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The benefit of radiation therapy for pancreatic ductal adenocarcinoma (PDAC) remains unclear. We hypothesized that a new mechanistic mathematical model of chemotherapy and radiation response could predict clinical outcomes a priori, using a previously described baseline measurement of perfusion from computed tomography scans, normalized area under the enhancement curve (nAUC).We simplified an existing mass transport model that predicted cancer cell death by replacing previously unknown variables with averaged direct measurements from randomly selected pathologic sections of untreated PDAC. This allowed using nAUC as the sole model input to approximate tumor perfusion. We then compared the predicted cancer cell death to the actual cell death measured from corresponding resected tumors treated with neoadjuvant chemoradiation in a calibration cohort (n = 80) and prospective cohort (n = 25). After calibration, we applied the model to 2 separate cohorts for pathologic and clinical associations: targeted therapy cohort (n = 101), cetuximab/bevacizumab + radiosensitizing chemotherapy, and standard chemoradiation cohort (n = 81), radiosensitizing chemotherapy to 50.4 Gy in 28 fractions.We established the relationship between pretreatment computed v nAUC to pathologically verified blood volume fraction of the tumor (r = 0.65; P = .009) and fractional tumor cell death (r = 0.97-0.99; P.0001) in the calibration and prospective cohorts. On multivariate analyses, accounting for traditional covariates, nAUC independently associated with overall survival in all cohorts (mean hazard ratios, 0.14-0.31). Receiver operator characteristic analyses revealed discrimination of good and bad prognostic groups in the cohorts with area under the curve values of 0.64 to 0.71.This work presents a new mathematical modeling approach to predict clinical response from chemotherapy and radiation for PDAC. Our findings indicate that oxygen/drug diffusion strongly influences clinical responses and that nAUC is a potential tool to select patients with PDAC for radiation therapy.

This paper reports on a case study that examined the challenges faced and strategies adopted by Thai teachers when remote teaching during the COVID-19 pandemic. It further provides a comprehensive strategy for addressing the ongoing global pandemic in terms of education. We used a mixed methods design to collect both quantitative and qualitative data from K-12 Thai teachers ( N = 235) and performed 42 semi-structured interviews. The results indicated that most Thai teachers have the necessary knowledge to design suitable content for remote teaching. However, they must further develop their administration and leadership skills. The main challenges and strategies for Thai teachers remain in the areas of student motivation, assessment, and classroom management. Furthermore, ranking from high to low, Thai teachers preferred face-to-face instruction, blended/hybrid instruction and hyflex among different instructional delivery modalities. We conclude the paper by discussing possible alternative instructional delivery modalities and their implications for K-12 remote learning and instruction.

A mathematical model of checkpoint inhibitor immunotherapy yields patient-specific prognosis of tumor kill and patient survival., We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti–CTLA-4 or anti–PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

Many manufacturers are offering some form of supply chain incentives to motivate their retailers to increase customer satisfaction (CS). In this paper, we focus on the manufacturer's two main CS incentives for the retailer: customer satisfaction index bonus (CSI bonus) and customer satisfaction assistance (CS assistance). When both manufacturer and retailer have strong market pricing power, prior research has shown that the manufacturer should offer both CSI bonus and CS assistance to the retailer. In contrast with prior research results, we find if the manufacturer has weak market pricing power, then she should only offer CS assistance but not CSI bonus to the retailer when the market wholesale price is relatively low. We also quantify the value of the CS incentive programs to the manufacturer's performance improvement in different supply chain settings. In general, we find the manufacturer's CS incentive program is more valuable when demand is more sensitive to the retailer's CS effort. Finally, we obtain additional insights from a few supply chain model extensions.

Homologous Recombination (HR) is a high-fidelity process with a range of biologic functions from generation of genetic diversity to repair of DNA double-strand breaks (DSBs). In mammalian cells, BRCA2 facilitates the polymerization of RAD51 onto ssDNA to form a presynaptic nucleoprotein filament. This filament can then strand invade a homologous dsDNA to form the displacement loop (D-loop) structure leading to the eventual DSB repair. Here, we have found that RAD51 in stoichiometric excess over ssDNA can cause D-loop disassembly in vitro; furthermore, we show that this RAD51 activity is countered by BRCA2. These results demonstrate that BRCA2 may have a previously unexpected activity: regulation of HR at a post-synaptic stage by modulating RAD51-mediated D-loop dissociation. Our in vitro results suggest a mechanistic underpinning of homeostasis between RAD51 and BRCA2, which is an important factor of HR in mammalian cells.

This study examines the relationship between disruptive technologies and their potential impacts on sustainable supply chain management (SSCM), with a focus on the following technologies: Big Data Analytics / Artificial Intelligence / Machine Learning, Blockchain, Industry 4.0 / Internet of Things (IoT), 3D Printing / Additive Manufacturing, and P2P / Sharing Economy. Based on a comprehensive literature review on both theoretical and practical roles of these disruptive technologies in SSCM, we conduct a cross-case study to analyze the impacts of disruptive technologies on sustainability performance. From 100 application cases of 41 companies in key supply chain management and sustainability journals, we develop a classification scheme based on implementation complexity and sustainability performance of disruptive technologies. The implementation complexity and sustainability performance matrix show that all the cases examined have a positive overall sustainability performance score which indicates that investment in disruptive technologies improves the sustainability performance of firms. However, the impact of each disruptive technology on sustainability performance varies with the types of technology and sustainability dimensions. We also utilize the cases to illustrate how disruptive technologies are applied to key areas of SSCM and identify opportunities for future research.

RAD52 is a member of the homologous recombination (HR) pathway that is important for maintenance of genome integrity. While single RAD52 mutations show no significant phenotype in mammals, their combination with mutations in genes that cause hereditary breast cancer and ovarian cancer like BRCA1, BRCA2, PALB2 and RAD51C are lethal. Consequently, RAD52 may represent an important target for cancer therapy. In vitro, RAD52 has ssDNA annealing and DNA strand exchange activities. Here, to identify small molecule inhibitors of RAD52 we screened a 372,903-compound library using a fluorescence-quenching assay for ssDNA annealing activity of RAD52. The obtained 70 putative inhibitors were further characterized using biochemical and cell-based assays. As a result, we identified compounds that specifically inhibit the biochemical activities of RAD52, suppress growth of BRCA1- and BRCA2-deficient cells and inhibit RAD52-dependent single-strand annealing (SSA) in human cells. We will use these compounds for development of novel cancer therapy and as a probe to study mechanisms of DNA repair.

In this paper we study closed-loop supply chain models for a high-tech product which is featured with a short life-cycle and volatile demand. We focus on the manufacturer׳s choice of three alternative reverse channel structures for collecting the used product from consumers for remanufacturing: (1) the manufacturer collects the used product directly; (2) the retailer collects the used product for the manufacturer; and (3) the manufacturer subcontracts the used product collection to a third-party firm. We characterize and compare the manufacturer׳s optimal production quantities and profits under the three alternative reverse channel structures. We also investigate the impacts of collection cost structures and implementations of product take-back laws on the manufacturer׳s choice of reverse channel structures.

This paper extends the standard newsvendor problem based upon risk neutrality to a game setting where multiple newsvendors with loss aversion preferences are competing for inventory from a risk-neutral supplier. We show that if the supplier allocates the total demand among the newsvendors proportional to their order quantities, then there exists a unique Nash equilibrium order quantity in this newsvendor game. We also find that while the demand-stealing effect increases the total order quantity of the newsvendors, the loss aversion effect decreases the newsvendors’ total order quantity and if strong enough, may lead to a lower total inventory level of the decentralized supply chain than that of an integrated supply chain.

Both random yield and uncertain demand are common occurrences in the semiconductor industry. This paper studies a decentralised supply chain comprised of a single manufacturer and a single distributor for a short life-cycle product with random yield and uncertain demand. We analyse two alternatives for doing business. One alternative is the traditional supply chain arrangement, where the distributor is fully responsible for the inventory decision whereas the manufacturer is fully responsible for the production decision. The other alternative is the vendor-managed-inventory (VMI) arrangement, where the manufacturer (vendor) is fully responsible for the entire production and inventory decisions in the supply chain. We characterise the optimal production and inventory decisions under both arrangements. We also compare the individual firms and supply chain performance under the traditional and VMI arrangements. Our results provide insights into how firms can choose the right supply chain arrangement to improve supply chain efficiency.

Newsvendor models are widely used in the literature, and usually based upon the assumption of risk neutrality. This paper uses loss aversion to model manager's decision-making behavior in the single-period newsvendor problem. We find that if shortage cost is not negligible, then a loss-averse newsvendor may order more than a risk-neutral newsvendor. We also find that the loss-averse newsvendor's optimal order quantity may increase in wholesale price and decrease in retail price, which can never occur in the risk-neutral newsvendor model.

While over the past 4 years more than 1000 B2B electronic markets that cater to a wide spectrum of industries have been established, many of them have already disappeared. This reality can be explained by several factors, two of which we think are important: the transaction fees that owners of these markets charge participants, and the supply chain coordination mechanisms that these markets do (or actually do not) facilitate. In this paper, we take the viewpoint of supply chain coordination to analyze the decision of suppliers and buyers to do or not do business in electronic markets while selling perishable products with random demand.

A supply chain is two or more parties linked by a flow of goods, information, and funds. When one or more parties of the supply chain try to optimize their own profits, system performance may be hurt. Supply chain contract is a coordination mechanism that provides incentives to all of its members so that the decentralized supply chain behaves nearly or exactly the same as the integrated one. We have seen a vast literature on supply chain contracts recently. However, little work has been done on the relationships of those supply chain contract models. In this paper, we provide a general framework that synthesizes existing results for a variety of supply chain contract forms.

Newsvendor models are widely used in the literature, and usually based upon the assumption of risk neutrality. Recently there is a growing body of literature that attempts to use alternative risk preferences rather than risk neutrality to describe the newsvendor decision-making behavior. In this chapter, we provide an overview of newsvendor models with alternative risk preferences within the expected utility theory and prospect theory frameworks and identify some directions for future research.