The Role of T cell Costimulation in the Development and Progression of Citrulline-induced Arthritis

MHC Class II molecules (e.g. DR4) expressing the Rheumatoid Arthritis (RA) shared epitope are strongly linked to the development of anti-citrulline (Cit) immune responses and the pathogenesis of RA. We have established a Cit-induced arthritis model (DR4 tg mice) where injection of citrullinated human fibrinogen (CithFib) induces anti- Cit immune responses and arthritis. The main objective of this study was to assess the role of T cells in this Cit- induced arthritis mouse model using CTLA4-Ig, an agent that blocks T cell activation. To accomplish this, DR4 tg mice were immunized with CithFib to induce arthritis. At the disease onset or peak, DR4 tg mice were treated with CTLA4-Ig or control human IgGl (hlgGl) or left untreated. Arthritis progression was monitored for 30 days, and then anti- Cit immune responses and the arthritogenicity of splenic lymphocytes from these mice were examined. The latter were done using adoptive lymphocyte transfers from CTLA4- Ig-treated mice or controls via intraperitoneal injection into naïve DR4 tg mice. The recipient mice also received intraarticular injection of CithFib or vehicle. The results demonstrated that CTLA4-Ig but not hlgGl treatment of arthritic DR4 tg mice significantly reduced ankle swelling and pathological joint damage in these mice. CTLA4-Ig, but not hlgGl treatment suppressed T cell proliferative responses to Cit. Unlike splenic lymphocytes from untreated arthritic mice, lymphocytes transferred from CTLA4-Ig-treated arthritic mice did not cause arthritis in recipient mice. The conclusion from this study is that Cit-specific T cells play a direct role in the development and progression of arthritis in this Cit-induced model for human RA

The Mason Test: A Defense Against Sybil Attacks in Wireless Networks Without Trusted Authorities

Wireless networks are vulnerable to Sybil attacks, in which a malicious node poses as many identities in order to gain disproportionate influence. Many defenses based on spatial variability of wireless channels exist, but depend either on detailed, multi-tap channel estimation - something not exposed on commodity 802.11 devices - or valid RSSI observations from multiple trusted sources, e.g., corporate access points - something not directly available in ad hoc and delay-tolerant networks with potentially malicious neighbors. We extend these techniques to be practical for wireless ad hoc networks of commodity 802.11 devices. Specifically, we propose two efficient methods for separating the valid RSSI observations of behaving nodes from those falsified by malicious participants. Further, we note that prior signalprint methods are easily defeated by mobile attackers and develop an appropriate challenge-response defense. Finally, we present the Mason test, the first implementation of these techniques for ad hoc and delay-tolerant networks of commodity 802.11 devices. We illustrate its performance in several real-world scenarios

Smart charging for electric vehicles to minimize charging cost

This paper assumes a smart grid framework where the driving patterns for electric vehicles are known, time variations in electricity prices are communicated to householders, and data on voltage variation throughout the distribution system is available. Based on this information an aggregator with access to this data can be employed to minimize EV owner charging costs whilst maintaining acceptable distribution system voltages. In this study EV charging is assumed to take place only in the home. A single-phase LV distribution network is investigated where the local EV penetration level is assumed to be 100%. EV use patterns have been extracted from the UK Time of Use Survey data with 10-minute resolution and the domestic base load is generated from an existing public domain model. Apart from the so-called real time price signal, which is derived from the electricity system wholesale price, the cost of battery degradation is also considered in the optimal scheduling of EV charging. A simple and effective heuristic method is proposed to minimize the EV charging cost whilst satisfying the requirement of state of charge for the EV battery. A simulation in OpenDSS over a period of 24 hours has been implemented, taking care of the network constraints for voltage level at the customer connection points. The optimization results are compared with those obtained using dynamic optimal power flow

The Fifth Epoch: Socio-Economic Approach to Sustainable Capitalism

The purpose of this conceptual essay is to challenge the inevitability of living with the destructive beast of speculative market economics in the 4th epoch of global capitalism. We are facing an existential socio-ecological threat from the short-term excesses of financial capitalism, a socially irresponsible form that consumes without producing value and without bearing entrepreneurial risk, benefitting only the few. The fate of roughly 90% of humanity hangs in the balance. The primary contribution of this paper proposes a 5th epoch of capitalism, inspired by Savall and Zardet’s socio-economic and sustainable approach that restores human potential and value creation to spacetimemattering. Applying their conceptual innovation moves capitalism to a Bernácer-Perroux economic universe, with a different curvature capable of reconfiguring organizational story spacetime and resituating the antenarrative of global capitalism