A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

We develop approximation algorithms for the problem of placing replicated data in arbitrary networks, where the nodes may both issue requests for data objects and have capacity for storing data objects so as to minimize the average data-access cost. We introduce the data placement problem to model this problem. We have a set of caches F , a set of clients D, and a set of data objects O. Each cache i can store at most u i data objects. Each client j ∈ D has demand d j for a specific data object o(j) ∈ O and has to be assigned to a cache that stores that object. Storing an object o in cache i incurs a storage cost of f o i , and assigning client j to cache i incurs an access cost of d j c ij . The goal is to find a placement of the data objects to caches respecting the capacity constraints, and an assignment of clients to caches so as to minimize the total storage and client access costs. We present a 10-approximation algorithm for this problem. Our algorithm is based on rounding an optimal solution to a natural linear-programming relaxation of the problem. One of the main technical challenges encountered during rounding is to preserve the cache capacities while incurring only a constant-factor increase in the solution cost. We also introduce the connected data placement problem to capture settings where write-requests are also issued for data objects, so that one requires a mechanism to maintain consistency of data. We model this by requiring that all caches containing a given object be connected by a Steiner tree to a root for that object, which issues a multicast message upon a write to (any copy of) that object. The total cost now includes the cost of these Steiner trees. We devise a 14-approximation algorithm for this problem. We show that our algorithms can be adapted to handle two variants of the problem: (a) a k-median variant, where there is a specified bound on the number of caches that may contain a given object, and (b) a generalization where objects have lengths and the total length of the objects stored in any cache must not exceed its capacity.

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An ad hoc wireless network, or simply an ad hoc network, consists of a collection of geographically distributed nodes that communicate with one other over a wireless medium. An ad hoc network differs from cellular networks in that there is no wired infrastructure and the communication capabilities of the network are limited by the battery power of the network nodes. One of the original motivations for ad hoc networks is found in military applications. A classic example of ad hoc networking is network of war fighters and their mobile platforms in battlefields. Indeed, a wealth of early research in the area involved the development of packet-radio networks (PRNs) and survivable radio networks [16]. While military applications still dominate the research needs in ad hoc networking, the recent rapid advent of mobile telephony and plethora of personal digital assistants has brought to the fore a number of potential commercial applications of ad hoc networks. Examples are disaster relief, conferencing, home networking, sensor networks, personal area networks, and embedded computing applications [37].The lack of a fixed infrastructure in ad hoc networks implies that any computation on the network needs to be carried out in a decentralized manner. Thus, many of the important problems in ad hoc networking can be formulated as problems in distributed computing. However, there are certain characteristics of ad hoc networks that makes this study somewhat different than traditional work in distributed computing. In this article, we review some of the characteristic features of ad hoc networks, formulate problems and survey research work done in the area. We focus on two basic problem domains: topology control, the problem of computing and maintaining a connected topology among the network nodes, and routing. This article is not intended to be a comprehensive survey on ad hoc networking. The choice of the problems discussed in this article are somewhat biased by the research interests of the author.The remainder of this article is organized as follows. In Section 2, we describe various aspects relevant to modeling ad hoc networks. In Section 3, we discuss topology control. Since the nodes of an ad hoc network are often associated with points in 2-dimensional space, topology control is closely tied to computational geometry; we will briefly review this relationship and extant work in the area. In Section 4, we discuss routing protocols for ad hoc networks. After a brief overview of the many protocols that have been proposed, we discuss alternative approaches based on the adversarial network model.