SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage

SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5′-end of a reporter mRNA having a short 5′ untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template, but not in those IRES elements from hepatitis C or cricket paralysis viruses. By using primarily cell-free, in vitro translation systems, the present study revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 5′ untranslated region of capped mRNA templates. Experiments using dicistronic mRNAs carrying different IRESes showed that nsp1 induced endonucleolytic RNA cleavage within the ribosome loading region of type I and type II picornavirus IRES elements, but not that of classical swine fever virus IRES, which is characterized as a hepatitis C virus-like IRES. The nsp1-induced RNA cleavage of template mRNAs exhibited no apparent preference for a specific nucleotide sequence at the RNA cleavage sites. Remarkably, SCoV mRNAs, which have a 5′ cap structure and 3′ poly A tail like those of typical host mRNAs, were not susceptible to nsp1-mediated RNA cleavage and importantly, the presence of the 5′-end leader sequence protected the SCoV mRNAs from nsp1-induced endonucleolytic RNA cleavage. The escape of viral mRNAs from nsp1-induced RNA cleavage may be an important strategy by which the virus circumvents the action of nsp1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection

Effective second moment of area of uniform built-up members

For built-up compression members, Eurocode 3 in part EN 1993-1-1 [1] includes the shear stiffness to account for the effect of shear deformations directly into the amplification factor when determining second-order forces. Built-up members loaded in bending are not treated at all in EN 1993-1-1 [1]. This article is based on a study [2] performed at Eindhoven University of Technology and introduces the concept of effective second moment of area to account for the influence of the finite shear stiffness of built-up members. This article is largely based on [3] but is an updated and improved version. The effective second moment of area is checked by numerical models. The shear stiffness is derived for a simple configuration of a battened built-up member and for more complex configurations and for laced built-up columns shear stiffnesses are presented. The design rules for built-up compression members in EN 1993-1-1 [1] are analysed and suggestions for modifications are made to include the concept of the effective second moment of area. It is advantageous that the concept of the effective second moment of area can be used for both built-up columns and beams. For built-up beams, the effective second moment of area including the shear stiffness allows the deflections to be calculated with the standard rules for flexural bending

Developments in matrials codes and applications of steel structures

This paper gives an overview of recent developments in materials, codes and applications of steel structures. There is a tendency towards using higher strength steel grades, and this asks for a different approach to the design of steel structures. Also work is underway for the next version of part 1-1 of Eurocode 3: EN 1993-1-1 [1]. Many design rules need improvement and the so-called ‘systematic review’ yielded topics that need to be considered. Amendments for EN 1993-1-1 were accepted already by the committee responsible for Eurocode 3, i.e. CEN/TC250/SC3, led very efficiently by Prof. Ulrike Kuhlmann. The paper gives an impression of some of these amendments. The scope of the design rules will be extended, amongst others by including high-strength steel grades. Apart from developments in materials and codes, also developments can be observed regarding the applications of steel structures. Of course the developments in materials, codes and applications mutually influence each other

Trends in steel structures concerning materials, codes and applications

This paper gives an overview of recent trends in steel structures\u3cbr/\u3econcerning materials, codes and applications. There is a trend\u3cbr/\u3etowards using higher strength steel grades, and this asks for a\u3cbr/\u3edifferent approach to the design of steel structures. Also work\u3cbr/\u3eis underway for the next version of part 1-1 of Eurocode 3:\u3cbr/\u3eEN 1993-1-1 [1]. Many design rules need improvement and the\u3cbr/\u3eso-\u3cbr/\u3ecalled ‘systematic review’ yielded topics that need to be considered.\u3cbr/\u3eAmendments for EN 1993-1-1 were accepted already by\u3cbr/\u3ethe committee responsible for Eurocode 3, i. e. CEN/TC250/SC3,\u3cbr/\u3eled very effectively by Prof. Ulrike Kuhlmann. The paper gives an\u3cbr/\u3eimpression of some of these amendments. The scope of the\u3cbr/\u3edesign\u3cbr/\u3erules will be extended, amongst others by including highstrength\u3cbr/\u3esteel grades. Apart from trends in materials and codes,\u3cbr/\u3ealso trends can be observed regarding the applications of steel\u3cbr/\u3estructures. Of course these trends in materials, codes and applications\u3cbr/\u3emutually influence each other

The next version of part 1-1 of Eurocode 3 on steel structures: needs for an update and amendments

This paper gives an overview of the work necessary and underway for the next version of part 1-1- of Eurocode 3 on steel structures: EN 1993-1-1. The work is until now done by Working Group 1 of subcommittee CEN/TC250/SC3 and soon the Project Team will start working on the next version of EN 1993-1-1. WG1 collected a longlist of items that may need improvement and the recently carried out systematic review also yielded topics that need to be considered for the next version of EN 1993-1-1. The work of WG1 already resulted in amendments for EN 1993-1-1 which were accepted by CEN/TC250/SC3. It was decided to include these amendments in the next version of EN 1993-1-1, that is due in a few years. In this paper, an overview is given of the already accepted amendments. They concern among others several strength and stability related design rules

Repair, strengthening and upgrading of steel bridges in The Netherlands

After World War II, many steel bridges were designed and built in The Netherlands. Many of these bridges are now of a substantial age and were designed for static and fatigue loading less severe than eventually present during their lifetime. Many of these bridges now show (fatigue) damage. Depending on the nature of the damage, these bridges can either be replaced, or a reinforcing substructure can be added, or the visible damage can be repaired and the bridge can be locally strengthened. In many cases, it has to be shown that the bridge is fit for purpose for future use, meaning that upgrading may be necessary. These bridges are now being reassessed and any possible conservatism in these assessments needs to be excluded to avoid unnecessary strengthening. The paper gives practical examples of repair, strengthening and upgrading techniques for steel bridges

About ECCS and its technical committee TC8 on the stability of steel structures

The mission, rich history and numerous achievements of the Technical Committee TC8 Stability of Steel Structures of the European Convention for Constructional Steelwork (ECCS), which is active since 1958, are highlighted by present and former chairpersons

Ontwerpen van stationsconstructies in dichtbevolkte stedelijke gebieden

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