The Role of TASK Two-Pore-Domain Potassium Channels in General Anaesthesia

TASK channels, members of the two-pore-domain potassium channel family, contribute towards the resting membrane potential and have been implicated in the mechanism of general anaesthesia. Previous work from our group with a TASK-3 channel knockout (T3KO) mouse showed a reduction in halothane sensitivity using a loss of righting reflex (LORR) assay, and absence of the theta brain oscillation induced in wild type (WT) mice by halothane anaesthesia. Two further strains of knockout mice, the TASK-1 knockout (T1KO) and the double knockout (DKO: TASK-1 and -3 channels), were compared with WT using the LORR assay, cortical electroencephalogram recording in response to halothane and during sleep. The mechanistic basis for the diminished theta oscillation in T3KO mice was investigated by recording in CA1 pyramidal cells of the hippocampus. The LORR assay revealed a decrease in halothane sensitivity in T1KO but not DKO compared with WT. The T1KO strain had a theta oscillation induced by exposure to halothane similar to that of WT mice, whereas that observed in the DKO was intermediate between WT and T3KO. T1KO differed from other strains in that the distribution of sleep and wake periods was uniform across the diurnal cycle. The resting membrane potential did not differ between strains during control or halothane exposure. During control there was no strain difference in action potential (AP). Halothane altered AP shape in WT but not the T3KO strain. WT had a greater ability to sustain AP firing than T3KO during halothane. These data show that T1KO mice have decreased anaesthetic sensitivity and altered sleep structure compared with WT, indicating a role for this channel in anaesthetic sensitivity and sleep. The similar resting membrane potential and lack of response to halothane in the T3KO makes pyramidal cells an unlikely source of the theta ablation observed

The preemptive use of inhaled nitric oxide during cardiopulmonary bypass in an experimental pig model

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Ecological User Equilibrium in Traffic Management (TM)?

With increasing environmental sustainability awareness significant attention on ecological traffic management (eco-TM) has come into the focus of researchers and practitioners. While different approaches have been applied to reach minimal pollutant production, the classic user equilibrium calculation with the pollutant production as travel costs instead of using travel times remains in the center of attention. However, the validity of such a direct transformation to find a user equilibrium is questionable. In this paper, a simplified analytical approach to examine the above aforementioned validity has been carried out, followed by a simulation approach to verify the results of the analytical approach. The result shows that the pollutant production function violates the usual assumption of a monotonous function (typically, emission has a minimum at travel speeds around 60 km/h). It also indicates that the respective algorithms to compute the user equilibrium must deal with the fact, that the equilibrium solution is not unique and is dependent on the initial solution. This means that substantial modifications to the algorithms that compute the user equilibrium have to be discussed since they do not work as intended when pollutant production is used as travel costs, especially in a transportation system with mixed speeds that cover a range around the minimum emission speed

Real and Complex Monotone Communication Games

Noncooperative game-theoretic tools have been increasingly used to study many important resource allocation problems in communications, networking, smart grids, and portfolio optimization. In this paper, we consider a general class of convex Nash Equilibrium Problems (NEPs), where each player aims to solve an arbitrary smooth convex optimization problem. Differently from most of current works, we do not assume any specific structure for the players' problems, and we allow the optimization variables of the players to be matrices in the complex domain. Our main contribution is the design of a novel class of distributed (asynchronous) best-response- algorithms suitable for solving the proposed NEPs, even in the presence of multiple solutions. The new methods, whose convergence analysis is based on Variational Inequality (VI) techniques, can select, among all the equilibria of a game, those that optimize a given performance criterion, at the cost of limited signaling among the players. This is a major departure from existing best-response algorithms, whose convergence conditions imply the uniqueness of the NE. Some of our results hinge on the use of VI problems directly in the complex domain; the study of these new kind of VIs also represents a noteworthy innovative contribution. We then apply the developed methods to solve some new generalizations of SISO and MIMO games in cognitive radios and femtocell systems, showing a considerable performance improvement over classical pure noncooperative schemes.Comment: to appear on IEEE Transactions in Information Theor

Role of the Regulator of G protein Signaling 4 in renal ischemic reperfusion injury and repair

Thesis (M.A.)--Boston UniversityRegulator of G protein Signaling 4 (RGS4) has previously been shown to prevent prolonged vasoconstriction by binding to the Gq heterodimer. However, the known anti-inflammatory role of RGS4 has not been applied to reperfusion injury in the context of G protein signaling. The aims of this study is to elucidate the expression pattern of RGS4 in renal reperfusion injury to determine if cell signaling initiated by Angiotensin II, a known ligand of Gαq coupled-receptors, is modulated by RGS4. LacZ reporter animals were used to characterize RGS4 expression during reperfusion. Human smooth muscle cells co-cultured with human endothelial cells demonstrated that AngII induces apoptosis in the absence of RGS4 and initiates RANTES expression in smooth muscle cells. SMMHC-Cre rgs4fl/fl confirmed the role of vascular smooth muscle cells to inhibit macrophage localization during reperfusion injury. RGS4 expression in vascular smooth muscle cells therefore inhibits AngII-mediated oxidative stress, leukocyte recruitment by the same cell type, and endothelial damage prior to tubular epithelial injury

Decomposition by Partial Linearization: Parallel Optimization of Multi-Agent Systems

We propose a novel decomposition framework for the distributed optimization of general nonconvex sum-utility functions arising naturally in the system design of wireless multiuser interfering systems. Our main contributions are: i) the development of the first class of (inexact) Jacobi best-response algorithms with provable convergence, where all the users simultaneously and iteratively solve a suitably convexified version of the original sum-utility optimization problem; ii) the derivation of a general dynamic pricing mechanism that provides a unified view of existing pricing schemes that are based, instead, on heuristics; and iii) a framework that can be easily particularized to well-known applications, giving rise to very efficient practical (Jacobi or Gauss-Seidel) algorithms that outperform existing adhoc methods proposed for very specific problems. Interestingly, our framework contains as special cases well-known gradient algorithms for nonconvex sum-utility problems, and many blockcoordinate descent schemes for convex functions.Comment: submitted to IEEE Transactions on Signal Processin

How Higher Mortgage Interest Rates Can Widen Racial Gaps in Housing Wealth: The Case of Newark, New Jersey

Trends in macroeconomic conditions and policy have helped to boost longer-term interest rates, including mortgage rates, over the past year. This has important implications for the wealth gap between white and Black or Hispanic households. The standard narrative is that higher interest rates, especially when combined with higher house prices and lower incomes, reduce homebuying affordability for Black and Hispanic households relative to white households. And this, in turn, implies that these households of color will find that achieving homeownership has become more difficult, thereby widening the racial wealth gap. This report illustrates that under a higher mortgage rate regime, the pace of principal reduction is slower over most of the life of a 30-year fixed-rate mortgage. Using data covering purchase loans on one-to-four family mortgages across the city of Newark, NJ, we also show that Black and Hispanic households buying in Newark obtain higher mortgage rates relative to their white peers and therefore pay more in interest for a slower principal reduction. In response, we suggest that more local policymakers assess the benefits of interest-rate buy-downs to improve affordability, close racial wealth gaps in housing, and better insulate historically marginalized communities from macroeconomic shocks

Explaining Latent Factor Models for Recommendation with Influence Functions

Latent factor models (LFMs) such as matrix factorization achieve the state-of-the-art performance among various Collaborative Filtering (CF) approaches for recommendation. Despite the high recommendation accuracy of LFMs, a critical issue to be resolved is the lack of explainability. Extensive efforts have been made in the literature to incorporate explainability into LFMs. However, they either rely on auxiliary information which may not be available in practice, or fail to provide easy-to-understand explanations. In this paper, we propose a fast influence analysis method named FIA, which successfully enforces explicit neighbor-style explanations to LFMs with the technique of influence functions stemmed from robust statistics. We first describe how to employ influence functions to LFMs to deliver neighbor-style explanations. Then we develop a novel influence computation algorithm for matrix factorization with high efficiency. We further extend it to the more general neural collaborative filtering and introduce an approximation algorithm to accelerate influence analysis over neural network models. Experimental results on real datasets demonstrate the correctness, efficiency and usefulness of our proposed method

Alterations in prefrontal-limbic functional activation and connectivity in chronic stress-induced visceral hyperalgesia.

Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([(14)C]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH