Improvement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and ...has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip-monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols-BB84, Coherent One Way and Differential Phase Shift-with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks.
Large-scale integrated quantum photonic technologies will require on-chip integration of identical photon sources with reconfigurable waveguide circuits. Relatively complex quantum circuits have been ...demonstrated already, but few studies acknowledge the pressing need to integrate photon sources and waveguide circuits together on-chip. A key step towards such large-scale quantum technologies is the integration of just two individual photon sources within a waveguide circuit, and the demonstration of high-visibility quantum interference between them. Here, we report a silicon-on-insulator device that combines two four-wave mixing sources in an interferometer with a reconfigurable phase shifter. We configured the device to create and manipulate two-colour (non-degenerate) or same-colour (degenerate) path-entangled or path-unentangled photon pairs. We observed up to 100.0 ± 0.4% visibility quantum interference on-chip, and up to 95 ± 4% off-chip. Our device removes the need for external photon sources, provides a path to increasing the complexity of quantum photonic circuits and is a first step towards fully integrated quantum technologies.
Radiation therapy is a staple approach for cancer treatment, whereas radioresistance of cancer cells remains a substantial clinical problem. In response to ionizing radiation (IR) induced DNA damage, ...cancer cells can sustain/activate pro-survival signaling pathways, leading to apoptotic resistance and induction of cell cycle checkpoint/DNA repair. Previous studies show that Rac1 GTPase is overexpressed/hyperactivated in breast cancer cells and is associated with poor prognosis. Studies from our laboratory reveal that Rac1 activity is necessary for G2/M checkpoint activation and cell survival in response to IR exposure of breast and pancreatic cancer cells. In this study, we investigated the effect of Rac1 on the survival of breast cancer cells treated with hyper-fractionated radiation (HFR), which is used clinically for cancer treatment. Results in this report indicate that Rac1 protein expression is increased in the breast cancer cells that survived HFR compared with parental cells. Furthermore, this increase of Rac1 is associated with enhanced activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways and increased levels of anti-apoptotic protein Bcl-xL and Mcl-1, which are downstream targets of ERK1/2 and NF-κB signaling pathways. Using Rac1-specific inhibitor and dominant-negative mutant N17Rac1, here we demonstrate that Rac1 inhibition decreases the phosphorylation of ERK1/2 and inhibitory κBα (IκBα), as well as the levels of Bcl-xL and Mcl-1 protein in the HFR-selected breast cancer cells. Moreover, inhibition of Rac1 using either small molecule inhibitor or dominant-negative N17Rac1 abrogates clonogenic survival of HFR-selected breast cancer cells and decreases the level of intact poly(ADP-ribose) polymerase, which is indicative of apoptosis induction. Collectively, results in this report suggest that Rac1 signaling is essential for the survival of breast cancer cells subjected to HFR and implicate Rac1 in radioresistance of breast cancer cells. These studies also provide the basis to explore Rac1 as a therapeutic target for radioresistant breast cancer cells.
Summary Background Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest ...randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. Methods The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov , number NCT01149044. Findings Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10 064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio HR 1·00 95% CI 0·87–1·15, p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 95% CI 0·76–1·14, p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 95% CI 1·10–2·51, p=0·015). Interpretation Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. Funding Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.
Abstract
We present estimates for the number of shadow-resolved supermassive black hole (SMBH) systems that can be detected using radio interferometers, as a function of angular resolution, flux ...density sensitivity, and observing frequency. Accounting for the distribution of SMBHs across mass, redshift, and accretion rate, we use a new semianalytic spectral energy distribution model to derive the number of SMBHs with detectable and optically thin horizon-scale emission. We demonstrate that (sub)millimeter interferometric observations with ∼0.1
μ
as resolution and ∼1
μ
Jy sensitivity could access >10
6
SMBH shadows. We then further decompose the shadow source counts into the number of black holes for which we could expect to observe the first- and second-order lensed photon rings. Accessing the bulk population of first-order photon rings requires ≲2
μ
as resolution and ≲0.5 mJy sensitivity, whereas doing the same for second-order photon rings requires ≲0.1
μ
as resolution and ≲5
μ
Jy sensitivity. Our model predicts that with modest improvements to sensitivity, as many as ∼5 additional horizon-resolved sources should become accessible to the current Event Horizon Telescope (EHT), whereas a next-generation EHT observing at 345 GHz should have access to ∼3 times as many sources. More generally, our results can help guide enhancements of current arrays and specifications for future interferometric experiments that aim to spatially resolve a large population of SMBH shadows or higher-order photon rings.
We present a joint optical/X-ray analysis of the massive galaxy cluster Abell 2744 (z = 0.308). Our strong- and weak-lensing analysis within the central region of the cluster, i.e. at R < 1 Mpc from ...the brightest cluster galaxy, reveals eight substructures, including the main core. All of these dark matter haloes are detected with a significance of at least 5s and feature masses ranging from 0.5 to 1.4 x 10 super( 14) M... within R < 150 kpc. Merten et al. and Medezinski et al. substructures are also detected by us. We measure a slightly higher mass for the main core component than reported previously and attribute the discrepancy to the inclusion of our tightly constrained strong-lensing mass model built on Hubble Frontier Fields data. X-ray data obtained by XMM-Newton reveal four remnant cores, one of them a new detection, and three shocks. Unlike Merten et al., we find all cores to have both dark and luminous counterparts. A comparison with clusters of similar mass in the Millennium XXL simulations yields no objects with as many massive substructures as observed in Abell 2744, confirming that Abell 2744 is an extreme system. We stress that these properties still do not constitute a challenge to ... cold dark matter, as caveats apply to both the simulation and the observations: for instance, the projected mass measurements from gravitational lensing and the limited resolution of the subhaloes finders. We discuss implications of Abell 2744 for the plausibility of different dark matter candidates and, finally, measure a new upper limit on the self-interaction cross-section of dark matter of sDM < 1.28 cm super( 2) g super( -1) (68 per cent CL), in good agreement with previous results from Harvey et al. (ProQuest: ... denotes formulae/symbols omitted.)
Single-photon detectors based on superconducting nanowires (SSPDs or SNSPDs) have rapidly emerged as a highly promising photon-counting technology for infrared wavelengths. These devices offer high ...efficiency, low dark counts and excellent timing resolution. In this review, we consider the basic SNSPD operating principle and models of device behaviour. We give an overview of the evolution of SNSPD device design and the improvements in performance which have been achieved. We also evaluate device limitations and noise mechanisms. We survey practical refrigeration technologies and optical coupling schemes for SNSPDs. Finally we summarize promising application areas, ranging from quantum cryptography to remote sensing. Our goal is to capture a detailed snapshot of an emerging superconducting detector technology on the threshold of maturity.
Purpose
To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT).
Methods
An international ...collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results.
Results
mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers.
Conclusions
The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.
Entanglement is a fundamental property of quantum mechanics, and is a primary resource in quantum information systems. Its manipulation remains a central challenge in the development of quantum ...technology. In this work, we demonstrate a device which can generate, manipulate, and analyse two-qubit entangled states, using miniature and mass-manufacturable silicon photonics. By combining four photon-pair sources with a reconfigurable six-mode interferometer, embedding a switchable entangling gate, we generate two-qubit entangled states, manipulate their entanglement, and analyse them, all in the same silicon chip. Using quantum state tomography, we show how our source can produce a range of entangled and separable states, and how our switchable controlled-Z gate operates on them, entangling them or making them separable depending on its configuration.
There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked.
Data were from three US cohorts in the ...After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803).
Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio HR = 1.22; 95% confidence interval CI = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54).
Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.
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