Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy

Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals. These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion. The parasites possess intracellular bacteria, Wolbachia, which are needed for worm survival. Clearance of these bacteria with certain antibiotics leads to parasite death. These findings have pioneered the approach of using antibiotics to treat and control filarial infections. In the present study, we have investigated the cell division process in Wolbachia for new drug target discovery. We have identified the essential cell division protein FtsZ, which has a GTPase activity, as an attractive Wolbachia drug target. We describe the molecular characterization and catalytic properties of the enzyme and demonstrate that the GTPase activity is inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. We also found that berberine was effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel antibiotic approach for controlling filarial infection

Restrain of a seismically isolated bridge by external stoppers

The current design of seismically isolated bridges usually combines the use of bearings and stoppers, as a second line of defence. The stoppers allow the development of the in-service movements of the bridge deck, without transmitting significant loads to the piers and their foundations, while during earthquake they transmit the entire seismic action. Despite the fact that stoppers, which restrain the transverse seismic movements of the deck, are used frequently in seismically isolated bridges, the use of longitudinal stoppers is relatively rare, mainly due to the large in-service constraint movements of bridges. The present paper proposes a new type of external longitudinal stoppers, which are installed in stiff sub-structures-boundaries, aiming at limiting the bridge seismic movements. The parametric investigation, which was conducted in order to identify the seismic efficiency of the external stoppers, showed that the interaction of the bridge with the stiff boundaries can lead to significant reductions in the seismic movements of the bridge. Serviceability is appropriately arranged in the paper by expansion joints and approach slabs. © 2010 Springer Science+Business Media B.V

Connection of bridges with neighborhooding tunnels

A large number of bridges are constructed between tunnels. This co-existence can be developed in order to reduce the seismic actions of bridges, as their end parts can be restrained by the tunnels. This restrain requires the accommodation of the resulting serviceability problems, which are possible to be arranged by means of appropriate approach elements and expansion joints. In the present study, an appropriately configured approach element is proposed with which a semi-connection of the bridge with both tunnels is achieved. This approach slab is designed in a manner to accommodate both serviceability and earthquake resistance of the bridge. The proposed semi-connection of the bridge with the neighborhooding tunnels was proven to be efficient as the parametric investigation showed that the interaction of the bridge with the stiff tunnels can lead to reductions in the seismic actions of the bridge

Seismic retrofitting of bridges based on indirect strategies

An indirect retrofitting scheme for bridges is analytically studied and evaluated. The scheme is based on the reduction in seismic actions of the bridge, namely the displacements of the deck and the bending moments of the piers by utilizing external key walls (barrettes) that participate in the earthquake resisting system (ERS) of the bridge as external supports. Simultaneously, the deck of the bridge is made partially continuous by replacing part of the existing sidewalks by new connecting slabs that are fixed on the existing ones. No strengthening of the existing members of the ERS of the bridge was attempted. The new sidewalk slabs respond as RC structural struts connecting the subsequent simply supported spans of the deck, while sliding on the rest of their lengths. The end spans of the deck are connected with the new key walls (barrettes) constructed behind the abutment. During the bridge service, the part of the RC struts, which are supported by the existing sidewalks, i.e. the unrestraint part of the struts, respond as concrete struts (during expansion of the deck) or ties (during the contraction of the deck). The role of these structural struts is to receive safely the deck constraint movements through their constraint shortening (struts) or lengthening (ties). During an earthquake the movements of the deck are effectively restrained by the external supports namely the key walls. Hence, the displacements of the deck and the resulting loading of the existing piers, bearings and foundations are reduced. The effectiveness of the above retrofitting scheme has been assessed on an existing bridge of Aliakmon River, actually built in the early '90s. The study revealed that this low cost retrofitting scheme can effectively reduce the seismic demand of the bridge

Two new earthquake resistant integral abutments for medium to long span bridges

A wide field of study is open to new abutment configurations and design innovation as no unified procedure is available for the design and construction of integral abutment bridges (IABs). In this framework, an extended state-of the-art review on the configuration of IABs, with emphasis on the European Bridge Engineering, was done and two new integral abutments were studied. The primary feature of both integral abutments is the de coupling of the in-service response of the bridge from the backfill soil and the utilization of the backfill's resistance during earthquake, aiming at reducing the seismic demand on bridges. This objective was achieved by accommodating the in-service constraint movements of the deck through the flexibility of the IAB and via as small as possible clearances. During an earthquake the IABs interact with the backfill soil and reduce the displacements of the deck and thereby the seismic demand on bridge piers and foundations. Abutments will be useful in future design of intermediate to long-span bridges

An unconventional restraining system for limiting the seismic movements of isolated bridges

An external restraining system with steel piles is introduced under the main objective of the study, which is the enhancement of the earthquake resistance of seismically isolated bridges. This objective is examined through the possibility of the improved seismic participation of the approach embankments, which are able to dissipate part of the induced seismic energy. The seismic participation of the embankments, which are seismically inactive, according to current conceptual design of bridges, is achieved through the extension of the continuous deck slab of the bridge onto the embankments and its restraint by the backfill through steel piles. The serviceability needs of the deck are accommodated by: (a) the flexibility of the steel piles, (b) the looseness of the backfill soil, (c) the partial replacement of the embankment's surface layers by expanded polystyrene (EPS) and (d) the in-service allowable cracking of the continuity slab. A parametric study was conducted and showed that the restraining system can effectively reduce the seismic displacements of the bridge. The proposed technique can be utilized in all bridge structures, and is more efficient in those exhibiting large displacements during an earthquake. Crown Copyright © 2009

An external restraining system for the seismic retrofit of existing bridges

An unconventional retrofitting measure is proposed for existing bridges, which has the ability to reduce the seismic actions. This is mainly achieved by an external restraining system consisting of IPE-steel piles driven in the existing backfill soil and a restraining slab. The slab interacts with the deck slab of the existing multi-span simply supported (MSSS) bridge system and transmits part of its seismic actions to the piles and therefore to the backfill soil, which has the ability to dissipate part of the induced seismic energy. The proposed unconventional restraining system was implemented and analytically assessed in an existing MSSS bridge system. The study showed that the unconventional restraining system has the ability to reduce effectively the actions and to enhance the earthquake resistance of the existing bridge

Seismic retrofitting of bridges based on indirect strategies

An indirect retrofitting scheme for bridges is analytically studied and evaluated. The scheme is based on the reduction in seismic actions of the bridge, namely the displacements of the deck and the bending moments of the piers by utilizing external key walls (barrettes) that participate in the earthquake resisting system (ERS) of the bridge as external supports. Simultaneously, the deck of the bridge is made partially continuous by replacing part of the existing sidewalks by new connecting slabs that are fixed on the existing ones. No strengthening of the existing members of the ERS of the bridge was attempted. The new sidewalk slabs respond as RC structural struts connecting the subsequent simply supported spans of the deck, while sliding on the rest of their lengths. The end spans of the deck are connected with the new key walls (barrettes) constructed behind the abutment. During the bridge service, the part of the RC struts, which are supported by the existing sidewalks, i.e. the unrestraint part of the struts, respond as concrete struts (during expansion of the deck) or ties (during the contraction of the deck). The role of these structural struts is to receive safely the deck constraint movements through their constraint shortening (struts) or lengthening (ties). During an earthquake the movements of the deck are effectively restrained by the external supports namely the key walls. Hence, the displacements of the deck and the resulting loading of the existing piers, bearings and foundations are reduced. The effectiveness of the above retrofitting scheme has been assessed on an existing bridge of Aliakmon River, actually built in the early '90s. The study revealed that this low cost retrofitting scheme can effectively reduce the seismic demand of the bridge

An unconventional restraining system for limiting the seismic movements of isolated bridges

An external restraining system with steel piles is introduced under the main objective of the study, which is the enhancement of the earthquake resistance of seismically isolated bridges. This objective is examined through the possibility of the improved seismic participation of the approach embankments, which are able to dissipate part of the induced seismic energy. The seismic participation of the embankments, which are seismically inactive, according to current conceptual design of bridges, is achieved through the extension of the continuous deck slab of the bridge onto the embankments and its restraint by the backfill through steel piles. The serviceability needs of the deck are accommodated by: (a) the flexibility of the steel piles, (b) the looseness of the backfill soil, (c) the partial replacement of the embankment's surface layers by expanded polystyrene (EPS) and (d) the in-service allowable cracking of the continuity slab. A parametric study was conducted and showed that the restraining system can effectively reduce the seismic displacements of the bridge. The proposed technique can be utilized in all bridge structures, and is more efficient in those exhibiting large displacements during an earthquake. Crown Copyright © 2009

An external restraining system for the seismic retrofit of existing bridges

An unconventional retrofitting measure is proposed for existing bridges, which has the ability to reduce the seismic actions. This is mainly achieved by an external restraining system consisting of IPE-steel piles driven in the existing backfill soil and a restraining slab. The slab interacts with the deck slab of the existing multi-span simply supported (MSSS) bridge system and transmits part of its seismic actions to the piles and therefore to the backfill soil, which has the ability to dissipate part of the induced seismic energy. The proposed unconventional restraining system was implemented and analytically assessed in an existing MSSS bridge system. The study showed that the unconventional restraining system has the ability to reduce effectively the actions and to enhance the earthquake resistance of the existing bridge