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Assembly of viral proteins at the site of release and subsequent budding of virions represent the late stages of Ebola virus replication. Recent ndings regarding the mechanisms of assembly and budding of Ebola virus have revealed the potential for developing antivirals to target these late steps in replication. For example, Ebola virus VP40 and GP, as well as lipid raft microdomains, are thought to be important for ef cient budding of progeny virions, and disruption of the functions of these components of budding through the use of antivirals may be feasible. 7.6.1 Late (L) Budding Domains

position estimator The idea is to use the least squares in the absence of attacks and the least median squares in the presence of attacks, since the latter alternative tolerates up to 50% outliers and still provides correct estimates The authors show that the use of traditional Euclidean distance is not robust to intentional attacks against base stations, and they introduce robustness to ngerprinting localization by means of a median-based distance metric Liu et al [31] propose a method that uses the MMSE (Minimum Mean Squared Estimation), which is a data fusion technique for obtaining improved estimations, to identify and remove malicious location information In this method, sensor locations are estimated using the MMSE-based method Then, the method veri es whether the estimated location can be estimated from a set of consistent location references.

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When a request is to be performed asynchronously, then its completion is signaled back to the LDD using the method Complete(). The local media LDD calls the method PartitionInfo() during drive mounting to get partition information for the media device. Again, this operation may be performed either synchronously or asynchronously as indicated by the method s return value. If performed asynchronously then the method PartitionInfoComplete() is used to signal back completion to the LDD. In response to a normal power down event, the local media LDD calls the method NotifyPowerDown() to allow the driver to terminate any outstanding requests and power down the device. However, for removable media devices, the peripheral bus controller takes care of powering down the bus.

If not, the most inconsistent reference is identi ed and removed, and the node location is estimated again It repeats this process until all inconsistent references are discarded The mean square error of the distance measurements is used as an inconsistency indicator A second method proposed by Liu et al [31] is a voting-based location estimation technique In this method, the sensor eld is quantized into a grid of cells, and each reference node votes on the cells to which an unknown node may belong Then, the method selects the most voted cell(s) and uses the center of these cell(s) as the estimated location Voting results can be re ned interactively to improve accuracy This method requires few resources and is suitable for current resource constrained sensor nodes 184.

The VP40 matrix protein alone can associate with the plasma membrane and induce the formation and release of virus-like particles (VLPs) from mammalian cells.111 These VLPs are morphologically similar to authentic Ebola virus particles.112 114 Thus, VP40 possesses all of the information necessary to promote virus budding. Ef cient release of VP40 VLPs is due in part to the presence of two proline-rich Ldomain motifs, 7PTAP10 and 10PPxY13, present at the N terminus of VP40.111,114,115 L-domain motifs are found in a variety of viral matrix proteins and are believed to serve as protein protein interaction modules, which recruit cellular machinery to the site of virus budding. Indeed, L-domain mutations lead to decreased budding ef ciency of both VLPs and infectious virus.116 One of the best characterized viral L-domains is the PTAP motif. PTAP is present in both the gag protein of HIV-1 and VP40 of Ebola virus and is known to interact with the cellular protein tsg101.115,117 119 On the other hand, the PPxYtype L-domain present in the M protein of VSV and VP40 of Ebola virus is known to interact with the cellular ubiquitin ligase Nedd4.111,112,119 122 In sum, host proteins that participate in endosomal sorting and multivesicular body (MVB) formation in cells are thought to play a role in facilitating virus budding (as reviewed116). While much has been learned regarding the molecular aspects of Ebola virus budding, the precise function of the L-domain motifs remains unclear. Nevertheless, it has been postulated that small molecule inhibitors designed to compete with host proteins for binding to viral L-domains may effectively interfere with budding of viruses such as Ebola. Subsequent reduction in virus budding and spread may allow for clearance of the virus by the host immune system. Since diverse viruses including retroviruses, loviruses, rhabdoviruses, and arenaviruses

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