Long coherence times are key to the performance of quantum bits (qubits). Here, we experimentally and theoretically show that the Hahn-echo coherence time of electron spins associated with divacancy ...defects in 4H-SiC reaches 1.3 ms, one of the longest Hahn-echo coherence times of an electron spin in a naturally isotopic crystal. Using a first-principles microscopic quantum-bath model, we find that two factors determine the unusually robust coherence. First, in the presence of moderate magnetic fields (30 mT and above), the
Si and
C paramagnetic nuclear spin baths are decoupled. In addition, because SiC is a binary crystal, homo-nuclear spin pairs are both diluted and forbidden from forming strongly coupled, nearest-neighbour spin pairs. Longer neighbour distances result in fewer nuclear spin flip-flops, a less fluctuating intra-crystalline magnetic environment, and thus a longer coherence time. Our results point to polyatomic crystals as promising hosts for coherent qubits in the solid state.
In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive ...patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.
Abstract We report the timing analysis of PSR J1846−0513, a pulsar discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. The pulsar ...possesses a spin period of 23.36 ms and a spin-down rate ( P ̇ ) of 1.0106(3) × 10 −18 s s −1 , and it is located in an eccentric orbit ( e ∼0.208) with an orbital period of 0.61 days. The characteristic age and surface magnetic field of the pulsar are found to be 366.62 Myr and 4.9178 × 10 9 G, respectively, indicating that it is a recycled pulsar. Using over two years of timing data, we measure the periastron advance ω ̇ = 0.8956(8) deg yr −1 . By assuming that this effect is purely relativistic, we have estimated the total mass M = 2.6287(35) M ⊙ and obtained an upper limit for the pulsar mass and a lower limit for the companion’s mass. Our results indicate that this is a double neutron star system.
Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of ...lorcaserin are undefined.
We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization extended major cardiovascular events) was assessed for superiority at the end of the trial.
At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval CI, 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04).
In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 ClinicalTrials.gov number, NCT02019264 .).
Monoclonal antibodies directed against cytotoxic T lymphocyte–associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by ...inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.
ABSTRACT
Background and objective
Bronchiolitis obliterans syndrome (BOS) after haematopoietic stem cell transplantation (HSCT) presents with lung function decline. The pattern of lung function ...decline after BOS diagnosis could impact prognostication of BOS as a complication after HSCT. The aim of this study was to assess the impact of lung function decline on overall survival (OS) in BOS subjects.
Methods
Subjects with BOS were compared to those without BOS and matched for age, gender, primary diagnoses, conditioning regimes and chronic graft versus host disease. Lung function tests at baseline, at BOS diagnosis and every 3 months after HSCT were evaluated.
Results
Of the 1461 subjects undergoing allogeneic HSCT (allo‐HSCT) between 1998 and 2015, 95 (6.5%) were diagnosed with BOS. A total of 159 matched HSCT recipients without BOS were identified. A 25% decline in FEV1 within the first 3 months after BOS diagnosis would separate BOS subjects into a subgroup with initial rapid decline and another subgroup with initial gradual decline in lung function. The rapid decline group showed lower subsequent lung function parameters and significantly worse OS compared to the gradual decline group (P = 0.013).
Conclusion
Post‐HSCT BOS subjects with initial rapid lung function decline within 3 months after BOS diagnosis will have significantly poorer lung function and worse OS compared to those with initial gradual decline in lung function after BOS diagnosis. HSCT BOS patients with rapid initial decline in lung function warrant closer monitoring for the development of other post‐HSCT complications that could affect their survival.
Patients with post‐haematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS) who manifested initial rapid lung function decline within 3 months of BOS diagnosis had significantly poorer lung function and worse overall survival compared to those with initial gradual decline in lung function after BOS diagnosis.
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ABSTRACT
The follow-up timing observations were carried out for 24 pulsars discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. ...We report their phase-connected timing ephemeris, polarization pulse profiles, and Faraday rotation measurements. With their spin periods spanning from 2.995 ms to 4.34 s, their period derivatives were determined to spread between 7.996(8) × 10−21 and 9.83(3) × 10−15 s s−1, which imply that they have characteristic ages from 1.97 × 106 to 5.93 × 109 yr. It is inferred that PSRs J0211+4235 and J0518+2431 are beyond the ‘traditional death line’. PSR J0211+4235 is beyond the ‘death valley’. The death line model of Zhang et al. also cannot explain the radio presence of PSR J0211+4235. This suggests that radiation theory needs to be improved. Besides, ten of the 22 canonical pulsars show nulling phenomena. Moreover, PSR J1617+1123 exhibits variation of emission and J0540+4542 shows subpulse drifting. The DM of five pulsars is larger than the estimated by the YMW16 electron density model, which could suggest that electron density models need updates for higher Galactic latitude regions. PSRs J0447+2447 and J1928−0548 are isolated millisecond pulsars. With their flux densities spanning from 5(1)–553(106) μJy, some of these new pulsars found by FAST are distant, dim, and low-$\dot{E}$ ones and are suitable for testing pulsar emission theories.
Transmission electron microscopy is a powerful imaging tool that has found broad application in materials science, nanoscience and biology. With the introduction of aberration-corrected electron ...lenses, both the spatial resolution and the image quality in transmission electron microscopy have been significantly improved and resolution below 0.5 ångströms has been demonstrated. To reveal the three-dimensional (3D) structure of thin samples, electron tomography is the method of choice, with cubic-nanometre resolution currently achievable. Discrete tomography has recently been used to generate a 3D atomic reconstruction of a silver nanoparticle two to three nanometres in diameter, but this statistical method assumes prior knowledge of the particle's lattice structure and requires that the atoms fit rigidly on that lattice. Here we report the experimental demonstration of a general electron tomography method that achieves atomic-scale resolution without initial assumptions about the sample structure. By combining a novel projection alignment and tomographic reconstruction method with scanning transmission electron microscopy, we have determined the 3D structure of an approximately ten-nanometre gold nanoparticle at 2.4-ångström resolution. Although we cannot definitively locate all of the atoms inside the nanoparticle, individual atoms are observed in some regions of the particle and several grains are identified in three dimensions. The 3D surface morphology and internal lattice structure revealed are consistent with a distorted icosahedral multiply twinned particle. We anticipate that this general method can be applied not only to determine the 3D structure of nanomaterials at atomic-scale resolution, but also to improve the spatial resolution and image quality in other tomography fields.
Nanoparticle drug formulations have been extensively investigated, developed, and in some cases, approved by the Food and Drug Administration (FDA). Synergistic combinations of drugs having distinct ...tumor-inhibiting mechanisms and non-overlapping toxicity can circumvent the issue of treatment resistance and may be essential for effective anti-cancer therapy. At the same time, co-delivery of a combined regimen by a single nanocarrier presents a challenge due to differences in solubility, molecular weight, functional groups and encapsulation conditions between the two drugs. This review discusses cellular and microenvironment mechanisms behind treatment resistance and nanotechnology-based solutions for effective anti-cancer therapy. Co-loading or cascade delivery of multiple drugs using of polymeric nanoparticles, polymer-drug conjugates and lipid nanoparticles will be discussed along with lipid-coated drug nanoparticles developed by our lab and perspectives on combination therapy.
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