Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Halide perovskites are a compelling candidate for the next generation of clean-energy-harvesting technologies owing to their low cost, facile fabrication and outstanding semiconductor properties. ...However, photovoltaic device efficiencies are still below practical limits and long-term stability challenges hinder their practical application. Current evidence suggests that strain in halide perovskites is a key factor in dictating device efficiency and stability. Here we outline the fundamentals of strain within halide perovskites relevant to photovoltaic applications and rationalize approaches to characterize the phenomenon. We examine recent breakthroughs in eliminating the adverse impacts of strain, enhancing both device efficiencies and operational stabilities. Finally, we discuss further challenges and outline future research directions for placing stress and strain studies at the forefront of halide perovskite research. An extensive understanding of strain in halide perovskites is needed, which would allow effective strain management and drive further enhancements in efficiencies and stabilities of perovskite photovoltaics.
Lung infections caused by
are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation.
is an ...intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of
lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an
clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three
subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains
subsp.
ATCC 19977,
subsp.
CCUG 50184-T, and
subsp.
CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the
complex bacteria
and may be considered for treatment of
lung disease.
Nitriding Iron at Lower Temperatures Tong, W. P.; Tao, N. R.; Wang, Z. B. ...
Science (American Association for the Advancement of Science),
01/2003, Letnik:
299, Številka:
5607
Journal Article
Recenzirano
The microstructure in the surface layer of a pure iron plate was refined at the nanometer scale by means of a surface mechanical attrition treatment that generates repetitive severe plastic ...deformation of the surface layer. The subsequent nitriding kinetics of the treated iron with the nanostructured surface layer were greatly enhanced, so that the nitriding temperature could be as low as 300°C, which is much lower than conventional nitriding temperatures (above 500°C). This enhanced processing method demonstrates the technological significance of nanomaterials in improving traditional processing techniques and provides a new approach for selective surface reactions in solids.
Abstract Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC). Our previous study has demonstrated that VPA ...pretreatment reduces lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity through the inhibition of microglia over-activation. The aim of this study was to determine the mechanism underlying VPA-induced attenuation of microglia over-activation using rodent primary neuron/glia or enriched glia cultures. Other histone deacetylase inhibitors (HDACIs) were compared with VPA for their effects on microglial activity. We found that VPA induced apoptosis of microglia cells in a time- and concentration-dependent manner. VPA-treated microglial cells showed typical apoptotic hallmarks including phosphatidylserine externalization, chromatin condensation and DNA fragmentation. Further studies revealed that trichostatin A (TSA) and sodium butyrate (SB), two structurally dissimilar HDACIs, also induced microglial apoptosis. The apoptosis of microglia was accompanied by the disruption of mitochondrial membrane potential and the enhancement of acetylation levels of the histone H3 protein. Moreover, pretreatment with SB or TSA caused a robust decrease in LPS-induced pro-inflammatory responses and protected DA neurons from damage in mesencephalic neuron–glia cultures. Taken together, our results shed light on a novel mechanism whereby HDACIs induce neuroprotection and underscore the potential utility of HDACIs in preventing inflammation-related neurodegenerative disorders such as Parkinson’s disease.
In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of ...protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and ...covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine ...degrading enzyme—arginine deiminase—conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy.
Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4–5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives.
A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion.
ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway.
www.clinicaltrials.gov (NCT 01287585).
Additive manufacturing (AM) offers a radical net-shape manufacturing approach for titanium aluminide alloys but significant challenges still remain. A study has been made of the AM of a high ...niobium-containing titanium aluminide alloy (Ti–45Al–7Nb–0.3W, in at% throughout the paper) using selective electron beam melting (SEBM). The formation of various types of microstructural defects, including banded structures caused by the vaporization of aluminum, was investigated with respect to different processing parameters. To avoid both micro- and macro-cracks, the use of higher preheating temperatures and an intermediate reheating process (to reheat each solidified layer during SEBM) was assessed in detail. These measures enabled effective release of the thermal stress that developed during SEBM and therefore the avoidance of cracks. In addition, the processing conditions for the production of a fine full lamellar microstructure were identified. As a result, the Ti–45Al–7Nb–0.3W alloy fabricated showed outstanding properties (compression strength: 2750MPa; strain-to-fracture: 37%). SEBM can be used to fabricate high performance titanium aluminide alloys with appropriate processing parameters and pathways.
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