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Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate-limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35-55 and MOG1-125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE-515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE-515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE-515 blocks activation-induced B and T cell proliferation and MOG35-55 -specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35-55 -specific lymphocyte activation-induced proliferation.

Preface to the Special Issue on Behavioral Queueing Science: The Need for a Multidisciplinary Approach Modern service systems are economically important but operationally complex. In "Preface to the Special Issue on Behavioral Queueing Science: The Need for a Multidisciplinary Approach," Ingolfsson, Mandelbaum, Schultz, and Yom-Tov discuss how this special issue advances the scientific study of queues in services systems by acknowledging the central role of human behavior. Behavioral queueing science requires a multidisciplinary approach, using tools that include mathematical modelling, lab experiments and field studies. Each discipline has strengths and weaknesses, but together they have complementing goals, and jointly they give rise to a scientific paradigm for behavioral queues. Cross-disciplinary work is challenging but necessary. The eleven papers in our special issue show how this can be done successfully while setting an example for future work. History: This paper has been accepted for the Operations Research Special Issue on Behavioral Queueing Science. [ABSTRACT FROM AUTHOR]

The literature on separatist groups has paid relatively little attention to groups' exact territorial claims and their influence on strategies. We explain the geographic distribution of separatist violence using new geospatial data on the location and extent of groups' territorial claims. We argue that variation in where separatists attack stems from variation in how groups allocate effort across two main objectives: control in the claimed region and the coercion of policy concessions from the center. We hypothesize that the relative importance of these objectives derives from features of the claim, the claimed region, and the separatist movement. We show that groups with "fuzzy" claims that do not follow administrative boundaries or clear geographic features attack more around their envisioned state's border, violence tends to concentrate within the claimed region when it is ethnically heterogeneous or the movement is fragmented, while relatively unified movements attack more in the national capital. La bibliografía sobre grupos separatistas ha pasado casi por alto los reclamos territoriales exactos y su repercusión en las estrategias que utilizan. Explicamos la distribución geográfica de la violencia separatista con información geoespacial nueva sobre la ubicación y la dimensión de los reclamos territoriales de los grupos. Sostenemos que la variación en los lugares donde atacan los grupos separatistas se debe a la variación en la forma en que los grupos distribuyen sus esfuerzos en base a dos objetivos principales: el control de la región reclamada y la coerción de las concesiones de política del centro. Nuestra hipótesis es que la importancia relativa de estos objetivos deriva de las características del reclamo, de la región reclamada y del movimiento separatista dado. Demostramos que los grupos con reclamos «difusos» que no siguen los límites administrativos o las características geográficas claras atacan más alrededor de su frontera de estado visualizada y que la violencia tiende a concentrarse dentro de la región reclamada cuando hay heterogeneidad étnica o cuando el movimiento está fragmentado, mientras que los movimientos relativamente unidos atacan más en la capital nacional. La littérature sur les groupes séparatistes a accordé relativement peu d'attention aux revendications territoriales précises de ces groupes et à leur influence sur les stratégies. Nous expliquons la répartition géographique de la violence séparatiste en nous appuyant sur de nouvelles données géospatiales sur la localisation et l'étendue des revendications territoriales des groupes. Nous soutenons que la variation des lieux d'attaque des séparatistes découle de la variation de la manière dont les groupes allouent leurs efforts entre deux objectifs principaux : le contrôle dans la région revendiquée et la coercition de concessions politiques de la part du pouvoir central. Nous émettons l'hypothèse que l'importance relative de ces objectifs découle des caractéristiques de la revendication, de la région revendiquée et du mouvement séparatiste. Nous montrons que les groupes dont les revendications sont « floues », c'est-à-dire qui ne suivent pas les frontières administratives ou de caractéristiques géographiques claires, attaquent davantage autour 'e la frontière de l'État qu'ils envisagent et que la violence tend à se concentrer dans la région revendiquée lorsqu'elle est ethniquement hétérogène ou que le mouvement est fragmenté, alors que les mouvements relativement unifiés attaquent davantage dans la capitale nationale. [ABSTRACT FROM AUTHOR]

Models and understanding of line design depend on accurate assessments of the effects of design parameters on human actions. Although equity theory predicts that workers will react to the speed of people around them, experimental work has failed to find this effect in an industrial setting with parallel workstations or a change in coworkers. With the current research we contribute to the understanding of line design by using archival data from a manufacturing line. We show that workers do react to the speed of their coworkers, but that individual reactions vary widely. Because workers are different both in speed and reaction, managerial implications are not straightforward. We model an optimal and a heuristic rearrangement of workers and suggest a modified heuristic that performs well for increasing throughput. Our methodology combines empirical approaches, analytical modeling, and Monte Carlo simulation. Key words: organizational studies; motivation incentives; inventory production; policies; capacity; line design; interdependence; equity theory History. Received September 7, 2007; accepted July 27, 2009, by Aleda Roth, operations and supply chain management. Published online in Articles in Advance October 30, 2009., 1. Introduction Researchers in the field of operations management (OM) have studied questions of line dynamics and concluded that factors such as line length, variability, and buffer size all affect [...]

An optimal algorithm for detecting a target using a ladar system employing Geiger-mode avalanche photodiodes (GAPDs) is presented. The algorithm applies to any scenario where a ranging direct detection ladar is used to determine the presence of a target against a sky background within a specified range window. A complete statistical model of the detection process for GAPDs is presented, including GAPDs that are inactive for a fixed period of time each time they fire. The model is used to develop a constant false alarm rate detection algorithm that minimizes acquisition time. Numerical performance predictions, simulation results, and experimental results are presented. OCIS codes: 040.1345, 280.3400, 040.3780, 280.3640.