Evaluation of Lead Time in Production/Inventory Systems with Non-stationary Stochastic Demand

For the past decade, new techniques for production management–such as kanban (pull-through) systems, internal set-ups, zero inventory, etc–have gained tremendous interest. However, research indicates that the production environment is more important than specific techniques. One aspect of this environment is the production lead time. This paper examines the impact of lead time, in conjunction with the characteristics of the demand process, on costs through the use of a periodic-review production/inventory model with a non-stationary stochastic demand process. Our results indicate that costs are affected by a combination of production lead time and demand variances. While the demand means have no effect on costs, both the shapes of the demand distributions and the relative magnitude of the penalty costs do have an effect.     

Characterisation of estrone-nucleic acid adducts formed by reaction of 3,4-estrone-o-quinone with 2'-deoxynucleosides/deoxynucleotides using capillary liquid chromatography/electrospray ionization mass spectrometry

Xenobiotic and endobiotic molecules can react with DNA leading to formation of so-called DNA adducts. This modified DNA can be repaired enzymatically, but, if not, these modifications are believed to be responsible for the initiation of carcinogenic processes. Hence, we studied the interaction of 2'-deoxynucleosides and 2'-deoxynucleotides with 3,4-estronequinone (3,4-E(1)Q), a metabolite of estrone (E(1)) and a supposed carcinogen. These estrone-nucleic acid adducts were analysed by capillary liquid chromatography (CapLC) coupled to electrospray ionization mass spectrometry (ESI-MS). Knowledge of their behaviour from in vitro studies is a prerequisite for detecting adducts in in vivo studies. Our initial attempts to synthesise nucleos(t)ide adducts of 3,4-E(1)Q in an aprotic solvent (dimethylformamide) yielded no adducts. However, under acidic aqueous conditions, adducts were obtained. With dGuo, a dGuo adduct was found in addition to a Gua adduct. Earlier publications on adduct formation in protic solvents failed to report formation of any adduct with dAdo. A N(3)-Ade adduct was reported upon reaction of 3,4-E(1)Q with Ade base and with DNA. With dAdo, we obtained two nucleoside adducts and six Ade adducts due to loss of 2'-deoxyribose. Thus, contrary to general belief that only 2,3-E(1)Q can form stable adducts, we showed formation of substantial amounts of intact DNA adducts with 3,4-E(1)Q in addition to deglycosylated adducts. Adducts were also obtained with dGMP and dAMP, but no phosphate alkylation was found. Adducts of dCyd, dCMP, dThd, and dTMP were not detected. Using chromatographic-MS data a structural relationship between the 2'-deoxynucleoside, 2'-deoxynucleotide and base adducts was found in the various reaction mixtures. The adducts of dGuo and dGMP reaction mixtures were alkylated at the same N(7)-position of the nucleobase, as indicated by the occurrence of a rapid deglycosylation reaction. In dAdo and dAMP reaction mixtures, 14 adducts were detected; their relationships from the LC and MS data reduced the number of structures to six adenine base alkylated adducts with respect to alkylation between N(1), N(3), N(7) and/or N(6) in the adenine and C(1), C(2) and/or C(6) in 3,4-E(1)Q. We could infer, in addition, whether they had an A ring attachment or a C(6) attachment on the estrone moiety.     

Pyridazine derivatives 32: Stille-based approaches in the synthesis of 5-substituted-6-phenyl-3(2H)-pyridazinones

A series of 6-phenyl-3(2H)-pyridazinones bearing different substituents in the 5-position of the pyridazinone ring were prepared using Stille-based approaches in the search for new platelet-aggregation inhibitors.     

New chelating agents for colorimetric determination of calcium

Two new calcium chromoionophores2 and3 are described and their potential application to colorimetric determination of calcium is assessed. Chromogenic compound2 bears two acetic acid chelating groups and a 4-(4-nitrophenyl)azophenol chromophore. Its complexation of Ca²⁺ at pH 9.0 is accompanied by a 109-nm bathochromic shift and increase in the absorptivity. Triaryl chromoionophore3 bears two phosphonic acid chelating groups and the same azophenol chromophore. Compound3 exhibits a 107-nm bathochromic shift of the absorption maximum, an increase in the absorptivity upon complexation with Ca²⁺, and good selectivity for Ca²⁺ over Mg²⁺ at pH 7.0. Both chromoionophores exhibit linear responses from 0 to 4×10^–3 M Ca²⁺.     

First results of a quantitative study of DNA adducts of melphalan in the rat by isotope dilution mass spectrometry using capillary liquid chromatography coupled to electrospray tandem mass spectrometry

Rats were intravenously injected with a single high dose (10 mg/kg) of the alkylating agent melphalan in order to study DNA-adduct formation. Quantitation of a dGuo-melphalan adduct was done by isotope dilution mass spectrometry using capillary liquid chromatography/mass spectrometry (LC/MS) and [15N5]-labeled dGuo-melphalan as internal standard. DNA-adduct levels were studied in bone marrow, liver and kidney. The instrumental detection limit of the method was determined to be 900 fg (S/N 3, pure standard). These first results clearly show a 10 times higher adduct level in bone marrow compared to kidney and a 6 times higher level compared to liver. More experiments will be necessary to gather more information on the pharmacokinetics of melphalan-DNA adducts under in vivo conditions.     

Intriguing Mass Spectrometric Behavior of Guanosine Under Low Energy Collision-Induced Dissociation: H<Subscript>2</Subscript>O Adduct Formation and Gas-Phase Reactions in the Collision Cell

An in-depth study of the fragmentation pathway of guanosine was conducted by using an in-source collision-induced dissociation high-mass accuracy tandem mass spectrometry experiment. The equivalent of MS4 data, a level of information normally achieved on ion trap instruments, was obtained on a Q-TOF mass spectrometer. The combination of the features of high-resolution, accuracy, and in-source CID permitted the unambiguous elucidation of the different fragmentation pathways. Furthermore the elemental compositions of the product ions generated were assigned and their mutual genealogical relationships established. Formerly proposed dissociation pathways of guanosine were revisited and elaborated on more deeply. Furthermore, the presence of H2O in the collision cell of several tandem MS instruments was demonstrated and its effect on the product ion spectra investigated. The neutral gain of H2O by particular fragments of guanosine was experimentally proven by using argon, saturated with H2(18)O, as the collision gas. Data indicating the occurrence of more complex reactions in the collision cell as a result of the presence of H2O were produced, specifically relating to neutral gain/neutral loss sequences. In silico calculations supported the experimental observation of neutral gain by guanosine fragments and predicted a similar behavior for adenosine. The latter was subsequently experimentally confirmed.     

A Thermodynamic Analysis of Nonequilibrium Argon Plasma Torches

The nonequilibrium process of argon plasma torches is analyzed theoretically. Thermodynamic diagrams of different degrees of ionization are developed to aid in understanding and analyzing the transition from chemical equilibrium to frozen flow in dc plasma torch operations. A thermodynamic model is developed to describe the nonequilibrium processes in a dc argon plasma torch. In the model the ionization process is approximated as a constant-pressure heating process, with little deviation from the equilibrium state upon completion of heating. If the plasma flow is frozen shortly after heating, the entropy increase is small during the transition from equilibrium to frozen flow. In this case the frozen flow will have nearly the same composition and entropy as the flow at the heating section exit. For singly ionized argon plasmas in the entropy range relevant to dc torch operation, the frozen flow solutions on the affinity–pressure diagram are found to be insensitive to entropy change. Therefore the present model predicts that argon plasmas generated at different power levels will have almost identical affinity at the torch exit for the same operating pressure. This prediction agrees with experimental observations except for very low torch power levels.     

The determination of zirconium and aluminium in alloys slags and fumes by 14-mev neutron activation analysis

Aluminium and zirconium have beendetermined in alloys, slags and fumes by 14-MeV neutron activation analysis. Nuclear reactions with zirconium have been investigated, and the radioisotopes produced by 14-MeV neutron activation have been determined. The results for alloys and slags agree well with those obtained by chemical methods; precisions of 1.8% were obtained in ideal cases. The neutron activation method is capable of analysing 10–12 samples, in duplicate, per man-day.     

The use of split-sample design for performance evaluation of screening kits

Laboratory medicine is an important discipline in health care with its remarkable effect on risk assessment, diagnosis of health, and disease state. This accounts describes a newborn screening approach involving retest, recall, and follow-up procedures. This real life trial emphasizes the need for split-sample design evaluation of newly opened test kits. Quantitative measurements of phenylalanine and neonatal thyroid stimulating hormone (nTSH) were performed in two laboratories. After validation of the calibration in the laboratory that was using the industrially prepared screening kits for the first time, the same real newborn blood spot samples were analyzed for phenylalanine and nTSH measurements in both laboratories and the results obtained were compared non-parametrically, and examined by Deming regression and difference plots. There was no problem with the phenylalanine results: similar results were obtained for the same blood spot cards in both laboratories (P=0.496; bias estimation 0.13). However, the nTSH values were found to be significantly higher in the laboratory that used the nTSH kit for the first time. Although the validation of the calibration of the nTSH kit was valid with the manufactures control materials, spilt-sample results showed that there was a significant difference between the two laboratories (P=0.005; bias estimation 28.6). This study implies that acceptable comparability of split-sample design analysis is needed for testing the analytical performance of industrially prepared tests kits, and this can only be achieved with certified reference materials.Presented at the 8th Conference on Quality in the Spotlight, 17–18 March 2003, Antwerp, Belgium