RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer

BackgroundColorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.MethodsSamples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.ResultsThis study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.ConclusionCollectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients

Approximation Algorithms for the Bid Construction Problem in Combinatorial Auctions for the Procurement of Freight Transportation Contracts

The bid valuation and construction problem for carriers facing combinatorial auctions for the procurement of freight transportation contracts is very difficult and involves the computation of a number of NP-hard sub problems. In this paper we examine computationally tractable approximation methods for estimating these values and constructing bids. The benefit of our approximation method is that it provides a way for carriers to construct optimal or near optimal bids by solving a single NP-hard problem. This represents a significant improvement in efficiency. In addition, this method can be extended to many other applications

Combinatorial Auctions for Transportation Service Procurement: The Carrier Perspective

The procurement of transportation services is an important task for shippers because of the need to control costs at the same time as providing high service levels. When shippers with goods and/or materials to transport seek transportation services from outside companies they typically put out a request for quotes from a set of carriers. They then assign contracts based on negotiated service charges. This process is similar to a simple sealed-bid auction in which each bidder submits a sealed bid for a single item. In the past, when shippers need to procure transportation services for a set of distinctive delivery routes (called lanes) they would obtain quotes for each lane individually and repeat the simple auction process for each lane. Alternatively, they might negotiate for bundles of lanes with a single carrier at a time. However, in the last few years software has been developed to allow shippers to make all lanes available for bidding simultaneously and to allow carriers to simultaneously bid upon combinations of individual lanes. This method of awarding contracts, conventionally called a combinatorial auction, has been reported to result in significant cost savings for shippers. Our research examines the benefits of combinatorial auctions primarily from the carrier's perspective. Preliminary findings, based on a simple simulation model suggest that benefits for carriers can also be significant

Approximation algorithms for the bid construction problem in combinatorial auctions for the procurement of freight transportation contracts

Trucking companies (carriers) are increasingly facing combinatorial auctions conducted by shippers seeking contracts for their transportation needs. The bid valuation and construction problem for carriers facing these combinatorial auctions is very difficult and involves the computation of a number of NP-hard sub problems. In this paper we examine computationally tractable approximation methods for estimating these values and constructing bids. The benefit of our approximation method is that it provides a way for carriers to discover their true costs and construct optimal or near optimal bids by solving a single NP-hard problem. This represents a significant improvement in computational efficiency. We examine our method both analytically and empirically using a simulation based analysis.

Combinatorial Auctions for Trucking Service Procurement: An Examination of Carrier Bidding Policies

Combinatorial auctions are increasingly used by large shippers as a method to establish service contracts with trucking companies. In order to achieve maximal benefits in these auctions, carriers must determine a bidding policy that can accurately evaluate the costs they will incur to fulfill these contracts and which can quickly examine many different possible options. In this paper, we analyze the complexity of this bidding problem for the procurement of truckload trucking service contracts; further, we propose an optimization-based approximation method to aid a carrier in constructing bids. Using a simulation framework, we examine the performance of this method elative to a straightforward bidding policy similar to those used in practice

An Auction Based Collaborative Carrier Network

In this paper, we examine the for-hire truckload trucking industry in the U.S. and propose a new auction based carrier collaboration mechanism designed to facilitate economically efficient cooperation among functionally equivalent small and medium sized trucking companies based on a post market exchange. An architecture for such a system is proposed and its economic benefits are examined. Analysis shows that the system is a Pareto efficient one in which no participants are harmed and many are better off. The complex decision problems associated with subcontracting, bidding and bid selection in such a system are investigated

Transition or Transformation? Emerging Freight Transportation Intermediaries

During the past two years, traditional freight transportation intermediaries, which include freight forwarders, brokers and third party logistics providers have been joined by a large number of intermediaries. The main drivers of the development of these new companies are advances in information and communications technologies, the development of web-based or on-line freight transportation marketplaces and the emergence worldwide of business-to-business (B2B) electronic marketplaces and business-to-consumer (B2C) e-tailers. Advances in Information Technologies make possible many new operational paradigms and potentially enable the efficient integration of supply chains. In this paper we examine these new companies, discuss the potential benefits and costs of shifting from traditional 3PL's to these on-line service providers and illustrate the extent to which changes in the industries appear to be more of a transition than a large scale transformation

Transition or Transformation? Emerging Freight Transportation Intermediaries

During the past two years, traditional freight transportation intermediaries, which include freight forwarders, brokers and third party logistics providers have been joined by a large number of intermediaries. The main drivers of the development of these new companies are advances in information and communications technologies, the development of web-based or on-line freight transportation marketplaces and the emergence worldwide of business-to-business (B2B) electronic marketplaces and business-to-consumer (B2C) e-tailers. Advances in Information Technologies make possible many new operational paradigms and potentially enable the efficient integration of supply chains. In this paper we examine these new companies, discuss the potential benefits and costs of shifting from traditional 3PL's to these on-line service providers and illustrate the extent to which changes in the industries appear to be more of a transition than a large scale transformation.Freight transportation, Intermediaries, Supply Chain Management, Third Party Logistics, Urban Studies and Planning