Coherent control of macroscopic quantum states in a single-Cooper-pair box

A small superconducting electrode (a single-Cooper-pair box) connected to a reservoir via a Josephson junction constitutes an artificial two-level system, in which two charge states that differ by 2e are coupled by tunneling of Cooper pairs. Despite its macroscopic nature involving a large number of electrons, the two-level system shows coherent superposition of the two charge states, and has been suggested as a candidate for a qubit, i.e. a basic component of a quantum computer. Here we report on time-domain observation of the coherent quantum-state evolution in the two-level system by applying a short voltage pulse that modifies the energies of the two levels nonadiabatically to control the coherent evolution. The resulting state was probed by a tunneling current through an additional probe junction. Our results demonstrate coherent operation and measurement of a quantum state of a single two-level system, i.e. a qubit, in a solid-state electronic device.Comment: 4 pages, 4 figures; to be published in Natur

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Exploring the usability of a connected autonomous vehicle human machine interface designed for older adults

Users of Level 4–5 connected autonomous vehicles (CAVs) should not need to intervene with the dynamic driving task or monitor the driving environment, as the system will handle all driving functions. CAV human-machine interface (HMI) dashboards for such CAVs should therefore offer features to support user situation awareness (SA) and provide additional functionality that would not be practical within non-autonomous vehicles. Though, the exact features and functions, as well as their usability, might differ depending on factors such as user needs and context of use. The current paper presents findings from a simulator trial conducted to test the usability of a prototype CAV HMI designed for older adults and/or individuals with sensory and/or physical impairments: populations that will benefit enormously from the mobility afforded by CAVs. The HMI was developed to suit needs and requirements of this demographic based upon an extensive review of HMI and HCI principles focused on accessibility, usability and functionality [1, 2], as well as studies with target users. Thirty-one 50-88-year-olds (M 67.52, three 50–59) participated in the study. They experienced four seven-minute simulated journeys, involving inner and outer urban settings with mixed speed-limits and were encouraged to explore the HMI during journeys and interact with features, including a real-time map display, vehicle status, emergency stop, and arrival time. Measures were taken pre-, during- and post- journeys. Key was the System Usability Scale [3] and measures of SA, task load, and trust in computers and automation. As predicted, SA decreased with journey experience and although cognitive load did not, there were consistent negative correlations. System usability was also related to trust in technology but not trust in automation or attitudes towards computers. Overall, the findings are important for those designing, developing and testing CAV HMIs for older adults and individuals with sensory and/or physical impairments

A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide

<p>Abstract</p> <p>Background</p> <p>Expression of neuronal elements has been identified in various glial tumors, and glioblastomas (GBMs) with neuronal differentiation patterns have reportedly been associated with longer survival. However, the neuronal class III β-tubulin has been linked to increasing malignancy in astrocytomas. Thus, the significance of neuronal markers in gliomas is not established.</p> <p>Methods</p> <p>The expressions of class III β-tubulin, neurofilament protein (NFP), microtubule-associated protein 2 (MAP2) and neuron-specific enolase (NSE) were investigated in five GBM cell lines and two GBM biopsies with immunocytochemistry and Western blot. Moreover, the expression levels were quantified by real-time qPCR under different culture conditions. Following NSE siRNA treatment we used Electric cell-substrate impedance sensing (ECIS) to monitor cell growth and migration and MTS assays to study viability after irradiation and temozolomide treatment. Finally, we quantitated NSE expression in a series of human glioma biopsies with immunohistochemistry using a morphometry software, and collected survival data for the corresponding patients. The biopsies were then grouped according to expression in two halves which were compared by survival analysis.</p> <p>Results</p> <p>Immunocytochemistry and Western blotting showed that all markers except NFP were expressed both in GBM cell lines and biopsies. Notably, qPCR demonstrated that NSE was upregulated in cellular stress conditions, such as serum-starvation and hypoxia, while we found no uniform pattern for the other markers. NSE knockdown reduced the migration of glioma cells, sensitized them to hypoxia, radio- and chemotherapy. Furthermore, we found that GBM patients in the group with the highest NSE expression lived significantly shorter than patients in the low-expression group.</p> <p>Conclusions</p> <p>Neuronal markers are aberrantly expressed in human GBMs, and NSE is consistently upregulated in different cellular stress conditions. Knockdown of NSE reduces the migration of GBM cells and sensitizes them to hypoxia, radiotherapy and chemotherapy. In addition, GBM patients with high NSE expression had significantly shorter survival than patients with low NSE expression. Collectively, these data suggest a role for NSE in the adaption to cellular stress, such as during treatment.</p

The effect of posterior capsule repair upon post-operative hip dislocation following primary total hip arthroplasty

<p>Abstract</p> <p>Background</p> <p>Herein, we evaluated, retrospectively, the effect of posterior capsular repair upon postoperative hip dislocation subsequent to total hip arthroplasty (THA) incorporating a posterolateral approach.</p> <p>Methods</p> <p>A total of 181 patients undergoing 204 primary non-complicated THA surgical procedures in the period from January 2000 to October 2005 inclusively were included in this study. The patients were separated into two groups by whether the posterior capsular repair had been incorporated in the surgical procedure. For the surgeon did not commence repairing the posterior capsule until July, 2003, all members in the group that did not undergo posterior capsular repair (142 hips from 131 patients) were collected since January, 2000 to July, 2003, while the members in the group that underwent posterior capsular repair (62 hips from 52 patients) were followed since July, 2003, to October, 2005. With a minimum follow-up period of 12 months, we evaluated the early post-operative dislocation rate.</p> <p>Results</p> <p>The early postoperative hip-dislocation rate for the group who did not undergo posterior capsular repair appeared to be substantially greater (6.38% versus 0%) than the corresponding figure for the group the members of which underwent posterior capsular repair. In addition, patient demographics and the orientation of acetabular components for the replaced hip joints, as presented in postoperative radiographs, did not differ between the two groups.</p> <p>Conclusion</p> <p>Thus, surgeons should include posterior capsular repair as an important step in the surgical procedures of posterolateral approach for all THA in order to reduce the likelihood of early hip dislocation subsequent to THA.</p

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

A New Microsphere-Based Immunoassay for Measuring the Activity of Transcription Factors

There are several traditional and well-developed methods for analyzing the activity of transcription factors, such as EMSA, enzyme-linked immunosorbent assay, and reporter gene activity assays. All of these methods have their own distinct disadvantages, but none can analyze the changes in transcription factors in the few cells that are cultured in the wells of 96-well titer plates. Thus, a new microsphere-based immunoassay to measure the activity of transcription factors (MIA-TF) was developed. In MIA-TF, NeutrAvidin-labeled microspheres were used as the solid phase to capture biotin-labeled double-strand DNA fragments which contain certain transcription factor binding elements. The activity of transcription factors was detected by immunoassay using a transcription factor-specific antibody to monitor the binding with the DNA probe. Next, analysis was performed by flow cytometry. The targets hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-κB) were applied and detected in this MIA-TF method; the results that we obtained demonstrated that this method could be used to monitor the changes of NF-κB or HIF within 50 or 100 ng of nuclear extract. Furthermore, MIA-TF could detect the changes in NF-κB or HIF in cells that were cultured in wells of a 96-well plate without purification of the nuclear protein, an important consideration for applying this method to high-throughput assays in the future. The development of MIA-TF would support further progress in clinical analysis and drug screening systems. Overall, MIA-TF is a method with high potential to detect the activity of transcription factors

CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response

Here, we report that genome editing by CRISPR-Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR-Cas9.Peer reviewe