bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics and neuromuscular diseases: theoretical concept and first results
Authors: van den Heuvel L.P. , Farhoud M.H. , Wevers R.A. , van Engelen B.G.M. , Smeitink J.A.M.
Published: January 2003

Although many patients suspected of suffering disturbances of the mitochondrial energy metabolism have been investigated, only a fraction of these patients have been diagnosed at the molecular level. Introduction of new techniques like proteomics will be necessary to understand the various clinical and biochemical aberrations in the field of mitochondrial disorders. Two-dimensional electrophoresis is the first, important step in the proteomics strategy. Separation of soluble proteins is performed on the basis of isoelectric point (net charge) in one direction and on molecular mass in the other. The technique provides an overview of the majority of proteins expressed in a sample (e.g. muscle biopsy, muscle cell or mitochondrial fraction). Once an abnormal spot is observed in the gel the responsible protein can be identified by analysing a limited part of its amino acid sequence by mass spectrometry. We optimized two-dimensional (2D) gel electrophoresis to obtain high resolution 2D-maps and tested the reproducibility of the technique. Potentially, this new technique is capable of identifying novel mitochondrial diseases and defining their molecular basis.
Proton nuclear magnetic resonance spectroscopy of body fluids in the field of inborn errors of metabolism
Authors: Moolenaar S.H. , Engelke U.F.H. , Wevers R.A.
Published: January 2003

Proton nuclear magnetic resonance (NMR) spectroscopy of body fluids has been successfully applied to the field of inborn errors of metabolism. This technique has the advantage of minimal sample pretreatment not requiring extraction or derivatization steps. Moreover, the spectrum provides a comprehensive metabolic profile of proton-containing, low-molecular-weight metabolites. The sensitivity limit is in the low micromolar range. This allows diagnosis of many inborn errors of metabolism. This review explains the key features of the NMR spectrum and reviews the available literature on metabolic diseases. Three novel diseases have been delineated with the technique. Relevant parts of the spectra from the urine samples of patients with these diseases are shown. NMR spectroscopy may develop to become a key tool in a metabonomics approach in clinical biochemistry.
Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases
Authors: Verbeek M.M. , de Jong D. , Kremer H.P.H.
Published: January 2003

Neurodegenerative disorders have traditionally been classified according to clinical criteria, e.g. as dementia syndromes (the best known is Alzheimer's disease) or as movement disorders (e.g. Parkinson's disease). Another subdivision is based on recent insights into the respective pathogenetic mechanisms, leading to the recognition of so-called tauopathies and α-synucleinopathies. It is this increased knowledge of the underlying (neuro)pathological mechanisms that has sparked interest in studies aimed at the identification of disease-specific biomarkers in cerebrospinal fluid (CSF) for this field of neurological disorders. This review deals with the recent progress that has been made in identification, quantification and subsequent validation of brain-specific proteins in CSF for the diagnosis of various neurodegenerative disorders. Development of disease-specific CSF biomarkers will undoubtedly add to the process of differential diagnosis early in the course of the disease.
Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency
Authors: van Kuilenburg André B.P. , De Abreu Ronney A. , van Gennip Albert H.
Published: January 2003

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). A deficiency of DPD is increasingly being recognized as the cause of an important pharmacogenetic syndrome. The importance of DPD deficiency in the aetiology of unexpected severe 5FU toxicity has been demonstrated by the fact that, in 39-;59% of cases, decreased DPD activity could be detected in peripheral blood mononuclear (PBM) cells. It was observed that 55% of the patients with a decreased DPD activity suffered from grade IV neutropenia compared with 13% of the patients with a normal DPD activity ( P = 0·01). Furthermore, toxicity developed significantly earlier in patients with low DPD activity than in patients with normal DPD activity (10·0 ± 7·6 versus 19·1 ± 15·3 days, P < 0·05). In patients suffering from severe 5FU-associated toxicity, 11 mutations have been identified in DPYD, including one splice-site mutation (IVS14 + 1G→A), one nonsense mutation (E386X), four missense mutations (M166V, V335L, I560S, D949V) and five polymorphisms (C29R, R21Q, S534N, I543V, V732I). Considering the common use of 5FU in the treatment of cancer patients, the severe 5FU-related toxicities in patients with a low DPD activity and the high prevalence of the IVS14 + 1G→A mutation, analysis of the DPD activity in PBM cells or screening for the IVS14 + 1G→A mutation should be routinely carried out prior to the start of treatment with 5FU.
Genetics of hyperhomocysteinaemia in cardiovascular disease
Authors: Lievers Karin J.A. , Kluijtmans Leo A.J. , Blom Henk J.
Published: January 2003

Homocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme deficiencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B12 and vitamin B6, may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also influenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date.
Is serum cystatin C the marker of choice to predict glomerular filtration rate in paediatric patients?
Authors: Willems Hans L. , Hilbrands Luuk B. , van de Calseyde John F. , Monnens Leo A.H. , Swinkels Dorine W.
Published: January 2003

Background: It has been suggested that serum cystatin C (cyst-C) concentration provides a better indication of changes in glomerular filtration rate (GFR) than does serum creatinine concentration.

Methods: Because of conflicting results as to the usefulness of cyst-C, we compared the GFRs calculated from serum cyst-C, inulin clearance and endogenous creatinine clearance in children. GFRs calculated from cystatin concentration, inulin clearance following a single injection and endogenous creatinine clearance using Jaffé and enzymic methods were compared in 66 children (1·3-21·9 years) with a variety of renal disorders. Receiver operating curve analysis was used to determine the cut-off value that would give the best discrimination between normal and decreased GFR.

Results: The serum cyst-C concentration ranged from 0·66 to 7·61 mg/L (median 1·94). Serum creatinine Jaffé concentration (creat-J) ranged from 38 to 871 µmol/L (median 105) and creatinine enzymatic concentration (creat-E) ranged from 28 to 862 µmol/L (median 126). The linear correlation coefficient ( R) of 1/cyst-C versus GFR ( R = 0·937) did not differ from either that of 1/creat-J versus GFR ( R = 0·918) or that of 1/creat-E versus GFR ( R = 0·901). These coefficients had overlapping confidence intervals. The areas under the curve for cyst-C, creat-J and creat-E were 0·967, 0·977 and 0·924, respectively, and were not significantly different from each other. For cyst-C, the optimal cut-off was 1·1 mg/L.

Conclusions: Serum cyst-C is equivalent to creat-J and creat-E as a marker for estimating the GFR in the paediatric population studied.
Cobalamin-binding proteins in normal and cobalamin-deficient older subjects
Authors: van Asselt Dieneke Z.B. , Thomas Chris M.G. , Segers Martin F.G. , Blom Henk J. , Wevers Ron A. , Hoefnagels Willibrord H.L.
Published: January 2003

Background: The causes of cobalamin (vitamin B12) deficiency in older people are only partly understood. We investigated the role of the cobalamin-binding proteins and tested the hypothesis that low saturated transcobalamin concentration is an early marker of cobalamin deficiency.

Methods: We measured saturated (holo) and unsaturated (apo) transcobalamin and haptocorrin concentrations in healthy middle-aged volunteers, healthy older volunteers, cobalamin-deficient older volunteers and cobalamin-deficient older patients.

Results: Holo and apo concentrations of transcobalamin and haptocorrin were similar in healthy middle-aged and older subjects. Holotranscobalamin concentrations were significantly decreased in cobalamin-deficient subjects but did not differ between healthy volunteers and patients. Furthermore, the relative amount of cobalamin on transcobalamin (i.e. holotranscobalamin/holotranscobalamin + holohaptocorrin) was similar in all four groups.

Conclusions: Abnormalities of the cobalamin-binding proteins are not a cause of cobalamin deficiency in the aged. Plasma holotranscobalamin concentration did not differ between stages of cobalamin deficiency in older persons. Therefore, plasma holotranscobalamin is not an early marker of cobalamin deficiency in older people and has no additional value in the diagnostic work-up of reduced plasma cobalamin concentrations in older people.
Combination therapy in childhood leukaemia: in vitro studies of thiopurines and inhibitors of purine metabolism on apoptosis
Authors: De Abreu Ronney A. , Trueworthy Robert C. , van Kuilenburg André B.P. , Vogels-Mentink Trude M. , Lambooy Lambert H.J. , van Gennip Albert H.
Published: January 2003

Background: Methotrexate (MTX) followed by 6-mercaptopurine (6MP) is one of the best known combinations for the treatment of childhood acute lymphoblastic leukaemia. Tiazofurin (TF) and 6-thioguanine (TG) are also used as chemotherapy agents in the treatment of malignancies. We have examined the induction of apoptosis by combinations of these drugs to gain more insights into their efficacy in the treatment of malignancies.

Methods: The induction of apoptosis was examined in Molt-4, a human malignant acute lymphoblastic T-cell line. The cells were exposed to increasing drug concentrations at various exposure times. Annexin V/FITC and propidium iodide (PI) were used as markers for apoptosis and cell death. Annexin V/FITC positive and PI positive cells were detected by flow-cytometric analysis.

Results: Sequential 24-h exposure with MTX (0·005-0·02 µmol) followed by 6MP (1-10 µmol) and 24-h exposure with TF (5·20 µmol) followed by TG (0·5-2 µmol) showed a more than additive induction of apoptosis compared with single-drug exposure. Simultaneous administration of the drugs does not show an additive effect on apoptosis.

Conclusions: The results of this study indicate that sequential administration of MTX before 6MP and of TF before TG may be essential for therapeutic success in the treatment of leukaemia.
An improved procedure for testing for assay linearity
Authors: Ross H.A. , Sweep C.G.J.
Published: January 2003

Background: Statistical testing of assay linearity using replicate measurements made on binary mixtures of samples provides no information about the significance of any detected deviations from linearity, which may often be desirable.

Method: Performance of additional statistical analysis of the assay data.

Result: Objective measures for non-linearity and the minimum detectable deviation from linearity of the assay are obtained.

Conclusion: A few additional calculations from the available data make it possible to assess whether or not an assay method needs improvement to achieve adequate performance within its intended application.
Kinetics of myo-inositol loading in women of reproductive age
Authors: Groenen Pascal M.W. , Merkus Hans M.W.M. , Sweep Fred C.G.J. , Wevers Ron A. , Janssen Fokje S.M. , Steegers-Theunissen Régine P.M.
Published: January 2003

Background: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age.

Methods: Five healthy non-obese females {mean age (standard deviation: SD) 22·8 (2·2) years} were recruited at the University Medical Center Nijmegen. Blood samples were drawn fasting and at 20, 40, 60, 90, 180 and 270 min after ingestion of 100 mg/kg body weight of myo-inositol. Urine samples were collected before myo-inositol loading and at 180 and 270 min post-loading. Samples were analysed for serum myo-, epi- and scyllo-inositol and glucose concentrations by gas chromatography. Plasma insulin concentrations were determined by radio-immunoassay. Random intercept models were fitted to evaluate the data.

Results: The estimated myo-inositol and scyllo-inositol concentrations both reached maximum values at 180 min post-loading, respectively: mean (SD) 101·5 (9·2) µmol/L and 1·09 (0·11) µmol/L. The estimated plasma insulin and serum glucose concentrations decreased slightly but significantly during the experiment: P < 0·0001 and P < 0·05, respectively. At 180 and 270 min post-loading, urinary myo-inositol concentrations were increased and urinary glucose concentrations were unchanged.

Conclusions: Myo-inositol enters the bloodstream quickly after oral ingestion and a small amount of myo-inositol is converted to scyllo-inositol. The synthesis of glucose from myo-inositol could not be detected by serum measurements. These data can be used in further research into the association between myo-inositol and neural tube defects.
Measurement of thiopurine S-methyltransferase activity in human blood samples based on high-performance liquid chromatography: reference values in erythrocytes from children
Authors: Keizer-Garritsen Jenneke J. , Brouwer Connie , Lambooy Lambert H.J. , Ter Riet Patricia , Bökkerink Jos P.M. , Trijbels Frans J.M. , De Abreu Ronney A.
Published: January 2003

Background: Monitoring 6-thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) activity is especially important when patients are treated with 6-thiopurine drugs, since severe bone marrow toxicity may be induced if patients have deficient TPMT activity.

Methods: We have developed a method based on high-performance liquid chromatography (HPLC) for the measurement of TPMT activity in various cell types: erythrocytes (RBC), human peripheral blood mononuclear cells (pMNC) and human malignant lymphoblasts (Molt-F4). The enzymatic activity is measured by the amount of 6-methylmercaptopurine formed, using 6-mercaptopurine (6MP) as substrate and S-adenosylmethionine as co-substrate.

Results: The Km values calculated for 6MP were 0·54 (RBC), 0·85 (pMNC) and 0·65 (Molt-F4 cells) mmol/L. The Km values for S-adenosylmethionine were 11·9 (RBC), 16·4 (pMNC) and 6·65 (Molt-F4 cells) µmol/L. The assay variation was 8·2-17%. TPMT activity was determined in a control group of 103 children and young adults (44 female, 59 male). The values observed were (mean ± standard deviation): female children and young adults, 15·1 ± 4·8 pmol/107 cells per h ( n = 44); male children and young adults, 15·8 ± 6·4 pmol/107 cells per h ( n = 59). No gender or age differences were found.

Conclusion: The HPLC-based method enables the rapid screening of TPMT activities in large groups of patients treated with 6-thiopurines.
Quantitative detection of peripheral thyroglobulin mRNA has limited clinical value in the follow-up of thyroid cancer patients
Authors: Span P.N. , Sleegers M.J.M. , van den Broek W.J. , Ross H.A. , Nieuwlaat W-A. , Hermus A.R.M.M. , Sweep C.G.J.
Published: January 2003

Background: As recurrences after treatment for differentiated thyroid cancer can occur many years after thyroidectomy, periodic monitoring of serum thyroglobulin (Tg) levels is performed in these patients. However, autoantibodies that can interfere with Tg immunoassays occur in the blood of approximately 25% of these patients. Several earlier reports suggest that measuring Tg mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR) could be of value, especially in patients with Tg autoantibodies.

Methods: Using an earlier described, real-time quantitative Taqman RT-PCR assay, Tg mRNA concentrations were assessed in peripheral blood taken from 58 patients treated for thyroid cancer and from two healthy controls.

Results: In all tested samples Tg mRNA could be found. No correlation between serum Tg protein and Tg mRNA could be found. Tg mRNA concentrations did not differ between serum Tg-negative and Tg-positive patients. No differences in the number of patients with high or low Tg/ β-actin ratios were found between the groups of patients without, 131I uptake on whole-body scan, or patients with thyroid bed uptake, uptake elsewhere in the neck, or distant metastases with or without regional uptake ( P = 0·871).

Conclusions: We were not able to confirm earlier positive reports on the clinical value of Tg mRNA measurement for the monitoring of patients treated for thyroid cancer.
Stability studies of ubiquinol in plasma
Authors: Hectors M.P.C. , van Tits L.J.H. , de Rijke Y.B. , Demacker P.N.M.
Published: January 2003

Background: Ubiquinol is a sensitive redox marker in the first line of the antioxidative defence mechanism and is increasingly being measured in oxidation studies. Because of its apparent instability during storage and processing, we compared various storage conditions.

Method: Blood was collected from three volunteers into tubes containing EDTA; it was then separated at 4°C and cryopreserved with saccharose (final concentration 6 g/L). Aliquots were stored with or without glutathione or butylated hydroxytoluene at -20°C and -80°C.

Results and conclusion: Ubiquinol in samples stored at -20°C was not stable; however, it was stable when stored at -80°C, even without addition of antioxidant. By contrast, α-tocopherol was stable under all conditions studied.
Moderate citrullinaemia without hyperammonaemia in a child with mutated and deficient argininosuccinate synthetase
Authors: Ruitenbeek Wim , Kobayashi Keiko , Iijima Mikio , Smeitink Jan A.M. , Engelke Udo F.H. , De Abreu Ronney A. , Kwast Hanneke T. , Saheki Takeyori , Boelen Carolien A. , De Jong Jan G.N. , Wevers Ron A.
Published: January 2003

In a patient with microcephaly, feeding problems and restlessness, moderately increased serum and urine citrulline concentrations were observed. Protein and allopurinol loading did not result in additional indications for a urea cycle defect. The diagnosis of citrullinaemia was made at both the enzyme and DNA level, resulting from a novel mutation in the argininosuccinate synthetase gene. The fact that the patient has not suffered from severe deterioration, and that there were only minor abnormalities in metabolite concentrations, suggests that the argininosuccinate synthetase capacity was less affected in vivo than in vitro. In vitro nuclear magnetic resonance investigation suggested an active acetylation mechanism for citrulline. This case illustrates the importance of performing extensive biochemical and molecular investigations in order to reach a definitive diagnosis, particularly in instances of moderate citrullinaemia.
Reversal of clinical symptoms and radiographic abnormalities with protein restriction and ascorbic acid in alkaptonuria
Authors: Morava Eva , Kosztolányi György , Engelke Udo F.H. , Wevers Ron A.
Published: January 2003

There is no definitive treatment protocol for alkaptonuria. A patient with alkaptonuria was treated with ascorbic acid (0·5 g/day) from the age of 4 years. He developed episodes of severe recurrent joint pain at 9·5 years of age after which a protein-restricted diet (1·3 g/kg/day) was started. Protein restriction in combination with ascorbic acid therapy (1 g/day in two divided doses) resulted in a significant decrease but not a normalization of the urinary homogentisic acid excretion. Joint pain resolved and the radiological evidence of 'moth-eaten' irregularities on the articular surface in both knees disappeared. He is currently well, growing normally and in nitrogen balance. Our findings document a reversal of bone abnormalities and clinical symptoms in a case of alkaptonuria. The results should be confirmed in a larger study. We suggest that protein restriction should be applied in combination with ascorbic acid in affected patients as soon as joint pain occurs.
Influence of Thermal Treatment on the Adsorption Ability of Amorphous Alloys
Authors: Hertsyk O.M. , Kovbuz M.O. , Bednars'ka L.M. , Kotur B.Ya.
Published: January 2003

The change in the adsorption abilities of surfaces of amorphous metallic alloys (AMA) after thermal treatment (at 77–773 K) was estimated by various physicochemical methods. It was shown that the extent of piperidine adsorption on an AMA surface subjected to thermal treatment correlated with the results of X-ray structural analysis.
Surface Properties of Manganese(II) Carbonate
Authors: Nikolenko Nikolai V. , Shapovalova Irina M.
Published: January 2003

The energies of unoccupied and occupied orbitals have been used as correlation parameters between the electronic and adsorptive properties of organic molecules. A model describing the chemisorption of organic compounds on MnCO3 was proposed. This involves three types of interaction: 1-, 2- and 3-electron donor–acceptor interaction between adsorbent and adsorbate frontier orbitals.
Influence of Added Molybdenum on the Activity of DESONOX Catalysts
Authors: Marcewicz-Kuba Agnieszka , Nazimek Dobiesław
Published: January 2003

The catalytic removal of SO2 from combustion gases has been studied on the grain plane of a hard coal, being competitive with classical desulphurization processes. The method proposed for the removal of SO2 from combustion gases described in this paper is quite different from wet classical desulphurization methods. Studies of the influence of molybdenum concentration on the catalytic activity of a number of DESONOX catalysts are reported. The influence of the total surface area and other physicochemical properties of the catalyst on its behaviour have been studied.
Adsorption of Oleate Anions on to Cationized Lignocelluloses
Authors: Zghida H. , Baouab M.H.V. , Gauthier R.
Published: January 2003

Oleic acid and its salts are present among the toxic pollutants in olive oil mill wastewaters. Four lignocellulosic materials modified by grafting quaternary ammonium groups have been tested for the adsorption of the oleate anion from aqueous solutions, viz. cotton fibres, viscose fabric, wood sawdust and maize cob powder. As a result of their strong ionic interactions, the carboxylate moities were entrapped at a rate equivalent to the ammonium content of the support. Furthermore, when this charged support was left in contact with the polluted solution without agitation, an additional quantity of pollutant was adsorbed due to associations by the hydrophobic tails of the oleate moities. Partial desorption was achieved in 1 M HCl solution.
The Use of Extraction Methods for Recovering Metals and Carriers from Spent Carbon Sorbents and Catalysts
Authors: Bezak-Mazur E. , Dąbek L. , Repelewicz M. , Świątkowski A.
Published: January 2003

The usefulness of extraction methods such as leaching, extraction with complex-forming organic solvents and supercritical extraction in recovering metals and carbon carriers from dangerous wastes such as carbon impregnates and catalysts is discussed.
The Influence of Surfactant (SDS) on the Adsorption Properties of Polyvinyl Alcohol and Polyethylene Glycol in an Alumina/Solution System
Authors: Chibowski S. , Paszkiewicz M. , Wiśniewska M.
Published: January 2003

The influence of sodium dodecyl sulphate (SDS) on the adsorption properties of non-ionic polymers, i.e. polyethylene glycol (PEG) and polyvinyl alcohol (PVA), at the Al2O3/solution interface was studied. Measurements for various molecular weights and for various amounts of functional groups on the polymer macromolecules were undertaken and the results obtained discussed in the light of these variations. Studies of the mutual interactions of the polymer–surfactant system in aqueous solution were helpful in explaining the equilibria involved in the Al2O3/polymer solution system in the presence of SDS. The thickness of the adsorption layer was determined by viscometric methods and the influence of the degree of hydrolysis of PVA on the structure of the adsorption layer demonstrated.
Changes in the Surface Chemistry and Adsorptive Properties of Active Carbon Previously Oxidised and Heat-Treated at Various Temperatures. II. Electrochemical Investigations of Surface Chemistry
Authors: Pakuła M. , Biniak S. , Świątkowski A.
Published: January 2003

Thermal treatment of oxidised active carbon under vacuum conditions led to changes in the chemical nature of its surface, e.g. a stepwise decrease in the total oxygen content and an increase in the pH of the carbon slurry. Annealing reduced the number of surface oxygen-containing groups and increased the overall number of basic groups. The results of the cyclic voltammetric studies analysed in this paper clearly indicate only a weak relationship between the presence and number of cathodic/anodic peaks, i.e. reduction/oxidation of electroactive surface groups, forming during cyclisation and the degree of surface oxidation (regulated by heat treatment) of the carbon samples tested. The electrochemical behaviour of powdered carbon suggested electro-oxidation of the surface of the electrode material with participation of adsorbed hydroxy ions and water molecules. The possible electrochemical reactions and mechanisms of the surface processes were discussed in order to explain the observed phenomena.
Adsorptive Properties of Template-Containing Silica-Based MCM-41 and MCM-50 Materials
Authors: Bobonich F.M. , Kovalenko A.S. , Voloshina Yu.G. , Korchev A.S. , Solomakha V.N. , Philippov A.P. , Il'in V.G.
Published: January 2003

Template-containing silica-based MCM-41 and MCM-50 materials have been shown to have microporous adsorbent properties, with the characteristic adsorption energy in such micropores being strongly dependent on the molecular mass of the adsorptives employed. The total adsorption volume was found to decrease as the molar volume of the adsorptive increased. A model explaining the peculiarities of the adsorptive properties of the template-containing materials is proposed.
Calculating the Distribution of a Linear Combination of Uniform Order Statistics
Authors: Diniz Morganna Carmem , Silva Edmundo de Souza e , Gail H. Richard
Published: January 2003

The calculation of the distribution of a linear combination of order statistics from random variables that are uniformly distributed is considered. A simple recursion to compute this distribution is presented that, unlike previous methods, is numerically stable and efficient. As such, this should be the algorithm of choice when the linear combination distribution needs to be obtained.
Solution of a Min-Max Vehicle Routing Problem
Authors: Applegate David , Cook William , Dash Sanjeeb , Rohe André
Published: January 2003

We use a branch-and-cut search to solve the Whizzkids'96 vehicle routing problem, demonstrating that the winning solution in the 1996 competition is in fact optimal. Our algorithmic framework combines the LP-based traveling salesman code of Applegate, Bixby, Chvátal, and Cook, with specialized cutting planes and a distributed search algorithm, permitting the use of a computing network located across Rice, Princeton, AT&T, and Bonn. The 1996 problem instance wasdeveloped by E. Aartsand J. K. Lenstra, and the competition was sponsored by the information technology firm CMG and the newspaper De Telegraaf.
Minimizing the Average Query Complexity of Learning Monotone Boolean Functions
Authors: Torvik Vetle I. , Triantaphyllou Evangelos
Published: January 2003

This paper addresses the problem of completely reconstructing deterministic monotone Boolean functions via membership queries. The minimum average query complexity is guaranteed via recursion, where partially ordered sets (posets) make up the overlapping subproblems. For problems with up to 4 variables, the posets' optimality conditions are summarized in the form of an evaluative criterion. The evaluative criterion extends then computational feasibility to problems involving up to about 20 variables. A frameworkfor unbiased average case comparison of monotone Boolean function inference algorithms is developed using unequal probability sampling. The unbiased empirical results show that an implementation of the subroutine considered as a standard in the literature performs almost twice as many queries as the evaluative criterion on the average. It should also be noted that the first algorithm ever designed for this problem performed consistently within two percentage points of the evaluative criterion. As such, it prevails, by far, as the most efficient of the many preexisting algorithms.
Experimental Comparison of Approximation Algorithms for Scheduling Unrelated Parallel Machines
Authors: Vredeveld Tjark , Hurkens Cor
Published: January 2003

This paper presents an empirical comparison of polynomial-time approximation algorithms and local search heuristics for the problem of minimizing total weighted completion time on unrelated parallel machines. Algorithms with a worst-case performance guarantee are based on rounding a fractional solution to an LP-relaxation or to a convex quadratic-programming relaxation. We also investigate dominance relations among the lower bounds resulting from these relaxations.
Contrasting Structured and Random Permutation Flow-Shop Scheduling Problems: Search-Space Topology and Algorithm Performance
Authors: Watson Jean-Paul , Barbulescu Laura , Whitley L. Darrell , Howe Adele E.
Published: January 2003

The use of random test problems to evaluate algorithm performance raises an important, and generally unanswered, question: Are the results generalizable to more realistic problems? Researchers generally assume that algorithms with superior performance on difficult, random test problems will also perform well on more realistic, structured problems. Our research explores this assumption for the permutation flow-shop scheduling problem. We introduce a method for generating structured flow-shop problems, which are modeled after features found in some real-world manufacturing environments. We perform experiments that indicate significant differences exist between the search-space topologies of random and structured flow-shop problems, and demonstrate that these differencescanaffect the performance of certain algorithms. Yet despite these differences, and in contrast to difficult random problems, the majority of structured flow-shop problems were easily solved to optimality by most algorithms. For the problems not optimally solved, differences in performance were minor. We conclude that more realistic, structured permutation flow-shop problems are actually relatively easy to solve. Our results also raise doubts as to whether superior performance on difficult random scheduling problems translates into superior performance on more realistic kinds of scheduling problems.
Feature Article: Optimization for simulation: Theory vs. Practice
Authors: Fu Michael C.
Published: January 2003

Probably one of the most successful interfaces between operations research and computer science has been the development of discrete-event simulation software. The recent integration of optimization techniques into simulation practice, specically into commercial software, has become nearly ubiquitous, as most discrete-event simulation packages now include some form of “optimization” routine. The main thesis of this article, how-ever,is that there is a disconnect between research in simulation optimization—which has addressed the stochastic nature of discrete-event simulation by concentratingon theoretical results of convergence and specialized algorithms that are mathematically elegant—and the recent software developments, which implement very general algorithms adopted from techniques in the deterministic optimization metaheuristic literature (e.g., genetic algorithms, tabu search, artificial neural networks). A tutorial exposition that summarizes the approaches found in the research literature is included, as well as a discussion contrasting these approaches with the algorithms implemented in commercial software. The article concludes with the author's speculations on promising research areas and possible future directions in practice.
A Hybrid GRASP with Perturbations for the Steiner Problem in Graphs
Authors: Ribeiro Celso C. , Uchoa Eduardo , Werneck Renato F.
Published: January 2003

We propose and describe a hybrid GRASP with weight perturbations and adaptive path-relinking heuristic (HGP + PR) for the Steiner problem in graphs. In this multi-start approach, the greedy randomized construction phase of a GRASP is replaced by the use of several construction heuristics with a weight perturbation strategy that combines intensification and diversification elements, as in a strategic oscillation approach. The improvement phase circularly explores two different local search strategies. The first uses anode-based neighborhood for local search, while the second uses a key-path-based neighborhood. An adaptive path-relinking technique is applied to a set of elite solutions as apost-optimization strategy. Computational results on a broad set of benchmark problems illustrate the effectiveness and the robustness of our heuristic, which is very competitive when compared to other approximate algorithms.
Capacitated Network Design with Uncertain Demand
Authors: Riis Morten , Andersen Kim Allan
Published: January 2003

We consider a capacity-expansion problem arising in the design of telecommunication networks. The problem is to install capacity on links of the network so as to meet customer demand while minimizing total costs incurred. When studying this and related problems it is customary to assume that point-to-point demands are given. This will not bethe case in practice, however, since future demand is generally unknown and the decision must be based on uncertain forecasts. We develop a stochastic integer programming formulation of the problem and propose an L-shaped solution procedure based on well-known cutting-plane procedures for the deterministic problem. The algorithm was tested on two sets of real-life problem instances and we present results of our computational experiments.
Symbolic Computation of Moments in Priority Queues
Authors: Derkic Steve , Stafford James E.
Published: January 2003

Analytical tools such as Laplace-Stieltjes transforms and z-transforms are commonly used to characterize queueing-theoretic quantities such as busy-period, waiting-time, and queue-size distributions. Many of these transforms, particularly in M/G/1 priority queueing applications, tend to be cumbersome expressions that involve both implicit and recursive functional relationships. Due to these complications, even the task of deriving moments becomes an algebraically intensive exercise. The focus of this paper is to describe a collection of efficient symbolic procedures useful for automating the tedious mathematical computations one encounters in working with these kinds of transforms. Central to this development is the introduction of a set-partition operator that enables moment expressions for delay cycles to be determined quickly and exactly, without having to derive any sort of higher-order derivative or Taylor-series expansion. Making use of this operator eliminates laborious derivations by hand and permits moments of various priority queueing-related quantities to be easily determined. In particular, the procedures are applied to the classical non-preemptive and preemptive resume queues, as well as two advanced variants of these models.
An Evolutionary Approach to Group Decision Making
Authors: Rees Jackie , Koehler Gary J.
Published: January 2003

We propose modeling Group Support System (GSS) search tasks with Genetic Algorithms. Using explicit mathematical models for Genetic Algorithms (GAs), we show how to estimate the underlying GA parameters from an observed GSS solution path. Once these parameters are estimated, they may be related to GSS variables such as group composition and membership, leadership presence, the specific GSS tools available, incentive structure, and organizational culture. The estimated Genetic Algorithm parameters can be used with the mathematical models for GAs to compute or simulate expected GSS process out comes.
A Multimethod Approach for Creating New Business Models: The General Motors OnStar Project
Authors: Barabba Vince , Huber Chet , Cooke Fred , Pudar Nick , Smith Jim , Paich Mark
Published: January 2003

We developed a multimethod modeling approach to evaluate strategic alternatives for GM's OnStar communications system. We used dynamic modeling to address some decisions GM faced in 1997, such as the company's choice between incremental and aggressive marketing strategies for OnStar. We used an integrated simulation model for analyzing the new telematics industry, consisting of six sectors: customer acquisition, customer choice, alliances, customer service, financial dynamics, and dealer behavior. The modeling effort had important financial, organizational, and societal results. The OnStar business now has two million subscribers, an 80 percent market share of the emerging telematics market, and has been valued at between $4 and $10 billion. The OnStar project set the stage for a broader GM initiative in service businesses that ultimately could yield billions in incremental earnings. Most important, OnStar has saved many lives that otherwise would have been lost in vehicle accidents.
Optimization of the Production Planning and Trade of Lily Flowers at Jan de Wit Company
Authors: Caixeta-Filho José Vicente , van Swaay-Neto Jan Maarten , Wagemaker Antonio de Pádua
Published: January 2003

Jan de Wit Company implemented a decision-support system based on linear programming as a production-planning and trade tool for the management of its lily flower business. The LP maximizes the farm's total contribution margin, subject to such constraints as market-defined sales limits, market requirements, characteristics of the production cycle duration, technical requirements, bulb inventory, and greenhouse limitations. The main decision variable to be calculated is the number of flower beds in a specific greenhouse, from a specific bulb batch, of a specific variety, for a specific purpose, taking into consideration planting and expected harvesting weeks. Between 1999 and 2000, company revenue grew 26 percent, sales increased 14.8 percent for pots of lilies and 29.3 percent for bunches of lilies, costs fell from 87.9 to 84.7 percent of sales, income from operations increased 60 percent, return on owner's equity went from 15.1 to 22.5 percent, and best quality cut lilies jumped from 11 to 61 percent of the quantities sold. The system also suggested changes in the product mix.
NBC's Optimization Systems Increase Revenues and Productivity
Authors: Bollapragada Srinivas , Cheng Hong , Phillips Mary , Garbiras Marc , Scholes Michael , Gibbs Tim , Humphreville Mark
Published: January 2003

The NBC television network, a subsidiary of the General Electric Company (GE), uses optimization-based sales systems to improve its revenues and productivity. GE's corporate research and development center (CRD) developed these systems using operations research and management science techniques to improve NBC's sales processes. These systems remove bottlenecks caused by manual development of sales plans, helping NBC to respond quickly to client requests with sales plans that meet their requirements. These systems also enable NBC to make the most profitable use of its limited inventory of valuable advertising slots by estimating demands for airtime by show and by week and to schedule commercials. Between 1996 and 2000, the systems increased revenues by over $200 million, improved sales-force productivity, reduced rework by over 80 percent, and improved customer satisfaction. They have become an integral and essential part of NBC's sales process.
Pricing Analysis for Merrill Lynch Integrated Choice
Authors: Altschuler Stuart , Batavia Donna , Bennett Jeff , Labe Russ , Liao Bonnie , Nigam Raj , Oh Je
Published: January 2003

In late 1998, Merrill Lynch and other full-service financial service firms were under assault. Electronic trading and the commoditization of trading threatened Merrill Lynch's value proposition—to provide advice and guidance through a financial advisor. Management decided to offer investors more choices for doing business with Merrill Lynch. A cross-functional team evaluated alternative product and service structures and pricing and constructed models to assess individual client's behavior. The models showed that revenue at risk to Merrill Lynch ranged from $200 million to $1 billion. The resulting Integrated Choice strategy enabled Merrill Lynch to seize the marketplace initiative, changed the financial services landscape, and mitigated the revenue risk. As of year-end 2000, client assets reached $83 billion in the new offer, net new assets to the firm totaled $22 billion, and incremental revenue reached $80 million.
SLIM: Short Cycle Time and Low Inventory in Manufacturing at Samsung Electronics
Authors: Leachman Robert C. , Kang Jeenyoung , Lin Vincent
Published: January 2003

SLIM is a set of methodologies and scheduling applications for managing cycle time in semiconductor manufacturing. SLIM includes methodology for calculating target cycle times and target WIP levels for individual manufacturing steps, heuristic algorithms for factory floor scheduling, and optimization-based capacity analysis. Between 1996 and 1999, Samsung Electronics Corp., Ltd., implemented SLIM in all its semiconductor manufacturing facilities. It reduced manufacturing cycle times to fabricate dynamic random access memory devices from more than 80 days to less than 30. Considering the decline of selling prices for dynamic random access memory devices, SLIM enabled Samsung to capture an additional $1 billion in sales revenue compared to the revenue it would have realized had cycle times not been reduced.
Reinventing Army Recruiting
Authors: Knowles James A. , Parlier Greg H. , Hoscheit Gregory C. , Ayer Rick , Lyman Kevin , Fancher Robert
Published: January 2003

Imminent catastrophic failure was the mantra as manpower shortfalls were becoming a constraint on the army's ability to support national strategy. The United States Army Recruiting Command (USAREC) reinvented recruiting by developing a Contract Forward methodology—a hybrid between a just-in-time and an inventory-based system. This methodology enabled the organization to better support national military security obligations while increasing military recruiting production by 17.5 percent and to completely eliminate a forecasted deficit. USAREC had cost-efficiency savings of $204 million out of a $1 billion program (20 percent savings).
Optimizing Plant-Line Schedules and an Application at Hidden Valley Manufacturing Company
Authors: Brown Gerald G. , Dell Robert F. , Davis Ray L. , Duff Richard H.
Published: January 2003

A plant line schedule specifies a plant's sustained batch operations over time with detail sufficient to manage all activities. Plantwide considerations include restrictions on how production centers can be formed from production lines, packaging lines, conveyers, and so forth; the cost and time of product-package item setups, changeovers, and shutdowns; honoring instock service levels, minimum inventory, and committed shipments; recognizing efficiency gains with longer batch runs; respecting crew constraints; and the costs of materials, labor, and carrying inventory. We developed a cost-minimizing optimization model, PROFITS, that features multiple independent time streams for various categories of events that mimic existing periodic reviews of operations. PROFITS is embedded in a graphical user interface that eases the grueling aspects of scheduling: preparing data, controlling scenarios, and visualizing results. At Hidden Valley Manufacturing Company, completing an eight-week plant-line schedule takes about an hour. This is much faster than manual scheduling was—and the schedules are better.
Australian Sugar Mills Optimize Harvester Rosters to Improve Production
Authors: Higgins Andrew J.
Published: January 2003

Increasing cost/price ratios in sugarcane production and the pressure to remain internationally competitive have forced Australian sugar mills to try to use their infrastructure more efficiently. Generating rosters for sugarcane harvesters manually is difficult because the mills have a large number of harvesters and tight capacities in the transportation facilities. The Cooperative Research Centre for Sustainable Sugar Production conducted a participatory research process with five mills in the Australian sugar industry to develop models to optimize harvester rosters. Embedded in the research process and underpinned by action learning was the development of a novel integer-programming model, its validation, and its implementation. The participatory research overcame barriers to implementation of the rosters produced by the model and allowed the five participating mills to realize benefits in terms of more efficient transport operations.
Tutorial on Computational Complexity
Authors: Tovey Craig A.
Published: January 2003

Computational complexity measures how much work is required to solve different problems. It provides a useful classification tool for OR/MS practitioners, especially when tackling discrete deterministic problems. Use it to tell, in advance, whether a problem is easy or hard. Knowing this won't solve your problem, but it will help you to decide what kind of solution method is appropriate. Complexity analysis helps you to understand and deal with hard problems. It can pinpoint the nasty parts of your problem, alert you to a special structure you can take advantage of, and guide you to model more effectively. You will solve your problem better when you know the borders between hard and easy. Locating the difficulty can indicate where to aggregate, decompose, or simplify. To detect and prove computational difficulty, show that a known hard problem from the literature is embedded within your problem. Fix parameters of your problem to arrive at the known hard problem, or use specialization, padding, forcing, or the more difficult gadget proofs. Study contrasting pairs of easy and hard problems to develop your intuitive ability to assess complexity.