In order to meet increasing customer demands for more diverse product offerings, firms are revising their supply chain structures to accommodate mass customization. The revised structures often involve delaying the delivery of the products until after the customer orders arrive, termed time postponement (TP), or delaying the differentiation of the products until later production stages, termed form postponement (FP). We develop models representing possible implementations of the TP and FP structures and compare their performance in total supply chain cost and expected customer waiting times. We find that once the number of different products increases above some threshold level, the TP structure is preferred under both performance metrics.For the most general model, a numerical experiment was designed to investigate how different factors affect the performance of the TP and FP structures. Through this experiment we show that higher arrival time and process time variations make the FP structure more favorable while increases in the number of products and higher interest rates make the TP structure more favorable. We also offer guidance to managers using either structure on where to allocate resources for performance improvement. For example, to improve the customer waiting times under the FP structure, increasing the coverage of the generic component and reducing the number of products provide larger benefits than reducing the variability of the arrival and process times. #
Cellular migrations through constricted spaces are a crucial aspect of many developmental and disease processes including hematopoiesis, inflammation and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model in which nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5% their width. This constriction is blocked by fibrous organelles, structures that pass through P cells to connect the muscles to cuticle. Fibrous organelles are removed just prior to nuclear migration, when nuclei and lamins undergo extreme morphological changes to squeeze through the space. Both actin and microtubule networks are organized to mediate nuclear migration. The LINC complex, consisting of the SUN protein UNC-84 and the KASH protein UNC-83, recruits dynein and kinesin-1 to the nuclear surface. Both motors function in P-cell nuclear migration, but dynein, functioning through UNC-83, plays a more central role as nuclei migrate towards minus ends of polarized microtubule networks. Thus, the nucleoskeleton and cytoskeleton are coordinated to move nuclei through constricted spaces.
We consider a single machine scheduling problem in which the objective is to minimize the mean absolute deviation of job completion times about a common due date. We present an algorithm for determining multiple optimal schedules under restrictive assumptions about the due date. and an implicit enumeration procedure when the assumptions do not hold. Wc also establish the similarity of this problem to the two parallel machines mean flow time problem.
Objective: Cancer-associated fibroblasts (CAFs) play an important role in the progression of pancreatic ductal adenocarcinoma (PDAC) by promoting tumor cell migration and drug resistance. We determined the impact of CAFs on PDAC cancer stem cells (CSCs).Methods: Fibroblast cell lines from patients' tumors were co-cultured with PDAC cells and examined for clonogenic growth and self-renewal using colony forming assays and migration in vitro. Changes in the frequency of CSCs was determined by flow cytometry. The effect of integrin-Focal Adhesion Kinase (FAK) signaling on CAF-mediated clonogenic growth was evaluated using shRNAs against β1 integrin and FAK as well as a small molecule FAK inhibitor.Results: Cancer-associated fibroblasts enhanced PDAC clonogenic growth, self-renewal, and migration that was associated with an increase in the frequency of CSCs. These fibroblast cells were activated by PDAC cells and increased collagen synthesis resulting in FAK activation in PDAC cells. Knock-down of β1-Integrin and FAK or the inhibition of FAK kinase activity in PDAC cells abrogated the impact of CAFs on clonogenic growth.
Conclusion:Therefore, CAFs enhance PDAC clonogenic growth, self-renewal, and the frequency of CSCs through type I collagen production that enhances integrin-FAK signaling in PDAC cells.
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