Exponential random graphs as models of overlay networks

In this paper, we give an analytic solution for graphs with n nodes and E edges for which the probability of obtaining a given graph G is specified in terms of the degree sequence of G. We describe how this model naturally appears in the context of load balancing in communication networks, namely Peer-to-Peer overlays. We then analyse the degree distribution of such graphs and show that the degrees are concentrated around their mean value. Finally, we derive asymptotic results on the number of edges crossing a graph cut and use these results $(i)$ to compute the graph expansion and conductance, and $(ii)$ to analyse the graph resilience to random failures.Comment: 18 page

On the stability of two-chunk file-sharing systems

We consider five different peer-to-peer file sharing systems with two chunks, with the aim of finding chunk selection algorithms that have provably stable performance with any input rate and assuming non-altruistic peers who leave the system immediately after downloading the second chunk. We show that many algorithms that first looked promising lead to unstable or oscillating behavior. However, we end up with a system with desirable properties. Most of our rigorous results concern the corresponding deterministic large system limits, but in two simplest cases we provide proofs for the stochastic systems also.Comment: 19 pages, 7 figure

Clustering and Sharing Incentives in BitTorrent Systems

Peer-to-peer protocols play an increasingly instrumental role in Internet content distribution. Consequently, it is important to gain a full understanding of how these protocols behave in practice and how their parameters impact overall performance. We present the first experimental investigation of the peer selection strategy of the popular BitTorrent protocol in an instrumented private torrent. By observing the decisions of more than 40 nodes, we validate three BitTorrent properties that, though widely believed to hold, have not been demonstrated experimentally. These include the clustering of similar-bandwidth peers, the effectiveness of BitTorrent's sharing incentives, and the peers' high average upload utilization. In addition, our results show that BitTorrent's new choking algorithm in seed state provides uniform service to all peers, and that an underprovisioned initial seed leads to the absence of peer clustering and less effective sharing incentives. Based on our observations, we provide guidelines for seed provisioning by content providers, and discuss a tracker protocol extension that addresses an identified limitation of the protocol

High Performance Liquid Chromatographic Fluorescence Detection Method for the Quantification of Rivastigmine in Rat Plasma and Brain: Application to Preclinical Pharmacokinetic Studies in Rats

A highly sensitive and selective high performance liquid chromatographic fluorescence detection method has been developed and validated for the quantification of rivastigmine in rat plasma and brain. Protein precipitation and one-step liquid–liquid extraction techniques were utilized for the extraction of RSM from brain and plasma, respectively, along with an internal standard. The chromatographic separation was achieved with a column inertsil ODS-3V and a mobile phase consisting of ammonium acetate buffer (20 mM, pH 4.5) and acetonitrile (76:24, v/v) delivered at a flow rate of 1 ml/min. The lower limit of quantitation for the developed method was 10 ng/mL for both matrices. The method was found to be accurate and reproducible and was successfully used to quantify levels of RSM in plasma and brain following intravenous administration of RSM in rats

Moment-Generating Algorithm for Response Time in Processor Sharing Queueing Systems

Response times are arguably the most representative and important metric for measuring the performance of modern computer systems. Further, service level agreements (SLAs), ranging from data centres to smartphone users, demand quick and, equally important, predictable response times. Hence, it is necessary to calculate moments, at least, and ideally response time distributions, which is not straightforward. A new moment-generating algorithm for calculating response times analytically is obtained, based on M/M/1 processor sharing (PS) queueing models. This algorithm is compared against existing work on response times in M/M/1-PS queues and extended to M/M/1 discriminatory PS queues. Two real-world case studies are evaluated

A Soluble Acetylcholinesterase Provides Chemical Defense against Xenobiotics in the Pinewood Nematode

The pinewood nematode genome encodes at least three distinct acetylcholinesterases (AChEs). To understand physiological roles of the three pinewood nematode AChEs (BxACE-1, BxACE-2, and BxACE-3), BxACE-3 in particular, their tissue distribution and inhibition profiles were investigated. Immunohistochemistry revealed that BxACE-1 and BxACE-2 were distributed in neuronal tissues. In contrast, BxACE-3 was detected from some specific tissues and extracted without the aid of detergent, suggesting its soluble nature unlike BxACE-1 and BxACE-2. When present together, BxAChE3 significantly reduced the inhibition of BxACE-1 and BxACE-2 by cholinesterase inhibitors. Knockdown of BxACE-3 by RNA interference significantly increased the toxicity of three nematicidal compounds, supporting the protective role of BxACE-3 against chemicals. In summary, BxACE-3 appears to have a non-neuronal function of chemical defense whereas both BxACE-1 and BxACE-2 have classical neuronal function of synaptic transmission

Heterologous Amyloid Seeding: Revisiting the Role of Acetylcholinesterase in Alzheimer's Disease

Neurodegenerative diseases associated with abnormal protein folding and ordered aggregation require an initial trigger which may be infectious, inherited, post-inflammatory or idiopathic. Proteolytic cleavage to generate vulnerable precursors, such as amyloid-β peptide (Aβ) production via β and γ secretases in Alzheimer's Disease (AD), is one such trigger, but the proteolytic removal of these fragments is also aetiologically important. The levels of Aβ in the central nervous system are regulated by several catabolic proteases, including insulysin (IDE) and neprilysin (NEP). The known association of human acetylcholinesterase (hAChE) with pathological aggregates in AD together with its ability to increase Aβ fibrilization prompted us to search for proteolytic triggers that could enhance this process. The hAChE C-terminal domain (T40, AChE575-614) is an exposed amphiphilic α-helix involved in enzyme oligomerisation, but it also contains a conformational switch region (CSR) with high propensity for conversion to non-native (hidden) β-strand, a property associated with amyloidogenicity. A synthetic peptide (AChE586-599) encompassing the CSR region shares homology with Aβ and forms β-sheet amyloid fibrils. We investigated the influence of IDE and NEP proteolysis on the formation and degradation of relevant hAChE β-sheet species. By combining reverse-phase HPLC and mass spectrometry, we established that the enzyme digestion profiles on T40 versus AChE586-599, or versus Aβ, differed. Moreover, IDE digestion of T40 triggered the conformational switch from α- to β-structures, resulting in surfactant CSR species that self-assembled into amyloid fibril precursors (oligomers). Crucially, these CSR species significantly increased Aβ fibril formation both by seeding the energetically unfavorable formation of amyloid nuclei and by enhancing the rate of amyloid elongation. Hence, these results may offer an explanation for observations that implicate hAChE in the extent of Aβ deposition in the brain. Furthermore, this process of heterologous amyloid seeding by a proteolytic fragment from another protein may represent a previously underestimated pathological trigger, implying that the abundance of the major amyloidogenic species (Aβ in AD, for example) may not be the only important factor in neurodegeneration