bluuebunny/crossref_metadata_2025 huggingface dataset:
On the retention of finished goods inventory when reorder‐occurrence is uncertain
Authors: Jesse Richard R.
Published: October 2002

Finished goods inventory may accumulate for a variety of reasons in the production of lowdemand or slow‐moving items. In this article a simple model is developed and some results are presented to aid in making inventory retention decisions when there exists uncertainty about whether reorders for a slow‐moving item will be received in the future. In formulating the model, it is assumed that some excess inventory remains after filling a customer order and that a single reorder for the item is possible. The problem is to determine how long to retain the inventory before disposing of it.

The relevant expected costs of retaining some quantity of inventory for a period of time consist of two types: (1) the inventory carrying cost less the salvage value from disposal; and (2) the future production cost incurred due to premature disposal. Using conventional optimization, a relationship for finding the optimal retention period is derived and conditions are identified that ensure that the optimal retention period can be obtained directly from the relationship.

To determine the optimal retention period, probability distributions are required for the interarrival time until the reorder occurs and for the reorder quantity. While it seems logical to assume that each item would have its own distributions, this argument leads to a specification problem since the data needed to establish distributions for individual items will generally not be available for slow‐moving items. One approach used to overcome this problem in practice is to combine data for a selected group of items and use the combined data to obtain distributions useful for any or all of the items in the group. An example illustrating this approach is provided.
The sources, measurements, and managerial implications of process commonality
Authors: Treleven Mark , Wacker John G.
Published: October 2002

This article explores the issue of commonality of processes. While the benefits of high process commonality (similarity of processes) are generally recognized, this research represents the first clear identification of the sources, development of measurements, and discussion of the managerial implications of process commonality.

The first section of the article identifies and categorizes the sources of process commonality. These categories are: low set‐up times, flexibility to change from one operation to another, and flexibility in making expedite decisions‐ Indices are developed in the second section for each of these three categories at the work center level. These indices are examined using sensitivity analysis and are found to respond appropriately to changes in parameters. Formulation of a composite index is also discussed.

The final section discusses the managerial implications of process commonality at the strategic, tactical, and operational levels. The impact of improved process commonality covers a wide range of decisions, including product/process selection, production/inventory control system selection, and definition of group technology cells, among others.
Operations management taxonomy
Authors: Prentis Eric L.
Published: October 2002

Operations management is responsible for achieving an effective and efficient transformation process. Changes taking place in the marketplace and in technology require the correct positioning of operations in the production of goods and services. The service sector within our economy has grown tremendously, representing an ever greater share of our gross national product. A general operations management (OM) paradigm, combining both goods and services, will help researchers as well as practitioners.

The operations classification schemes proposed previously have been narrower in scope and incorporated primarily manufacturing systems. The transformation process is universal; major constraints and standard approaches need to be identified regardless of whether it is a good or service produced. This article presents and defines a descriptive OM model. Sample industries and companies are positioned in the market and product/service matrix; in addition, operations activities and their long‐, medium‐, and short‐term solution approaches to operations problems are identified.

This operations model keys on the definition of the product/service produced. The major groupings of the first two dimensions of the model depend on (1) market requirements, and (2) whether the product/service is discrete or divisible, fixed site or transportable. Major groupings of the operations activities, required to effectively and efficiently transform the product/service, define the management approach and product/process technology used. These represent the third dimension to our model. The fourth dimension is the time available to plan and implement solutions to operations problems.

The four dimensional space‐time paradigm is cohesive and inclusive, and better identifies the major constraints on goods and/or services production. It is intended to analyze and synthesize both the similarities and differences among industries and companies positioned in matrix categories, and thus to help determine the appropriate actions of operations managers during the transformation process.

The complexity of the OM paradigm shows realistically the trade‐offs that have to be made in this dynamic area. Changing markets, technology, management, and economics all play a part in positioning operations. Resulting changes in the market requirement and product/service positioning matrix can change unit costs. Movement in any direction on the matrix should not be thought of as a natural evolution but should be meticulously planned. Goods and services producers grouped in each of nine major transformation categories may be able to use similar planning, implementation, and control approaches.
A table for the calculation of safety stock
Authors: Aucamp Donald C. , Barringer Robert L.
Published: October 2002

Safety stock is often calculated to accommodate a given service level (SL), where service is defined in some manner by the user. In this regard, the two favorite definitions of service are the percent of good cycles and the fraction of demand satisfied by off‐the‐shelf inventory.

Judging from its increased appearance in the literature, especially in textbooks, the latter definition apparently is gaining in popularity. Unfortunately, this definition requires a little more effort to use. A procedure originally worked out by Brown (Brown's Method) shows how the calculations are to proceed. The partial expectation, E(z), is first calculated as a function of the expected lead time demand (μ), the standard deviation (σ) of lead time demand, and the required service level. Once E(z) is found, a table is consulted (Brown's Table) to determine z. Finally, the safety stock is calculated from the formula, zσ.

There are several problems with using Brown's Table. First, z is given as the dependent variable rather than the independent variable, so the user has to search a bit to find the nearest pair of entries that straddle the required value of E(z). Then the user must perform an awkward interpolation, something many business students find very confusing.

An additional problem with the table is that it is both sparse and inaccurate for high values of z. In fact, there are no entries at all for z 4.50, and there is only one significant digit of accuracy for z 3.93. Finally, Brown does not supply a computer program that calculates z directly from E(z). While this lack of a program is not important to the casual user of the tables, it can be important when one wishes to set safety stock levels automatically and internally by the computer.

This article presents a new table, in which E(z) is the dependent variable rather than the independent variable. The computer program used to evaluate the entries yields solutions that are accurate to about fourteen decimal places. With this kind of precision the authors were able to extend Brown's Table to high values of z, while at the same time providing for virtually any number of significant digits. Incidentally, the entry density in this table is nonuniform (somewhat logarithmic) to accommodate usage over various orders of magnitude of z and E(z).

The article also includes a simpler version of our computer program (single precision), which yields about four decimal place accuracy. The double precision program actually used is available on request, but it is somewhat complicated and depends on the computer used (the authors used a TRS‐80).
Tooling constraints and shop floor scheduling: A simulation study
Authors: Melnyk Steven A. , Ghosh Soumen , Ragatz Gary L.
Published: October 2002

Research into the problems of job shop scheduling has dealt with two of three major categories of shop floor resources: machine capacity and labor. Generally ignored has been the impact of tooling constraints, the third form of shop floor resource, on the scheduling process. The impact of tooling is the focus of this study.

Using a simple simulation model of a shop operating under varying levels of tooling availability, it is shown that the level of tooling availability has a significant impact on shop floor performance as measured in terms of mean flow time, mean tardiness, number jobs tardy and number of tool changes. Four different tooling assignment rules are evaluated and their effect on system performance is described.

The results indicate that tooling assignment rules should consider both job priorities and tooling availability in order to achieve good shop performance. The paper concludes with general recommendations for the management of shop orders facing limited tooling availability.
Due date based scheduling in a general flexible manufacturing system
Authors: Raman N. , Talbot F.B. , Rachamadugu R.V.
Published: October 2002

Dynamic scheduling of manufacturing systems for due date based objectives has received considerable attention from practitioners and researchers due to the importance of meeting due dates in most industries. Research investigations have focused primarily on the relative effectiveness of various dispatching rules in job shops. These rules operate by prioritizing jobs using a “criticality index” based on job and system status. Jobs are then scheduled from most critical to least, with the indexes typically being updated as the system changes.

This study considers two important issues which have not been addressed previously in the literature. First, we investigate the impact of unequal machine workloads on the relative effectiveness of dispatching rules. This is significant because workloads are likely to be unbalanced in most real systems. While it is clear, intuitively, that this imbalance in machine workloads is likely to deteriorate system performance, it is not obvious whether the superiority of certain dispatching rules established in earlier studies for balanced workloads is carried forward to this case. We show that the performance of different dispatching rules does indeed depend upon the degree of workload imbalance. We also propose and test a scheduling procedure which performs well in both balanced and unbalanced systems.

Next, we develop a scheduling approach which shows promise as being an improved alternative to the use of dispatching rules. This approach decomposes the dynamic scheduling problem into a series of static problems.

These static problems are then solved using an optimum‐seeking method, and the solutions are implemented on a rolling basis. We show through a simulation experiment that adopting this approach over dispatching rules leads to an improvement in the overall solution quality, even in a dynamic environment.

The two very practical implications of our study are: (1) that commonly used dispatching rules in job shops or automated manufacturing systems may not be the best approach when capacity utilization is unbalanced (2) a job shop or automated manufacturing system would likely benefit from implementing optimal‐seeking scheduling rules instead of the traditional job dispatching rules.
Measurement of manufacturing flexibility: A value based approach
Authors: Ramasesh Ranga V. , Jayakumar Maliyakal D.
Published: October 2002

Flexibility is emerging as one of the key competitive strengths in today's manufacturing systems. Measuring the flexibility of manufacturing systems is important to operations managers engaged in decision making on strategic issues related to flexibility. Flexibility is widely recognized as a multidimensional attribute. Most of the studies reported in the literature have focused on measuring separate dimensions independently and also have tended to be non‐financial in nature. As a result, many of these measures have only limited application in strategic decision making. In this paper we consider the measurement of the aggregate flexibility of a manufacturing system by investigating the joint effect of the flexibilities on a variety of dimensions when measurement for a medium‐term time horizon is appropriate. We propose a value‐based approach in which flexibility is measured by the ability of a manufacturing system to generate high net revenues consistently across all conceivable states of the nature in which it may be called upon to function. We suggest the ratio of the mean to the standard deviation of the distribution of optimal net revenues as the flexibility measure.

We develop a stochastic mathematical programming formulation that facilitates the modeling of the manufacturing flexibility on different dimensions and the determination of the distribution of the net optimal revenues across all possible states. We exploit the special structure of our formulation to efficiently solve large problems that arise in some practical situations. We illustrate the application of the model using a numerical example which shows that the value of each type of flexibility varies depending on how it enhances the revenues generated by the system. We also find that synergistic benefits can be gained by combining different types of flexibilities. Our model provides an approach to determine the aggregate value of manufacturing flexibility and to explore the trade‐offs that may exist among the different dimensions of flexibility.
Production flow analysis for planning group technology
Authors: Burbidge John L.
Published: October 2002

Group technology (GT) is a method of organization for factories in which organizational units known as “groups” each complete a particular set or “family” of parts with no backflow, or crossflow between groups, and are equipped with all the facilities they need to do so.

Production flow analysis (PFA) is a technique for planning the change to GT in existing batch and jobbing production factories. It finds a total division into groups, using the existing machines and methods to make the existing parts, without any need to buy additional machine tools.

Because the change to GT is generally both possible (if PFA is used for planning) and profitable, process organization, in which organizational units specialize in particular processes, is now obsolete.
Accounting for the multi‐period impact of service when determining employee requirements for labor scheduling
Authors: Thompson Gary M.
Published: October 2002

Providing good customer service, inexpensively, is a problem commonly faced by managers of service operations. To tackle this problem, managers must do four tasks: forecast customer demand for the service; translate these forecasts into employee requirements; develop a labor schedule that provides appropriate numbers of employees at appropriate times; and control the delivery of the service in real‐time.

This paper focuses upon the translation of forecasts of customer demand into employee requirements. Specifically, it presents and evaluates two methods for determining desired staffing levels. One of these methods is a traditional approach to the task, while the other, by using modified customer arrival rates, offers a better means of accounting for the multi‐period impact of customer service. To calculate the modified arrival rates, the latter method reduces (increases) the actual customer arrival rate for a period to account for customers who arrived in the period (in earlier periods) but have some of their service performed in subsequent periods (in the period). In an experiment simulating 13824 service delivery environments, the new method demonstrated its superiority by serving 2.74% more customers within the specified waiting time limit while using 7.57% fewer labor hours.
The crystal structure of N1‐[2‐(2‐amino‐ethylamino)‐ethyl]‐ethane‐1,2‐diamine (polyamines) binding to the minor groove of d(CGCGCG)2, hexamer at room temperature
Authors: Ohishi Hirofumi , Suzuki Kenji , Ohtsuchi Masahiro , Hakoshima Toshio , Rich Alexander
Published: October 2002

The crystal structure of a left‐handed Z‐DNA hexamer, d(CG)3 in complex with a synthetic polyamine, N
1‐[2‐(2‐amino‐ethylamino)‐ethyl]‐ethane‐1,2‐diamine, NH3
+‐(CH2)2‐NH2
+‐(CH2)2‐NH2
+‐(CH2)2‐NH3
+ [PA(222)], has been determined by the X‐ray diffraction method at 1.0 Å resolution. In an orthorhombic crystal, the d(CG)3 duplex binds two PA(222) molecules, and this synthetic polyamine exhibits dual conformational properties. One of the two PA(222) molecules resides on the floor of the minor groove of a Z‐DNA duplex and imino groups bridge the two phosphate chains across a double helix, while the terminal amino groups link the oxygen atoms O2 of four cytosine bases. This PA(222) molecule makes a U‐turn like a fishhook at one of its ends to provide a micro‐environmental network previously unseen in complexes of DNA with polyamines. The width of the minor groove does not become considerably greater with the looped end of the polyamine, indicating conformational rigidity of the Z‐DNA backbone imposed by the high stacking energy of the GC base pairs. While polyamine binding to the minor groove has been postulated by theoretical studies for stabilizing the Z‐DNA double helical conformation, the finding in the crystal of the looped polyamine chain binding the minor groove of Z‐DNA is observed for the first time from the data collected at 10°C (so‐called room temperature data). Another PA(222) molecule binds on the convex outer surface of the major groove of the Z‐DNA duplex and links three d(CG)3 duplexes which are symmetrically related to each other. The structure of this PA(222) presents the previously reported zig‐zag type conformation [Egli et al., Biochemistry 30 (1991) 11388–11402]. Comparison of this structure with other polyamine–DNA cocrystals reveals structural themes and differences that may relate to the length of the polyamine.
Specific monitoring of Syk protein kinase activity by peptide substrates including constrained analogs of tyrosine
Authors: Donella-Deana Arianna , Ruzza Paolo , Cesaro Luca , Brunati Anna Maria , Calderan Andrea , Borin Gianfranco , Pinna Lorenzo A
Published: October 2002

The ability of Syk protein tyrosine kinase (PTK) to phosphorylate peptides, where tyrosine had been replaced by conformationally constrained analogs, has been exploited to develop highly selective substrates suitable for the specific monitoring of Syk activity. In particular we have synthesized a peptidomimetic, RRRAAEDDE(L‐Htc)EEV (syktide), with the 3(S)‐7‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxyl acid residue (L‐Htc) replaced for tyrosine, which is phosphorylated by Syk with remarkable efficiency (K
cat=73 min−1, K
m=11 μM), while it is not affected to any appreciable extent by a number of PTKs tested so far. These properties make syktide the first choice substrate for the specific monitoring of Syk.
The Aspergillus nidulans cyclin PclA accumulates in the nucleus and interacts with the central cell cycle regulator NimXCdc2
Authors: Schier Niklas , Fischer Reinhard
Published: October 2002

The filamentous fungus Aspergillus nidulans reproduces asexually through conidiospores, which are continuously generated at morphologically differentiated structures, the conidiophores. In contrast to vegetative, multinucleate cells, spore formation requires a strict coordination of mitosis and cytokinesis. It was shown recently that the key regulator of the cell cycle in A. nidulans NimXCdc2 and a G1/S cyclin, PclA, are transcriptionally upregulated during development. Here we show that PclA accumulates in the nucleus and interacts with NimXCdc2. We propose that PclA modulates the kinase activity of NimXCdc2 during spore formation.
Agonist‐promoted heteromeric oligomerization between adenosine A1 and P2Y1 receptors in living cells
Authors: Yoshioka Kazuaki , Saitoh Osamu , Nakata Hiroyasu
Published: October 2002

We have explored the process of oligomerization of G protein‐coupled purinergic receptors, adenosine A1 receptor (A1R) and P2Y1 receptor (P2Y1R), in intact HEK293T cells by means of modified bioluminescence resonance energy transfer technology (BRET2) that offers greatly improved separation of the emission spectra of the donor and acceptor moieties compared to traditional BRET. This approach identified both constitutive and agonist‐promoted heteromeric oligomerization between Myc‐tagged P2Y1R fused to a donor, Renilla luciferase (Myc‐P2Y1R‐Rluc) and HA‐tagged A1R fused to an acceptor, a different form of green fluorescent protein (HA‐A1R‐GFP2). The BRET2 signal increased in a time‐dependent manner in the cells expressing HA‐A1R‐GFP2/Myc‐P2Y1R‐Rluc upon addition of agonists for both receptors, which could be inhibited by pretreatment with the P2Y1R antagonist MRS2179. A high degree of HA‐A1R‐GFP2 and Myc‐P2Y1R‐Rluc co‐localization in the co‐transfected HEK293T cells was also observed by confocal laser microscopy. These results indicate that A1R and P2Y1R can form constitutive hetero‐oligomers in living cells and this process is promoted by the simultaneous activation of both receptors.
The human dynamin‐related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter‐membrane space
Authors: Olichon Aurélien , Emorine Laurent J , Descoins Eric , Pelloquin Laetitia , Brichese Laetitia , Gas Nicole , Guillou Emmanuelle , Delettre Cécile , Valette Annie , Hamel Christian P , Ducommun Bernard , Lenaers Guy , Belenguer Pascale
Published: October 2002

Mutations in the OPA1 gene are associated with autosomal dominant optic atrophy. OPA1 encodes a dynamin‐related protein orthologous to Msp1 of Schizosaccharomyces pombe and Mgm1p of Saccharomyces cerevisiae, both involved in mitochondrial morphology and genome maintenance. We present immuno‐fluorescence and biochemical evidences showing that OPA1 resides in the mitochondria where it is imported through its highly basic amino‐terminal extension. Proteolysis experiments indicate that OPA1 is present in the inter‐membrane space and electron microscopy further localizes it close to the cristae. The strong association of OPA1 with membranes suggests its anchoring to the inner membrane.
The lactose analog GalNAcβ1→4Glc is present in bovine colostrum
Authors: Van den Nieuwenhof Ingrid M , Schiphorst Wietske E.C.M , Van den Eijnden Dirk H
Published: October 2002

We have isolated from bovine colostrum the lactose analog GalNAcβ1→4Glc. The enzymatic basis for its occurrence was studied by assaying the activities of GlcNAcβ‐R β4‐N‐acetylgalactosaminyltransferase (β4‐GalNAcT) and GlcNAcβ‐R β4‐galactosyltransferase (β4‐GalT) in primary milk and several lactating bovine mammary gland fractions. As the β4‐GalNAcT, which appears to be tightly membrane bound, is induced by the milk protein α‐lactalbumin (α‐LA) to act on Glc, it is concluded that β4‐GalNAcT is responsible for the synthesis of GalNAcβ1→4Glc in the gland. The comparatively low level (15–20 mg/l) at which this disaccharide is produced may be due to the relatively poor interaction of β4‐GalNAcT with α‐LA as well as to the fact that α‐LA does not inhibit the action of the enzyme on N‐acetylglucosaminides.
Functional complementation of the Schizosaccharomyces pombe wis1 mutant by Arabidopsis MEK1 and non‐catalytic enhancement by CTR1
Authors: Pan Zaiqun , Chang Caren
Published: October 2002

Arabidopsis thaliana MEK1 encodes a MAPKK homolog whose role in plants is currently unknown. High (but not low) expression of MEK1 rescued the Δwis1 (MAPKK) mutant of the Schizosaccharomyces pombe Win1/Wis4‐Wis1‐Sty1 stress‐activated MAPK pathway. Rescue was dependent upon upstream and downstream components of the pathway, suggesting that MEK1 might function in a homologous MAPK pathway in plants. When MEK1 was expressed at a low level, rescue of Δwis1 was achieved by co‐expressing Arabidopsis CTR1 (a putative MAPKK kinase (MAPKKK)). CTR1 constructs alone did not rescue the pathway, indicating that CTR1 augmented MEK1 function. Further data indicated that this enhancement was not due to CTR1 kinase activity.
Improving the assessment of gestational age in a Zimbabwean population
Authors: Feresu S.A , Gillespie B.W , Sowers M.F , Johnson T.R.B , Welch K , Harlow S.D
Published: October 2002

Objectives: To evaluate the performance and the utility of using birthweight‐adjusted scores of Dubowitz and Ballard methods of estimating gestational age in a Zimbabwean population. Method: The Dubowitz and the Ballard methods of estimating gestational age were administered to 364 African newborn infants with a known last menstrual period (LMP) at Harare Maternity Hospital. Results: Both methods were good predictors of gestational age useful in differentiating term from pre‐term infants. Our regression line was Y(LMP gestational age)=23.814+0.301*score for the Dubowitz and Y(LMP gestational age)=24.493+0.420*score for the Ballard method. Addition of birthweight to the regression models improved prediction of gestational age; Y(LMP gestational age)=23.512+0.219*score+0.0015*grams for Dubowitz and Y(LMP gestational age)=24.002+0.292*score+0.0016*grams for Ballard method. Conclusions: We recommend the use of our birthweight‐adjusted maturity scales; the Dubowitz for studies of prematurity, and the Ballard for routine clinical practice.
Continua of states in boundary-layer flows
Authors: HEWITT R. E. , DUCK P. W. , STOW S. R.
Published: October 2002

We consider a class of three-dimensional boundary-layer flows, which may be viewed
as an extension of the Falkner–Skan similarity form, to include a cross-flow velocity
component, about a plane of symmetry. In general, this provides a range of three-
dimensional boundary-layer solutions, parameterized by a Falkner–Skan similarity
parameter, n, together with a further parameter, Ψ∞, which is associated with a
cross-flow velocity component in the external flow. In this work two particular cases
are of special interest: for n = 0 the similarity equations possess a family of solutions
related to the Blasius boundary layer; for n = 1 the similarity solution provides an
exact reduction of the Navier–Stokes equations corresponding to the flow near a
saddle point of attachment. It is known from the work of Davey (1961) that in
this latter class of flow, a continuum of solutions can be found. The continuum
arises (in general) because it is possible to find states with an algebraic, rather than
exponential, behaviour in the far field. In this work we provide a detailed overview
of the continuum states, and show that a discrete infinity of ‘exponential modes’ are
smoothly embedded within the ‘algebraic modes’ of the continuum. At a critical value
of the cross-flow, these exponential modes appear as a cascade of eigensolutions to
the far-field equations, which arise in a manner analogous to the energy eigenstates
found in quantum mechanical problems described by the Schrödinger equation.

The presence of a discrete infinity of exponential modes is shown to be a generic
property of the similarity equations derived for a general n. Furthermore, we show
that there may also exist non-uniqueness of the continuum; that is, more than one
continuum of states can exist, that are isolated for fixed n and Ψ∞, but which are
connected through an unfolded transcritical bifurcation at a critical value of the
cross-flow parameter, Ψ∞.

The multiplicity of states raises the question of solution selection, which is addressed
using two stability analyses that assume the same basic symmetry properties as the
base flow. In one case we consider a steady, algebraic form in the ‘streamwise’
direction, whilst in the other a temporal form is assumed. In both cases it is possible
to extend the analysis to consider a continuous spectrum of disturbances that decay
algebraically in the wall-normal direction. We note some obvious parallels that exist
between such stability analyses and the approach to the continua of states described
earlier in the paper.

We also discuss the appearance of analogous non-unique states to the Falkner–Skan
equation in the presence of an adverse pressure gradient (i.e. n < 0) in an appendix.
Salinity and temperature effects on sea lice over-wintering on sea trout (Salmo trutta) in coastal areas of the Skagerrak
Authors: Heuch P.A. , Knutsen J.A. , Knutsen H. , Schram T.A.
Published: October 2002

Both the salmon louse Lepeophtheirus salmonis and its close relative Caligus elongatus are ectoparasitic on Salmonidae in salt water in the northern hemisphere. In this study we monitored population dynamics of these parasites on anadromous brown trout, i.e. sea trout, on the Norwegian Skagerrak coast in the winters of 1998–1999 and 1999–2000. The low salinity was expected to reduce sea lice populations as lice do not tolerate sojourns of more than a few weeks, at most, in freshwater. Results confirmed the presence of both parasite species on estuarine sea trout in winter, and showed that the lice populations go through a bottleneck in this period. Prevalences of infection of both parasite species were very different in the two sampling periods, but fell below 10% in March in both winters. Median infection intensity was 1–2 fish−1. Salinity was statistically related to the presence of C. elongatus both winters, and to L. salmonis in 1999–2000. Temperature appeared to be less important for the abundance of lice.
Increasing abundance of Calanus finmarchicus in the central and eastern North Atlantic between 1958 and 1996
Authors: Beare D.J. , Gislason A. , Astthorsson O.S. , McKenzie E.
Published: October 2002

The abundance of Calanus finmarchicus is known to have fallen between the present and the late 1950s in north-eastern Atlantic shelf waters. Further west in deeper water, however, long-term abundance of the copepod has risen.
IMPLEMENTATION OF INTERNATIONAL HUMAN RIGHTS STANDARDS THROUGH THE NATIONAL COURTS IN MALAWI
Authors: HANSEN THOMAS TRIER
Published: October 2002

This article discusses the application of international human rights law by the courts in Malawi. It is divided into five parts. The first part examines the constitutional position of international law at the municipal level and will focus primarily on the position under the current Constitution of Malawi. The second discusses the relevance of international human rights law before national court, with the third part then analysing the relevance of such law in the courts. The fourth part considers the reasons for the attitude of the courts to international human rights law, whilst the final part contains some concluding remarks. The case law discussed is largely that handed down by the Supreme Court and the High Court since 1994.
The Residues modulo m of
Products of Random Integers
Authors: STADJE WOLFGANG
Published: October 2002

For two stochastically dependent random variables X and Y taking values in
{0,…, m−1},
we study the distribution of the random residue U = XY mod m. Our main result
is an upper bound for the distance Δm =
supx∈[0,1]
[mid ] P(U/m [les ] x)−x[mid ]. For independent
and uniformly distributed X and Y, the exact distribution of U is derived and shown to
be stochastically smaller than the uniform distribution on {0,…, m−1}. Moreover, in this
case Δm is given explicitly.
Enzyme Reaction Engineering: Effect of Methanol on the Synthesis of Antibiotics Catalyzed by Immobilized Penicillin G Acylase under Isothermal and Non‐Isothermal Conditions
Authors: Travascio P. , Zito E. , Portaccio M. , Diano N. , Grano V. , Martino S. Di , Bertolini T. , Rossi S. , Mita D. G.
Published: October 2002

The effect of methanol on the kinetically controlled synthesis of cephalexin by free and immobilized penicillin G acylase (PGA) was investigated. Catalytic and hydrophobic membranes were obtained by chemical grafting, activation, and PGA immobilization on hydrophobic nylon supports. Butyl methacrylate (BMA) was used as graft monomer. Increasing concentrations of methanol were found to cause a greater deleterious effect on the activity of free than on that of the immobilized enzyme. Methanol, however, improved the kinetic stability of cephalexin synthesized by free PGA, resulting in higher maximum yields. By contrast, immobilized PGA reached 100% yields even in the absence of the cosolvent. Cephalexin synthesis by the catalytic membrane was also performed in a non‐isothermal bioreactor. Under these conditions, a 94% increase of the synthetic activity and complete conversion of the limiting substrate to cephalexin were obtained. The addition of methanol reduced the non‐isothermal activity increase. The physical cause responsible for the non‐isothermal behavior of the hydrophobic catalytic membrane was identified in the process of thermodialysis.
Feedback Stabilization of Fed‐Batch Bioreactors: Non‐Monotonic Growth Kinetics
Authors: Smets Ilse Y. , Bastin Georges P. , Van Impe Jan F.
Published: October 2002

This paper deals with the design of a feedback controller for fed‐batch microbial conversion processes that forces the substrate concentration CS to a desired setpoint CS*, starting from an arbitrary (initial) substrate concentration when non‐monotonic growth kinetics apply. This problem is representative for a lot of industrial fermentation processes, with the baker's yeast fermentation as a well‐known example. It is assumed that the specific growth rate μ is function of the substrate concentration only. A first approach exploits the availability of on‐line measurements of both the substrate and biomass concentration. A second approach is merely based on on‐line measurements of the biomass concentration, which provide an estimate for the specific growth rate. After a reformulation of the substrate concentration setpoint into a specific growth rate setpoint, it is demonstrated that the fed‐batch process can still be stabilized around any desired operating point along the non‐monotonic kinetics.
Pulse Experiments as a Prerequisite for the Quantification of in Vivo Enzyme Kinetics in Aromatic Amino Acid Pathway of Escherichia coli
Authors: Schmitz M. , Hirsch E. , Bongaerts J. , Takors R.
Published: October 2002

Glucose pulse experiments were performed to elucidate their effects on the carbon flux into the aromatic amino acid pathway in different Escherichia coli strains. Using a 3‐deoxy‐d‐ arabino‐heptulosonate 7‐phosphate (DAHP, aroB‐)‐producing strain, a fed‐batch fermentation strategy specialized for glucose pulse experiments was developed and further applied for 3‐dehydroshikimate (DHS, aroE‐)‐ and shikimate 3‐phosphate (S3P, aroA‐)‐producing E. coli strains. The strains overexpress a feedback‐resistant DAHP synthase and additional enzymes to prevent rate‐limiting steps in the aromatic amino acid pathway. Changes of carbon flux into the aromatic amino acid pathway were determined via extracellular metabolite accumulations using 1H NMR and HPLC measurements. As an important result, a close relationship between pulse intensity and aromatic metabolite formation rates was identified. The more downstream an aromatic pathway intermediate was located, the stronger the glucose pulse intensity had to be in order to detect significant changes in product formation. However, with the experimental conditions chosen, changes after pulse were detected even for shikimate 3‐phosphate, the most downstream accumulating metabolite of this experimental series. Hence glucose pulse experiments are assumed to be a promising tool even for the analysis of final pathway products such as, for example, l‐phenylalanine.
Validation and Use of an Enzymic Time‐Temperature Integrator to Monitor Thermal Impacts Inside a Solid/Liquid Model Food
Authors: Guiavarc'h Yann P. , Dintwa Edward , Van Loey Ann M. , Zuber François T. , Hendrickx Marc E.
Published: October 2002

Heat denaturation kinetics of Bacillus licheniformis α‐amylase, equilibrated at 81% equilibrium relative humidity at 4 °C (BLA81), was studied with help of isothermal and nonisothermal conditions by monitoring the decrease in enthalpy associated with the heat denaturation of the enzyme. Due to its low water content, BLA81 denaturation could be studied in the range of 118–124 °C. Two batches of BLA81 were successfully validated under nonisothermal conditions allowing the determinations of process values (reference temperature of 121.1 °C) in the range of 1–15 min. In a second step, BLA81 was used as a time‐temperature integrator (TTI) to investigate potential differences of process values received by freely moving spherical particles as compared to a centrally fixed particle (single‐position impact) inside cans containing water as brine. Results showed that the process value received by freely moving particles can be from 5.6% (4 rpm) to 19.7% (8 rpm) smaller than the process value received by the centrally fixed sphere. This means that evaluating the process value by means of a particle fixed at the critical point in a package can lead to potentially overestimations of the actual process value with possible hazardous quality/safety implications. These results highlight the potentials of the TTI technology to monitor the safety of heat‐processed agitated solid/liquid foodstuffs.
Picoliter‐Scale Protein Microarrays by Laser Direct Write
Authors: Ringeisen B. R. , Wu P. K. , Kim H. , Piqué A. , Auyeung R. Y. C. , Young H. D. , Chrisey D. B. , Krizman D. B.
Published: October 2002

We demonstrate the accurate picoliter‐scale dispensing of active proteins using a novel laser transfer technique. Droplets of protein solution are dispensed onto functionalized glass slides and into plastic microwells, activating as small as 50‐μm diameter areas on these surfaces. Protein microarrays fabricated by laser transfer were assayed using standard fluorescent labeling techniques to demonstrate successful protein and antigen binding. These results indicate that laser transfer does not damage the active site of the dispensed protein and that this technique can be used to successfully fabricate a functioning protein microarray. Also, as a result of the efficient nature of the process, material usage is reduced by two to four orders of magnitude compared to conventional pin dispensing methods for protein spotting.
Using a CFD Model To Understand the Fluid Dynamics Promoting E. coli Breakage in a High‐Pressure Homogenizer
Authors: Miller J. , Rogowski M. , Kelly W.
Published: October 2002

A Computational Fluid Dynamic (CFD) model of flow in a high‐pressure homogenizing valve (APV Gaulin model 30CD) was developed with the Fluent software. The 2D model consists of an unstructured hexagonal mesh, dense in the regions of high gradients. The flow (single‐phase) was modeled as laminar upstream of and in the channel (gap) and turbulent downstream of the channel exit. Applying a realizable κ‐ϵ turbulence model, the CFD model accurately predicted the effect of gap space on fluid dynamic conditions upstream (inlet pressure and pressure gradient) and downstream (impact pressure) of the channel for a valve with a standard (CD‐0) impact distance (0.25 mm) and a 1 cP fluid. This CFD model was then used to estimate the magnitude of the fluid dynamic parameters (except cavitation effects) presumed to be responsible for cell breakage, as a function of gap space, impact distance and fluid viscosity. The CFD models predicted that for a given volumetric flowrate the upstream fluid conditions (inlet pressure gradient, maximum channel strain rate) and the maximum energy dissipation rate in the post‐gap jet depend only on the gap space and the fluid viscosity and not on the impact distance. The impact pressure however depends on the gap spacing, the fluid viscosity and especially the impact distance. Experimental results indicate that higher inlet pressures are required to break cells, if the impact distance is increased. By conducting experiments to isolate individual cell breakage mechanisms for a single pass, threshold values were identified for breaking Escherichia coli cells: pressure gradient, 1.2 × 1012 Pa/m; energy dissipation rate, 1.0 × 1010 m3/s2; and impact pressure, 160 psig. By isolating the wall impact as the sole mechanism responsible for breaking the E. coli cells between 3000 and 6000 psig inlet pressure, a relationship between E. coli cell breakage rate and maximum wall impact pressure was established (eq 5).
Factors Affecting the Composition of Oligosaccharides Produced in Chitosan Hydrolysis Using Immobilized Chitosanases
Authors: Kuroiwa Takashi , Ichikawa Sosaku , Hiruta Osamu , Sato Seigo , Mukataka Sukekuni
Published: October 2002

The hydrolysis reaction of chitosan using immobilized chitosanases with regard to the composition of its products and the yield of the intermediate target products, pentamer and hexamer of chitosan oligosaccharides, was investigated. Chitosanase was immobilized onto agar or agarose gel particles by the multipoint attachment method. In batch experiments, surface enzyme density, support particle size, temperature, agitator speed, and initial substrate concentration significantly affected the composition of the oligosaccharides produced. It was believed that these factors all related to the reaction rate and mass transfer rate at the surface of the support materials immobilizing the enzymes. These effects were summarized as a correlation with Damköhler number ( Da), defined as the ratio of the maximum reaction rate to the maximum mass transfer rate. The result showed that the reaction conditions that give a low value of Da provide a high yield of pentamer and hexamer oligosaccharides.
Polymerization of Glucans by Enzymatically Active Membranes
Authors: Becker Margot , Provart Nicholas , Lehmann Ingeburg , Ulbricht Mathias , Hicke Hans‐Georg
Published: October 2002

Conventional enzyme membrane reactors are not appropriate for a continuous synthesis of macromolecules and simultaneous product release. By immobilizing the enzyme in sufficiently large pores of a membrane an ensemble of miniaturized bioreactors is created. Product molecules are continuously removed from the enzyme by the flow of the reaction mixture across the membrane. Additionally, by varying the flow rate, it ought to be possible to influence the substrate as well as the enzyme‐product residence times and thereby the product macromolecule's size. In this paper we present the first results of experiments involving enzymatic 1,4‐α‐glucan synthesis, using sucrose as substrate, maltooligosaccharides (DP 3–6) as primers, and membrane‐immobilized amylosucrase. Epoxy groups for a covalent enzyme immobilization were generated on polypropylene microfiltration membranes by heterogeneous photoinitiated graft polymerization of glycidyl methacrylate. The influence of primer concentration and flow rate through the enzyme‐membrane on amylosucrase activity, molecule growth, and coupling efficiency for glucose (% of coupled glucose versus free glucose) were investigated. The enzymatically mediated chain elongation of maltooligosaccharides by the successive addition of glucose units was achieved for the first time in a transmembrane process utilizing amylosucrase membranes.
Adaptive, Model‐Based Control by the Open‐Loop‐Feedback‐Optimal (OLFO) Controller for the Effective Fed‐Batch Cultivation of Hybridoma Cells
Authors: Frahm Björn , Lane Paul , Atzert Hendrik , Munack Axel , Hoffmann Martin , Hass Volker C. , Pörtner Ralf
Published: October 2002

Although fed‐batch suspension culture of animal cells continues to be of industrial importance for the large scale production of pharmaceutical products, existing control concepts are still insufficient. Changes in cell metabolism during cultivation and between similar cultivations, the complexity of the cell metabolism, and the lack of on‐line state variables restrict the transfer of available control strategies established in bioprocess engineering. A process control strategy designed to achieve optimized process control must account for all these difficulties and fit sophisticated requirements toward adaptability and flexibility. The combination of a fed‐batch process and an Open‐Loop‐Feedback‐Optimal (OLFO) control provides a new approach for cell culture process control that couples an efficient cultivation concept to a capable process control strategy. The application of an adaptive, model‐based OLFO controller to a hybridoma cultivation and experimental results are presented.
Enzyme‐Carrying Polymeric Nanofibers Prepared via Electrospinning for Use as Unique Biocatalysts
Authors: Jia Hongfei , Zhu Guangyu , Vugrinovich Bradley , Kataphinan Woraphon , Reneker Darrell H. , Wang Ping
Published: October 2002

Improvement of catalytic efficiency of immobilized enzymes via materials engineering was demonstrated through the preparation of bioactive nanofibers. Bioactive polystyrene (PS) nanofibers with a typical diameter of 120 nm were prepared and examined for catalytic efficiency for biotransformations. The nanofibers were produced by electrospinning functionalized PS, followed by the chemical attachment of a model enzyme, α‐chymotrypsin. The observed enzyme loading as determined by active site titration was up to 1.4% (wt/wt), corresponding to over 27.4% monolayer coverage of the external surface of nanofibers. The apparent hydrolytic activity of the nanofibrous enzyme in aqueous solutions was over 65% of that of the native enzyme, indicating a high catalytic efficiency as compared to other forms of immobilized enzymes. Furthermore, nanofibrous α‐chymotrypsin exhibited a much‐improved nonaqueous activity that was over 3 orders of magnitude higher than that of its native counterpart suspended in organic solvents including hexane and isooctane. It appeared that the covalent binding also improved the enzyme's stability against structural denaturation, such that the half‐life of the nanofibrous enzyme in methanol was 18‐fold longer than that of the native enzyme.
Production of a Polyester Degrading Extracellular Hydrolase from Thermomonospora fusca
Authors: Gouda Mona K. , Kleeberg Ilona , van den Heuvel Joop , Müller Rolf‐Joachim , Deckwer Wolf‐Dieter
Published: October 2002

The production of a polyester‐degrading hydrolase from the thermophilic actinomycete Thermomonospora fusca was investigated with regard to its potential technical application. Only in the presence of a polyester (random aliphatic‐aromatic copolyester from 1,4‐butanediol, terephthalic acid, and adipic acid with around 40–50 mol % terephthalic acid in the acid component), the excretion of the extracellular enzyme could be achieved with an optimized synthetic medium using pectin and NH4Cl as nitrogen source. Compared to complex media, a significantly higher specific activity at comparable volumetric yields could be obtained, thus reducing the expenditure for purification. The activity profile in the medium is controlled by a complex process involving (1) induction of enzyme excretion, (2) enzyme adsorption on the hydrophobic polyester surface, (3) inhibition of enzyme generation by monomers produced by polyester cleavage, and (4) enzyme denaturation. Diafiltration with cellulose acetate membranes as the sole downstream processing step led to a product of high purity and with sufficient yield (60% of total activity). Scaling‐up from shaking flasks to a fermentor scale of 100 L revealed no specific problems. However, the excretion of the hydrolase by the actinomycete turned out to be inhibited by the degradation products (monomers) of the aliphatic‐aromatic copolyester used as inductor for the enzyme production. The crude enzyme exhibited generally similar properties (temperature and pH optimum) as the highly purified hydrolase described previously; however, the storage capability and thermal stability is improved when the crude enzyme solution is diafiltrated.