We demonstrate entangling quantum gates within a chain of five trapped ion qubits by optimally shaping optical fields that couple to multiple collective modes of motion. We individually address ...qubits with segmented optical pulses to construct multipartite entangled states in a programmable way. This approach enables high-fidelity gates that can be scaled to larger qubit registers for quantum computation and simulation.
Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and ...consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Randomness is a fundamental feature of nature and a valuable resource for applications ranging from cryptography and gambling to numerical simulation of physical and biological systems. Random ...numbers, however, are difficult to characterize mathematically, and their generation must rely on an unpredictable physical process. Inaccuracies in the theoretical modelling of such processes or failures of the devices, possibly due to adversarial attacks, limit the reliability of random number generators in ways that are difficult to control and detect. Here, inspired by earlier work on non-locality-based and device-independent quantum information processing, we show that the non-local correlations of entangled quantum particles can be used to certify the presence of genuine randomness. It is thereby possible to design a cryptographically secure random number generator that does not require any assumption about the internal working of the device. Such a strong form of randomness generation is impossible classically and possible in quantum systems only if certified by a Bell inequality violation. We carry out a proof-of-concept demonstration of this proposal in a system of two entangled atoms separated by approximately one metre. The observed Bell inequality violation, featuring near perfect detection efficiency, guarantees that 42 new random numbers are generated with 99 per cent confidence. Our results lay the groundwork for future device-independent quantum information experiments and for addressing fundamental issues raised by the intrinsic randomness of quantum theory.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Natural sediment flocs are fragile, highly irregular, loosely bound aggregates comprising minerogenic and organic material. They contribute a major component of suspended sediment load and are ...critical for the fate and flux of sediment, carbon and pollutants in aquatic environments. Understanding their behaviour is essential to the sustainable management of waterways, fisheries and marine industries. For several decades, modelling approaches have utilised fractal mathematics and observations of two dimensional (2D) floc size distributions to infer levels of aggregation and predict their behaviour. Whilst this is a computationally simple solution, it is highly unlikely to reflect the complexity of natural sediment flocs and current models predicting fine sediment hydrodynamics are not efficient. Here, we show how new observations of fragile floc structures in three dimensions (3D) demonstrate unequivocally that natural flocs are non-fractal. We propose that floc hierarchy is based on observations of 3D structure and function rather than 2D size distribution. In contrast to fractal theory, our data indicate that flocs possess characteristics of emergent systems including non-linearity and scale-dependent feedbacks. These concepts and new data to quantify floc structures offer the opportunity to explore new emergence-based floc frameworks which better represent natural floc behaviour and could advance our predictive capacity.
We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006–2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric ...monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions.The inverse models infer total CH4 emissions of 26.8 (20.2–29.7) Tg CH4 yr-1 (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006–2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 Tg CH4 yr-1 (2006) to 18.8 Tg CH4 yr-1 (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3–8.2) Tg CH4 yr-1 from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain.Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon Cycle (IMECC) aircraft campaign. We present a novel approach to estimate the biases in the derived emissions, based on the comparison of simulated and measured enhancements of CH4 compared to the background, integrated over the entire boundary layer and over the lower troposphere. The estimated average regional biases range between -40 and 20 % at the aircraft profile sites in France, Hungary and Poland.
Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that ...the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m²) compared to obese cases (BMI≥30 Kg/m²). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m²) or 4,123 obese cases (BMI≥30 kg/m²), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4×10⁻⁹, OR = 1.13 95% CI 1.09-1.18), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 95% CI 1.00-1.06). A variant in HMG20A--previously identified in South Asians but not Europeans--was associated with type 2 diabetes in obese cases (P = 1.3×10⁻⁸, OR = 1.11 95% CI 1.07-1.15), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 95% CI 1.02-1.17). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 95% CI 1.10-1.17, P = 3.2×10⁻¹⁴. This was larger than the same model fitted in the obese analysis where the OR = 1.06 95% CI 1.05-1.08, P = 2.2×10⁻¹⁶. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives: Inflammation in diseases such as rheumatoid arthritis (RA) stimulates osteoclast-mediated articular bone erosion and inhibits osteoblast-mediated bone formation, leading to a net loss of ...bone. Pro-inflammatory cytokines and antagonists of the Wnt signalling pathway have been implicated in the inhibition of osteoblast differentiation and activity in RA, contributing to the erosive process and impairing erosion healing. Importantly, osteoblast differentiation and function are also regulated by the osteogenic bone morphogenetic protein (BMP) signalling pathway, which is antagonized by BMP3. We therefore examined the potential role of BMP3 in inflammatory arthritis.
Method: Two murine models of RA, K/BxN serum transfer arthritis (STA) and antigen-induced arthritis (AIA), were used to establish the temporal expression of BMP3 and the cellular sources of BMP3 mRNA and protein in inflammatory arthritis. To determine the effects of inflammation on the expression of BMP3 in osteoblasts, murine calvarial osteoblasts were treated with pro-inflammatory cytokines and BMP3 expression was assessed.
Results: In both murine models of RA, BMP3 mRNA and protein are highly expressed by osteoblasts lining inflammation-bone interfaces late in the course of arthritis. Synovial tissues are not a significant source of BMP3. BMP3 expression is induced in osteocalcin-expressing osteoblasts in vitro following stimulation by tumour necrosis factor (TNF).
Conclusions: These data implicate BMP3 as a novel factor that may act locally to contribute to the erosive process and inhibit the repair of articular bone in RA through inhibition of osteoblast differentiation and function.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We present an estimate of net ecosystem exchange (NEE) of CO₂ in Europe for the years 2001-2007. It is derived with a data assimilation that uses a large set of atmospheric CO₂ mole fraction ...observations (~70 000) to guide relatively simple descriptions of terrestrial and oceanic net exchange, while fossil fuel and fire emissions are prescribed. Weekly terrestrial sources and sinks are optimized (i.e., a flux inversion) for a set of 18 large ecosystems across Europe in which prescribed climate, weather, and surface characteristics introduce finer scale gradients. We find that the terrestrial biosphere in Europe absorbed a net average of -165 Tg C yr⁻¹ over the period considered. This uptake is predominantly in non-EU countries, and is found in the northern coniferous (-94 Tg C yr⁻¹) and mixed forests (-30 Tg C yr⁻¹) as well as the forest/field complexes of eastern Europe (-85 Tg C yr⁻¹). An optimistic uncertainty estimate derived using three biosphere models suggests the uptake to be in a range of -122 to -258 Tg C yr⁻¹, while a more conservative estimate derived from the a-posteriori covariance estimates is -165±437 Tg C yr⁻¹. Note, however, that uncertainties are hard to estimate given the nature of the system and are likely to be significantly larger than this. Interannual variability in NEE includes a reduction in uptake due to the 2003 drought followed by 3 years of more than average uptake. The largest anomaly of NEE occurred in 2005 concurrent with increased seasonal cycles of observed CO₂. We speculate these changes to result from the strong negative phase of the North Atlantic Oscillation in 2005 that lead to favorable summer growth conditions, and altered horizontal and vertical mixing in the atmosphere. All our results are available through http://www.carbontracker.eu
European CH 4 and N 2 O emissions are estimated for 2006 and 2007 using four inverse modelling systems, based on different global and regional Eulerian and La-grangian transport models. This ensemble ...approach is designed to provide more realistic estimates of the overall uncertainties in the derived emissions, which is particularly important for verifying bottom-up emission inventories. We use continuous observations from 10 European stations (including 5 tall towers) for CH 4 and 9 continuous stations for N 2 O, complemented by additional European and global discrete air sampling sites. The available observations mainly constrain CH 4 and N 2 O emissions from northwestern and eastern Europe. The inversions are strongly driven by the observations and the derived total emissions of larger countries show little dependence on the emission inventories used a priori. Three inverse models yield 26-56 % higher total CH 4 emissions from northwestern and eastern Europe compared Published by Copernicus Publications on behalf of the European Geosciences Union. 716 P. Bergamaschi et al.: Top-down estimates of European CH 4 and N 2 O emissions to bottom-up emissions reported to the UNFCCC, while one model is close to the UNFCCC values. In contrast, the inverse modelling estimates of European N 2 O emissions are in general close to the UNFCCC values, with the overall range from all models being much smaller than the UNFCCC uncertainty range for most countries. Our analysis suggests that the reported uncertainties for CH 4 emissions might be underestimated , while those for N 2 O emissions are likely overestimated .
Background
Nipple‐sparing mastectomy (NSM) is associated with improved cosmesis and is being performed increasingly. Its role in BRCA mutation carriers has not been well described. This was a study ...of the indications for, and outcomes of, NSM in BRCA mutation carriers.
Methods
BRCA mutation carriers who underwent NSM were identified. Details of patient demographics, surgical procedures, complications, and relevant disease stage and follow‐up were recorded.
Results
A total of 177 NSMs were performed in 89 BRCA mutation carriers between September 2005 and December 2013. Twenty‐six patients of median age 41 years had NSM for early‐stage breast cancer and a contralateral prophylactic mastectomy. Mean tumour size was 1·4 (range 0·1–3·5) cm. Sixty‐three patients of median age 39 years had prophylactic NSM, eight of whom had an incidental diagnosis of ductal carcinoma in situ. There were no local or regional recurrences in the 26 patients with breast cancer at a median follow‐up of 28 (i.q.r. 15–43) months. There were no newly diagnosed breast cancers in the 63 patients undergoing prophylactic NSM at a median follow‐up of 26 (11–42) months. All patients had immediate breast reconstruction. Five patients (6 per cent) required subsequent excision of the nipple–areola complex for oncological or other reasons. Skin desquamation occurred in 68 (38·4 per cent) of the 177 breasts, and most resolved without intervention. Debridement was required in 13 (7·3 per cent) of the 177 breasts, and tissue‐expander or implant removal was necessary in six instances (3·4 per cent).
Conclusion
NSM is an acceptable choice for patients with BRCA mutations, with no evidence of compromise to oncological safety at short‐term follow‐up. Complication rates were acceptable, and subsequent excision of the nipple–areola complex was rarely required.
Appears safe but longer follow‐up is needed
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