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The bespoke interface between a lower limb residuum and a prosthetic socket is critical for an amputee's comfort and overall rehabilitation outcomes. Analysis of interface kinematics and kinetics is important to gain full understanding of the interface biomechanics, which could aid clinical socket fit, rehabilitation and amputee care. This pilot study aims to investigate the dynamic correlation between kinematic movement and kinetic stresses at the interface during walking tests on different terrains. One male, knee disarticulation amputee participated in the study. He was asked to walk on both a level surface and a 5° ramped surface. The movement between the residuum and the socket was evaluated by the angular and axial couplings, based on the outputs from a 3D motion capture system. The corresponding kinetic stresses at anterior-proximal (AP), posterior-proximal (PP) and anterior-distal (AD) locations of the residuum were measured, using individual stress sensors. Approximately 8° of angular coupling and up to 32 mm of axial coupling were measured when walking on different terrains. The direction of the angular coupling shows strong correlation with the pressure difference between the PP and AP sensors. Higher pressure was obtained at the PP location than the AP location during stance phase, associated with the direction of the angular coupling. A strong correlation between axial coupling length, L , and longitudinal shear was also evident at the PP and AD locations i.e. the shortening of L corresponds to the increase of shear in the proximal direction. Although different terrains did not affect these correlations in principle, interface kinematic and kinetic values suggested that gait changes can induce modifications to the interface biomechanics. It is envisaged that the reported techniques could be potentially used to provide combined kinematics and kinetics for the understanding of biomechanics at the residuum/socket interface, which may play an important role in the clinical assessment of prosthetic component settings, including socket fit quality. [ABSTRACT FROM AUTHOR]

Design and fitting of artificial limbs to lower limb amputees are largely based on the subjective judgement of the prosthetist. Understanding the science of three-dimensional (3D) dynamic coupling at the residuum/socket interface could potentially aid the design and fitting of the socket. A new method has been developed to characterise the 3D dynamic coupling at the residuum/socket interface using 3D motion capture based on a single case study of a trans-femoral amputee. The new model incorporated a Virtual Residuum Segment (VRS) and a Socket Segment (SS) which combined to form the residuum/socket interface. Angular and axial couplings between the two segments were subsequently determined. Results indicated a non-rigid angular coupling in excess of 10° in the quasi-sagittal plane and an axial coupling of between 21 and 35 mm. The corresponding angular couplings of less than 4° and 2° were estimated in the quasi-coronal and quasi-transverse plane, respectively. We propose that the combined experimental and analytical approach adopted in this case study could aid the iterative socket fitting process and could potentially lead to a new socket design. [ABSTRACT FROM AUTHOR]

Retinoic acid-inducible-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and cyclic GMP-AMP synthase (cGAS) genes encode essential cytosolic receptors mediating antiviral immunity against viruses. Here, we show that OTUD3 has opposing role in response to RNA and DNA virus infection by removing distinct types of RIG-I/MDA5 and cGAS polyubiquitination. OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination. This serves to reduce the binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS, leading to the suppression of the RNA virus-triggered innate antiviral responses. Meanwhile, OTUD3 associates with cGAS and targets at Lys279 to deubiquitinate K48-linked ubiquitination, resulting in the enhancement of cGAS protein stability and DNA-binding ability. As a result, Otud3 -deficient mice and zebrafish are more resistant to RNA virus infection but are more susceptible to DNA virus infection. These findings demonstrate that OTUD3 limits RNA virus-triggered innate immunity but promotes DNA virus-triggered innate immunity. [Display omitted] • OTUD3 removes ubiquitination of RIG-I/MDA5 to suppress RNA virus-triggered immunity • OTUD3 removes K48 ubiquitination of cGAS to promote DNA virus-triggered immunity • OTUD3 exhibits opposing effects in innate immunity against RNA and DNA viruses Cai et al. demonstrate that OTUD3 removes K63-linked ubiquitination of RIG-I/MDA5 to suppress RNA virus-triggered innate immune response and removes K48-linked ubiquitination of cGAS to promote DNA virus-triggered innate immune response. Therefore, OTUD3 exhibits opposing effects in innate immunity against RNA and DNA viruses. [ABSTRACT FROM AUTHOR]

Summary: The encapsidated genome in all double-strand DNA bacteriophages is packaged to liquid crystalline density through a unique vertex in the procapsid assembly intermediate, which has a portal protein dodecamer in place of five coat protein subunits. The portal orchestrates DNA packaging and exit, through a series of varying interactions with the scaffolding, terminase, and closure proteins. Here, we report an asymmetric cryoEM reconstruction of the entire P22 virion at 7.8 Å resolution. X-ray crystal structure models of the full-length portal and of the portal lacking 123 residues at the C terminus in complex with gene product 4 (Δ123portal-gp4) obtained by were fitted into this reconstruction. The interpreted density map revealed that the 150 Å, coiled-coil, barrel portion of the portal entraps the last DNA to be packaged and suggests a mechanism for head-full DNA signaling and transient stabilization of the genome during addition of closure proteins. [ABSTRACT FROM AUTHOR]

Summary: We present here the first asymmetric, three-dimensional reconstruction of a tailed dsDNA virus, the mature bacteriophage ϕ29, at subnanometer resolution. This structure reveals the rich detail of the asymmetric interactions and conformational dynamics of the ϕ29 protein and DNA components, and provides novel insight into the mechanics of virus assembly. For example, the dodecameric head-tail connector protein undergoes significant rearrangement upon assembly into the virion. Specific interactions occur between the tightly packed dsDNA and the proteins of the head and tail. Of particular interest and novelty, an ∼60Å diameter toroid of dsDNA was observed in the connector-lower collar cavity. The extreme deformation that occurs over a small stretch of DNA is likely a consequence of the high pressure of the packaged genome. This toroid structure may help retain the DNA inside the capsid prior to its injection into the bacterial host. [Copyright &y& Elsevier]

A bionic surface based on the wing structure of the dragon louse is developed and applied in the thermal management system of electronic components. Fe 3 O 4 -water nanofluids are introduced and their thermal-hydrodynamic behaviors under magnetic field are studied. The influence of nanofluids concentration (ξ = 0.1–0.5%), Reynolds numbers (Re = 712–1400), tilt angles of magnetic field (θ = 0°, 30°, 60°) and intensity of magnetic field (β = 0.0 T, 0.005 T, 0.010 T, 0.015 T) on the heat transfer are considered in the system. Exergy efficiency and entropy production of CPU cooling system are analyzed. Results presented that the bionic surface based on the wing structure of the dragon louse shows an excellent drag reduction effect compared with the smooth surface, which can reach 35.4%. The maximal reduced ratio of CPU surface temperature under magnetic field is 34.42% in comparison with that under no magnetic field, and the maximal reduced ratio of CPU surface temperature with θ = 60° is 14.96% in comparison with θ = 0°. It shows an augmentation of heat transfer for most cases with the identical rate of flow from the point of exergy efficiency. When nanofluids concentration is ξ = 0.3%, Reynolds number is Re = 1402, tilt angle is θ = 60°, and magnetic field strength is β = 0.015 T, the minimum entropy production is obtained. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by various factors. The present study aimed to determine whether prenatal hypoxia can lead to ASD and the role of hypoxia-inducible factor-1α (HIF-1α) in this process. We constructed a prenatal hypoxia model of pregnant rats by piping nitrogen and oxygen mixed gas, with an oxygen concentration of 10 ± 0.5 %, into the self-made hypoxia chamber. Rats were subjected to different extents of hypoxia treatments at different points during pregnancy. The results showed that hypoxia for 6 h on the 17th gestation day is most likely to lead to autistic behavior in offspring rats, including social deficits, repetitive behaviors, and impaired learning and memory. The mRNA expression level of TNF-α also increased in hypoxia-induced autism group and valproic acid (VPA) group. Western blotting analysis showed increased levels of hypoxia inducible factor 1 alpha (HIF-1α) and decreased levels of phosphatase and tensin homolog (PTEN) in the hypoxic-induced autism group. Meanwhile, N -methyl d -aspartate receptor subtype 2 (NR2A) and glutamate ionotropic receptor AMPA type subunit 2 (GluR2) were upregulated in the hypoxic-induced autism group. HIF-1α might play a role in hypoxia-caused autism-like behavior and its regulatory effect is likely to be achieved by regulating synaptic plasticity. [ABSTRACT FROM AUTHOR]

To investigate the natural convection heat transfer of Fe 3 O 4 -water nanofluids in a rectangular cavity under an adjustable magnetic field, two experimental systems are established. Meanwhile, several factors, such as nanoparticle mass fractions (ω = 0%, 0.1%, 0.3%, 0.5%), magnetic field directions (horizontal and vertical), magnetic field intensities (B = 0.0 T, 0.01 T, 0.02 T), rotation angles of the cavity (α = 0°, 45°, 90°, 135°), and PPI of Cu metal foam (PPI = 0, 5, 15) are taken into consideration to research the natural convection of Fe 3 O 4 -water nanofluids in a rectangular cavity. With the increasing nanoparticle mass fraction, Nusselt number firstly rises but then falls, and the maximum value of which appears at a nanoparticle mass fraction ω = 0.3%. Horizontal magnetic field is not significant to the thermal performance enhancement, but vertical magnetic field shows an opposite trend and makes a positive contribution to the thermal performance. The cavity with a rotation angle α = 90° shows the highest thermal performance. Nusselt number of the cavity filled with metal foam can be improved obviously compared with that without metal foam. But the increasing PPI of metal foam is disadvantageous to heat transfer performance. [ABSTRACT FROM AUTHOR]

• Effect of tube structure on heat transfer and flow performance is studied. • Thermo-hydraulic performance is analyzed by thermal efficiency R 3. • Thermo-hydraulic performance is analyzed by exergy efficiency. An experiment is carried out to research the thermo-hydraulic performance of TiO 2 -H 2 O nanofluids in triangle tubes while taking the effect of twisted tapes into consideration. The theories of thermal and exergy efficiency are applied to estimate this system. The influence of mass fractions of nanoparticles (0.1 wt%, 0.3 wt% and 0.5 wt%), Reynolds numbers (Re = 800–9000), different structures of triangle tubes (isosceles right triangle tube (tube 1), isosceles 45° triangle tube (tube 2)) and twisted tape on the Nusselt number, Nusselt number ratio, resistance coefficient, resistance coefficient ratio and pressure drop are experimentally studied respectively. Results show that there are three positive factors for heat transfer performance including large nanoparticles concentration, large Reynolds number and existence of the twisted tape. Compared with the smooth tube, tubes (tubes 1 and 2) with twisted tape can enhance heat transfer, but that without twisted tape can deteriorate heat transfer, for heat transfer performance, tube 2 is better than tube 1. Tube 2 with twisted tape has the biggest value of comprehensive performance index R 3. A better exergy efficiency performance can be obtained when Reynolds number is greater than 5000 and the exergy efficiency reaches the best when Re = 8000. [ABSTRACT FROM AUTHOR]

Nav1.5, encoded by SCN5A, has been associated with metastasis in colorectal cancer (CRC). Here, we investigated the mechanism by which Nav1.5 regulates tumor progression and whether Nav1.5 influences chemosensitivity to 5-fluorouracil (5-FU) in CRCs. CRC cases were evaluated for Nav1.5 expression. Elevated Nav1.5 expression was associated with poor prognosis in CRCs, whereas stage II/III patients with upregulated SCN5A expression could have better survival after receiving 5-FU-based adjuvant chemotherapy. In CRC cells, SCN5A knockdown reduced the proliferation, migration and invasion. According to RNA sequencing, SCN5A knockdown inhibited both the cell cycle and epithelial-mesenchymal transition. In addition, Nav1.5 stabilized the KRas-calmodulin complex to modulate Ras signaling, promoting Ca2+ influx through the Na+-Ca2+ exchanger and Ca2+ release-activated calcium channel. Meanwhile, SCN5A knockdown increased the 50% inhibitory concentration to 5-FU by upregulating 5-FU-stimulated apoptosis in CRCs. In conclusion, Nav1.5 could progress to proliferation and metastasis through Ca2+/calmodulin-dependent Ras signaling in CRC, and it could also enhance 5-FU-stimulated apoptosis. Clinically, patients with stage II/III CRCs with elevated SCN5A expression demonstrated poor prognosis, yet those patients could benefit more from 5-FU-based chemotherapy than patients with lower SCN5A expression. [ABSTRACT FROM AUTHOR]

Graphical abstract Schematic diagram of experimental system. Highlights • Effects of groove depth and arrangement mode on cooling performance are studied. • CPU temperature is reduced by about 3.3 °C(8.2%) compared with deionized water. • For aligned and staggered arrangement, Nusselt number increases by 31.3%, 30.9%. • Aligned arrangement shows more excellent entropy generation performance. Abstract An experiment set for researching the flow and heat transfer characteristics of nanofluids flowing through CPU is established and validated. The influences of groove depths (1 mm, 2 mm, 3 mm) and arrangement modes (aligned and staggered arrangements) on thermo-hydraulic performances of CPU cooled by TiO 2 -water nanofluids are explored. In addition, the influences of nanoparticle mass fractions (0.0, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%) and Reynolds numbers (472–1198) are studied. It is found that there is a most appropriate nanoparticle mass fraction (0.3%) and groove depth (2 mm) for the lowest CPU temperature. Heat transfer augmentation of CPU heat sink is more sensitive to staggered arrangement grooves and high Reynolds number. Nanofluids (0.3%) in CPU heat sink with staggered arrangement grooves (2 mm) show the best heat transfer performances. Lastly, thermal efficiency, exergy efficiency and entropy generation are applied to analyze the cooling performance of enhanced structure. Results show that the thermal efficiency decreases with mass fraction when Reynolds number is less than 791, but increases with the depth of groove. Exergy efficiency of the groove structure can be obviously strengthened under the same pumping power and mass flow rate. From entropy generation analysis, it is found that the aligned arrangement shows lower entropy generation performance than aligned arrangement. [ABSTRACT FROM AUTHOR]