Single HA2 Mutation Increases the Infectivity and Immunogenicity of a Live Attenuated H5N1 Intranasal Influenza Vaccine Candidate Lacking NS1

Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may play a substantial role in the infectivity of HPAIVs for mammals

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

To study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney. LPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group. In our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenatio

System-level Generalized Component Mode Synthesis: an efficient small deformation flexible multibody framework

status: publishe

A non-invasive system-level model order reduction scheme for flexible multibody models

status: Published onlin

A noninvasive system‐level model order reduction scheme for flexible multibody simulation

This paper presents a novel system‐level model order reduction scheme for flexible multibody simulation, namely the system‐level affine projection (SLAP). Contrary to existing system‐level model order reduction approaches for multibody systems simulation, this methodology allows to obtain a constant reduced order basis which can be obtained in a noninvasive fashion with respect to the original flexible multibody model. It is shown that this scheme enables an automatic joint constraint elimination which can be obtained at low computational cost through exploitation of the component level modes typically employed in flexible multibody simulation. The equations of motion are derived such that the computational cost of the resulting SLAP model is independent of the original model size. This approach results in a set of ordinary differential equations with a constant mass matrix and nonlinear internal forces. This structure makes the resulting model suitable for a range of estimation, control, and design applications. The proposed approach is validated numerically on a flexible four‐bar mechanism and shows good accuracy for a very low‐order SLAP model.status: Published onlin

Generalized Component Mode Synthesis for the Spatial Motion of Flexible Bodies With Large Rotations About One Axis 1

In industrial practice, the floating frame of reference formulation (FFRF)-often combined with the component mode synthesis (CMS) in order to reduce the number of flexible degrees-of-freedom-is the common approach to describe arbitrarily shaped bodies in flexible multibody systems. Owed to the relative formulation of the flexible deformation with respect to the reference frame, the equations of motion show state-dependent nonconstant inertia terms. Such relative description, however, comes along with considerable numerical costs, since both the mass matrix and gyroscopic forces, i.e., the quadratic velocity vector, need to be evaluated in every integration step. The state dependency of the inertia terms can be avoided by employing an alternative formulation based on the mode shapes as in the classical CMS approach. In this approach, which is referred to as generalized component mode synthesis (GCMS), the total (absolute) displacements are approximated directly. Consequently, the mass matrix is constant, no quadratic velocity vector appears, and the stiffness matrix is a corotated but otherwise constant matrix. In order to represent the same flexible deformation as in the classical FFRF-based CMS, however, a comparatively large number of degrees-of-freedom is required. The approach described in the present paper makes use of the fact that a majority of components in technical systems are constrained to motions showing large rotations only about a single spatially fixed axis. For this reason, the GCMS is adapted for multibody systems that are subjected to small flexible deformations and undergo a rigid body motion showing large translations, large rotations about one axis, but small rotations otherwise. Thereby, the number of shape functions representing the flexible deformation is reduced, which further increases numerical efficiency compared to the original GCMS formulation for arbitrary rotations

Accelerator Reliability Information System Data Quality Concept

This work is part of ARIES EU project task to study feasibility of reliability information sharing within the accelerator community. In practice, this means establishing an Accelerator Reliability Information System (ARIS) where users could upload and access the reliability data. This approach has been successfully used in industry and this experience is detailed by our earlier literature review. We have also published a report describing the use cases of the ARIS. This report presents a literature review on maintenance data quality estimators

Bibliography and state of the art of reliability information systems

Reliability and availability have been identified as a key topic for cost and energy efficient operations in research of industrially used particle accelerators and medical particle facilities. The scope of this document is to reference documents of existing reliability information systems in industries, lists of relevant standards and best-practices and a summary with an assessment of those documents, which can be considered suitable for a reliability and availability information system in a multi-national, collaborative technical research infrastructure environment

Haemodynamic influences on kidney oxygenation:Clinical implications of integrative physiology

<p>Renal blood flow, local tissue perfusion and blood oxygen content are the major determinants of oxygen delivery to kidney tissue. Arterial pressure and segmental vascular resistance influence kidney oxygen consumption through effects on glomerular filtration rate and sodium reabsorption. Diffusive shunting of oxygen from arteries to veins in the cortex and from descending to ascending vasa recta in the medulla limits oxygen delivery to renal tissue. Oxygen shunting depends on the vascular network, renal haemodynamics and kidney oxygen consumption. Consequently, the impact of changes in renal haemodynamics on tissue oxygenation cannot necessarily be predicted intuitively and, instead, requires the integrative approach offered by computational modelling and multiple measuring modalities. Tissue hypoxia is a hallmark of acute kidney injury (AKI) arising from multiple initiating insults, including ischaemiareperfusion injury, radiocontrast administration, cardiopulmonary bypass surgery, shock and sepsis. Its pathophysiology is defined by inflammation and/or ischaemia resulting in alterations in renal tissue oxygenation, nitric oxide bioavailability and oxygen radical homeostasis. This sequence of events appears to cause renal microcirculatory dysfunction, which may then be exacerbated by the inappropriate use of therapies common in peri-operative medicine, such as fluid resuscitation. The development of new ways to prevent and treat AKI requires an integrative approach that considers not just the molecular mechanisms underlying failure of filtration and tissue damage, but also the contribution of haemodynamic factors that determine kidney oxygenation. The development of bedside monitors allowing continuous surveillance of renal haemodynamics, oxygenation and function should facilitate better prevention, detection and treatment of AKI.</p>