Graphene is increasingly explored as a possible platform for developing novel separation technologies. This interest has arisen because it is a maximally thin membrane that, once perforated with ...atomic accuracy, may allow ultrafast and highly selective sieving of gases, liquids, dissolved ions and other species of interest. However, a perfect graphene monolayer is impermeable to all atoms and molecules under ambient conditions: even hydrogen, the smallest of atoms, is expected to take billions of years to penetrate graphene's dense electronic cloud. Only accelerated atoms possess the kinetic energy required to do this. The same behaviour might reasonably be expected in the case of other atomically thin crystals. Here we report transport and mass spectroscopy measurements which establish that monolayers of graphene and hexagonal boron nitride (hBN) are highly permeable to thermal protons under ambient conditions, whereas no proton transport is detected for thicker crystals such as monolayer molybdenum disulphide, bilayer graphene or multilayer hBN. Protons present an intermediate case between electrons (which can tunnel easily through atomically thin barriers) and atoms, yet our measured transport rates are unexpectedly high and raise fundamental questions about the details of the transport process. We see the highest room-temperature proton conductivity with monolayer hBN, for which we measure a resistivity to proton flow of about 10 Ω cm(2) and a low activation energy of about 0.3 electronvolts. At higher temperatures, hBN is outperformed by graphene, the resistivity of which is estimated to fall below 10(-3) Ω cm(2) above 250 degrees Celsius. Proton transport can be further enhanced by decorating the graphene and hBN membranes with catalytic metal nanoparticles. The high, selective proton conductivity and stability make one-atom-thick crystals promising candidates for use in many hydrogen-based technologies.
The exceptional electronic properties of graphene, with its charge carriers mimicking relativistic quantum particles and its formidable potential in various applications, have ensured a rapid growth ...of interest in this new material. We report on electron transport in quantum dot devices carved entirely from graphene. At large sizes (>100 nanometers), they behave as conventional single-electron transistors, exhibiting periodic Coulomb blockade peaks. For quantum dots smaller than 100 nanometers, the peaks become strongly nonperiodic, indicating a major contribution of quantum confinement. Random peak spacing and its statistics are well described by the theory of chaotic neutrino billiards. Short constrictions of only a few nanometers in width remain conductive and reveal a confinement gap of up to 0.5 electron volt, demonstrating the possibility of molecular-scale electronics based on graphene.
The ultimate aim of any detection method is to achieve such a level of sensitivity that individual quanta of a measured entity can be resolved. In the case of chemical sensors, the quantum is one ...atom or molecule. Such resolution has so far been beyond the reach of any detection technique, including solid-state gas sensors hailed for their exceptional sensitivity. The fundamental reason limiting the resolution of such sensors is fluctuations due to thermal motion of charges and defects, which lead to intrinsic noise exceeding the sought-after signal from individual molecules, usually by many orders of magnitude. Here, we show that micrometre-size sensors made from graphene are capable of detecting individual events when a gas molecule attaches to or detaches from graphene's surface. The adsorbed molecules change the local carrier concentration in graphene one by one electron, which leads to step-like changes in resistance. The achieved sensitivity is due to the fact that graphene is an exceptionally low-noise material electronically, which makes it a promising candidate not only for chemical detectors but also for other applications where local probes sensitive to external charge, magnetic field or mechanical strain are required.
Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time ...with outcomes would help to guide implementation.
To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage.
Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites.
Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment.
The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation.
Among all 1287 patients (endovascular thrombectomy + medical therapy n = 634; medical therapy alone n = 653) enrolled in the 5 trials (mean age, 66.5 years SD, 13.1; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 95% CI, 0.76 to 0.93; ARD, -6.7%) and less functional independence (OR, 0.81 95% CI, 0.71 to 0.92, ARD, -5.2% 95% CI, -8.3% to -2.1%), but no change in mortality (OR, 1.12 95% CI, 0.93 to 1.34; ARD, 1.5% 95% CI, -0.9% to 4.2%).
In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
We present deep photometry in the B, V and I filters from CTIO/MOSAIC for about 270 000 stars in the Fornax dwarf spheroidal galaxy, out to a radius of rell ≈ 0.8 degrees. By combining the accurately ...calibrated photometry with the spectroscopic metallicity distributions of individual red giant branch stars we obtain the detailed star formation and chemical evolution history of Fornax. Fornax is dominated by intermediate age (1−10 Gyr) stellar populations, but also includes ancient (10−14 Gyr), and young (≤1 Gyr) stars. We show that Fornax displays a radial age gradient, with younger, more metal-rich populations dominating the central region. This confirms results from previous works. Within an elliptical radius of 0.8 degrees, or 1.9 kpc from the centre, a total mass in stars of 4.3 × 107 M⊙ was formed, from the earliest times until 250 Myr ago. Using the detailed star formation history, age estimates are determined for individual stars on the upper RGB, for which spectroscopic abundances are available, giving an age-metallicity relation of the Fornax dSph from individual stars. This shows that the average metallicity of Fornax went up rapidly from Fe/H ≤ −2.5 dex to Fe/H = −1.5 dex between 8−12 Gyr ago, after which a more gradual enrichment resulted in a narrow, well-defined sequence which reaches Fe/H ≈ −0.8 dex, ≈3 Gyr ago. These ages also allow us to measure the build-up of chemical elements as a function of time, and thus determine detailed timescales for the evolution of individual chemical elements. A rapid decrease in Mg/Fe is seen for the stars with Fe/H ≥ −1.5 dex, with a clear trend in age.
The Global Coupled 3 (GC3) configuration of the Met Office Unified Model is presented. Among other applications, GC3 is the basis of the United Kingdom's submission to the Coupled Model ...Intercomparison Project 6 (CMIP6). This paper documents the model components that make up the configuration (although the scientific descriptions of these components are in companion papers) and details the coupling between them. The performance of GC3 is assessed in terms of mean biases and variability in long climate simulations using present‐day forcing. The suitability of the configuration for predictability on shorter time scales (weather and seasonal forecasting) is also briefly discussed. The performance of GC3 is compared against GC2, the previous Met Office coupled model configuration, and against an older configuration (HadGEM2‐AO) which was the submission to CMIP5. In many respects, the performance of GC3 is comparable with GC2, however, there is a notable improvement in the Southern Ocean warm sea surface temperature bias which has been reduced by 75%, and there are improvements in cloud amount and some aspects of tropical variability. Relative to HadGEM2‐AO, many aspects of the present‐day climate are improved in GC3 including tropospheric and stratospheric temperature structure, most aspects of tropical and extratropical variability and top‐of‐atmosphere and surface fluxes. A number of outstanding errors are identified including a residual asymmetric sea surface temperature bias (cool northern hemisphere, warm Southern Ocean), an overly strong global hydrological cycle and insufficient European blocking.
Key Points
Description of the Global Coupled 3 (GC3) configuration of the Met Office Unified Model
A cross‐time‐scale evaluation of the GC3 configuration is presented
Overall, GC3 is an improvement on previous configurations
Increasing numbers of women undergo breast implantation for cosmetic and reconstructive purposes. Contracture of the fibrous capsule, which encases the implant leads to significant pain and ...reoperation. Texture, wettability and the cellular reaction to implant surfaces are poorly understood determinants of implant biocompatibility. The aim of this study was to evaluate the in-vitro characteristics of a range of commercial available implants using a macrophage based assay of implant biocompatibility and a quantitative assessment of wettability and texture.
Thirteen commercially available surfaces were subjected to wettability and texture characterisation using scanning and laser confocal microscopy. THP-1 macrophages were cultured on their surfaces and assessed using Integrin αV immunocytochemistry, SEM and RT-PCR for the expression of TNF-Alpha, IL-6, IL-10 and a cytokine array for the production of TNF-alpha, IL-10, IL-1RA and IL1β; important indicators of inflammation and macrophage polarization.
Textured surfaces can be accurately sub-categorized dependent upon roughness and re-entrant features into four main types (macro, micro, meso and nano-textured surfaces). Significant (P < 0.0001) differences in implant hydrophobicity and texture exist. Certain surfaces promoted poor macrophage polarization and an innate potential to foster a proinflammatory response. A subgroup analysis showed that texture had a variable effect on markers of inflammation in these surfaces.
We propose a classification of implant surfaces based on roughness and present a macrophage based assay of breast implant biocompatibility with a quantitative assessment of implant wettability and texture. The breast implant surface-cell interaction is variable and sufficient to alter healing response and capsular contracture fate in-vivo.
Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by ...mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice.
EMT/MET markers were assessed in xenograft tumors by immunohistochemistry. Stable E-cadherin manipulation was effected by transfection and verified by Western blotting, immunocytochemistry, and quantitative polymerase chain reaction (qPCR). Effects of E-cadherin manipulation on proliferation and chemomigration were assessed in vitro by performing sulforhodamine B assays and Transwell assays, respectively. Invasion was assessed by Matrigel outgrowth; growth in vivo was assessed in SCID mice; and EMT status was assessed by qPCR. Hypoxic response of E-cadherin knockdown cell lines was assessed by qPCR after hypoxic culture. Repeated measures analysis of variance (ANOVA), one- and two-way ANOVA with posttests, and paired Student's t tests were performed to determine significance (p < 0.05).
EMT occurred at the necrotic interface of MDA-MB-468 xenografts in regions of hypoxia. Extratumoral deposits (vascular and lymphatic inclusions, local and axillary nodes, and lung metastases) strongly expressed E-cadherin. MDA-MB-468 cells overexpressing E-cadherin were more proliferative and less migratory in vitro, whereas E-cadherin knockdown (short hairpin CDH1 shCDH1) cells were more migratory and invasive, less proliferative, and took longer to form tumors. shCDH1-MDA-MB-468 xenografts did not contain the hypoxia-induced necrotic areas observed in wild-type (WT) and shSCR-MDA-MB-468 tumors, but they did not exhibit an impaired hypoxic response in vitro. Although vimentin expression was not stimulated by E-cadherin knockdown in 2D or 3D cultures, xenografts of these cells were globally vimentin-positive rather than exhibiting regional EMT, and they expressed higher SNA1 than their in vitro counterparts. E-cadherin suppression caused a trend toward reduced lung metastasis, whereas E-cadherin overexpression resulted in the reverse trend, consistent with the increased proliferation rate and predominantly epithelial phenotype of MDA-MB-468 cells outside the primary xenograft. This was also originally observed in WT xenografts. Furthermore, we found that patients with breast cancer that expressed E-cadherin were more likely to have metastases.
E-cadherin expression promotes growth of primary breast tumors and conceivably the formation of metastases, supporting a role for MET in metastasis. E-cadherin needs to be reevaluated as a tumor suppressor.
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Breast implant use has tripled in the last decade with over 320,000 breast implant based reconstructions and augmentations performed in the US per annum. Unfortunately a considerable ...number of women will experience capsular contracture, the irrepressible and disfiguring, tightening and hardening of the fibrous capsule that envelops the implant. Functionalising implant surfaces with biocompatible tissue-specific textures may improve in vivo performance. A novel biomimetic breast implant is presented here with anti-inflammatory in vitro abilities.
Topographical assessment of native breast tissue facilitated the development of a statistical model of adipose tissue. 3D grayscale photolithography and ion etching were combined to successfully replicate a surface modelled upon the statistics of breast tissue.
Pro-inflammatory genes ILβ1, TNFα, and IL6 were downregulated (p<0.001) and anti-inflammatory gene IL-10 were upregulated on the novel surface. Pro-inflammatory cytokines Gro-Alpha, TNFα and neutrophil chemoattractant IL8 were produced in lower quantities and anti-inflammatory IL-10 in higher quantities in culture with the novel surface (p<0.01). Immunocytochemistry and SEM demonstrated favourable fibroblast and macrophage responses to these novel surfaces.
This study describes the first biomimetic breast tissue derived breast implant surface. Our findings attest to its potential translational ability to reduce the inflammatory phase of the implant driven foreign body reaction.
Breast implants are still manufactured using outdated techniques and have changed little since their inception in the 1960’s. Breast implants can cause a medical condition, capsular contracture which often results in disfigurement, pain, implant removal and further surgery. This condition is due to the body’s reaction to these breast implants. This article describes the successful development and testing of a novel breast implant surface inspired by the native shapes present in breast tissue. Results show that this novel implant surface is capable of reducing the negative reaction of human cells to these surfaces which may help reduce capsular contracture formation. This work represents the first steps in producing a biocompatible breast implant.
The Society of Neurointerventional Surgery revised its operational definition of emergent large vessel occlusion (ELVO) recently to include proximal M2 segment middle cerebral artery (MCA) ...occlusions. We sought to assess the benefit of endovascular thrombectomy (EVT) over best medical care for M2 segment MCA occlusion.
Patient level data from trials in the HERMES Collaboration were included. The HERMES core laboratory identified patients with M2 segment MCA occlusions and further classified them as proximal versus distal, anterior versus posterior division, and dominant versus co-dominant versus non-dominant. Primary outcome was modified Rankin Scale (mRS) score 0-2 at 90 days. Secondary outcomes were modified Thrombolysis in Cerebral Infarction (mTICI) rates at end of procedure, 90-day mRS shift, 90-day mRS 0-1, 24 hours National Institute of Health Stroke Scale (NIHSS) score 0-2, symptomatic intracerebral hemorrhage (ICH), and death.
130 patients with M2 MCA (proximal location n=116 vs distal n=14, anterior division n=72 vs posterior n=58, dominant n=73 vs co-dominant n=50 vs non-dominant n=7) were included. Successful reperfusion (mTICI 2b or 3) among those undergoing EVT was seen in 59.2% of patients. Treatment effect favored EVT (adjusted OR 2.39, 95% CI 1.08 to 5.28, p=0.03) for 90-day mRS 0-2 (58.2% EVT vs 39.7% control). Direction of benefit favored EVT for other outcomes. Treatment effect favoring EVT was maximal in patients with proximal M2 segment MCA occlusions (n=116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in dominant M2 segment MCA occlusions (n=73, adjusted OR 4.08, 95% CI 1.08 to 15.48). No sICH (0%) was observed in patients treated with EVT compared with five (7.9%) in the control arm.
Patients with proximal M2 segment MCA occlusions eligible for EVT trial protocols benefited from EVT.