Mimicking memory processes, including encoding, storing, and retrieving information, is critical for neuromorphic computing and artificial intelligence. Synaptic behavior simulations through ...electronic, magnetic, or photonic devices based on metal oxides, 2D materials, molecular complex and phase change materials, represent important strategies for performing computational tasks with enhanced power efficiency. Here, a special class of memristive materials based on persistent luminescent memitters (termed as a portmanteau of “memory” and “emitter”) with optical characteristics closely resembling those of biological synapses is reported. The memory process and synaptic plasticity can be successfully emulated using such memitters under precisely controlled excitation frequency, wavelength, pulse number, and power density. The experimental and theoretical data suggest that electron‐coupled trap nucleation and propagation through clustering in persistent luminescent memitters can explain experience‐dependent plasticity. The use of persistent luminescent memitters for multichannel image memorization that allows direct visualization of subtle changes in luminescence intensity and realization of short‐term and long‐term memory is also demonstrated. These findings may promote the discovery of new functional materials as artificial synapses and enhance the understanding of memory mechanisms.
A new class of memristive materials based on persistent luminescent memitters emulates synaptic plasticity and memory without requiring sophisticated devices. Experimental and theoretical data suggest that electron‐coupled trap nucleation and propagation through clustering in persistent luminescent memitters can explain experience‐dependent plasticity. Multichannel image memorization involving persistent luminescent memitters allows direct visualization of short‐term and long‐term memory.
Pure copper and copper–aluminum alloys (aluminum content of 2.3at%, 7.2at%, and 11.6at% with stacking fault energies (SFEs) of about 48mJ/m2, 21mJ/m2, and 8mJ/m2, respectively) were processed by ...equal channel angular pressing (ECAP) at room temperature for 8 passes to generate a nanoscale grain size. The effect of SFE on microstructure refinement and tensile properties of these materials were investigated. Microstructural observations indicated that the grain size of as-ECAPed alloy decreased monotonically with increasing Al concentration, i.e. with decreasing SFE. A very low SFE was especially favorable for achieving a true nanocrystalline structure (e.g. d≈57nm in Cu–11.6at% Al) by twinning and shear banding. The tensile strength and uniform elongation of nanostructured copper–aluminum alloys were simultaneously enhanced owing to the significant grain size refinement, solid solution strengthening and enhanced strain hardening capability.
Objective
To evaluate the clinical feasibility of noninvasive prenatal diagnosis (NIPD) for β‐thalassaemia using circulating single molecule amplification and re‐sequencing technology (cSMART).
...Design
Through carrier screening, 102 pregnant Chinese couples carrying pathogenic HBB gene variants were recruited to the study. Pregnancies were managed using traditional invasive prenatal diagnosis (IPD). Retrospectively, we evaluated the archived pregnancy plasma DNA by NIPD to evaluate the performance of our cSMART assay for fetal genotyping.
Setting
Chinese prenatal diagnostic centres specialising in thalassaemia testing.
Population
Chinese carrier couples at high genetic risk for β‐thalassaemia.
Methods
Fetal cell sampling was performed by amniocentesis and HBB genotypes were determined by reverse dot blot. NIPD was performed by a newly designed HBB cSMART assay and fetal genotypes were called by measuring the allelic ratios in the maternal cell‐free DNA.
Main outcome measures
Concordance of HBB fetal genotyping between IPD and NIPD and the sensitivity and specificity of NIPD.
Results
Invasive prenatal diagnosis identified 29 affected homozygotes or compound heterozygotes, 54 heterozygotes and 19 normal homozygotes. Compared with IPD results, 99 of 102 fetuses (97%) were correctly genotyped by our NIPD assay. Two of three discordant samples were false positives and the other sample involved an incorrect call of a heterozygote carrier as a homozygote normal. Overall, the sensitivity and specificity of our NIPD assay was 100% (95% CI 88.06–100.00%) and 97.26% (95% CI 90.45–99.67%), respectively.
Conclusions
This study demonstrates that our cSMART‐based NIPD assay for β‐thalassaemia has potential clinical utility as an alternative to IPD for pregnant HBB carrier couples.
Tweetable
A new noninvasive test for pregnancies at risk for β‐thalassaemia.
Tweetable
A new noninvasive test for pregnancies at risk for β‐thalassaemia.
Numerous studies have compared the outcomes of two competing interventions for multivessel coronary artery disease: coronary-artery bypass grafting (CABG) and coronary stenting. However, little ...information has become available since the introduction of drug-eluting stents.
We identified patients with multivessel disease who received drug-eluting stents or underwent CABG in New York State between October 1, 2003, and December 31, 2004, and we compared adverse outcomes (death, death or myocardial infarction, or repeat revascularization) through December 31, 2005, after adjustment for differences in baseline risk factors among the patients.
In comparison with treatment with a drug-eluting stent, CABG was associated with lower 18-month rates of death and of death or myocardial infarction both for patients with three-vessel disease and for patients with two-vessel disease. Among patients with three-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.80 (95% confidence interval CI, 0.65 to 0.97) and the adjusted survival rate was 94.0% versus 92.7% (P=0.03); the adjusted hazard ratio for death or myocardial infarction was 0.75 (95% CI, 0.63 to 0.89) and the adjusted rate of survival free from myocardial infarction was 92.1% versus 89.7% (P<0.001). Among patients with two-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.71 (95% CI, 0.57 to 0.89) and the adjusted survival rate was 96.0% versus 94.6% (P=0.003); the adjusted hazard ratio for death or myocardial infarction was 0.71 (95% CI, 0.59 to 0.87) and the adjusted rate of survival free from myocardial infarction was 94.5% versus 92.5% (P<0.001). Patients undergoing CABG also had lower rates of repeat revascularization.
For patients with multivessel disease, CABG continues to be associated with lower mortality rates than does treatment with drug-eluting stents and is also associated with lower rates of death or myocardial infarction and repeat revascularization.
We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university ...hospital (National University Cancer Institute, Singapore NCIS). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient = −2.621; 95% confidence interval CI: −4.923, −0.319;
p
= 0.026) and all evaluated antibiotics (coefficient = −4.069; 95% CI: −8.075, −0.063;
p
= 0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes—the majority unavoidable—occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients.
Shear stability of metallic glasses Wu, F.F.; Zheng, W.; Wu, S.D. ...
International journal of plasticity,
04/2011, Letnik:
27, Številka:
4
Journal Article
Recenzirano
The effect of sample size on the shear deformation and compressive plasticity of different metallic glasses were investigated. The experimental results showed that the deformation and fracture ...behaviors of samples prepared from chemically identical Zr-, Ti-, Fe-, or Mg-based metallic glass ingots were strongly dependent on the sample size and machine stiffness, and a super-high compressive plasticity was achieved in the Zr-based metallic glasses with sample size of 1.0
mm in width. It is also found that the sample size can significantly influence the
density of elastic energy dissipated in the shear band: with sample size decreasing and machine stiffness increasing, the density of the elastic energy dissipated in the shear band of metallic glasses is prominently decreased, thus the shear deformation turns to be more stable, resulting in the improvement of plasticity in ductile metallic glasses and the transition from fragmentation fracture to shear fracture in brittle metallic glasses. This finding is important for the potential applications of the present metallic glasses and for designing new metallic glasses with better mechanical properties.
Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA ...remains challenging, partially because of the undefined biological background of cf-DNA.
We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10−7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA.
Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely ‘passenger mutations’ of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors.
Hematopoietic clone-derived mutations, including ‘driver mutations’ and ‘passenger mutations’, are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
The first large outbreak of hand, foot, and mouth disease (HFMD) with severe complications primarily caused by enterovirus 71 was reported in Taiwan in 1998. Surveillance of HFMD to evaluate the ...spread of HFMD with and without infection control policy is needed. We developed a new dynamic epidemic Susceptible-Infected-Recovered (SIR) model to fit the surveillance data on containing valuable information on the severity of HFMD in order to accurately estimate the basic reproductive number (R
0) of HFMD. After fitting the empirical data, in conjunction with other relevant parameters extracted from the literature, the estimated transmission coefficients were close to 5 × 10−7 (per day) and the proportion of severe HFMD cases ranged between 0 and 0·0036 (per day). Taking into account the distribution of all parameters considered in our dynamic epidemic model, the R
0 computed was 1·37 (95% confidence interval 0·24–5·84), suggesting a higher likelihood of the spread of HFMD if no infection control policy is provided. The isolation strategy against the spread of HFMD not only delayed the epidemic peak with the delayed time ranging from 4 weeks for only 20% isolation to 47 weeks for 100% isolation but also reduced total number of HFMD cases with the percentage of reduction ranging from 1·3% for only 20% isolation to 13·3% for 100% isolation. The proposed model can also be flexible for evaluating the effectiveness of two other possible policies for containing HFMD, quarantine and vaccination (if the vaccine can be developed).
Summary
Dysfunction of the immune regulatory system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Vasoactive intestinal peptide (VIP) has multiple bioactivities. This ...study aims to investigate the role of VIP in the maintenance of the immune regulatory capacity of monocytes (Mos). Human peripheral blood samples were collected from RA patients and healthy control (HC) subjects. Mos and CD14+ CD71–CD73+CD25+ regulatory Mos (RegMos) were isolated from the blood samples and characterized by flow cytometry. A rat RA model was developed to test the role of VIP in the maintenance of the immune regulatory function of Mos. The results showed that RegMos of HC subjects had immune suppressive functions. RegMos of RA patients expressed less interleukin (IL)‐10 and showed an incompetent immune regulatory capacity. Serum levels of VIP were lower in RA patients, which were positively correlated with the expression of IL‐10 in RegMos. In‐vitro experiments showed that the IL‐10 mRNA decayed spontaneously in RegMos, which could be prevented by the presence of VIP in the culture. VIP suppressed the effects of tristetraprolin (TTP) on inducing IL‐10 mRNA decay in RegMos. Administration of VIP inhibited experimental RA in rats through restoring the IL‐10 expression in RegMos. RegMos have immune suppressive functions. VIP is required in maintaining IL‐10 expression in RegMos. The data suggest that VIP has translational potential in the treatment of immune disorders such as RA.
A fraction of peripheral monocyte has immune regulatory function, which is impaired in patients with rheumatoid arthritis.
Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current ...treatments continue to be limited and ineffective. Therefore, there remains an unmet need for a novel therapeutic approach. One potential strategy is to target the altered metabolic state that is rewired by oncogenic transformation. Specifically, this rewiring may render certain outside nutrients indispensable. To identify such a nutrient, we performed a nutrigenetic screen by removing individual amino acids to identify possible addictions across a panel of breast cancer cells. This screen revealed that cystine deprivation triggered rapid programmed necrosis, but not apoptosis, in the basal-type breast cancer cells mostly seen in TNBC tumors. In contrast, luminal-type breast cancer cells are cystine-independent and exhibit little death during cystine deprivation. The cystine addiction phenotype is associated with a higher level of cystine-deprivation signatures noted in the basal type breast cancer cells and tumors. We found that the cystine-addicted breast cancer cells and tumors have strong activation of TNFα and MEKK4-p38-Noxa pathways that render them susceptible to cystine deprivation-induced necrosis. Consistent with this model, silencing of TNFα and MEKK4 dramatically reduces cystine-deprived death. In addition, the cystine addiction phenotype can be abrogated in the cystine-addictive cells by miR-200c, which converts the mesenchymal-like cells to adopt epithelial features. Conversely, the introduction of inducers of epithelial-mesenchymal transition (EMT) in cystine-independent breast cancer cells conferred the cystine-addiction phenotype by modulating the signaling components of cystine addiction. Together, our data reveal that cystine-addiction is associated with EMT in breast cancer during tumor progression. These findings provide the genetic and mechanistic basis to explain how cystine deprivation triggers necrosis by activating pre-existing oncogenic pathways in cystine-addicted TNBC with prominent mesenchymal features.
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