85 research outputs found
Symbiotic Nitrogen Fixation and the Challenges to Its Extension to Nonlegumes
Access to fixed or available forms of nitrogen limits the productivity of crop plants and thus food production. Nitrogenous fertilizer production currently represents a significant expense for the efficient growth of various crops in the developed world. There are significant potential gains to be had from reducing dependence on nitrogenous fertilizers in agriculture in the developed world and in developing countries, and there is significant interest in research on biological nitrogen fixation and prospects for increasing its importance in an agricultural setting. Biological nitrogen fixation is the conversion of atmospheric N2 to NH3, a form that can be used by plants. However, the process is restricted to bacteria and archaea and does not occur in eukaryotes. Symbiotic nitrogen fixation is part of a mutualistic relationship in which plants provide a niche and fixed carbon to bacteria in exchange for fixed nitrogen. This process is restricted mainly to legumes in agricultural systems, and there is considerable interest in exploring whether similar symbioses can be developed in nonlegumes, which produce the bulk of human food. We are at a juncture at which the fundamental understanding of biological nitrogen fixation has matured to a level that we can think about engineering symbiotic relationships using synthetic biology approaches. This minireview highlights the fundamental advances in our understanding of biological nitrogen fixation in the context of a blueprint for expanding symbiotic nitrogen fixation to a greater diversity of crop plants through synthetic biology.Biotechnology and Biological Sciences Research Council (Great Britain) (Grants BB/L011484/1 and BB/L011476/1)National Science Foundation (U.S.) (Grant 1331098
Developing a core outcome set for fistulising perianal Crohn's disease
OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback fromtheir panel(in the second round) andall participants(in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study.The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care
Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy
Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n = 152) and 3, 311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P = 1.42 x 10(-12)),8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472;P = 3.41 x 10(-8)),and 2p22 at SOS1 (rs963731;P = 1.76 x 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22;rs1768208;P = 2.07 x 10(-7)) and MAPT H1c (17q21;rs242557;P = 7.91 x 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein)
Readout of a quantum processor with high dynamic range Josephson parametric amplifiers
We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in
which the active nonlinear element is implemented using an array of rf-SQUIDs.
The device is matched to the 50 environment with a Klopfenstein-taper
impedance transformer and achieves a bandwidth of 250-300 MHz, with input
saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor
was used to benchmark these devices, providing a calibration for readout power,
an estimate of amplifier added noise, and a platform for comparison against
standard impedance matched parametric amplifiers with a single dc-SQUID. We
find that the high power rf-SQUID array design has no adverse effect on system
noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on
amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with
this design show no degradation in readout fidelity due to gain compression,
which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure
Measurement-Induced State Transitions in a Superconducting Qubit: Within the Rotating Wave Approximation
Superconducting qubits typically use a dispersive readout scheme, where a
resonator is coupled to a qubit such that its frequency is qubit-state
dependent. Measurement is performed by driving the resonator, where the
transmitted resonator field yields information about the resonator frequency
and thus the qubit state. Ideally, we could use arbitrarily strong resonator
drives to achieve a target signal-to-noise ratio in the shortest possible time.
However, experiments have shown that when the average resonator photon number
exceeds a certain threshold, the qubit is excited out of its computational
subspace, which we refer to as a measurement-induced state transition. These
transitions degrade readout fidelity, and constitute leakage which precludes
further operation of the qubit in, for example, error correction. Here we study
these transitions using a transmon qubit by experimentally measuring their
dependence on qubit frequency, average photon number, and qubit state, in the
regime where the resonator frequency is lower than the qubit frequency. We
observe signatures of resonant transitions between levels in the coupled
qubit-resonator system that exhibit noisy behavior when measured repeatedly in
time. We provide a semi-classical model of these transitions based on the
rotating wave approximation and use it to predict the onset of state
transitions in our experiments. Our results suggest the transmon is excited to
levels near the top of its cosine potential following a state transition, where
the charge dispersion of higher transmon levels explains the observed noisy
behavior of state transitions. Moreover, occupation in these higher energy
levels poses a major challenge for fast qubit reset
Suppressing quantum errors by scaling a surface code logical qubit
Practical quantum computing will require error rates that are well below what
is achievable with physical qubits. Quantum error correction offers a path to
algorithmically-relevant error rates by encoding logical qubits within many
physical qubits, where increasing the number of physical qubits enhances
protection against physical errors. However, introducing more qubits also
increases the number of error sources, so the density of errors must be
sufficiently low in order for logical performance to improve with increasing
code size. Here, we report the measurement of logical qubit performance scaling
across multiple code sizes, and demonstrate that our system of superconducting
qubits has sufficient performance to overcome the additional errors from
increasing qubit number. We find our distance-5 surface code logical qubit
modestly outperforms an ensemble of distance-3 logical qubits on average, both
in terms of logical error probability over 25 cycles and logical error per
cycle ( compared to ). To investigate
damaging, low-probability error sources, we run a distance-25 repetition code
and observe a logical error per round floor set by a single
high-energy event ( when excluding this event). We are able
to accurately model our experiment, and from this model we can extract error
budgets that highlight the biggest challenges for future systems. These results
mark the first experimental demonstration where quantum error correction begins
to improve performance with increasing qubit number, illuminating the path to
reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references,
Fig. S12, Table I
Justify your alpha
Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive
Development and validation of a targeted gene sequencing panel for application to disparate cancers
Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy
Non-Abelian braiding of graph vertices in a superconducting processor
Indistinguishability of particles is a fundamental principle of quantum
mechanics. For all elementary and quasiparticles observed to date - including
fermions, bosons, and Abelian anyons - this principle guarantees that the
braiding of identical particles leaves the system unchanged. However, in two
spatial dimensions, an intriguing possibility exists: braiding of non-Abelian
anyons causes rotations in a space of topologically degenerate wavefunctions.
Hence, it can change the observables of the system without violating the
principle of indistinguishability. Despite the well developed mathematical
description of non-Abelian anyons and numerous theoretical proposals, the
experimental observation of their exchange statistics has remained elusive for
decades. Controllable many-body quantum states generated on quantum processors
offer another path for exploring these fundamental phenomena. While efforts on
conventional solid-state platforms typically involve Hamiltonian dynamics of
quasi-particles, superconducting quantum processors allow for directly
manipulating the many-body wavefunction via unitary gates. Building on
predictions that stabilizer codes can host projective non-Abelian Ising anyons,
we implement a generalized stabilizer code and unitary protocol to create and
braid them. This allows us to experimentally verify the fusion rules of the
anyons and braid them to realize their statistics. We then study the prospect
of employing the anyons for quantum computation and utilize braiding to create
an entangled state of anyons encoding three logical qubits. Our work provides
new insights about non-Abelian braiding and - through the future inclusion of
error correction to achieve topological protection - could open a path toward
fault-tolerant quantum computing
Overcoming leakage in scalable quantum error correction
Leakage of quantum information out of computational states into higher energy
states represents a major challenge in the pursuit of quantum error correction
(QEC). In a QEC circuit, leakage builds over time and spreads through
multi-qubit interactions. This leads to correlated errors that degrade the
exponential suppression of logical error with scale, challenging the
feasibility of QEC as a path towards fault-tolerant quantum computation. Here,
we demonstrate the execution of a distance-3 surface code and distance-21
bit-flip code on a Sycamore quantum processor where leakage is removed from all
qubits in each cycle. This shortens the lifetime of leakage and curtails its
ability to spread and induce correlated errors. We report a ten-fold reduction
in steady-state leakage population on the data qubits encoding the logical
state and an average leakage population of less than
throughout the entire device. The leakage removal process itself efficiently
returns leakage population back to the computational basis, and adding it to a
code circuit prevents leakage from inducing correlated error across cycles,
restoring a fundamental assumption of QEC. With this demonstration that leakage
can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure
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