Molecular mechanisms of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease

Dynamic Modeling and Identification of the Puma Robot

The article presents an original procedure to identify the inertial parameters which affect the dynamic behaviour of a robot manipulator. The procedure is based on the fact that all the relevant parameters for the dynamic model also explicitly appear in the equations which relate the robot motion to its reaction forces and torques on the bedplate. This property allows to use external measurements obtained independently from the robot control unit. Moreover, identification accuracy is improved since the reaction equations are not affected by internal effects such as friction or backlash in the joint transmissions

Two-Phase Flow Modelling of Sediment Transport: Challenges and Potential Applications

Sediment transport is induced by the interaction between turbulence and the solid particles that comprise the sediment. Due to the permeability of the sediment, water can penetrate it, thus forming a heterogeneous, immiscible mixture. As water flows through and over the sediment, it exerts both normal and shear stresses that engender its erosion. Traditional single-phase flow models, and their incarnations, cannot properly account for the complex interactions between the solid particles and water. The circumvention of this difficulty necessitates the employment of two-phase flow models. This type of models take into consideration the dynamics of both phases and, as such, are well adapted for the description of the problem at hand. However, two-phase flow models are characterized by both a large size and a high complexity which have, in turn, impeded the development of algorithms for their integration. Consequently, the predictive capacity of these models and their applicability remain unclear. In the first part of this talk, we present a two-phase flow model for sediment transport and we elaborate on the challenging issues that render the algorithm development for its integration an arduous task. Subsequently, we delineate a recently proposed algorithm for the model at hand and we demonstrate its efficiency and robustness via simulating numerically gravity-driven flows of subaqueous granular beds and granular columns. In the second part of this talk, the focus is shifted to the applicability of the presented simulation tool to realistic large-scale flows. For this, we clearly identify the strengths and limitations of our simulation tool; given the complexity of the phenomenon that is envisioned to be described, such a scrutiny is deemed vital. Finally, we expound the bottlenecks and critical points that have to be properly addressed before the present simulation tool can be employed in real-life applications

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis