A methodology for unified hardware-software design

Unified hardware-software design for digital computer

SARS-CoV-2 vaccines: Inactivation by gamma irradiation for T and B cell immunity

Despite accumulating preclinical data demonstrating a crucial role of cytotoxic T cell immunity during viral infections, ongoing efforts on developing COVID-19 vaccines are mostly focused on antibodies. In this commentary article, we discuss potential benefits of cytotoxic T cells in providing long-term protection against COVID-19. Further, we propose that gamma-ray irradiation, which is a previously tested inactivation method, may be utilized to prepare an experimental COVID-19 vaccine that can provide balanced immunity involving both B and T cells

β-decay half-lives and β-delayed neutron emission probabilities for several isotopes of Au, Hg, Tl, Pb, and Bi, beyond N = 126

Background: There have been measurements on roughly 230 nuclei that are β-delayed neutron emitters. They range from 8 He up to 150La. Apart from 210Tl, with a branching ratio of only 0.007%, no other neutron emitter has been measured beyond A = 150. Therefore, new data are needed, particularly in the region of heavy nuclei around N = 126, in order to guide theoretical models and help understand the formation of the third r-process peak at A ∼ 195. Purpose: To measure both β-decay half-lives and neutron branching ratios of several neutron-rich Au, Hg, Tl, Pb, and Bi isotopes beyond N = 126. Method: Ions of interest were produced by fragmentation of a 238U beam, selected and identified via the GSI-FRS fragment separator. A stack of segmented silicon detectors (SIMBA) was used to measure ion implants and β decays. An array of 30 3 He tubes embedded in a polyethylene matrix (BELEN) was used to detect neutrons with high efficiency and selectivity. A self-triggered digital system is employed to acquire data and to enable time correlations. The latter were analyzed with an analytical model and results for the half-lives and neutron-branching ratios were derived by using the binned maximum-likelihood method. Results: Twenty new β-decay half-lives are reported for 204−206Au, 208–211Hg, 211–216Tl, 215–218Pb, and 218–220Bi, nine of them for the first time. Neutron emission probabilities are reported for 210,211Hg and 211–216Tl. Conclusions: The new β-decay half-lives are in good agreement with previous measurements on nuclei in this region. The measured neutron emission probabilities are comparable to or smaller than values predicted by global models such as relativistic Hartree Bogoliubov plus the relativistic quasi-particle random phase approximation (RHB + RQRPA).Spanish Ministerio de Economía y Competitividad-FPA2011- 28770-C03-03, FPA2008-04972-C03-3, AIC-D2011-0705, FPA2011-24553, FPA2008-6419, FPA2010-17142, FPA2014-52823-C2-1-P, FPA2014- 52823-C2-2-P, and CPAN CSD-2007-00042 (Ingenio2010)Program Severo Ochoa-SEV-2014-0398German Helmholtz Association (Young Investigators)-VH-NG 627 (LISA-Lifetime Spectroscopy for Astrophysics)Nuclear Astrophysics Virtual Institute-VH-VI-417German Bundesministerium für Bildung und Forschung-06MT7178 / 05P12WOFNFSpanish Nuclear Security Council (CSN)-Catedra ArgosUK Science & Technology Facilities Council (STFC)-ST/F012012/

Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer

Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic

Effects on Berry Shrinkage in Vitis vinifera. L cv. ‘Merlot’ From Changes in Canopy/Root Ratio: A Preliminary Approach

A trial was conducted to find a possible relationship between the canopy/root ratio and the incidence and severity of premature berry shrinkage, and to propose an alternative to avoid this phenomenon in ‘Merlot’ grapevines. The ratio was changed by cutting foliage at a certain height 15 days before véraison, and by delaying the removal of trunk shoots. Treatments were the control (T1), 50% foliage area of control (T2), 75% foliage area of control (T3), and delayed trunk shoot removal (T4). Foliage area and the canopy/root ratio were lower in the T2 and T3 treatments. T4 was ineffective in changing the parameters. The incidence of berry shrinkage was lower for the T2 and T3 treatments, with the percentage of affected plants dropping from the 52% of the control to 22.9% and 31.3% for T2 and T3 respectively, and from 52.4% of the affected bunches to 16.6% and 21.2% for the same treatments respectively. The percentage of affected bunches falling into the range of moderate to severe damage fell from the 24% of the control to 5.2% and 3.9% for T2 and T3 respectively. Therefore, it is possible to avoid the incidence and severity of berry shrinkage by decreasing the canopy/root ratio in ‘Merlot’ grapevines

ac Losses in a Finite Z Stack Using an Anisotropic Homogeneous-Medium Approximation

A finite stack of thin superconducting tapes, all carrying a fixed current I, can be approximated by an anisotropic superconducting bar with critical current density Jc=Ic/2aD, where Ic is the critical current of each tape, 2a is the tape width, and D is the tape-to-tape periodicity. The current density J must obey the constraint \int J dx = I/D, where the tapes lie parallel to the x axis and are stacked along the z axis. We suppose that Jc is independent of field (Bean approximation) and look for a solution to the critical state for arbitrary height 2b of the stack. For c<|x|<a we have J=Jc, and for |x|<c the critical state requires that Bz=0. We show that this implies \partial J/\partial x=0 in the central region. Setting c as a constant (independent of z) results in field profiles remarkably close to the desired one (Bz=0 for |x|<c) as long as the aspect ratio b/a is not too small. We evaluate various criteria for choosing c, and we show that the calculated hysteretic losses depend only weakly on how c is chosen. We argue that for small D/a the anisotropic homogeneous-medium approximation gives a reasonably accurate estimate of the ac losses in a finite Z stack. The results for a Z stack can be used to calculate the transport losses in a pancake coil wound with superconducting tape.Comment: 21 pages, 17 figures, accepted by Supercond. Sci. Techno

Impact of pre-existing immunity on live attenuated influenza vaccine-induced cross-protective immunity

The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, pre-exposure to the intramuscularly (i.m.) delivered inactivated influenza vaccine (IIV) severely impaired LAIV-induced cross-protection against heterologous challenge, potentially by inhibiting replication of LAIV. Our findings suggest that pre-existing immunity afforded by IIV suppresses cross-protective T cell immunogenicity of LAIV