bluuebunny/crossref_metadata_2025 huggingface dataset:
The cost of inflated planned lead times in MRP systems
Authors: John Ralph St.
Published: October 2002

Much of the current literature in the field of production and inventory control systems stresses the need to revise traditional forms of thinking regarding production processes, the role of inventories for work in process, and the need for reduced lead times or flow times. Group technology, manufacturing cells, and other means of incorporating repetitive manufacturing techniques into traditional job‐shop settings constitute the leading edge in system development.

Still, there is resistance to these dramatic changes, and traditional “business as usual” methods still predominate. This study attempts to illustrate graphically the cost justification associated with reduction in lead times which generally results from these new concepts. In most job shops today, lead times are much longer than they need to be due to inflation of lead time estimates. Actual lead times for the manufacture of fabricated and assembled products have been shown to be a direct consequence of the planning lead times used in the MRP planning process—a form of self‐fulfilling prophesy.

The research employs a simulation model of a factory using MRP as a planning tool in a multiproduct, multilevel production environment. Manufacturing costs constitute the dependent variable in the experiments, defined as the sum of material costs (including expedite premiums), direct labor costs (including overtime premiums), inventory carrying costs, and overhead costs. The independent variable being manipulated is the planned lead time offset used in the MRP planning process. Twenty values of planned lead time are evaluated ranging from a value that includes no slack time at all (pure assembly line) up to a value that allows 95% slack (queue) time which, unfortunately, is not uncommon in many job shops today. Stochastic variables in the model include customer demand and actual processing times—the sum of set‐up and run times.

The result of the study is a cost curve formed over the range of independent lead time variables that is constructed using nonlinear regression techniques. The conclusions from the resultant graph clearly indicate the cost consequences of long lead times, with exponential cost increases beyond the 80–90% queue time level. Total costs are 41% higher at the maximum lead time allowance compared to the minimum. Clearly, this study demonstrates the need for lead time reduction, either through downward adjustment of MRP planned lead times or by introducing new manufacturing concepts.
Production lot sizing for deterministic rolling schedules
Authors: Bookbinder James H. , H'ng Bak‐Tee
Published: October 2002

In this article, we study production planning for a rolling horizon in which demands are known with certainty for a given number of periods in the future (the forecast window M). The rolling horizon approach implements only the earliest production decision before the model is rerun. The next production plan will again be based on M periods of future demand information, and its first lot‐sizing decision will be implemented.

Six separate lot‐sizing methods were evaluated for use in a rolling schedule. These include the Wagner‐Whitin algorithm, the Silver‐Meal heuristic, Maximum Part‐Period Gain of Karni, Heuristics 1 and 2 of Bookbinder and Tan, and Modification 1 to the Silver‐Meal heuristic by Silver and Miltenburg.

The performance of each lot‐sizing rule was studied for demands simulated from the following distributions: normal, uniform (each with four different standard deviations); bimodal uniform (two types); and trend seasonal (both increasing and decreasing trends). We considered four values of the setup cost (leading to natural ordering cycles in an EOQ model of three, four, five, and six periods) and forecast windows in the range 2 ⩽ M ⩽ 20.

Eight 300‐period replications were performed for each combination of demand pattern, setup cost, and lot‐sizing method. The analysis thus required consideration of 2304 300‐period replications (6 lot‐sizing methods × 12 demand patterns × 4 values of setup cost × 8 realizations), each of which was solved for nineteen different values of the forecast window M. The performance of the lot‐sizing methods was evaluated on the basis of their average cost increase over the optimal solution to each 300‐period problem, as though all these demands were known initially.

For smaller forecast windows, say 4 ⩽ M ⩽ 8, the most effective lot‐sizing rules were Heuristic 2 of Bookbinder and Tan and the modified Silver‐Meal heuristic. Rolling schedules from each were generally 1% to 5% in total cost above that of the optimal 300‐period solution. For larger forecast windows, M ⩾ 10 or so, the most effective lot‐sizing method was the Wagner‐Whitin algorithm. In agreement with other research on this problem, we found that the value of M at which the Wagner‐Whitin algorithm first becomes the most effective lot‐sizing rule is a decreasing function of the standard deviation of the demand distribution.
Coping with the build‐to‐forecast environment
Authors: Raturi Amitabh S. , Meredith Jack R. , McCutcheon David M. , Camm Jeffrey D.
Published: October 2002

High‐value‐added manufacturing companies today confront a competitive trend toward greater product customization in the face of reduced response times. This scenario is encountered most often in industries like machine tools, heavy construction equipment, heavy manufacturing in general and computer software and hardware. The product is highly customized, yet competition requires manufacturers to deliver it with lead times significantly shorter than the manufacturing lead time. Generally, the scheduling practice here is to release the manufacturing order before the customer order is released and subsequently match incoming customer orders to units in progress. This is referred to as the “build‐to‐forecast” (BTF) approach. This study investigated the coping mechanisms used by manufacturing firms to alleviate this dilemma. The tactics vary with the firm's business strategy, its operating environment, and its capabilities.

We report on three case studies from firms building heavy machinery. The firms are similar in terms of the range of final product values, build times, customer delivery times and the very large number of components. Also, their operations require the use of a variety of flexible and dedicated resources. Flexibility in manufacturing processes, modular bills of materials, subcontracting and expediting are some of the approaches that these firms use to help resolve the double bind of short lead times and high levels of customization.

We review some of the operational problems peculiar to the build‐to‐forecast environment and suggest alternative approaches for dealing with them. The coping mechanisms are grouped according to the manner by which they help relieve the BTF problem's severity. One set of mechanisms makes the problem less complex by simplifying products or the production process. Another set reduces the risks due to uncertainty in demand or supply. The third set provides engineering and manufacturing slack. While some or all of the mechanisms are used by the manufacturing firms studied, the predominance of particular mechanisms in each firm is explained by a contingency model developed in this paper.

The case studies provide useful insights into the nature of the problem and how the firm's organizational environment often dictates the choice of mechanisms used to alleviate it. For example, these firms minimized their scheduling dilemmas with modular product designs, flexible processes, informal organization structures, or formal control mechanisms for limiting customization. We conclude by framing a number of research questions whose solutions would help such firms better manage their operations.
A goal programming approach to the cell formation problem
Authors: Shafer Scott M. , Rogers David F.
Published: October 2002

Cellular manufacturing is employed to achieve efficiencies in production by exploiting similarities inherent in the production of parts. Specifically, parts with similar processing requirements are identified and the equipment necessary to process these groups of parts is identified and located together. Several important design objectives associated with cellular manufacturing are to: 1) reduce setup times, 2) produce parts cell complete, i.e., minimize intercellular movements of parts, 3) minimize investment in new equipment, and 4) maintain acceptable machine utilization levels.

The goal of this research was to develop a cell formation procedure that directly addressed these design objectives. To achieve this, three goal programming models were developed corresponding to three unique situations: (1) setting up an entirely new system and purchasing all new equipment, (2) reorganizing the system using only existing equipment, and (3) reorganizing the system using existing equipment and some new equipment.

Several assumptions were made in the development of the goal programming models. First, it was assumed that each part had a fixed routing. Also, it was assumed that the processing times for the parts at each machine, the demand for each part, and the capacity and cost of each machine were known. In addition it was assumed that a given machine type could be placed in more than one cell and that the sequence in which the parts are processed affects setup times. Finally, it was assumed that a batch of each part is produced every production cycle and that only one batch of parts is processed in a particular cell at any given time.

Clearly defining the objectives and constraints associated with the cell formation problem is the major contribution of the three formulations. Correct identification of the problem and the relationships inherent to cellular manufacturing is a necessary first step in the decision process that heretofore has not received adequate attention. However, because of the large number of 0/1 variables contained in the goal programming formulations they are very difficult to solve for realistically‐sized problems. Thus, a heuristic solution procedure is presented. The heuristic solution procedure involved partitioning the goal programming formulations into two Subproblems and solving them in successive stages. A numerical example is presented that illustrates the two‐stage heuristic procedure.
Detection of a very rapid first phase in complex formation of DnaK and peptide substrate
Authors: Koller Michael F. , Baici Antonio , Huber Michael , Christen Philipp
Published: October 2002

Complex formation of the Hsp70 chaperone DnaK with the fluorescence‐labeled peptide ALLLSAPRR shows a very rapid first phase that has as yet not been observed with other peptides. This first phase is completed within the dead time (1–2 ms) of the stopped‐flow instrument and corresponds to two thirds of the total increase in fluorescence. It occurs both in the presence and in the absence of ATP and is followed by a fast, a slow and a very slow step. These binding kinetics that are vastly different from those observed with other peptides might indicate the existence of a second substrate‐binding site of DnaK.
Identification of the first Rho–GEF inhibitor, TRIPα, which targets the RhoA‐specific GEF domain of Trio
Authors: Schmidt Susanne , Diriong Sylvie , Méry Jean , Fabbrizio Eric , Debant Anne
Published: October 2002

The Rho–guanine nucleotide exchange factors (Rho–GEFs) remodel the actin cytoskeleton via their Rho–GTPase targets and affect numerous physiological processes such as transformation and cell motility. They are therefore attractive targets to design specific inhibitors that may have therapeutic applications. Trio contains two Rho–GEF domains, GEFD1 and GEFD2, which activate the Rac and RhoA pathways, respectively. Here we have used a genetic screen in yeast to select in vivo peptides coupled to thioredoxin, called aptamers, that could inhibit GEFD2 activity. One aptamer, TRIAPα (TRio Inhibitory APtamer), specifically blocks GEFD2‐exchange activity on RhoA in vitro. The corresponding peptide sequence, TRIPα, inhibits TrioGEFD2‐mediated activation of RhoA in intact cells and specifically reverts the neurite retraction phenotype induced by TrioGEFD2 in PC12 cells. Thus TRIPα is the first Rho–GEF inhibitor isolated so far, and represents an important step in the design of inhibitors for the expanding family of Rho–GEFs.
Scaling limits and regularity results for a class of Ginzburg–Landau systems
Authors: Jerrard Robert L. , Soner Halil Mete
Published: October 2002

We study a class of parabolic systems which includes the Ginzburg–Landau heat flow equation,

u_{t}^{ \epsilon } - \Delta u^{ \epsilon } + \frac{1}{ \epsilon ^{2}}(|u^{ \epsilon }|^{2} - 1)u^{ \epsilon } = 0

for

u^ϵ: \mathbf R^d → \mathbf R^2

, as well as some natural quasilinear generalizations for functions taking values in

\mathbf R^k

,

k ≥ 2

.

We prove that for solutions of the general system, the limiting support as

ϵ → 0

of the energy measure is a codimension

k

manifold which evolves via mean curvature.

We also establish some local regularity results which hold uniformly in

ϵ

. In particular, we establish a small-energy regularity theorem for the general system, and we prove a stronger regularity result for the usual Ginzburg–Landau equation on

\mathbf R^2

.

Nous étudions une classe de systèmes paraboliques qui comprennent l’equation de chaleur Ginzburg–Landau,

u_{t}^{ ϵ } - \Delta u^{ ϵ } + \frac{1}{ ϵ ^{2}}(|u^{ϵ }t|^{2} - 1)u^{ ϵ } = 0

pour

u^ϵ : \mathbf R^d → \mathbf R^2

, ainsi que des généralisations quasilinéaires pour des fonctions prenant leurs valeurs dans

\mathbf R^k

,

k ≥ 2

.

Nous prouvons que, pour les solutions du système général, le support limite (lorsque

ϵ → 0

) de mèsure d’énergie est une varieté de codimension

k

qui évolue selon sa courbure moyenne.

Nous établissons en addition quelques resultats de regularité locale, qui sont valides uniformement en

ϵ

.
Happy birthday neuroleptics! 50 years later: la folie du doute
Authors: Stip Emmanuel
Published: October 2002

Given that we are celebrating the 50th birthday of neuroleptics introduction in psychiatry, the author proposes to take a look at certain results related to therapeutic practice. After a brief chronological literature review of the clinical practices and theoretical models that have controlled drug treatment of schizophrenia, the author presents a critical review of four meta-analyses. Since Delay, Deniker and Harl’s initial report, the story of neuroleptics comprises several periods. In 1963, the hyper-dopaminergic theory of psychoses was proposed. Another period began with models mainly based on the serotonin/dopamine relative blockade receptor hypothesis. More recently, a new framework to understand the differential effect of antipsychotics is related to the appropriate modulation (e.g., fast dissociation) of the D2 receptor alone. The concept of atypicality has become a new vista for research and to market new compounds. However, after 50 years of neuroleptic drugs, are we able to answer the following simple questions: Are neuroleptics effective in treating schizophrenia? Is there a difference between atypical and conventional neuroleptics? How do the efficacy and safety of newer antipsychotic drugs compare with those of clozapine? Actually, the answers yielded by these simple questions by meta-analysis should elicit in us a good deal of humility. If we wish to base psychiatry on evidence-based medicine, we run a genuine risk in taking a closer look at what has long been considered fact. Each psychiatrist must continue to be critical, sceptical, optimistic (not overoptimistic) and to learn in order to integrate the positive aspects of our growing knowledge base.
The CCK-A receptor gene possibly associated with auditory hallucinations in schizophrenia
Authors: Wei J. , Hemmings G.P.
Published: October 2002

In this study, a PstI polymorphic site with two individual alleles, namely A1 and A2, was identified within the boundary between intron 1 and exon 2 of the cholecystokinin (CCK) type A receptor gene. The PstI polymorphic site was used as a genetic marker to study its association with psychotic symptoms in schizophrenia. A significant difference in allelic frequency was found between schizophrenic patients with and without auditory hallucinations (χ2 = 6.26, df = 1, P = 0.012), and the odds ratio for the allelic association was 2.21 (95% CI 1.18–4.15) with an attributable fraction of 0.1. The frequency of A1-A1 and A1-A2 genotypes showed a significant excess in schizophrenic patients with auditory hallucinations as compared to those without such symptoms (χ2 = 5.45, df = 1, P = 0.02), and the odds ratio for the genotypic association was 2.27 (95% CI 1.13–4.57) with an attributable fraction of 0.177. The haplotype-based haplotype relative risk (HHRR) test revealed a significant difference between transmitted and non-transmitted alleles in nuclear families of schizophrenic patients with auditory hallucinations (χ2 = 4.54, df = 1,P = 0.033) but not in those of schizophrenic patients without them. The present study suggests that the CCK-A receptor gene may be associated with auditory hallucinations in schizophrenia.
A new questionnaire assessing the opinions of the relatives of patients with schizophrenia on the causes and social consequences of the disorder: reliability and validity
Authors: Magliano L. , Marasco C. , Guarneri M. , Malangone C. , Lacrimini G. , Zanus P. , Maj M.
Published: October 2002

This paper describes the development and the validation of a questionnaire assessing the opinions of the relatives of patients with schizophrenia on the causes and the social consequences of the disorder. The final version of the questionnaire includes 28 items, grouped in four sub-scales (social restrictions, social distance, utility of treatments, biopsychosocial causes of schizophrenia), whose intra-rater reliability ranges from 0.36 to 0.84. Cronbach's alpha coefficient, which tests the content validity of the sub-scales, ranges from 0.56 to 0.66. Factor analysis identifies two factors (opinions on social consequences and the utility of treatments, and the beliefs on the causes of schizophrenia), which account for the 73% of the total variance. This questionnaire may be particularly useful to assess relatives'beliefs about schizophrenia and to target psychosocial interventions in the families of patients with schizophrenia.
Huxley and scientific agnosticism: the strange history of a failed rhetorical strategy
Authors: LIGHTMAN BERNARD
Published: October 2002

Huxley's invention of the term ‘agnostic’ in 1869 is often seen as a brilliant rhetorical strategy. Portrayed as an effective weapon in Huxley's public debates with defenders of the Anglican establishment, the creation of scientific agnosticism has been interpreted as a turning point in the relationship between science and religion. In this paper I will challenge this interpretation of the rise of scientific agnosticism. Huxley was reluctant to identify himself unambiguously as an agnostic in public until 1883 and his restricted use of agnostic concepts during the 1870s and 1880s was compromised when other unbelievers, with different agendas, sought to capitalize on the polemical advantages of referring to themselves as agnostics. As a result, he was not always associated with agnosticism in the public mind and his original conception of it was modified by others to the point where he felt compelled to intervene in 1889 to set the record straight. But Huxley could not control the public meaning of ‘agnosticism’ and its value to him as a rhetorical strategy was severely limited.
Occurrence of the lessepsian species Leonnates persicus (Polychaeta: Nereididae) in Izmir Bay, Aegean Sea
Authors: Çinar Melih Ertan , Ergen Zeki , Dağli Ertan
Published: October 2002

The recent establishment of the lessepsian species Leonnates persicus (Annelida: Polychaeta: Nereididae) in Izmir Bay (Aegean Sea) was investigated. A total of four specimens were collected at three stations in December 2001, with two specimens having eggs within their coelomic cavities and parapodia. A re-description of the species together with its ecological and distributional aspects are provided.
Concentration of statolith trace elements in the jumbo flying squid during El Niño and non-El Niño years in the eastern Pacific
Authors: Ikeda Yuzuru , Yatsu Akihiko , Arai Nobuaki , Sakamoto Wataru
Published: October 2002

Statoliths of the jumbo flying squid Dosidicus gigas (Cephalopoda: Ommastrephidae) in the eastern Pacific in 1995, 1996 (non-El Niño years) and 1997 (El Niño year) were analysed to observe whether unusual temperature increases due to El Niño was recorded in the concentration of trace elements. In addition to calcium (the major element), trace elements of manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), and strontium (Sr) were detected. Strontium concentration in the calcified tissue of some aquatic animals changes with environmental variables. However, yearly comparisons revealed that Sr concentration did not significantly differ between the El Niño year and non-El Niño years. Instead, the Sr concentration differed with squid habitats. Strontium concentration in statoliths of D. gigas from Peruvian waters (high salinity) was significantly higher than those from Costa Rican waters (low salinity) regardless of El Niño.
Resistant Medium: The Voices of Zulu Radio Drama in the 1970s
Authors: Gunner Liz
Published: October 2002

The making of culture in South Africa through different but linked forms and genres focuses on the medium of radio, and the ‘emergent genre’ of Zulu serial radio drama. Using Benedict Anderson's notion of ‘socioscape’ a link is drawn between the wide sweep of historical events and the production of culture. Beginning with the case of the musical, uMabatha [Macbeth], its performance history, and its links with serial radio drama in Zulu, this article focuses on the ways in which this, in turn was linked to the ‘performance’ of African football commentary on radio, and points to the national resonances that the act, and art, of commentating built up for both announcers and listeners. Finally, three representative radio serial plays from the 1970s are examined in relation to the ways in which they engaged with the social and political realities of the time. Through the multi-accentual nature of language and the polysemic nature of the plays themselves these plays might appear to endorse or, at least, acquiesce in the dominant apartheid ideology of the era, yet at the same time they offered resistant alternatives to it.
Staphylococcus aureus nasal carriage in the community: a survey from central Italy
Authors: ZANELLI G. , SANSONI A. , ZANCHI A. , CRESTI S. , POLLINI S. , ROSSOLINI G. M. , CELLESI C.
Published: October 2002

Recently, concern has increased regarding the spread of methicillin-resistant Staphylococcus aureus (MRSA) in the community. We studied 812 subjects from central Italy to establish the rates of nasal carriage of S. aureus, and antibiotic susceptibility patterns, in the community. The prevalence of S. aureus nasal carriage was 30.5%. Only one subject, with predisposing risk factors for acquisition, was identified as carrier of MRSA (prevalence of 0.12%). The presence of MRSA in the community of our area still appears to be a rare event. Among methicillin-susceptible S. aureus (MSSA) isolates, a surprisingly high rate (18%) of resistance to rifampin was observed.
Nucleotide substitutions in vanC-2 gene of Enterococcus casseliflavus isolates obtained from chickens
Authors: MURASE T. , MITO Y. , OTSUKI K. , SUZUKI R. , YAMAI S.
Published: October 2002

DNA sequencing of the vanC-2 gene was partially carried out on 10 isolates of Enterococcus casseliflavus obtained from 8 samples of imported chickens in Japan between July 1999 and June 2001 to evaluate the variation in the gene. Forty nucleotide substitutions in 36 codons were identified within 345 base pairs when compared with the vanC-2 sequence of the reference strain E. casseliflavus ATCC25788. Identical nucleotide substitutions were commonly found in the isolates recovered from chickens imported from both Brazil and China. Pulsed-field gel electrophoresis (PFGE) patterns of NotI-digested chromosomal DNA of these strains were distinguished by two, or more than six, band differences. These observations suggest that sequencing of the vanC-2 gene may be helpful for epidemiological investigation in combination with the PFGE analyses of the isolates, although particular genotypes are unlikely to be restricted to each of the countries that exported chickens.
Networks, environments and the American city
Authors: Hassan John
Published: October 2002

American fascination with the frontier and concern that economic progress might waste the beauty and vast resources of the wilderness has helped environmental history in the United States to thrive for some time. Many publications tended to be conservationist and ‘foundationalist’ in terms of the lofty place ascribed to nature. These traits were shaped by the subject's formative links with political environmentalism, as both phenomena came to life in the 1960s as self-conscious and independent activities. Even after scholars became more interested in the role played by the capitalist system in conditioning the way that cities made demands on the environment, environmental historians’ study of urban growth, including the search for water supplies, tended to focus upon the impacts on the land or its original Indian inhabitants, on how rural harmonies were disrupted by urban greed – in sum to cede to a ‘broader agroecological approach’ as the dominant orthodoxy within the discipline. American environmental historians, of course, are fixated by these issues and have engaged in subtle and profound debates about the proper purpose and methods of their calling.
Genome-Wide Identification of Nodule-Specific Transcripts in the Model Legume Medicago truncatula
Authors: Fedorova Maria , van de Mortel Judith , Matsumoto Peter A. , Cho Jennifer , Town Christopher D. , VandenBosch Kathryn A. , Gantt J. Stephen , Vance Carroll P.
Published: October 2002

The Medicago truncatula expressed sequence tag (EST) database (Gene Index) contains over 140,000 sequences from 30 cDNA libraries. This resource offers the possibility of identifying previously uncharacterized genes and assessing the frequency and tissue specificity of their expression in silico. BecauseM. truncatula forms symbiotic root nodules, unlike Arabidopsis, this is a particularly important approach in investigating genes specific to nodule development and function in legumes. Our analyses have revealed 340 putative gene products, or tentative consensus sequences (TCs), expressed solely in root nodules. These TCs were represented by two to 379 ESTs. Of these TCs, 3% appear to encode novel proteins, 57% encode proteins with a weak similarity to the GenBank accessions, and 40% encode proteins with strong similarity to the known proteins. Nodule-specific TCs were grouped into nine categories based on the predicted function of their protein products. Besides previously characterized nodulins, other examples of highly abundant nodule-specific transcripts include plantacyanin, agglutinin, embryo-specific protein, and purine permease. Six nodule-specific TCs encode calmodulin-like proteins that possess a unique cleavable transit sequence potentially targeting the protein into the peribacteroid space. Surprisingly, 114 nodule-specific TCs encode small Cys cluster proteins with a cleavable transit peptide. To determine the validity of the in silico analysis, expression of 91 putative nodule-specific TCs was analyzed by macroarray and RNA-blot hybridizations. Nodule-enhanced expression was confirmed experimentally for the TCs composed of five or more ESTs, whereas the results for those TCs containing fewer ESTs were variable.
Role of ANC-1 in Tethering Nuclei to the Actin Cytoskeleton
Authors: Starr Daniel A. , Han Min
Published: October 2002

Mutations in
anc-1
(nuclear anchorage defective) disrupt the positioning of nuclei and mitochondria in
Caenorhabditis elegans
. ANC-1 is shown to consist of mostly coiled regions with a nuclear envelope localization domain (called the KASH domain) and an actin-binding domain; this structure was conserved with the
Drosophila
protein Msp-300 and the mammalian Syne proteins. Antibodies against ANC-1 localized cytoplasmically and were enriched at the nuclear periphery in an UNC-84–dependent manner. Overexpression of the KASH domain or the actin-binding domain caused a dominant negative anchorage defect. Thus, ANC-1 may connect nuclei to the cytoskeleton by interacting with UNC-84 at the nuclear envelope and with actin in the cytoplasm.
A strategy for the one-pot synthesis of sialylated oligosaccharides
Authors: Zhang Zhiyuan , Niikura Kenichi , Huang Xue-Fei , Wong Chi-Huey
Published: October 2002

A new strategy has been developed for the synthesis of branched sialylated oligosaccharides using one-pot technology. Sialyl donors are in general too weak in reactivity to be used as the first glycosyl donors in the one-pot synthesis. When sialic acid is linked to a different sugar such as galactose, the reactivity is, however, significantly enhanced and can be tuned to enable the one-pot synthesis. A combination of NISTfOHAgOTf was used for activation of the thioglycosides to improve the glycosylation yield when a hindered acceptor was used, as illustrated in the one-pot assembly of sialylated hexasaccharide.Key words: one-pot synthesis, sialyl oligosaccharides, new activation.
Crystal structure and spectral considerations of 5-methyl-2-nitraminopyridine N-oxide
Authors: Szemik-Hojniak A , Glowiak T , Deperasinska I , Puszko A
Published: October 2002

The crystal structure of 5-methyl-2-nitraminopyridine N-oxide (5M) has been determined and its electronic absorption spectra in the solution have been investigated. In the solid, two monomeric proton-transferred (PT) units of 5M are perpendicularly located in the crystal lattice. They are connected by two intermolecular hydrogen bonds of different strength (O-H···N 2.647(3) and 2.695(3) Å). In the gas phase the same relative arrangement of both 5M (PT) monomers has been found. As results from semiempirical PM3-CI calculations (1214), the prototropic amino (H) [Formula: see text] imino (PT) equilibrium may occur in the solution. Assignment of experimental absorption bands to the calculated transition energies of both forms of 5M reveals that hydrogen bonded 5M (PT) dimers are dominant in cyclohexane while imino (PT) monomers seem to prevail in acetonitrile solution. The different character of electronic transitions and different relative arrangement of both monomers in amino (H) than in imino (PT) dimers are responsible for very low oscillator strengths and dipole moments of the former.Key words: crystal structure, methylated nitraminopyridine N-oxides, semiempirical PM3-CI computations, intermolecular hydrogen bonding.
Synthesis and reactivity of palladium and platinum diimine complexes containing boronate esters
Authors: King Arienne S , Nikolcheva Liliya G , Graves Christopher R , Kaminski Anna , Vogels Christopher M , Hudson Robert HE , Ireland Robert J , Duffy Stephen J , Westcott Stephen A
Published: October 2002

Condensation of α-diketones (2,3-butanedione, benzil, and acenaphthenequinone) with 3-H2NC6H4Bpin (pin = 1,2-O2C2Me4) gave the corresponding boron-containing α-diimines. The addition of these ligands to [MCl2(coe)]2 (coe = cis-cyclooctene, M = Pd or Pt) gave complexes of the type cis-MCl2(α-diimine) in moderate to high yields. The platinum complexes have been examined for their ability to bind to DNA using enzyme digest studies. These complexes were found to bind to single-stranded DNA as well as, or better than, the non-boron containing controls, and showed binding similar to that of cisplatin (cis-PtCl2(NH3)2).Key words: boronate esters, diazabutadienes, DNA-binding, platinum.
Synthesis of a polyphosphorylated GPI-anchor core structure
Authors: Lahmann Martina , Garegg Per J , Konradsson Peter , Oscarson Stefan
Published: October 2002

Using a linear assembly approach a highly differentially protected derivative of the common GPI-anchor core structure (α-D-Man-(1[Formula: see text]6)-α-D-Man-(1[Formula: see text]2)-α-D-Man-(1[Formula: see text]4)-α-D-GlcNH2-(1[Formula: see text]6)-D-myo-inositol) has been synthesized. All mannose donors were prepared from a common thioglycoside precursor (1), and coupled to GlcN3-myo-inositol acceptor 5 in a linear five-step glycosylationdeprotection sequence in 49% overall yield, to give the key intermediate 10, with orthogonal temporary protecting groups at the 6'', 2'', 6', and 2 positions of the trimannoside motif and at the 1 and 2 positions of the inositol part. Consecutive removal of the temporary protecting groups in the trimannoside moiety followed by phosphorylation, gave a tetraphosphosphate derivative in 60% overall yield. Removal of a camphor acetal afforded a 1,2-inositol diol, which was converted to a 1,2-cyclic phosphate using commercial methyl dichlorophosphate ([Formula: see text]17, 95%). One-step deprotection using sodium in liquid ammonia afforded the target polyphosphorylated core structure 18 (60%), which will be tested for metabolic insulin action.Key words: glycophosphatidylinositols, linear synthesis, glycosylations, inositolphosphoglycans, IPG.
Thermodynamic binding studies of cell surface carbohydrate epitopes to galectins-1, -3, and -7: Evidence for differential binding specificities
Authors: Ahmad Nisar , Gabius Hans -J , Kaltner Herbert , André Sabine , Kuwabara Ichiro , Liu Fu-Tong , Oscarson Stefan , Norberg Thomas , Brewer C Fred
Published: October 2002

Binding of a series of sialylated and non-sialylated cell surface carbohydrates to bovine heart galectin-1, recombinant murine galectin-3, and recombinant human galectin-7 was investigated by isothermal titration microcalori metry (ITC) and hemagglutination inhibition measurements. Galectin-7 shows nearly equal affinities for lactose and Galbeta(14)GlcNAc (LacNAc-II). Galectin-7, however, displays six- and 11-fold weaker affinity for LacNAc-II compared with galectins-1 and -3, respectively. The affinity of galectin-7 for LacNAc-II containing oligosaccharides is also weaker than the other two galectins. ITC measurements show that all three galectins bind to di- and trimeric oligomers of LacNAc-II, which are epitopes found in poly-N-acetyllactosamine chains of glycoprotein receptors, with affinity constants similar to that of LacNAc-II. The binding valencies of the di- and trimeric LacNAc-II oligomers were observed to be one from ITC measurements, indicating formation of 1:1 complexes with all three galectins. Thus, galectins-1, -3, and -7 all possess binding sites that primarily accommodate one LacNAc-II moiety per monomer of protein. Sialylated oligosaccharides show different specificities for the three galectins. While 2,3-sialyl LacNAc-II binds to all three galectins, 2,6-sialyl LacNAc-II fails to bind to any of the galectins; 2,6-sialylated diLacNAc binds well to galectin-3 and galectin-7, but only weakly to galectin-1. Similar results are obtained with 2,6-sialyl lacto-N-neo-tetraose, which has a reducing end lactose moiety. Thus, unlike galectin-1, which predominantly recognizes non-reducing terminal LacNAc-II residues in oligosaccharides, galectins-3 and -7 recognize both non-reducing terminal LacNAc-II residues as well as internal LacNAc-II and lactose residues in sialylated and non-sialylated oligosaccharides.Key words: isothermal titration microcalorimetry, galectins, binding specificities, lectins, carbohydrates.
QUANTUM GRAVITY CORRECTIONS TO PARTICLE INTERACTIONS
Authors: URRUTIA LUIS
Published: October 2002

An heuristic semiclassical procedure that incorporates quantum gravity induced corrections in the description of photons and spin 1/2 fermions is reviewed. Such modifications are calculated in the framework of loop quantum gravity and they arise from the granular structure of space at short distances. The resulting effective theories are described by power counting non-renormalizable actions which exhibit Lorentz violations at Planck length scale. The modified Maxwell an Dirac equations lead to corrections of the energy momentum relations for the corresponding particle at such scale. An action for the relativistic point particle exhibiting such modified dispersion relations is constructed and the first steps towards the study of a consistent coupling between these effective theories are presented.
INTERFACE OF GRAVITATIONAL AND QUANTUM REALMS
Authors: AHLUWALIA D. V.
Published: October 2002

The talk centers around the question: Can general-relativistic description of physical reality be considered complete? On the way I argue how – unknown to many a physicists, even today – the "forty orders of magnitude argument" against quantum gravity phenomenology was defeated more than a quarter of a century ago, and how we now stand at the possible verge of detecting a signal for the spacetime foam, and studying the gravitationally-modified wave particle duality using superconducting quantum interference devices.
NON-LOCALITY OF QUANTUM MECHANICS AND THE LOCALITY OF GENERAL RELATIVITY
Authors: ANANDAN JEEVA
Published: October 2002

The conflict between the locality of general relativity, reflected in its space-time description, and the non-locality of quantum mechanics, contained in its Hilbert space description, is discussed. Gauge covariant non-local observables that depend on gauge fields and gravity as well as the wave function are used in order to try to understand and minimize this conflict within the frame-work of these two theories. Applications are made to the Aharonov-Bohm effect and its generalizations to non Abelian gauge fields and gravity.
EMISSION OF CERENKOV RADIATION BY CHARGED PARTICLES IN STATIONARY GEOMETRIES
Authors: LAMBIASE G.
Published: October 2002

The emission of the Cerenkov radiation by charged particles is analyzed for stationary metrics. Results are applied to the Kerr geometry and the scalar–tensor theories of gravity. Particular emphasis is given to Brans–Dicke theory of gravity where the Cerenkov effect turns out to be kinematically allowed. It is related to the Brans–Dicke parameter ω, and vanishes in the limit in which general relativity is recovered (ω → ∞).
ANALYSIS AND PROBABILITY LAWS
Authors: CHIN C. H. , CHUNG C. L.
Published: October 2002

The analysis and probability laws are proposed. The goal is to interpret the recent observations of the universe from the cosmological point of view.
Hydrops fetalis–associated congenital dyserythropoietic anemia treated with intrauterine transfusions and bone marrow transplantation
Authors: Remacha Angel F. , Badell Isabel , Pujol-Moix Núria , Parra Juan , Muñiz-Diaz Eduardo , Ginovart Gemma , Sardà M. Pilar , Hernández Angel , Moliner Elisenda , Torrent Montserrat
Published: October 2002

Hydrops fetalis is rarely caused by congenital dyserythropoietic anemia (CDA). We report a patient with hydrops fetalis as a result of severe anemia. This patient needed intrauterine transfusions from 21 weeks of gestation until birth. The hematologic study showed an atypical CDA (hydrops fetalis–associated CDA) characterized by features resembling CDA type II, but negative acidified serum lysis test (HEMPAS negative). The patient was regularly transfused for a year, after which an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling was successfully carried out. His actual hemoglobin is 127 g/L, and he has not received transfusions for more than a year. In conclusion, intrauterine transfusions and BMT could cure an otherwise lethal atypical CDA.
Complete remission through blast cell differentiation inPLZF/RARα-positive acute promyelocytic leukemia: in vitro and in vivo studies
Authors: Petti Maria C. , Fazi Francesco , Gentile Massimo , Diverio Daniela , De Fabritiis Paolo , De Propris M. Stefania , Fiorini Roberto , Spiriti Maria A. Aloe , Padula Fabrizio , Pelicci Pier Giuseppe , Nervi Clara , Lo Coco Francesco
Published: October 2002

Acute leukemia with the t(11;17) expressing the PLZF-RARαgene fusion is a rare variant of acute promyelocytic leukemia (APL) that has been associated with poor clinical response to all-trans retinoic acid (ATRA) treatment. However, some recent reports have put into question the absolute refractoriness of this leukemia to ATRA. We describe here a patient withPLZF/RARα APL who was treated at relapse with ATRA and low-dose hydroxyurea. Complete hematologic remission was obtained through differentiation of leukemic blasts, as proven by morphologic, immunophenophenotypic, and genetic studies carried out in sequential bone marrow samples. Moreover, in vitro studies indicated that blast differentiation was potentiated by the addition of the histone deacetylase inhibitor tricostatin A, but not of hydroxyurea, to ATRA. Our findings indicate that the maturation block may be overcome and terminal differentiation obtained in this leukemia subset and support the view that sensitivity/refractoriness of this form to ATRA should be revisited.
Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease
Authors: Gorgun Gullu , Miller Kenneth B. , Foss Francine M.
Published: October 2002

Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but its biologic mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios but also with an increase in CD3−/CD56+ natural killer cells and a decrease in the number of CD80+ and CD123+ circulating dendritic cells (DCs). To further elucidate the effects of ECP on activated lymphocyte subpopulations and the interaction between effector lymphocytes and antigen-presenting DCs, we isolated and characterized DC populations from patients with chronic GVHD undergoing ECP therapy. Antigen-presenting activity of DCs was measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed-lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84% (range, 75%-95%; P ≤ .002) after a 2-day cycle of ECP and longitudinally over the 12-month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients before the initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2 and as a concordant shift from a predominantly Th1 (interleukin-2 [IL-2], interferon-γ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting allo-targeted effector T cells and antigen-presenting DCs.
NAD(P)H oxidase–dependent platelet superoxide anion release increases platelet recruitment
Authors: Krötz Florian , Sohn Hae Young , Gloe Torsten , Zahler Stefan , Riexinger Tobias , Schiele Thomas M. , Becker Bernhard F. , Theisen Karl , Klauss Volker , Pohl Ulrich
Published: October 2002

Platelets, although not phagocytotic, have been suggested to release O2−. Since O2−-producing reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases can be specifically activated by certain agonists and are found in several nonphagocytotic tissues, we investigated whether such an enzyme is the source of platelet-derived O2−. We further studied which agonists cause platelet O2−release and whether platelet-derived O2− influences thrombus formation in vitro. Collagen, but not adenosine 5′-diphosphate (ADP) or thrombin, increased O2− formation in washed human platelets. This was a reduced nicotinamide adenine dinucleotide (NADH)–dependent process, as shown in platelet lysates. Consistent with a role of a platelet, NAD(P)H oxidase expression of its subunits p47phox and p67phoxand inhibition of platelet O2− formation by diphenylene-iodoniumchloride (DPI) and by the specific peptide-antagonist gp91ds-tat were observed. Whereas platelet-derived O2− did not influence initial aggregation, platelet recruitment to a preformed thrombus following collagen stimulation was significantly attenuated by superoxide dismutase (SOD) or DPI. It was also inhibited when ADP released during aggregation was cleaved by the ectonucleotidase apyrase. ADP in supernatants of collagen-activated platelets was decreased in the presence of SOD, resulting in lower ADP concentrations available for recruitment of further platelets. Exogenous O2−increased ADP- concentrations in supernatants of collagen-stimulated platelets and induced irreversible aggregation when platelets were stimulated with otherwise subthreshold concentrations of ADP. These results strongly suggest that collagen activation induces NAD(P)H oxidase–dependent O2− release in platelets, which in turn enhances availability of released ADP, resulting in increased platelet recruitment.
Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution
Authors: Klangsinsirikul Phennapha , Carter G. Ian , Byrne Jennifer L. , Hale Geoff , Russell Nigel H.
Published: October 2002

Graft-versus-host disease (GVHD), a major complication after allogeneic transplantation, can be abrogated by the Campath (anti-CD52) monoclonal antibody. The induction of acute GVHD requires host antigens to be presented to donor T cells by antigen-presenting cells (APCs). Recent evidence has suggested that only host APCs can interact with donor T cells in the induction of GVHD. Because CD52 has been reported to be expressed on DCs, we reasoned that pretransplant Campath-1G might have a direct effect on circulating DCs in addition to any effects on donor T cells. Using direct immunostaining, we demonstrated expression of CD52 on DCs and that Campath-1G killed purified DCs in vitro. In vivo Campath also depleted DCs. Twenty-four hours after the first dose of Campath-1G, circulating DCs were reduced by a mean of 79% (range, 44%-96%). By day 0 after 5 doses of Campath-1G and chemoradiotherapy conditioning, DCs became undetectable in 7 of 9 cases, whereas in 6 of 7 patients receiving conditioning therapy without Campath-1G, host DCs were still detectable. The reconstitution of circulating DCs after transplantation was not affected by Campath-1G and in both groups DC1 (CD11c+) recovered more rapidly than DC2 (CD11c−). Analysis of chimerism confirmed that the DCs recovering after transplantation in patients receiving Campath-1G were of donor origin. We conclude that in vivo Campath-1G causes a rapid depletion of host circulating DCs and that this may, in part, explain the low incidence of acute GVHD. The reconstitution of donor DCs was not delayed, which may be important in preserving immune reconstitution.