Speeding up Markov Chain Monte Carlo without Likelihood

This article presents the implementation and initial test results for an algorithm called SuffStat MCMC, which aims to speed up Approximate Bayesian Computation without likelihood

Using a random walker on gene expression and protein-protein interaction networks to prioritize candidate genes

Identification of genes underlying human diseases is an important step in understanding and treating genetic disorders. Based on the assumption that related diseases are caused by related genes, several methods for candidate gene prioritization have been proposed in the past to refine lists of suspect genes obtained by linkage analysis or other methods. The large increase in publicly available -omics data has made it possible to implement prioritization methods that combine information from multiple data sources to make better rankings. In this work, we present a new method for prioritization of candidate disease genes based on gene expression data, that ranks 12851 genes for 5080 phenotypes. The performance is comparable to previous methods which used hand-curated protein-protein data on smaller test sets. We also propose a method for combining multiple gene networks into a single one with which we ranked up to 14612 genes for 5080 phenotypes, more than any previous method. Our evaluation shows, that the performance of the fused network is superior to that of its separate component networks

Heuristics for Distributed Pseudo-tree Regeneration

The goal of this project is to develop a new heuristic for pseudo-tree regeneration in S-DPOP. S-DPOP is a version of DPOP which should show performance improvements when resolving problems after small changes. Examples of such problems are: tracking moving targets in sensor networks, truck-task scheduling and also matching patients and donors in kidney exchanges - a new problem for DCOP, which we investigate in this project . In this project, the DCOP-platform FRODO, developed by the artificial intelligence lab (LIA) at EPFL, will be used. Because there is no existing im- plementation of S-DPOP on FRODO, a significant part of the project consists in implementing S-DPOP on FRODO for the first time. The most important part of the project is the development and validation of a new DFS heuristic, which should maximize the amount of reuse when a problem is resolved after a minor change. Furthermore, we want to evaluate the performance of S-DPOP and the new heuristic on a real-life problem. For this, we use the kidney exchange problem, which is a problem class that has been studied in the centralized setting, but which is new to the DCOP community

Building web applications on top of encrypted data using Mylar

Web applications rely on servers to store and process confidential information. However, anyone who gains access to the server (e.g., an attacker, a curious administrator, or a government) can obtain all of the data stored there. This paper presents Mylar, a platform that provides end-to-end encryption to web applications. Mylar protects the confidentiality of sensitive data fields against attackers that gained access to servers. Mylar stores sensitive data encrypted on the server, and decrypts that data only in users’ browsers. Mylar addresses three challenges in making this approach work. First, Mylar allows the server to perform keyword search over encrypted documents, even if the documents are encrypted with different keys. Second, Mylar allows users to share keys securely in the presence of an active adversary. Finally, Mylar ensures that client-side application code is authentic, even if the server is malicious. Results with a prototype of Mylar built on top of the Meteor framework are promising: porting 6 applications required changing just 36 lines of code on average, and the performance overheads are modest, amounting to a 17% throughput loss and a 50 ms latency increase for sending a message in a chat application

Photoperiodic and diurnal regulation of WNT signalling in the arcuate nucleus of the 1 female Djungarian hamster, Phodopus sungorus

yesThe WNT pathway was shown to play an important role in the adult central nervous system. We previously identified the WNT pathway as a novel integration site of the adipokine leptin in mediating its neuroendocrine control of metabolism in obese mice. Here we investigated the implication of WNT signaling in seasonal body weight regulation exhibited by the Djungarian hamster (Phodopus sungorus), a seasonal mammal that exhibits profound annual changes in leptin sensitivity. We furthermore investigated whether crucial components of the WNT pathway are regulated in a diurnal manner. Gene expression of key components of the WNT pathway in the hypothalamus of hamsters acclimated to either long day (LD) or short day (SD) photoperiod was analyzed by in situ hybridization. We detected elevated expression of the genes WNT-4, Axin-2, Cyclin-D1, and SFRP-2, in the hypothalamic arcuate nucleus, a key energy balance integration site, during LD compared with SD as well as a diurnal regulation of Axin-2, Cyclin-D1, and DKK-3. Investigating the effect of photoperiod as well as leptin on the activation (phosphorylation) of the WNT coreceptor LRP-6-(Ser1490) by immunohistochemistry, we found elevated activity in the arcuate nucleus during LD relative to SD as well as after leptin treatment (2 mg/kg body weight). These findings indicate that differential WNT signaling may be associated with seasonal body weight regulation and is partially regulated in a diurnal manner in the adult brain. Furthermore, they suggest that this pathway plays a key role in the neuroendocrine regulation of body weight and integration of the leptin signal

Photoperiodic and diurnal regulation of WNT signalling in the arcuate nucleus of the 1 female Djungarian hamster, Phodopus sungorus

yesThe WNT pathway was shown to play an important role in the adult central nervous system. We previously identified the WNT pathway as a novel integration site of the adipokine leptin in mediating its neuroendocrine control of metabolism in obese mice. Here we investigated the implication of WNT signaling in seasonal body weight regulation exhibited by the Djungarian hamster (Phodopus sungorus), a seasonal mammal that exhibits profound annual changes in leptin sensitivity. We furthermore investigated whether crucial components of the WNT pathway are regulated in a diurnal manner. Gene expression of key components of the WNT pathway in the hypothalamus of hamsters acclimated to either long day (LD) or short day (SD) photoperiod was analyzed by in situ hybridization. We detected elevated expression of the genes WNT-4, Axin-2, Cyclin-D1, and SFRP-2, in the hypothalamic arcuate nucleus, a key energy balance integration site, during LD compared with SD as well as a diurnal regulation of Axin-2, Cyclin-D1, and DKK-3. Investigating the effect of photoperiod as well as leptin on the activation (phosphorylation) of the WNT coreceptor LRP-6-(Ser1490) by immunohistochemistry, we found elevated activity in the arcuate nucleus during LD relative to SD as well as after leptin treatment (2 mg/kg body weight). These findings indicate that differential WNT signaling may be associated with seasonal body weight regulation and is partially regulated in a diurnal manner in the adult brain. Furthermore, they suggest that this pathway plays a key role in the neuroendocrine regulation of body weight and integration of the leptin signal

A systems approach to software security in aviation

Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 44-45).Field Loadable Software in commercial aviation is indispensable for vital avionics functions yet its security has never been studied in depth. Due to the recent introduction of wireless software loading capabilities and Internet-connected in-flight entertainment systems along with several high-profile information security breaches in other sectors, the security of Field Loadable software has come under closer scrutiny. Conventional information systems security analysis approaches focus on finding and preventing vulnerabilities in the implementation of a system, but they are not designed to include the organizational "soft" components of a system. The aim of this thesis is to provide a comprehensive security analysis of Field Loadable Software that includes organizational aspects in order to find existing vulnerabilities and propose security constraints that would fix the vulnerabilities or prevent them from being exploited. A novel safety approach from safety engineering, called Systems Theoretic Process Analysis (STPA) was adapted and used to perform the security analysis of Field Loadable Software in commercial aviation. The analysis produced a simple systems model for Field Loadable Software and found that current regulations and practices are not sufficient: there several significant vulnerabilities in the way Field Loadable Software is currently designed and distributed. However, the analysis also showed that the vulnerabilities could be removed with the addition of simple technical measures and security constraints.by Jonas Helfer.S.M

Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig

There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved