Optimal robust inventory management with volume flexibility: matching capacity and demand with the lookahead peak-shaving policy

We study inventory control with volume flexibility: A firm can replenish using period-dependent base capacity at regular sourcing costs and access additional supply at a premium. The optimal replenishment policy is characterized by two period-dependent base-stock levels but determining their values is not trivial, especially for nonstationary and correlated demand. We propose the Lookahead Peak-Shaving policy that anticipates and peak shaves orders from future peak-demand periods to the current period, thereby matching capacity and demand. Peak shaving anticipates future order peaks and partially shifts them forward. This contrasts with conventional smoothing, which recovers the inventory deficit resulting from demand peaks by increasing later orders. Our contribution is threefold. First, we use a novel iterative approach to prove the robust optimality of the Lookahead Peak-Shaving policy. Second, we provide explicit expressions of the period-dependent base-stock levels and analyze the amount of peak shaving. Finally, we demonstrate how our policy outperforms other heuristics in stochastic systems. Most cost savings occur when demand is nonstationary and negatively correlated, and base capacities fluctuate around the mean demand. Our insights apply to several practical settings, including production systems with overtime, sourcing from multiple capacitated suppliers, or transportation planning with a spot market. Applying our model to data from a manufacturer reduces inventory and sourcing costs by 6.7%, compared to the manufacturer's policy without peak shaving.info:eu-repo/semantics/publishedVersio

Forecasting spare part demand with installed base information: A review

The classical spare part demand forecasting literature studies methods for forecasting intermittent demand. However, the majority of these methods do not consider the underlying demand-generating factors. The demand for spare parts originates from the replacement of parts in the installed base of machines, either preventively or upon breakdown of the part. This information from service operations, which we refer to as installed base information, can be used to forecast the future demand for spare parts. This paper reviews the literature on the use of such installed base information for spare part demand forecasting in order to asses (1) what type of installed base information can be useful; (2) how this information can be used to derive forecasts; (3) the value of using installed base information to improve forecasting; and (4) the limits of the existing methods. This serves as motivation for future research

Coalition theories: empirical evidence for dutch municipalities

The paper analyzes coalition formation in Dutch municipalities. After discussing the main features of the institutional setting, several theories are discussed, which are classified as size oriented, policy oriented and actor oriented models. A test statistic is proposed to determine the predictive power of these models. The empirical analysis shows that strategic positions as well as some of the distinguished preferences are important in the setting of Dutch municipalities. Especially, the dominant minimum number principle yields highly significant results for coalition formations in the period 1978–1986

Active-Sterile neutrino oscillations and BBN+CMBR constraints

We show how active-sterile neutrino oscillations in the early Universe can play an interesting role in explaining the current observations of CMBR anisotropies and light element abundances. We describe different possible phenomenological scenarios in the interpretation of present data and how active-sterile neutrino oscillations can provide a viable theoretical framework.Comment: Some changes, to appear in Phys. Rev.

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer

Background: Prone whole breast irradiation (WBI) leads to reduced heart and lung doses in breast cancer patients receiving adjuvant radiotherapy. In this feasibility trial, we investigated the prone position for whole breast + lymph node irradiation (WB + LNI). Methods: A new support device was developed for optimal target coverage, on which patients are positioned in a position resembling a phase from the crawl swimming technique (prone crawl position). Five left sided breast cancer patients were included and simulated in supine and prone position. For each patient, a treatment plan was made in prone and supine position for WB + LNI to the whole axilla and the unoperated part of the axilla. Patients served as their own controls for comparing dosimetry of target volumes and organs at risk (OAR) in prone versus in supine position. Results: Target volume coverage differed only slightly between prone and supine position. Doses were significantly reduced (P < 0.05) in prone position for ipsilateral lung (Dmean, D2, V5, V10, V20, V30), contralateral lung (Dmean, D2), contralateral breast (Dmean, D2 and for total axillary WB + LNI also V5), thyroid (Dmean, D2, V5, V10, V20, V30), oesophagus (Dmean and for partial axillary WB + LNI also D2 and V5), skin (D2 and for partial axillary WB + LNI V105 and V107). There were no significant differences for heart and humeral head doses. Conclusions: Prone crawl position in WB + LNI allows for good breast and nodal target coverage with better sparing of ipsilateral lung, thyroid, contralateral breast, contralateral lung and oesophagus when compared to supine position. There is no difference in heart and humeral head doses

How are podocytes affected in nail–patella syndrome?

Nail–patella syndrome is an autosomal-dominant hereditary disease named for dysplastic fingernails and toenails and hypoplastic or absent kneecaps evident in patients with the syndrome. Prognosis is determined by the nephropathy that develops in many such patients. Besides podocyte foot-process effacement, pathognomonic changes in the kidney comprise electron-lucent areas and fibrillar inclusions in the glomerular basement membrane. These characteristic symptoms are caused by mutations in the gene encoding the transcription factor LMX1B, a member of the LIM-homeodomain gene family. Comparable with the human syndrome, homozygous Lmx1b knockout mice lack patellae and suffer from severe podocyte damage. In contrast, however, podocin and the α3 and α4 chains of collagen IV are absent in the glomeruli of Lmx1b knockout mice. Further studies with podocyte-specific Lmx1b knockout mice have confirmed the importance of LMX1B in podocytes, as these mice apparently develop foot processes initially but lose them later on. We therefore conclude that LMX1B is essential for the development of metanephric precursor cells into podocytes and possibly also for maintaining the differentiation status of podocytes. LMX1B can serve as a model system to elucidate a genetic program in podocytes

Establishment of Protein Delivery Systems Targeting Podocytes

Podocytes are uniquely structured cells that are critical to the kidney filtration barrier. Their anatomic location on the outer side of the glomerular capillaries expose podocytes to large quantities of both plasma and urinary components and thus are reachable for drug delivery. Recent years have made clear that interference with podocyte-specific disease pathways can modulate glomerular function and influence severity and progression of glomerular disease.Here, we describe studies that show efficient transport of proteins into the mammalian cells mouse 3T3 fibroblasts and podocytes, utilizing an approach termed profection. We are using synthetic lipid structures that allow the safe packing of proteins or antibodies resulting in the subsequent delivery of protein into the cell. The uptake of lipid coated protein is facilitated by the intrinsic characteristic of cells such as podocytes to engulf particles that are physiologically retained in the extracellular matrix. Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an increase in DNA degradation. Moreover, purified proteins such as beta-galactosidase and the large GTPase dynamin could be profected into podocytes using two different profection reagents with the success rate of 95-100%. The delivered beta-galactosidase enzyme was properly folded and able to cleave its substrate X-gal in podocytes. Diseased podocytes are also potential recipients of protein cargo as we also delivered fluorophore labeled IgG into puromycin treated podocytes. We are currently optimizing our protocol for in vivo profection.Protein transfer is developing as an exciting tool to study and target highly differentiated cells such as podocytes

Investigation of KIT gene mutations in women with 46,XX spontaneous premature ovarian failure

BACKGROUND: Spontaneous premature ovarian failure presents most commonly with secondary amenorrhea. Young women with the disorder are infertile and experience the symptoms and sequelae of estrogen deficiency. The mechanisms that give rise to spontaneous premature ovarian failure are largely unknown, but many reports suggest a genetic mechanism in some cases. The small family size associated with infertility makes genetic linkage analysis studies extremely difficult. Another approach that has proven successful has been to examine candidate genes based on known genetic phenotypes in other species. Studies in mice have demonstrated that c-kit, a transmembrane tyrosine kinase receptor, plays a critical role in gametogenesis. Here we test the hypothesis that human KIT mutations might be a cause of spontaneous premature ovarian failure. METHODS AND RESULTS: We examined 42 women with spontaneous premature ovarian failure and found partial X monosomy in two of them. In the remaining 40 women with known 46,XX spontaneous premature ovarian failure we evaluated the entire coding region of the KIT gene. We did this using polymerase chain reaction based single-stranded conformational polymorphism analysis and DNA sequencing. We did not identify a single mutation that would alter the amino acid sequence of the c-KIT protein in any of 40 patients (upper 95% confidence limit is 7.2%). We found one silent mutation at codon 798 and two intronic polymorphisms. CONCLUSION: Mutations in the coding regions of the KIT gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women

Genetics of focal segmental glomerulosclerosis

The recent advances in understanding the pathophysiology of focal segmental glomerulosclerosis (FSGS) and molecular function of glomerular filtration barrier come directly from genetic linkage and positional cloning studies. The exact role and function of the newly discovered genes and proteins are being investigated by in vitro and in vivo mechanistic studies. Those genes and proteins interactions seem to change susceptibility to kidney disease progression. Better understanding of their exact role in the development of FSGS may influence future therapies and outcomes in this complex disease