Cargo adaptors regulate stepping and force generation of mammalian dynein-dynactin.

Cytoplasmic dynein is an ATP-driven motor that transports intracellular cargos along microtubules. Dynein adopts an inactive conformation when not attached to a cargo, and motility is activated when dynein assembles with dynactin and a cargo adaptor. It was unclear how active dynein-dynactin complexes step along microtubules and transport cargos under tension. Using single-molecule imaging, we showed that dynein-dynactin advances by taking 8 to 32-nm steps toward the microtubule minus end with frequent sideways and backward steps. Multiple dyneins collectively bear a large amount of tension because the backward stepping rate of dynein is insensitive to load. Recruitment of two dyneins to dynactin increases the force generation and the likelihood of winning against kinesin in a tug-of-war but does not directly affect velocity. Instead, velocity is determined by cargo adaptors and tail-tail interactions between two closely packed dyneins. Our results show that cargo adaptors modulate dynein motility and force generation for a wide range of cellular functions

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

High Penetration Performance of Powder Metallurgy Copper-Tungsten Shaped Charge Liners

Copper tungsten liner manufactured using uniaxial pressing technique has been characterized numerically and experimentally in comparison with a baseline shaped charge copper liner produced by deep drawing technique. The jet properties resulted from these two shaped charges were different according to their liner types and relevant densities which affect the resultant penetration depths into rolled homogeneous armour (RHA) targets. Different copper-tungsten powder liners have been studied and analysed using Autodyn hydrocode, from which an optimum powder design was chosen based on its maximum jet kinetic energy that can be coherent. The compacted liner elastic properties have been measured using SONELASTIC apparatus, whereas its real density is determined using helium gas pycnometer. Baseline copper liner obtained by deep drawing technique of uniform density exhibited lower penetration depth in comparison with the copper-tungsten liner (higher density powder). Besides, the penetration crater resulted from the powder liner showed clean hole without clogging because there was no massive slug as in the case of the copper liners. Experimental field tests of the two liners against (RHA) targets exhibited different penetrations depths, which have been accounted in this research

Performance and Detonation Characteristics of Polyurethane Matrix Bonded Attractive Nitramines

Several cast-cured plastic bonded explosives (PBXs) based on cyclic nitramines bonded by a polyurethane matrix have been prepared and studied. The nitramines were ε-CL20 (ε-2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, ε-HNIW), BCHMX (bicyclo-HMX, cis-1,3,4,6-tetranitro-octahydroimidazo-[4,5-d]imidazole), RDX (1,3,5-trinitro-1,3,5-triazacyclohexane) and HMX (1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane). The detonation velocities were measured experimentally. The brisance of the prepared compositions was determined by the Kast method. The penetration performance of shaped charges filled with the prepared compositions was measured experimentally. The detonation parameters of the studied compositions and the individual explosives were calculated using the EXPLO5 thermodynamic code. It was concluded that CL20-HTPB has the highest detonation characteristics and performance of all of the prepared PBXs. BCHMX-HTPB is an interesting PBX with performance and detonation characteristics higher than those of RDX-HTPB. A linear relationship between the detonation pressures of the prepared PBXs and their performances in terms of the explosive brisance was observed; while the penetration depths formed by the shaped charge jets depended on the Gurney velocity of the studied PBXs samples

Green2.0 : enabling complex interactions between buildings and people

Professionals and researchers of the Architectural, Engi-neering & Construction (AEC) industry are challenged by the increasing complexity of designing, constructing and op-erating a building. This typically requires close cooperation of actors having different backgrounds and interests. Tra-ditionally, this cooperation happens in an ad-hoc way and information exchange occurs through conventional general-purpose communication channels, such as paper or email. This communication and collaboration process can be inad-equate and inef�cient, as it makes room for many different interpretations, mistakes and errors and can eventually lead to schedule and cost alterations. We present Green2.0, a system that tries to leverage advancements in building in-formation modeling to facilitate the collaboration process. The system integrates energy-ef�ciency simulation tools, and methods for online social network analysis to enable a data-driven approach to building design, construction and operation. By sharing all information online, all project ac-tors can access relevant information when they need so that everyone can work ef�cient together. The system aims to advance the current state of the art by bringing about a fundamental shift in the way that AEC professionals work together throughout a building’s lifecycle