Most mathematical models for the spread of disease use differential equations based on uniform mixing assumptions or ad hoc models for the contact process. Here we explore the use of dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations. The graphs are generated by large-scale individual-based urban traffic simulations built on actual census, land-use and population-mobility data. We find that the contact network among people is a strongly connected small-world-like graph with a well-defined scale for the degree distribution. However, the locations graph is scale-free, which allows highly efficient outbreak detection by placing sensors in the hubs of the locations network. Within this large-scale simulation framework, we then analyse the relative merits of several proposed mitigation strategies for smallpox spread. Our results suggest that outbreaks can be contained by a strategy of targeted vaccination combined with early detection without resorting to mass vaccination of a population.

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Abstract-We consider the problem of determining the maximum capacity of the media access (MAC) layer in wireless ad hoc networks. Due to spatial contention for the shared wireless medium, not all nodes can concurrently transmit packets to each other in these networks. The maximum number of possible concurrent transmissions is, therefore, an estimate of the maximum network capacity, and depends on the MAC protocol being used. We show that for a large class of MAC protocols based on virtual carrier sensing using RTS/CTS messages, which includes the popular IEEE 802.11 standard, this problem may be modeled as a maximum Distance-2 matching (D2EMIS) in the underlying wireless network: Given a graph ( ), find a set of edges such that no two edges in are connected by another edge in .D2EMIS is NP-complete. Our primary goal is to show that it can be approximated efficiently in networks that arise in practice. We do this by focusing on an admittedly simplistic, yet natural, graph-theoretic model for ad hoc wireless networks based on disk graphs, where a node can reach all other nodes within some distance (nodes may have unequal reach distances). We show that our approximation yields good capacity bounds.Our work is the first attempt at characterizing an important "maximum" measure of wireless network capacity, and can be used to shed light on previous topology formation protocols like Span and GAF that attempt to produce "good" or "capacity-preserving" topologies, while allowing nodes to alternate between sleep and awake states. Our work shows an efficient way to compute an upper bound on maximum wireless network capacity, thereby allowing topology formation algorithms to determine how close they are to optimal. We also outline a distributed algorithm for the problem for unit disk graphs, and briefly discuss extensions of our results to: 1) different node interference models; 2) directional antennas; and 3) other transceiver connectivity structures besides disk graphs.

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function1–3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)4–6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin–KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

This paper considers two inter-related questions: (i) Given a wireless ad-hoc network and a collection of source-destination pairs {(si, ti)}, what is the maximum throughput capacity of the network, i.e. the rate at which data from the sources can be transferred to their corresponding destinations in the network? (ii) Can network protocols be designed that jointly route the packets and schedule transmissions at rates close to the maximum throughput capacity? Much of the earlier work focused on random instances and proved analytical lower and upper bounds on the maximum throughput capacity. Here, in contrast, we consider arbitrary wireless networks. Further, we study the algorithmic aspects of the above questions: the goal is to design provably good algorithms for arbitrary instances. We develop analytical performance evaluation models and distributed algorithms for routing and scheduling which incorporate fairness, energy and dilation (path-length) requirements and provide a unified framework for utilizing the network close to its maximum throughput capacity.Motivated by certain popular wireless protocols used in * Basic and Applied Simulation Science (CCS-5) and Na- Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. To copy otherwise, to republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. practice, we also explore "shortest-path like" path selection strategies which maximize the network throughput. The theoretical results naturally suggest an interesting class of congestion aware link-metrics which can be directly plugged into several existing routing protocols such as AODV, DSR, etc. We complement the theoretical analysis with extensive simulations. The results indicate that routes obtained using our congestion aware link-metrics consistently yield higher throughput than hop-count based shortest path metrics.