Optimal transshipments and reassignments under periodic orcyclic holding cost accounting

Cataloged from PDF version of article.In a centrally managed system, inventory at a retailer can be transshipped to a stocked-out retailer to meet demand. As the inventory at the former retailer may be demanded by future customers of that retailer and transshipment time/cost is non-negligible, it can be more profitable to not transship in some situations. When unsatisfied demand is backordered, reassignment of inventory to a previously backordered demand can perhaps become profitable as demand uncertainty resolves over time. Despite this intuition, we prove that no reassignments are necessary for cost optimality under periodic holding cost accounting in a two-retailer system. This remains valid for multi-retailer systems according to numerical analyses. When holding costs are accounted for only at the end of each replenishment cycle, reassignments are necessary for optimality but insignificant in reducing the total cost. In most instances tested, the decrease in total cost from reassignments is below 2% for end of cycle holding cost accounting. These results simplify transshipment policies and facilitate finding good policies in both implementation and future studies, as reassignments can be omitted from consideration in optimization models under periodic holding cost accounting and in approximation models under cyclical cost accounting

In-Season Transshipments Among Competitive Retailers

Cataloged from PDF version of article.A decentralized system of competing retailers that order and sell the same product in a sales season is studied. When a customer demand occurs at a stocked-out retailer, that retailer requests a unit to be transshipped from another retailer who charges a transshipment price. If this request is rejected, the unsatisfied customer may go to another retailer with a customer overflow probability. Each retailer decides on the initial order quantity from a manufacturer and on the acceptance/rejection of each transshipment request. For two retailers, we show that retailers' optimal transshipment policies are dynamic and characterized by chronologically nonincreasing inventory holdback levels. We analytically study the sensitivity of holdback levels to explain interesting findings, such as smaller retailers and geographically distant retailers benefit more from transshipments. Numerical experiments show that retailers substantially benefit from using optimal transshipment policies compared to no sharing. The expected sales increase in all but a handful of over 3,000 problem instances. Building on the two-retailer optimal policies, we suggest an effective heuristic transshipment policy for a multiretailer system

Susceptibility functions for slow relaxation processes in supercooled liquids and the search for universal relaxation patterns

In order to describe the slow response of a glass former we discuss some distribution of correlation times, e.g., the generalized gamma distribution (GG) and an extension thereof (GGE), the latter allowing to reproduce a simple peak susceptibility such as of Cole-Davidson type as well as a susceptibility exhibiting an additional high frequency power law contribution (excess wing). Applying the GGE distribution to the dielectric spectra of glass formers exhibiting no beta-process peak (glycerol, propylene carbonate and picoline) we are able to reproduce the salient features of the slow response (1e-6 Hz - 1e9 Hz). A line shape analysis is carried out either in the time or frequency domain and in both cases an excess wing can be identified. The latter evolves in a universal way while cooling and shows up for correlation times tau_alpha > 1e-8 s. It appears that its first emergence marks the break down of the high temperature scenario of mode coupling theory. - In order to describe a glass former exhibiting a beta-process peak we have introduced a distribution function which is compatible with assuming a thermally activated process in contrast to some commonly used fit functions. Together with the GGE distribution this function allows in the frame of the Williams-Watts approach to completely interpolate the spectra, e.g. of fluoro aniline (1e-6 Hz - 1e9 Hz). The parameters obtained indicate an emergence of both the excess wing and the beta-process again at tau_alpha > 1e-8s.Comment: 22 pages, 12 figure

Fluorescently tagged nanobodies and NanoBRET to study ligand-binding and agonist-induced conformational changes of full-length EGFR expressed in living cells

Introduction: The Epidermal Growth Factor Receptor is a member of the Erb receptor tyrosine kinase family. It binds several ligands including EGF, betacellulin (BTC) and TGF-α, controls cellular proliferation and invasion and is overexpressed in various cancer types. Nanobodies (VHHs) are the antigen binding fragments of heavy chain only camelid antibodies. In this paper we used NanoBRET to compare the binding characteristics of fluorescent EGF or two distinct fluorescently labelled EGFR directed nanobodies (Q44c and Q86c) to full length EGFR. Methods: Living HEK293T cells were stably transfected with N terminal NLuc tagged EGFR. NanoBRET saturation, displacement or kinetics experiments were then performed using fluorescently labelled EGF ligands (EGF-AF488 or EGF-AF647) or fluorescently labelled EGFR targeting nanobodies (Q44c-HL488 and Q86c-HL488). Results: These data revealed that the EGFR nanobody Q44c was able to inhibit EGF binding to full length EGFR, while Q86c was able to recognise agonist bound EGFR and act as a conformational sensor. The specific binding of fluorescent Q44c-HL488 and EGF-AF488 was inhibited by a range of EGFR ligands (EGF> BTC>TGF-α). Discussion: EGFR targeting nanobodies are powerful tools for studying the role of the EGFR in health and disease and allow real time quantification of ligand binding and distinct ligand induced conformational changes

Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3)

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluorescent probes, based on a series of small molecule ACKR3 agonists, were synthesized. Three fluorescent probes, which showed specific binding to ACKR3 through a luminescence-based NanoBRET binding assay (pKd ranging from 6.8 to 7.8) are disclosed. Due to their high affinity at the ACKR3, we have shown their application in both competition binding experiments and confocal microscopy studies showing the cellular distribution of this receptor

Botulinum toxin injections for blepharospasm prior to ocular surgeries

Seydi Okumus1, Erol Coskun1, İbrahim Erbagci1, M Gürkan Tatar2, Aysegul Comez1, Erdal Kaydu1, Ramazan Yayuspayi1, Bulent Gurler11Department of Ophthalmology, University of Gaziantep, 2Ophthalmology Clinic, Nizip State Hospital, Nizip, Gaziantep, TurkeyPurpose: The aim of this study was to show the efficiency of preoperative botulinum toxin A (Botox A) in patients with benign essential blepharospasm who were to undergo ocular surgery with local anesthesia.Materials and methods: Twenty-eight benign essential blepharospasm patients who were administered unilateral Botox A prior to ocular surgery between January 2004 and May 2011 were included in this study. Eleven cases had pterygiums, ten had cataracts, and four had glaucomas, while the remaining three had aphakia. All cases’ severity of spasm (stage 0–4) and eyelid closing forces (stage 1–4) were evaluated according to the Jankovic scale prior to the injection, at 3 days, 14 days, 1 month, and 3 months after Botox A injection.Results: Of the patients enrolled in the study, 16 were female and 12 were male, with an average age of 55.52 ± 1.53 years (52–65). Average onset of the Botox injection's effect was 2.8 ± 0.9 (2–5) days. Its effect lingered for about 11.5 ± 3.6 (8–22) weeks. The severity of spasm and eyelid closing forces of all the patients enrolled were compared prior to the injection at 3 and 14 days and the first and third months after the injection. There were statistically significant differences between prior to the injection and 3 days (P = 0.001), 14 days (P < 0.001) and 1 month after the injection (P <0.001). There was no statistically significant difference between prior to the injection and 3 months after the injection (P = 0.513). Fourteen days following the injection, the surgeries were successfully performed.Conclusion: Botox A administered prior to ocular surgery will control both blepharospasm and lower the risks that can be encountered before and during surgery, thus increasing the comfort of the patient and the surgeon.Keywords: botulinum toxin A, blepharospasm, ocular surger