Setting safety stocks for stable rotation cycle schedules

The article of record as published may be found at http://dx.doi.org/10.1016/j.ijpe.2014.05.020In the process industries, specialized equipment and production processes often necessitate the manufacture of products in a pre-determined sequence to minimize change over time and to simplify scheduling complexity; these types of schedules are referred to as pure rotation schedules, or product wheels, where the circumference of the wheel is the production cycle length. In these industries change over times between the production of individual products can consume considerable time as well as raw materials and it is therefore often desirable to stabilize the production cycles in order to minimize unplanned change overs as well as quote accurate lead times to customers. Materials requirements planning (MRP) systems are often used to plan and coordinate production and supply resources with demand in these environments. Central to the effectiveness of the MRP system is the dependability of the lead time parameters. In this paper, we introduce an optimization model to determine safety stock levels that minimize long run expected costs where as table, cyclic schedule is used. Our model may be used strategically to assess inventory investment requirements as a function of capacity investment, product mix, production technology, demand volatility, and customer service levels. It may be used tactically to optimize item-level planning parameters such as lot size, safety stock and lead time in an MRP system and to support sales and operations planning(S&OP) processes where knowing the future costs associated with current decisions is highly desirable

Fish Oil Blunts Lung Function Decrements Induced by Acute Exposure to Ozone in Young Healthy Adults: A Randomized Trial

Background: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O3). Dietary supplementation with fish oil (FO) or olive oil (OO) has shown protection against other air pollutants. This study evaluates potential cardiopulmonary benefits of FO or OO supplementation against acute O3 exposure in young healthy adults. Methods: Forty-three participants (26 ± 4 years old; 47% female) were randomized to receive 3 g/day of FO, 3 g/ day OO, or no supplementation (CTL) for 4 weeks prior to undergoing 2-hour exposures to filtered air and 300 ppb O3 with intermittent exercise on two consecutive days. Outcome measurements included spirometry, sputum neutrophil percentage, blood markers of inflammation, tissue injury and coagulation, vascular function, and heart rate variability. The effects of dietary supplementation and O3 on these outcomes were evaluated with linear mixed-effect models. Results: Compared with filtered air, O3 exposure decreased FVC, FEV1, and FEV1/FVC immediately post exposure regardless of supplementation status. Relative to that in the CTL group, the lung function response to O3 exposure in the FO group was blunted, as evidenced by O3-induced decreases in FEV1 (Normalized CTL − 0.40 ± 0.34 L, Normalized FO − 0.21 ± 0.27 L) and FEV1/FVC (Normalized CTL − 4.67 ± 5.0 %, Normalized FO − 1.4 ± 3.18 %) values that were on average 48% and 70% smaller, respectively. Inflammatory responses measured in the sputum immediately post O3 exposure were not different among the three supplementation groups. Systolic blood pressure elevations 20-h post O3 exposure were blunted by OO supplementation. Conclusion: FO supplementation appears to offer protective effects against lung function decrements caused by acute O3 exposure in healthy adults

Dietary Supplementation with Olive Oil or Fish Oil and Vascular Effects of Concentrated Ambient Particulate Matter Exposure in Human Volunteers

BackgroundExposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for cardiovascular disease. Olive oil (OO) and fish oil (FO) supplements have beneficial effects on endothelial function.ObjectiveIn this study we evaluated the potential efficacy of OO and FO in mitigating endothelial dysfunction and disruption of hemostasis caused by exposure to particulate matter (PM).Methods and ResultsForty-two participants (58 ± 1 years of age) received either 3 g/day of OO or FO, or no supplements (naive) for 4 weeks prior to undergoing 2-hr exposures to filtered air and concentrated ambient particulate matter (CAP; mean, 253 ± 16 μg/m3). Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery preexposure, immediately postexposure, and 20 hr postexposure. Levels of endothelin-1 and markers of fibrinolysis and inflammation were also measured. The FMD was significantly lower after CAP exposure in the naive (–19.4%; 95% CI: –36.4, –2.3 per 100 μg/m3 CAP relative to baseline; p = 0.03) and FO groups (–13.7%; 95% CI: –24.5, –2.9; p = 0.01), but not in the OO group (–7.6%; 95% CI: –21.5, 6.3; p = 0.27). Tissue plasminogen activator levels were significantly increased immediately after (11.6%; 95% CI: 0.8, 22.2; p = 0.04) and 20 hr after CAP exposure in the OO group. Endothelin-1 levels were significantly increased 20 hr after CAP exposure in the naive group only (17.1%; 95% CI: 2.2, 32.0; p = 0.03).ConclusionsShort-term exposure to CAP induced vascular endothelial dysfunction. OO supplementation attenuated CAP-induced reduction of FMD and changes in blood markers associated with vasoconstriction and fibrinolysis, suggesting that OO supplementation may be an efficacious intervention to protect against vascular effects of exposure to PM.CitationTong H, Rappold AG, Caughey M, Hinderliter AL, Bassett M, Montilla T, Case MW, Berntsen J, Bromberg PA, Cascio WE, Diaz-Sanchez D, Devlin RB, Samet JM. 2015. Dietary supplementation with olive oil or fish oil and vascular effects of concentrated ambient particulate matter exposure in human volunteers. Environ Health Perspect 123:1173–1179; http://dx.doi.org/10.1289/ehp.140898

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

XRN2 Links Transcription Termination to DNA Damage and Replication Stress

We thank the Proteomics Core Facility. We thank Dr. Robert J. Crouch for providing us with GFP- and GFP-RNase H expression plasmids. We also thank Dr. Stephen H. Leppla for providing us with antibodies directed against RNA:DNA hybrids (R loops) (S9.6). We thank Novus Biologicals for generously providing XRN2 and Rrp45 antibodies. We also thank the members of the Boothman lab for critical reading of this manuscript.Author Summary Genomic instability is one of the primary causes of disease states, in particular cancer. One major cause of genomic instability is the formation of DNA double strand breaks (DSBs), which are one of the most dangerous types of DNA lesions the cell can encounter. If not repaired in a timely manner, one DSB can lead not only to cell death. If misrepaired, one DSB can lead to a hazardous chromosomal aberration, such as a translocation, that can eventually lead to cancer. The cell encounters and repairs DSBs that arise from naturally occurring cellular processes on a daily basis. A number of studies have demonstrated that aberrant structures that form during transcription under certain circumstances, in particular RNA:DNA hybrids (R loops), can lead to DSB formation and genomic instability, especially during DNA synthesis. Thus, it is important to understand how the cell responds and repairs transcription-mediated DNA damage in general and R loop-related DNA damage in particular. This paper both demonstrates that the XRN transcription termination factor links transcription and DNA damage, but also provides a better understanding of how the cell prevents transcription-related DNA damage.Yeshttp://www.plosgenetics.org/static/editorial#pee

A Stochastic Inventory Model for the Stock Versus Non-Stock Decision

The most fundamental decision in inventory management is whether or not to stock a particular item. Despite its importance, the preponderance of the literature on inventory systems is concerned with how much to order and when to order which assume the stocking decision has been made. In this research we examine an inventory stocking decision model that is based upon an item’s demand history. In this model every item must earn its way into the catalogue of stocked items by receiving a given number of demands over a specified time period and will likewise be de-stocked and taken out of the catalogue (or burned) if it receives fewer than a given number of demands over a specified time period. We show the stability of such a policy and discuss implications for its use by firms that compete on product assortment. This research should be of interest to the Department of Defense as well as commercial firms that have large numbers of items in their product catalogues

Beyond lean: production and inventory policy for the old economy

Lean manufacturing has fundamentally changed the way business leaders think about the production of manufactured goods and services. Over the past three decades, firms have dedicated considerable resources to reducing production setup times, shrinking inventories, and organizing work into cellular flows. Discrete parts manufacturing has benefited from production planning schemes that smooth production and levelload the plant to reduce idle time and overtime. But in the process industries, where production occurs 24 hours a day, seven days a week, what does it mean to level-load the production facility? In those industries, capacity stabilization is defined as creating production cycles that are predictable, and level-loading consists of stabilizing manufacturing lead times. In this article, we describe the differences between what we call inventory-centric versus capacity-centric modes of production and inventory control, and we present data collected from a large chemical plant operation that illustrates a mismatch between inventory policy and capacity characteristics. We also describe policies appropriate for old economy firms in the face of increasing consolidation and pressures to reduce costs and increase responsiveness

Designing multi-echelon service parts networks with finite repair capacity

We propose an approach to model and solve the joint problem of facility location, inventory allocation and capacity investment in a two echelon, single-item, service parts supply chain with stochastic demand. The objective of the decision problem is to minimize the total expected costs associated with (1) opening repair facilities, (2) assigning each field service location to an opened facility, (3) determining capacity levels of the opened repair facilities, and (4) optimizing inventory allocation among the locations. Due to the size of the problem, computational efficiency is essential. The accuracy of the approximations and effectiveness of the approach are analyzed with two numerical studies. The approach provides optimal results in 90% of scenarios tested and was within 2% of optimal when it did not.We explore the impact of capacity utilization, inventory availability, and lead times on the performance of the approach. We show that including tactical considerations jointly with strategic network design resulted in additional cost savings from 3% to 12%. Our contribution is the development of a practical model and approach to support the decision making process of joint facility location and multi-echelon inventory optimization.Inventory Maintenance Queueing OR in military Stochastic processes Integer programming Non-linear programming

Integrated Real-Time Capacity and Inventory Allocation for Reparable Service Parts in a Two-Echelon Supply System

Two critical decisions must be made daily when managing multiechelon repair and distribution systems for service parts: (1) allocating available repair capacity among different items and (2) allocating available inventories to field stocking locations to support service operations. In many such systems, procurement lead times for service parts are lengthy and variable, repair capacity is limited, and operational requirements change frequently--resulting in demand processes that are highly uncertain and nonstationary. As a consequence, it is common to have many items in short supply while others are abundant. In such environments, integrated real-time decision-support tools can provide significant value by reducing the impact of inventory imbalances and responding appropriately to the volatile nature of the demand processes. By "integrated" and "real-time," we mean (respectively) tools that simultaneously consider key aspects of the current state of the operating environment in deciding what items to repair, where to ship available units, and by what mode to ship them. In this paper, we develop an integrated real-time model for making repair and inventory allocation decisions in a two-echelon reparable service parts system. We formulate the decision problem as a finite-horizon, periodic-review mathematical program, we show it can be formulated as a large-scale linear program, and we develop a practical heuristic method for solving the problem approximately. By simulating the operation of a service parts supply chain, we demonstrate the value of employing integrated decision models over using separate repair and inventory allocation rules for a range of environments where inventory imbalances exist. We also show that our heuristic approach is highly effective and that its inventory allocation subroutine, used as a stand-alone tool for making distribution decisions, outperforms a commonly used inventory allocation rule in most circumstances tested.inventory, periodic review, multiechelon system, real-time allocation, limited capacity, reparable service parts, priority dispatch rule, emergency shipment