Multiscale model of defective interfering particle replication for influenza A virus infection in animal cell culture

Cell culture-derived defective interfering particles (DIPs) are considered for antiviral therapy due to their ability to inhibit influenza A virus (IAV) production. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNAs) rendering them replication-incompetent. However, they can propagate alongside their homologous standard virus (STV) during infection in a competition for cellular and viral resources. So far, experimental and modeling studies for IAV have focused on either the intracellular or the cell population level when investigating the interaction of STVs and DIPs. To examine these levels simultaneously, we conducted a series of experiments using highly different multiplicities of infections for STVs and DIPs to characterize virus replication in Madin-Darby Canine Kidney suspension cells. At several time points post infection, we quantified virus titers, viable cell concentration, virus-induced apoptosis using imaging flow cytometry, and intracellular levels of vRNA and viral mRNA using real-time reverse transcription qPCR. Based on the obtained data, we developed a mathematical multiscale model of STV and DIP co-infection that describes dynamics closely for all scenarios with a single set of parameters. We show that applying high DIP concentrations can shut down STV propagation completely and prevent virus-induced apoptosis. Interestingly, the three observed viral mRNAs (full-length segment 1 and 5, defective interfering segment 1) accumulated to vastly different levels suggesting the interplay between an internal regulation mechanism and a growth advantage for shorter viral RNAs. Furthermore, model simulations predict that the concentration of DIPs should be at least 10000 times higher than that of STVs to prevent the spread of IAV. Ultimately, the model presented here supports a comprehensive understanding of the interactions between STVs and DIPs during co-infection providing an ideal platform for the prediction and optimization of vaccine manufacturing as well as DIP production for therapeutic use

Intra-arterial thrombolysis of occluded middle cerebral artery by use of collateral pathways in patients with tandem cervical carotid artery/middle cerebral artery occlusion

BACKGROUND AND PURPOSE: Cervical internal carotid artery (ICA) occlusion with middle cerebral artery (MCA) embolic occlusion is associated with a low rate of recanalization and poor outcome after intravenous thrombolysis. Prompt revascularization is required to prevent disabling stroke. We report our experience on acute ischemic stroke patients with tandem ICA or MCA occlusions treated with microcathether navigation and intra-arterial thrombolysis by use of collateral pathways including the posterior or anterior communicating arteries, or both pathways. MATERIALS AND METHODS: We retrospectively identified 8 patients with proximal ICA occlusion associated with MCA embolic occlusions treated with intra-arterial thrombolysis (IA rtPA). Access to the occluded MCA was obtained via catheter navigation through intact collateral pathways, including posterior communicating (PcomA) or anterior communicating (AcomA) arteries, without passing a microcathether through the acutely occluded ICA. We assessed clinical outcomes using modified Rankin scale (mRS) and National Institutes of Health Stroke Scale (NIHSS). RESULTS: Eight patients with a mean age of 57 ± 4 years and median NIHSS of 14 were identified. Mean time from stroke onset to intra-arterial thrombolysis was 292 ± 44 minutes. The MCA was revascularized completely in 5 of the 8 patients via collateral intra-arterial rtPA administration. All of the patients had a favorable outcome defined as a mRS of ≤2 or more at 1 and 3 months\u27 follow-up after thrombolytic therapy. One patient had an asymptomatic petechial hemorrhage. CONCLUSION: In this small number of patients with tandem occlusions of the ICA and MCA, intraarterial thrombolysis and recanalization of the MCA by use of collateral pathways to bypass the occluded ICA is a safe and efficacious therapeutic option

Management actions to address the climate emergency: Motivations and barriers for SMEs and other societal micro/meso-level groups

Initiatives to tackle the climate emergency have tended to focus on large-scale actions that governments and investors (societal macro-levels) can take and smaller-scale individual habits, with limited attention given to the groups that form society between those ends of the spectrum (societal micro/meso-levels). This research aims to traverse that gap by studying three societal micro/meso-level groups; from the private, public and voluntary sectors, as represented by business, community and campaign groups. Existing literature and focus groups are used to identify what motivates actions on climate change, while exposing barriers that may drive choices of inaction. The study shows that concerns for the future and personal ethics play vital roles across business, community and campaign groups, while the principal barriers include difficulties in accessing support schemes and changes in political priorities. Better networking and knowledge exchange are considered essential for meaningful progress. This provides a new framework for management education to support organisations in tackling climate-related issues. Action guides may be developed and task-forces trained to provide hands-on support, especially for SMEs and local communities. The enthusiasm of younger people and campaigners, combined with others’ experiences, would create a powerful platform for climate emergency actions

Nonexistence of self-similar singularities for the 3D incompressible Euler equations

We prove that there exists no self-similar finite time blowing up solution to the 3D incompressible Euler equations. By similar method we also show nonexistence of self-similar blowing up solutions to the divergence-free transport equation in $\Bbb R^n$. This result has direct applications to the density dependent Euler equations, the Boussinesq system, and the quasi-geostrophic equations, for which we also show nonexistence of self-similar blowing up solutions.Comment: This version refines the previous one by relaxing the condition of compact support for the vorticit

Lack of the Ig cell adhesion molecule BT-IgSF (IgSF11) induced behavioral changes in the open maze, water maze and resident intruder test

The brain- and testis-specific Ig superfamily protein (BT-IgSF, also termed IgSF11) is a homotypic cell adhesion protein. In the nervous system, BT-IgSF regulates the stability of AMPA receptors in the membrane of cultured hippocampal neurons, modulates the connectivity of chandelier cells and controls gap junction-mediated astrocyte-astrocyte communication. Here, we performed behavioral tests in BT-IgSF-deficient mice. BT-IgSF-deficient mice were similar to control littermates with respect to their reflexes, motor coordination and gating, and associative learning. However, BT-IgSF-deficient mice displayed an increased tendency to stay in the central illuminated areas in the open field and O-Maze paradigms suggesting reduced anxiety or increased scotophobia (fear of darkness). Although BT-IgSF-deficient mice initially found the platform in the water maze their behavior was compromised when the platform was moved, indicating reduced behavioral flexibility. This deficit was overcome by longer training to improve their spatial memory. Furthermore, male BT-IgSF-deficient mice displayed increased aggression towards an intruder. Our results show that specific behaviors are modified by the lack of BT-IgSF and demonstrate a contribution of BT-IgSF to network functions

The analytic structure of 2D Euler flow at short times

Using a very high precision spectral calculation applied to the incompressible and inviscid flow with initial condition $\psi_0(x_1, x_2) = \cos x_1+\cos 2x_2$, we find that the width $\delta(t)$ of its analyticity strip follows a $\ln(1/t)$ law at short times over eight decades. The asymptotic equation governing the structure of spatial complex-space singularities at short times (Frisch, Matsumoto and Bec 2003, J.Stat.Phys. 113, 761--781) is solved by a high-precision expansion method. Strong numerical evidence is obtained that singularities have infinite vorticity and lie on a complex manifold which is constructed explicitly as an envelope of analyticity disks.Comment: 19 pages, 14 figures, published versio

Multipole optimization of turbine arrays in tidal flows

This paper proposes a multipole optimization as introduced by Holl et al. (2016) for the requirement-based dimensioning of a turbine fence considering technical and economical scaling functions. The considered fence of N stream generators with characteristic size dT is situated in a generic tidal channel with typical flow state. The system is formulated by the energy, mass and cash flows through which the components (turbine, generator, tower/foundation and grid connection) communicate with each other and the tidal system. It is shown, that the levelized cost of energy (LCOE) can be reduced above all by increasing the channel blockage, i.e. by using more or larger turbines

Venous Leak Embolization in Patients with Venogenic Erectile Dysfunction via Deep Dorsal Penile Vein Access: Safety and Early Efficacy.

PURPOSE This all-comers registry aimed to assess safety and early efficacy of venous embolization in patients with venogenic erectile dysfunction due to venous leak in an unselected cohort. METHODS Between October 2019 and September 2022, patients with venogenic erectile dysfunction resistant to phosphodiesterase-5-inhibitors were treated with venous embolization using ultrasound-guided anterograde access via a deep dorsal penile vein in a single center. A mix of ethiodized oil and modified cyanoacrylate-based glue n-butyl 2 cyanoacrylate (NBCA) monomer plus methacryloxy-sulpholane monomer (Glubran-2, GEM, Italy) was used as liquid embolic agent. Prior to embolization, venous leak had been verified based on penile duplex sonography and computed tomography cavernosography. Procedural success was defined as technically successful and complete target vein embolization. The primary safety outcome measure was any major adverse event 6 weeks after the procedure. The primary feasibility outcome measure was IIEF-15 (International Index of Erectile Function-15) score improvement ≥ 4 points in ≥ 50% of subjects on 6 weeks follow-up post intervention. RESULTS Fifty consecutive patients (mean age 61.8 ± 10.0 years) with severe erectile dysfunction due to venous leak underwent venous embolization. Procedural success was achieved in 49/50 (98%) of patients with no major adverse events on follow-up. The primary feasibility outcome measure at 6 weeks was reached by 34/50 (68%) of patients. CONCLUSION Venous leak embolization via deep dorsal penile vein access using a liquid embolic agent was safe for all and efficacious in the majority of patients with severe venogenic erectile dysfunction on 6 weeks follow-up

Multipole optimization of turbine arrays in tidal flows

This paper proposes a multipole optimization as introduced by Holl et al. (2016) for the requirement-based dimensioning of a turbine fence considering technical and economical scaling functions. The considered fence of N stream generators with characteristic size dT is situated in a generic tidal channel with typical flow state. The system is formulated by the energy, mass and cash flows through which the components (turbine, generator, tower/foundation and grid connection) communicate with each other and the tidal system. It is shown, that the levelized cost of energy (LCOE) can be reduced above all by increasing the channel blockage, i.e. by using more or larger turbines