Dual Sourcing and Smoothing under Non-Stationary Demand Time Series: Re-shoring with SpeedFactories

This is the author accepted manuscript. The final version is available from INFORMS via the DOI in this recordWe investigate near-shoring a small part of the global production to local SpeedFactories that serve only the variable demand. The short lead time of the responsive SpeedFactory reduces the risk of making large volumes in advance, yet it does not involve a complete re-shoring of demand. Using a break-even analysis we investigate the lead time, demand, and cost characteristics that make dual sourcing with a SpeedFactory desirable compared to complete off-shoring. Our analysis employs a linear generalization of the celebrated order-up-to inventory policy to settings where capacity costs exist. The policy allows for order smoothing to reduce capacity costs and performs well relative to the (unknown) optimal policy. We highlight the significant impact of auto-correlated and non-stationary demand series, which are prevalent in practice yet challenging to analyze, on the economic benefit of re-shoring. Methodologically, we adopt a linear policy and normally distributed demand and use Z−transforms to present exact analyses

Mechanisms of progression of chronic kidney disease

Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin–angiotensin–aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number

Volume flexibility at responsive suppliers in reshoring decisions: Analysis of a dual sourcing inventory model

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordWe investigate how volume flexibility, defined by a sourcing cost premium beyond a base capacity, at a local responsive supplier impacts the decision to reshore supply. The buyer also has access to a remote supplier that is cheaper with no restrictions on volume flexibility. We show that with unit lead time difference between both suppliers, the optimal dual sourcing policy is a modified dual base-stock policy with three base-stock levels S_2^f , S_1^f, and S_s. The replenishment orders are generated by first placing a base order from the fast supplier of at most k units to raise the inventory position to S_1^f, if that is possible. After this base order, if the adjusted inventory position is still below S_2^f, additional units are ordered from the fast supplier at an overtime premium to reach S_2^f. Finally, if the adjusted inventory position is below S_s, an order from the slow supplier is placed to bring the final inventory position to S_s. Surprisingly, in contrast to single sourcing with limited volume flexibility, a more complex dual sourcing model often results in a “simpler” policy that replaces demand in each period. The latter allows analytical insights into the sourcing split between the responsive and the remote supplier. Our analysis shows how increased volume flexibility at the responsive supplier promotes the decision to reshore operations and effectively serves as a cost benefit. It also shows how investing in base capacity or additional volume flexibility act as strategic substitutes

Decision-Making Process for Buffer Dimensioning in Manufacturing

Part 3: Production Management Theory and MethodologyInternational audienceSystematic and stochastic variations, both endogenous and exogenous to companies, are a constant challenge for decision makers struggling to maintain a competitive advantage for the business. In response the decision maker introduces buffers to absorb variations but this does not target the source of the problem. The first step should instead be to focus on how to reduce variations and then to handle the remnant variations. In summary the first step should be to perform variation management and then as the second step buffer management should be applied. The combination of these two subprocesses represent service performance management and within this context is buffer dimensioning a key challenge. Input data, decision maker and process logic are identified as three key aspects of buffer dimensioning which are integrated and resulting in six scenarios. These scenarios unravel different conditions for performing buffer dimensioning and facilitate an awareness of a match or mismatch between current and desired situation

The human glomerular podocyte is a novel target for insulin action

Microalbuminuria is significant both as the earliest stage of diabetic nephropathy and as an independent cardiovascular risk factor in nondiabetic subjects, in whom it is associated with insulin resistance. The link between disorders of cellular insulin metabolism and albuminuria has been elusive. Here, we report using novel conditionally immortalized human podocytes in vitro and human glomeruli ex vivo that the podocyte, the principal cell responsible for prevention of urinary protein loss, is insulin responsive and able to approximately double its glucose uptake within 15 min of insulin stimulation. Conditionally immortalized human glomerular endothelial cells do not respond to insulin, suggesting that insulin has a specific effect on the podocyte in the glomerular filtration barrier. The insulin response of the podocyte occurs via the facilitative glucose transporters GLUT1 and GLUT4, and this process is dependent on the filamentous actin cytoskeleton. Insulin responsiveness in this key structural component of the glomerular filtration barrier may have central relevance for understanding of diabetic nephropathy and for the association of albuminuria with states of insulin resistance. © 2005 by the American Diabetes Association.link_to_subscribed_fulltex