 ENU-induced mutations in the Mutagenetix database, we calculate that putative null mutations, and PolyPhen-2-classified “probably damaging”, “possibly damaging”, or “probably benign” mutations have, respectively, 61%, 17%, 9.8%, and 4.5% probabilities of causing phenotypically detectable damage in the homozygous state. We use these probabilities in the estimation of genome saturation and the probability that individual proteins have been adequately tested for function in specific genetic screens. We estimate the proportion of essential autosomal genes in Mus musculus (C57BL/6J) and show that viable mutations in essential genes are more likely to induce phenotype than mutations in non-essential genes., Programs such as PolyPhen-2 predict the relative severity of damage by missense mutations. Here, Wang et al estimate probabilities that putative null or missense alleles would reduce protein function to cause detectable phenotype by analyzing data from ENU-induced mouse mutations.

While Si and Si-based materials have dominated classical electronic device technology for 50 years, quantum information processing requires very different types of devices. Silicon has also been found to be an ideal host for long-coherence quantum bits, or qubits, which are based upon the spins of electrons. The spins of electrons bound to donor impurities in isotopically enriched 28Si have been shown to have coherence times of 10 seconds or longer, at least three orders of magnitude longer than in any other solid. Considerable progress also is being made in understanding decoherence processes and extending coherence times for electrons at hetero-interfaces and in quantum dots.

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The electronic and nuclear spin degrees of freedom of donor impurities in silicon form ultra-coherent two-level systems that are potentially useful for applications in quantum information and are intrinsically compatible with industrial semiconductor processing. However, because of their smaller gyromagnetic ratios, nuclear spins are more difficult to manipulate than electron spins and are often considered too slow for quantum information processing. Moreover, although alternating current magnetic fields are the most natural choice to drive spin transitions and implement quantum gates, they are difficult to confine spatially to the level of a single donor, thus requiring alternative approaches. In recent years, schemes for all-electrical control of donor spin qubits have been proposed but no experimental demonstrations have been reported yet. Here, we demonstrate a scalable all-electric method for controlling neutral 31 P and 75 As donor nuclear spins in silicon. Using coplanar photonic bandgap resonators, we drive Rabi oscillations on nuclear spins exclusively using electric fields by employing the donor-bound electron as a quantum transducer, much in the spirit of recent works with single-molecule magnets. The electric field confinement leads to major advantages such as low power requirements, higher qubit densities and faster gate times. Additionally, this approach makes it possible to drive nuclear spin qubits either at their resonance frequency or at its first subharmonic, thus reducing device bandwidth requirements. Double quantum transitions can be driven as well, providing easy access to the full computational manifold of our system and making it convenient to implement nuclear spin-based qudits using 75 As donors.

We report on electron spin resonance measurements of phosphorus donors localized in a 200 μm^{2} area below the inductive wire of a lumped element superconducting resonator. By combining quantum limited parametric amplification with a low impedance microwave resonator design, we are able to detect around 2×10^{4} spins with a signal-to-noise ratio of 1 in a single shot. The 150 Hz coupling strength between the resonator field and individual spins is significantly larger than the 1-10 Hz coupling rates obtained with typical coplanar waveguide resonator designs. Because of the larger coupling rate, we find that spin relaxation is dominated by radiative decay into the resonator and dependent upon the spin-resonator detuning, as predicted by Purcell.

Color centers in diamond are a promising platform for quantum technologies, and understanding their interactions with the environment is crucial for these applications. We report a study of spin-lattice relaxation $({T}_{1})$ of the neutral charge state of the silicon vacancy center in diamond. Above 20 K, ${T}_{1}$ decreases rapidly with a temperature-dependence characteristic of an Orbach process and is strongly anisotropic with respect to magnetic-field orientation. As the angle of the magnetic field is rotated relative to the symmetry axis of the defect, ${T}_{1}$ is reduced by over three orders of magnitude. The electron spin coherence time $({T}_{2})$ follows the same temperature dependence but is drastically shorter than ${T}_{1}$. We propose that these observations result from phonon-mediated transitions to a low-lying excited state that are spin conserving when the magnetic field is aligned with the defect axis, and we discuss likely candidates for this excited state.

We investigate the neutral charge state of the interstitial silicon split-vacancy defect in diamond for use in quantum communication applications using pulsed electron spin resonance at X-Band magnetic fields (∼3500 G) and confocal microscopy.

Color centers in diamond are a promising platform for quantum communication, as they can serve as solid state quantum memories with efficient optical transitions. Much recent attention has focused on the negatively charged NV center in diamond, which has a spin triplet ground state electronic configuration that can be measured and initialized optically, exhibits long spin coherence times at room temperature, and has narrow, spin-conserving optical transitions. However, the NV center exhibits a large static and dynamic inhomogeneous linewidth, and over 97% of its emission is in a broad, incoherent phonon side band, severely limiting scalability. Alternatively, the negatively charged SiV center exhibits excellent optical properties, with 70% of its emission in the zero phonon line and a narrow inhomogeneous linewidth. However, SiV− suffers from short electron spin coherence times, limited by an orbital relaxation rate (T 1 ) of around 40 ns at 5 K.

Electron-beam (e-beam) lithography is commonly used in fabricating metal-oxide-silicon (MOS) quantum devices but creates defects at the Si/SiO$_2$ interface. Here we show that a forming gas anneal is effective at removing shallow defects ($\leq$ 4 meV below the conduction band edge) created by an e-beam exposure by measuring the density of shallow electron traps in two sets of high-mobility MOS field-effect transistors (MOSFETs). One set was irradiated with an electron-beam (10 keV, 40 $\mu$C/cm$^2$) and was subsequently annealed in forming gas while the other set remained unexposed. Low temperature (335 mK) transport measurements indicate that the forming gas anneal recovers the e-beam exposed sample's peak mobility (14,000 cm$^2$/Vs) to within a factor of two of the unexposed sample's mobility (23,000 cm$^2$/Vs). Using electron spin resonance (ESR) to measure the density of shallow traps, we find that the two sets of devices are nearly identical, indicating the forming gas anneal is sufficient to anneal out shallow defects generated by the e-beam exposure. Fitting the two sets of devices' transport data to a percolation transition model, we extract a T=0 percolation threshold density in quantitative agreement with our lowest temperature ESR-measured trap densities.

(Received 4 May 2005; published 8 November 2005) Systematic errors in spin rotation operations using simple rf pulses place severe limitations on the usefulness of the pulsed magnetic resonance methods in quantum computing applications. In particular, the fidelity of quantum logic operations performed on electron spin qubits falls well below the threshold for the application of quantum algorithms. Using three independent techniques, we demonstrate the use of composite pulses to improve this fidelity by several orders of magnitude. The observed high-fidelity operations are limited by pulse phase errors, but nevertheless fall within the limits required for the application of quantum error correction.

We have measured the electrically detected magnetic resonance of channel-implanted donors in silicon field-effect transistors in resonant X- ($9.7\:$GHz) and W-band ($94\:$GHz) microwave cavities, with corresponding Zeeman fields of $0.35\:$T and $3.36\:$T, respectively. It is found that the conduction electron resonance signal increases by two orders of magnitude from X- to W-band, while the hyperfine-split donor resonance signals are enhanced by over one order of magnitude. We rule out a bolometric origin of the resonance signals, and find that direct spin-dependent scattering between the two-dimensional electron gas and neutral donors is inconsistent with the experimental observations. We propose a new polarization transfer model from the donor to the conduction electrons as the main contributer to the spin resonance signals observed., Comment: 5 pages, 3 figures

The transfer of information between different physical forms is a central theme in communication and computation, for example between processing entities and memory. Nowhere is this more crucial than in quantum computation, where great effort must be taken to protect the integrity of a fragile quantum bit. Nuclear spins are known to benefit from long coherence times compared to electron spins, but are slow to manipulate and suffer from weak thermal polarisation. A powerful model for quantum computation is thus one in which electron spins are used for processing and readout while nuclear spins are used for storage. Here we demonstrate the coherent transfer of a superposition state in an electron spin 'processing' qubit to a nuclear spin 'memory' qubit, using a combination of microwave and radiofrequency pulses applied to 31P donors in an isotopically pure 28Si crystal. The electron spin state can be stored in the nuclear spin on a timescale that is long compared with the electron decoherence time and then coherently transferred back to the electron spin, thus demonstrating the 31P nuclear spin as a solid-state quantum memory. The overall store/readout fidelity is about 90%, attributed to systematic imperfections in radiofrequency pulses which can be improved through the use of composite pulses. We apply dynamic decoupling to protect the nuclear spin quantum memory element from sources of decoherence. The coherence lifetime of the quantum memory element is found to exceed one second at 5.5K., v2: Tomography added and storage of general initial states

Given the effectiveness of semiconductor devices for classical computation one is naturally led to consider semiconductor systems for solid state quantum information processing. Semiconductors are particularly suitable where local control of electric fields and charge transport are required. Conventional semiconductor electronics is built upon these capabilities and has demonstrated scaling to large complicated arrays of interconnected devices. However, the requirements for a quantum computer are very different from those for classical computation, and it is not immediately obvious how best to build one in a semiconductor. One possible approach is to use spins as qubits: of nuclei, of electrons, or both in combination. Long qubit coherence times are a prerequisite for quantum computing, and in this paper we will discuss measurements of spin coherence in silicon. The results are encouraging - both electrons bound to donors and the donor nuclei exhibit low decoherence under the right circumstances. Doped silicon thus appears to pass the first test on the road to a quantum computer., Comment: Submitted to J Cond Matter on Nov 15th, 2005

Quantum computers hold the promise of massive performance enhancements across a range of applications, from cryptography and databases to revolutionary scientific simulation tools. Such computers would make use of the same quantum mechanical phenomena that pose limitations on the continued shrinking of conventional information processing devices. Many of the key requirements for quantum computing differ markedly from those of conventional computers. However, silicon, which plays a central part in conventional information processing, has many properties that make it a superb platform around which to build a quantum computer.

The formation of InAs self-assembled quantum dots on (110) GaAs substrates is demonstrated. These dots form with significantly lower densities than InAs dots grown on (100) GaAs. The low density growth mode of these InAs nanostructures allows for the fabrication of devices capable of electroluminescence from individual quantum dots. Such a device has been fabricated with conventional photolithography and its emission spectra characterized. Additionally, because GaAs cleaves naturally along the (110) crystal plane, the ability to grow InAs quantum dots on (110) GaAs substrates allows for the growth of these dots on the cleaved edges of GaAs first growth samples containing InGaAs strain layers of varying thickness and In fraction. 100% linear alignment of InAs quantum dots over these InGaAs strain layers is demonstrated.

Over the past 50 years, electron-nuclear double resonance (ENDOR) has become a fairly ubiquitous spectroscopic technique, allowing the study of spin transitions for nuclei which are coupled to electron spins. However, the low spin number sensitivity of the technique continues to pose serious limitations. Here we demonstrate that signal intensity in a pulsed Davies ENDOR experiment depends strongly on the nuclear relaxation time T1n, and can be severely reduced for long T1n. We suggest a development of the original Davies ENDOR sequence that overcomes this limitation, thus offering dramatically enhanced signal intensity and spectral resolution. Finally, we observe that the sensitivity of the original Davies method to T1n can be exploited to measure nuclear relaxation, as we demonstrate for phosphorous donors in silicon and for endohedral fullerenes N@ C60 in C S2. © 2006 American Institute of Physics.

The authors demonstrate the selective addressability of two nearly degenerate clock transitions in bismuth-doped ${}^{28}$Si without tuning the magnetic field or microwave frequency. Rather, they vary the microwave polarization between clockwise and counterclockwise circular polarizations, which can be done rapidly. To generate the circularly polarized microwaves, a superconducting coplanar waveguide microresonator was oriented inside a tunable dielectric resonator such that their microwave magnetic fields can be superimposed to give any arbitrary microwave polarization. This work not only opens up additional states near the Si:Bi clock transition, which can be used for different quantum computing schemes, it also demonstrates a clever method for generating arbitrarily polarized microwaves.

Pulsed ESR experiments are reported for ensembles of negatively-charged nitrogen-vacancy centers (NV$^-$) in diamonds at X-band magnetic fields (280-400 mT) and low temperatures (2-70 K). The NV$^-$ centers in synthetic type IIb diamonds (nitrogen impurity concentration $, 10 pages, 5 figures

A scaled quantum computer with donor spins in silicon would benefit from a viable semiconductor framework and a strong inherent decoupling of the qubits from the noisy environment. Coupling neighbouring spins via the natural exchange interaction according to current designs requires gate control structures with extremely small length scales. We present a silicon architecture where bismuth donors with long coherence times are coupled to electrons that can shuttle between adjacent quantum dots, thus relaxing the pitch requirements and allowing space between donors for classical control devices. An adiabatic SWAP operation within each donor/dot pair solves the scalability issues intrinsic to exchange-based two-qubit gates, as it does not rely on sub-nanometer precision in donor placement and is robust against noise in the control fields. We use this SWAP together with well established global microwave Rabi pulses and parallel electron shuttling to construct a surface code that needs minimal, feasible local control., Comment: Published version - more detailed discussions, robustness to dephasing pointed out additionally

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway® entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines.

Each person's genome sequence has thousands of missense variants. Practical interpretation of their functional significance must rely on computational inferences in the absence of exhaustive experimental measurements. Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequencing in first-generation progeny of N-ethyl-N-nitrosourea-treated mice, involving 23 essential immune system genes. PolyPhen2, SIFT, MutationAssessor, Panther, CADD, and Condel were used to predict each mutation's functional importance, whereas the actual effect was measured by breeding and testing homozygotes for the expected in vivo loss-of-function phenotype. Only 20% of mutations predicted to be deleterious by PolyPhen2 (and 15% by CADD) showed a discernible phenotype in individual homozygotes. Half of all possible missense mutations in the same 23 immune genes were predicted to be deleterious, and most of these appear to become subject to purifying selection because few persist between separate mouse substrains, rodents, or primates. Because defects in immune genes could be phenotypically masked in vivo by compensation and environment, we compared inferences by the same tools with the in vitro phenotype of all 2,314 possible missense variants in TP53; 42% of mutations predicted by PolyPhen2 to be deleterious (and 45% by CADD) had little measurable consequence for TP53-promoted transcription. We conclude that for de novo or low-frequency missense mutations found by genome sequencing, half those inferred as deleterious correspond to nearly neutral mutations that have little impact on the clinical phenotype of individual cases but will nevertheless become subject to purifying selection.

Dopants in silicon have been studied for many decades using optical and electron spin resonance (ESR) spectroscopy. Recently, new features have been observed in the spectra of dopants in isotopically enriched $^{28}\mathrm{Si}$ since the reduced inhomogeneous linewidth in this material improves spectral resolution. With this in mind, we measured ESR on exchange coupled phosphorus dimers in $^{28}\mathrm{Si}$ and report two results. First, a fine structure is observed in the ESR spectrum arising from state mixing by the hyperfine coupling to the $^{31}\mathrm{P}$ nuclei, which is enhanced when the exchange energy is comparable to the Zeeman energy. This fine structure enables us to spectroscopically address two separate dimer subensembles, the first with exchange $(J)$ coupling ranging from 2 to 7 GHz and the second with $J$ ranging from 6 to 60 GHz. Next, the average spin relaxation times ${T}_{1}$ and ${T}_{2}$ of both dimer subensembles were measured using pulsed ESR at 0.35 T. Both ${T}_{1}$ and ${T}_{2}$ for transitions between triplet states of the dimers were found to be identical to the relaxation times of isolated phosphorus donors in $^{28}\mathrm{Si}$, with ${T}_{2}=4$ ms at 1.7 K limited by spectral diffusion due to dipolar interactions with neighboring donor electron spins. This result, consistent with theoretical predictions, implies that an exchange coupling of 2--60 GHz does not limit the dimer ${T}_{1}$ and ${T}_{2}$ in bulk Si at the 10-ms time scale.

We report the use of novel, capacitively terminated coplanar waveguide (CPW) resonators to measure the quadratic Stark shift of phosphorus donor qubits in Si. We confirm that valley repopulation leads to an anisotropic spin-orbit Stark shift depending on electric and magnetic field orientations relative to the Si crystal. By measuring the linear Stark effect, we estimate the effective electric field due to strain in our samples. We show that in the presence of this strain, electric-field sources of decoherence can be non-negligible. Using our measured values for the Stark shift, we predict magnetic fields for which the spin-orbit Stark effect cancels the hyperfine Stark effect, suppressing decoherence from electric-field noise. We discuss the limitations of these noise-suppression points due to random distributions of strain and propose a method for overcoming them.

We discuss pulsed electron spin resonance measurements of electrons in Si and determine the spin coherence from the decay of the spin echo signals. Tightly bound donor electrons in isotopically enriched 28 Si are found to have exceptionally long spin coherence. Placing the donors near a surface or interface is found to decrease the spin coherence time, but it is still in the range of milliseconds. Unbound twodimensional electrons have shorter coherence times of a few microseconds, though still long compared to the Zeeman frequency or the typical time to manipulate a spin with microwave pulses. Longer spin coherence is expected in two-dimensional systems patterned into quantum dots, but relatively small dots will be required. Data from dots with a lithographic size of 400 nm do not yet show longer spin coherence.

Spins of electrons bound to donor electrons are attractive candidates for exploration of quantum information processing in silicon. We present results from our development of donor electron spin qubit structures. Donors are placed into isotopically enriched ^2^8Si by ion implantation. The coherence properties of donor implants in pre-device structures are probed by pulsed electron spin resonance (ESR). The spin de-coherence time, T"2, for ^1^2^1Sb donors implanted into a peak depth of 50nm from a thermal oxide interface is 0.3ms at 5K, increasing to 0.75ms when the silicon surface is passivated with hydrogen. A technique for formation of donor arrays by ion implantation with scanning force microscope alignment is presented, and we discuss coherence limiting factors with respect to the implementation of a single spin readout scheme.

We present an investigation of the g-factor and the spin coherence time of electrons confined in regular SiGe quantum dot arrays deposited on prepatterned Si substrates. These structures were investigated by photoluminescence and electron paramagnetic resonance both in continuous wave and pulsed mode. The dot structures consist of regular arrays of about 1010 SiGe quantum dots on a Si(1 0 0) substrate that was prepatterned by e-beam lithography or holographic lithography. These quantum dot systems show an EPR line with a g-factor of conduction electrons in Si. The spin lifetime fits to that of two-dimensional SiGe structures, but the EPR line width shows inhomogeneous broadening. A 2D anisotropy is no longer visible

A key issue in nanoimprint lithography (NIL) is determining the ultimate pitch resolution achievable for various pattern shapes and their critical dimensional control. To this end, we demonstrated the fabrication of 6 nm half-pitch gratings and 0.04 µm2 cell area SRAM metal interconnects with 20 nm line half-pitch in resist by NIL. The mould for the 6 nm half-pitch grating was fabricated by cleaving a GaAs /Al0.7Ga0.3As superlattice grown on GaAs with molecular beam epitaxy, and selectively etching away the Al0.7Ga0.3As layers in dilute hydrofluoric acid. The mould for the 0.04 µm2 SRAM metal interconnects was fabricated in silicon dioxide using 35 kV electron beam lithography with polystyrene as a negative resist and a reactive ion etch with the resist as mask. Imprints from both moulds showed excellent fidelity and critical dimension control.