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Materials with perpendicular anisotropy receive considerable attention owing to their potential in being employed in efficient memory devices. It is now shown that a type of magnetic tunnel junction widely studied for in-plane magnetic anisotropy has all the properties necessary to realize stable and efficient devices based on perpendicular magnetic anisotropy. Magnetic tunnel junctions (MTJs) with ferromagnetic electrodes possessing a perpendicular magnetic easy axis are of great interest as they have a potential for realizing next-generation high-density non-volatile memory and logic chips with high thermal stability and low critical current for current-induced magnetization switching 1 , 2 , 3 . To attain perpendicular anisotropy, a number of material systems have been explored as electrodes, which include rare-earth/transition-metal alloys 4 , 5 , L1 0 -ordered (Co, Fe)–Pt alloys 3 , 6 , 7 and Co/(Pd, Pt) multilayers 1 , 8 , 9 , 10 . However, none of them so far satisfy high thermal stability at reduced dimension, low-current current-induced magnetization switching and high tunnel magnetoresistance ratio all at the same time. Here, we use interfacial perpendicular anisotropy between the ferromagnetic electrodes and the tunnel barrier of the MTJ by employing the material combination of CoFeB–MgO, a system widely adopted to produce a giant tunnel magnetoresistance ratio in MTJs with in-plane anisotropy 11 , 12 , 13 . This approach requires no material other than those used in conventional in-plane-anisotropy MTJs. The perpendicular MTJs consisting of Ta/CoFeB/MgO/CoFeB/Ta show a high tunnel magnetoresistance ratio, over 120%, high thermal stability at dimension as low as 40 nm diameter and a low switching current of 49 μA.

Amphotericin B (AmB) is a prototypical small molecule natural product that can form ion channels in living eukaryotic cells and has remained refractory to microbial resistance despite extensive clinical utilization in the treatment of life-threatening fungal infections for more than half a century. It is now widely accepted that AmB kills yeast primarily via channel-mediated membrane permeabilization. Enabled by the iterative cross-coupling-based synthesis of a functional group deficient derivative of this natural product, we have discovered that channel formation is not required for potent fungicidal activity. Alternatively, AmB primarily kills yeast by simply binding ergosterol, a lipid that is vital for many aspects of yeast cell physiology. Membrane permeabilization via channel formation represents a second complementary mechanism that further increases drug potency and the rate of yeast killing. Collectively, these findings (i) reveal that the binding of a physiologically important microbial lipid is a powerful and clinically validated antimicrobial strategy that may be inherently refractory to resistance, (ii) illuminate a more straightforward path to an improved therapeutic index for this clinically vital but also highly toxic antifungal agent, and (iii) suggest that the capacity for AmB to form proteinlike ion channels might be separable from its cytocidal effects.

Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.

Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro . Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.

Chlorine resistant reverse osmosis (RO) membranes were fabricated using a multi-walled carbon nanotube-polyamide (MWCNT-PA) nanocomposite. The separation performance of these membranes after chlorine exposure (4800 ppm·h) remained unchanged (99.9%) but was drastically reduced to 82% in the absence of MWCNT. It was observed that the surface roughness of the membranes changed significantly by adding MWCNT. Moreover, membranes containing MWCNT fractions above 12.5 wt.% clearly improved degradation resistance against chlorine exposure, with an increase in water flux while maintaining salt rejection performance. Molecular dynamics and quantum chemical calculations were performed in order to understand the high chemical stability of the MWCNT-PA nanocomposite membranes, and revealed that high activation energies are required for the chlorination of PA. The results presented here confirm the unique potential of carbon nanomaterials embedded in polymeric composite membranes for efficient RO water desalination technologies.

Background/objectives: Post-exercise hypotension (PEH) is a sustained reduction in mean arterial blood pressure (MAP) after prolonged exercise. As water drinking is known to elicit a large acute pressor response, we aimed to explore the effect of drinking water during exercise on PEH. Subjects/methods: Ten normotensive male volunteers performed the control protocol: 30 min supine rest, 60 min cycling exercise in moderate intensity, and 60 min supine rest recovery. In the water drinking protocol, the same procedure was followed but with water intake during exercise to compensate for exercise-induced body weight lost. Heart rate, MAP, cardiac output and blood flow in the brachial artery were measured pre- and post-exercise. The total vascular conductance (TVC) and the vascular conductance (VC) in the brachial artery were calculated pre- and post-exercise, and the relative change in plasma volume (ΔPV) was also measured. Results: Body weight loss during exercise was 0.65±0.24 kg in the control. ΔPV was not different during recovery in either protocol. MAP in the control was significantly reduced during the latter half of the recovery compared with baseline. In contrast, MAP in the water drinking showed no reduction during recovery, and was significantly higher than in the control. TVC and VC in the brachial artery were lower in the water drinking, in which vasoconstriction was relatively exaggerated. Conclusions: Prevention of dehydration after exercise by oral water intake, or oral water intake per se has a role in maintaining post-exercise MAP and it may be related to reduction in TVC.

We study a heuristic, core-scale model for the transport of polymer particles in a two-phase (oil and water) porous medium. We are motivated by recent experimental observations which report increased oil recovery when polymers are injected after the initial waterflood. We propose the recovery mechanism to be microscopic diversion of the flow, where injected particles can accumulate in narrow pore throats and clog it, in a process known as a log-jamming effect. The blockage of the narrow pore channels leads to a microscopic diversion of the water flow, causing a redistribution of the local pressure, which again can lead to the mobilization of trapped oil, enhancing its recovery. Our objective herein is to develop a core-scale model that is consistent with the observed production profiles. We show that previously obtained experimental results can be qualitatively explained by a simple two-phase flow model with an additional transport equation for the polymer particles. A key aspect of the formulation is that the microscopic heterogeneity of the rock and a dynamic altering of the permeability must be taken into account in the rate equations.

In November 2016, a woman in her 30s who stayed at an insecure, temporary housing facility, a manga café in Tokyo, Japan, for a year was diagnosed with sputum smear-positive tuberculosis (TB). Since the café had 31 staff members and provided with accommodation to many people, the local health office initiated a contact investigation. This study aims to characterise the cases found in the outbreak. ATB casewas defined as a person tested bacteriologically positive for TB, or was determined to have TB by a physician. A latent TB infection case was defined as a person tested positive by interferon-𝛾 release assay. From January 2016 through November 2017, there were 31 staff members at the manga café, of which, six developed TB disease (one smearnegative, culture-positive and five smear- and culture-negative) in addition to seven LTBI. Another long-term customer was found having sputum smear-positive TB. Variable numbers tandem repeat (VNTR) test revealed that the index patient and the long-term customer had the identical type of VNTR; however, one staff member had a different VNTR. Local health authorities should intensify screening long-term customers of such facilities for TB regularly as well as once a TB outbreak occurs.

Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.

Background: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. Methods: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro . In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. Results: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. Conclusions: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.