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Abstract Mitochondrial dysfunction is important in various chronic degenerative disorders, and aberrant immune responses elicited by cytoplasmic mitochondrial DNA (mtDNA) may be related. Here, we developed mtDNA-targeted MTERF1-FokI and TFAM-FokI endonuclease systems to induce mitochondrial DNA double-strand breaks (mtDSBs). In these cells, the mtDNA copy number was significantly reduced upon mtDSB induction. Interestingly, in cGAS knockout cells, synthesis of interferon β1 and interferon-stimulated gene was increased upon mtDSB induction. We found that mtDSBs activated DNA-PKcs and HSPA8 in a VDAC1-dependent manner. Importantly, the mitochondrial E3 ligase MARCH5 bound active DNA-PKcs in cells with mtDSBs and reduced the type І interferon response through the degradation of DNA-PKcs. Likewise, mitochondrial damage caused by LPS treatment in RAW264.7 macrophage cells increased phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA in a DNA-PKcs-dependent manner. Accordingly, in March5 knockout macrophages, phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA were prolonged after LPS stimulation. Together, cytoplasmic mtDNA elicits a cellular immune response through DNA-PKcs, and mitochondrial MARCH5 may be a safeguard to prevent persistent inflammatory reactions.

During cell division, chromosome alignment is engendered by connection of microtubules to kinetochores, coordinated by Aurora B and PLK1. Here, the authors show that the RSF1-PLK1 axis creates an activating phosphorylation on T236 in the GT motif of Aurora B and this is indispensable for Aurora B activation.

The chromatin remodeler RSF1 is enriched at mitotic centromeres but its function there is poorly understood. Here, the authors show that RSF1 regulates H2A phosphorylation and acetylation at mitotic centromeres and contributes to chromosome stability.

One of the key elements of e-commerce systems is the online product catalog. It provides sellers with a content management system that assembles, aggregates, normalizes, and distributes product information. It also provides potential buyers with an interactive interface that offers a multimedia representation of the product information as well as retrieval, classification and ordering services. In this paper, we discuss the interface aspect of online product catalogs, focusing on its ability to help shoppers navigate and analyze product information. Specifically, we present a new interactive interface for online product catalogs that effectively enables the shopper to navigate through the product information space and analytically select suitable products. [ABSTRACT FROM AUTHOR]

Planners in the steel industry design a set of steel slabs to satisfy the order book subject to constraints on (1) achieving a total designed weight for each order using multiples of an order-specific production size range, (2) minimum and maximum sizes for each slab, and (3) feasible assignments of multiple orders to the same slab. We developed a heuristic solution based on matchings and bin packing that a large steel plant uses daily in mill operations. [ABSTRACT FROM AUTHOR]

Simple auctions neglect the complex business constraints required by strategic sourcing. The Mars-IBM team created a procurement auction Web site (www.number1traders.com) that enables buyers to incorporate complex bid structures (such as bundled all-or-nothing bids and quantity-discounted bids) and business constraints into strategic-sourcing auctions. Outcomes in such auctions must lead to win-win solutions to sustain long-term relationships between procurer and suppliers. These factors are as important or more important than price. The Mars procurement auction Web site supports several alternatives to simple auctions that help match its needs as procurer and the capabilities of suppliers by incorporating optimal bid selection subject to constraints based on business rules in a dynamic environment. The ability to consider geographic, volume, and quality factors helps both parties. Feedback from participant suppliers has highlighted the benefits of time efficiency, transparency, and fairness. Although they reflect just one side of the benefits ledger, the monetary benefits to Mars (a $14 billion company) and to its suppliers are significant. [ABSTRACT FROM AUTHOR]

We introduce a new problem that arises from operations planning in the process industry. This problem involves matching an order book against surplus inventory before production planning. It can be formulated by generalizing the multiple knapsack problem along three dimensions: (i) adding assignment restrictions on items that can be assigned to a knapsack, (ii) adding a new attribute (called ‘color’ in this paper) to an item and then adding the associated ‘color’ constraints that restrict the number of distinct colors that can be assigned to a knapsack, and (iii) considering multiple objectives for optimization. We formulate the problem, provide a result regarding its complexity, and report on our computational experience with solving a set of real instances based on data from the operations of a large steel plant. We then propose a network-flow-based heuristic that yields solutions within 3% of optimal (or the best known feasible solution). This system has been successfully deployed and is now used daily in the mill operations. [ABSTRACT FROM AUTHOR]

Examines applications of flexible pricing in electronic commerce. Discussion on flexible pricing and the supply chain; Negotiation mechanisms for procurement; Applications of flexible pricing on the sell side.