Decomposition Based Solution Approaches for Multi-product Closed-Loop Supply Chain Network Design Models

Closed-loop supply chain (CLSC) management provides opportunity for cost savings through the integration of product recovery activities into traditional supply chains. Product recovery activities, such as remanufacturing, reclaim a portion of the previously added value in addition to the physical material. Our problem setting is motivated by the practice of an Original Equipment Manufacturer (OEM) in the automotive service parts industry, who operates a well established forward network. The OEM faces customer demand due to warranty and beyond warranty vehicle repairs. The warranty based demand induces part returns. We consider a case where the OEM has not yet established a product recovery network, but has a strategic commitment to implement remanufacturing strategy. In accomplishing this commitment, complications arise in the network design due to activities and material movement in both the forward and reverse networks, which are attributed to remanufacturing. Consequently, in implementing the remanufacturing strategy, the OEM should simultaneously consider both the forward and reverse flows for an optimal network design, instead of an independent and sequential modeling approach. In keeping with these motivations, and with the goal of implementing the remanufacturing strategy and transforming independent forward and reverse supply chains to CLSCs, we propose to investigate the following research questions: 1. How do the following transformation strategies leverage the CLSC?s overall cost performance? ? Extending the already existing forward channel to incorporate reverse channel activities. ? Designing an entire CLSC network. 2. How do the following network flow integration strategies influence the CLSC?s overall cost performance? ? Using distinct forward and reverse channel facilities to manage the corresponding flows. ? Using hybrid facilities to coordinate the flows. In researching the above questions, we address significant practical concerns in CLSC network design and provide cost measures for the above mentioned strategies. We also contribute to the current literature by investigating the optimal CLSC network design. More specifically, we propose three models and develop mathematical formulations and novel solution approaches that are based on decomposition techniques, heuristics, and meta-heuristic approaches to seek a solution that characterizes the configuration of the CLSC network, along with the coordinated forward and reverse flows

Design and development of a vehicle routing system under capacity, time-windows and rush-order reloading considerations

The purpose of this research is to present the design and development of a routing system, custom developed for a fence manufacturing company in the continental US. The objective of the routing module of the system is to generate least cost routes from the home-center of the company to a set of delivery locations. Routes are evolved for a set of customer locations based on the sales order information and are frequently modified to include rush orders. These routes are such that each delivery is made within a given time window. Further, total truckload of all delivery locations over any particular route is not allowed to exceed the weight and volume capacities of the truck. The basic system modules such as user interface functions and database are designed using MS Access 2000. An interface module to retrieve data from existing ERP system of the company is developed to import pick-ticket information. A customer inter-distance maintenance module is designed with the abilities of a learning tool to reduce information retrieval time between the routing system and the GIS server. The Graphical User Interface with various screen forms and printable reports is developed along with the routing module to achieve complete system functionality and to provide an efficient logistics solution. This problem, formulated as a mixed-integer program, is of particular interest due to its generality to model problem scenarios in the production shop such as job-shop scheduling, material handling, etc. This problem is coded and solved for instances with different input parameters using AMPL/CPLEX. Results of test runs for the company data show that the solution time increases exponentially with the number of customers. Hence, a heuristic approach is developed and implemented. Sample runs with small instances are solved for optimality using AMPL/CPLEX and are used to compare the performance of the heuristics. However, test runs solved using the heuristics for larger instances are compared with the manual routing costs. The comparison shows a considerable cost savings for heuristic solutions. Further, a what-if analysis module is implemented to aid the dispatcher in choosing input parameters based on sensitivity analysis. In conclusion, further improvement of the routing system and future research directions are proposed

Employing bioactive compounds derived from Ipomoea obscura (L.) to evaluate potential inhibitor for SARS‐CoV‐2 main protease and ACE2 protein

Abstract Angiotensin converting enzyme 2 (ACE2) and main protease (MPro) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome‐coronaviruses or SARS‐CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of Ipomoea obscura (L.) by using GC‐MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and MPro target proteins to determine the antiviral effects against SARS‐COV. Results exhibits that among 11 compounds from I. obscura (L.), urso‐deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso‐allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in I. obscura (L.) will address inhibition of corona viral replication in host cells

Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery

DNA methylation is an epigenetic mark critical for regulating transcription, chromatin structure and genome stability. Although many studies have shed light on how methylation impacts transcription and interfaces with the histone code, far less is known about how it regulates genome stability. We and others have shown that DNA methyltransferase 1 (DNMT1), the maintenance methyltransferase, contributes to the cellular response to DNA damage, yet DNMT1's exact role in this process remains unclear. DNA damage, particularly in the form of double-strand breaks (DSBs), poses a major threat to genome integrity. Cells therefore possess a potent system to respond to and repair DSBs, or to initiate cell death. In the current study, we used a near-infrared laser microirradiation system to directly study the link between DNMT1 and DSBs. Our results demonstrate that DNMT1 is rapidly but transiently recruited to DSBs. DNMT1 recruitment is dependent on its ability to interact with both PCNA and the ATR effector kinase CHK1, but is independent of its catalytic activity. In addition, we show for the first time that DNMT1 interacts with the 9-1-1 PCNA-like sliding clamp and that this interaction also contributes to DNMT1 localization to DNA DSBs. Finally, we demonstrate that DNMT1 modulates the rate of DSB repair and is essential for suppressing abnormal activation of the DNA damage response in the absence of exogenous damage. Taken together, our studies provide compelling additional evidence for DNMT1 acting as a regulator of genome integrity and as an early responder to DNA DSBs