bluuebunny/crossref_metadata_2025 huggingface dataset:
A developmental decrease in NMDA‐mediated spontaneous firing in cultured rat cerebral cortex
Authors: Ramakers G.J.A. , de Wit C. , Wolters P.S. , Corner M.A.
Published: April 2003

In primary cultures of fetal rat cerebral cortex chronic manipulation of the level and/or pattern of bioelectric activity leads to plastic changes in bioelectric activity, opposite to those seen during the manipulation. This suggests the presence of adaptive mechanisms which regulate functional development in the neuronal network. Since NMDA receptors play an important role in early postnatal bioelectric activity and have been implicated in activity‐dependent plasticity in vivo, the involvement of NMDA and non‐NMDA receptors in spontaneously occurring bioelectric activity was investigated in cultured rat cerebral cortex by assaying the effects of NMDA and non‐NMDA antagonists on neuronal firing. In addition, the physiological consequences of chronic suppression of bioelectric activity were investigated following development in the presence of tetrodotoxin. NMDA receptors appeared at all ages to be more crucial for spontaneous bioelectric activity than non‐NMDA receptors, although their relative importance decreased during the first 3 weeks. Whereas the NMDA antagonist APV strongly reduced burst firing, the non‐NMDA antagonist DNQX tended to increase burst firing slightly. Following chronic suppression of bioelectric activity, non‐variable burst firing was increased, thus replicating previous findings in cerebral cortex culture grown under different conditions. The prominence of NMDA receptor activation in spontaneous bioelectric activity in early cultures suggests a role for these receptors in activity‐dependent functional plasticity, as found in vivo.
Reactive astrocytes in neonate brain upregulate intermediate filament gene expression in response to axonal injury
Authors: Oblinger∗ Monica M. , Singh Leelabai D.
Published: April 2003

We have examined the injury response of astrocytes in the immature hamster brain in this study, focusing on alterations in the expression of glial fibrillary acidic protein (GFAP) and vimentin. In the adult CNS these two type III intermediate filament (IF) proteins have been shown to undergo robust increases in expression in response to axonal injury. Since injury to the immature CNS reportedly elicits less glial scar formation than adult brain injury, we examined the possibility that immature astrocytes respond differently than adult astrocytes to CNS injury with respect to IF gene expression. In situ hybridization using a 35S‐labeled cDNA GFAP probe was done on brainstem sections obtained 2,7 and 14 days after unilateral transection of the corticospinal tract in P8 hamster pups. The results indicated that substantial increases in GFAP mRNA were associated with the degenerating portion of the corticospinal tract by 2 days after axotomy and that the levels remained elevated for at least 14 days. Double‐label immunofluorescence studies of this material suggested that GFAP as well as vimentin protein levels were also increased in many astrocytes in and around the degenerating corticospinal tract 2–14 days after axotomy. Most of the reactive astocytes in the degenerating regions exhibited increases in GFAP and vimentin immunostaining but some vimentin‐negative GFAP‐positive reactive astrocytes were also observed, particularly in regions surrounding the actual degenerative zones. The results from these experiments revealed that immature astrocytes have the potential for altering their normal developmental program of GFAP and vimentin expression after injury and mount a response that is qualitatively similar to that of astrocytes after CNS injury in the adult animal.
Differential expression of immediate‐early proteins in non‐nerve cells after focal brain injury
Authors: Dragunow M. , Hughes P.
Published: April 2003

We investigated the expression of the immediate‐early proteins (IEPs, Fos, Fos B, Jun, Jun B, Jun D, Krox 20 and Krox 24) in non‐nerve cells in rat brain after mechanical brain injury. Injury produced by infusion of 5 μl of saline into the hippocampus produced a time‐dependent expression of Fos, Jun and Krox 24, but not Fos B, Krox 20 or in non‐nerve cells around the wound margin, in cells lining the lateral and third ventricles and in cells in the pial surfaces of the brain. Jun B and D were weakly induced in non‐nerve cells 1–4 hr after brain injury. This differential expression of IEPs in non‐nerve cells contrasted with neurons which expressed all IEPs measured. Thus, brain injury is associated with a differential expression of IEPs in non‐nerve cells around the wound. The functional implications of this IEP expression after brain injury are presently unclear, but may be related to cellular proliferation after brain injury.
Neuronal phenotypes in mouse dorsal root ganglion cell cultures: Enrichment of substance P and calbindin D‐28k expressing neurons in a defined medium
Authors: Ninomiya T. , Barakat‐Walter I. , Droz B.
Published: April 2003

The primary sensory neurons in mouse dorsal root ganglia consist of diversified subpopulations which express distinct phenotypic characteristics such as substance P or calbindin D‐28k. To determine whether neuronal phenotypes are altered or not in in vitro cultures carried out in a defined synthetic medium, dissociated dorsal root ganglion cells from newborn mice were grown in the alpha‐modified minimum essential medium either supplemented with 10% fetal calf serum or serum‐free. About 80% of the neurons survived after 5 days of culture in both media, but only 35% or 65% were rescued after 12 days in serum‐free or fetal calf serum supplemented medium, respectively. The neuronal subpopulations expressing substance P or calbindin D‐28k displayed similar morphological properties in both media and a higher resistance to culture conditions than the whole neuronal cell population, especially in serum‐free medium. It is therefore concluded that a defined synthetic medium offers reproducible conditions to culture dorsal root ganglion cells for at least 5 days, stimulates the expression of substance P and enriches preferentially neuronal phenotypes expressing substance P or calbindin D‐28k, for a longer period of culture.
Maturational changes in sympathetic and sensory innervation of the rat uterus: Effects of neonatal capsaicin treatment
Authors: Brauer M.M. , Lincoln J. , Sarner S. , Blundell D. , Milner P. , Passaro M. , Burnstock G.
Published: April 2003

The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline‐containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene‐related peptide‐containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long‐lasting depletion of substance P‐ and calcitonin gene‐related peptide‐containing nerves. In the uterine horn and parametrial tissue, capsaicin‐resistant calcitonin gene‐related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non‐vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non‐vascular noradrenaline‐containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.
Gm1 ganglioside and darkly staining neurons in brains of rats subjected to neonatal hypoxia‐ischemia
Authors: Aguis Lawrence , Hadjiconstantinou Maria , Qu Zan‐Xi , Neff Norton H. , Pearl Dennis K. , Yates Allan J.
Published: April 2003

Rat pups, seven days old, with right carotid artery ligations were exposed to an atmosphere of oxygen 8% remainder nitrogen for 2 hr. The animals that survived for three weeks after the hypoxic‐ischemic episode had clusters of darkly stained (hematoxylin‐eosin) neurons in the cortex and reduced uptake of dopamine (frontal cortex) and choline (frontal cortex, hippocampus and striatum) in preparations of synaptosomes. Treatment with GM1 ganglioside partially corrected the loss of uptake activity and increased the number of darkly stained neurons.
Horizontal cells in the rabbit retina: Differentiation of subtypes at neonatal and postnatal stages
Authors: Lyser Katherine M. , Li Anne I. , Nuñez Maribel
Published: April 2003

We are investigating the differentiation of the major subtypes of horizontal cell in the rabbit retina in order to learn more about developmental controls responsible for the variety of neuronal phenotypes. Immunohistochemistry with anti‐neurofilament and anti‐calbindin‐D antibodies, followed by epoxy resin embedding, has facilitated study of these neurons. In the mature rabbit retina, axonless (A‐type) horizontal cells reacted strongly in procedures using either antibody; short axon (B‐type) somas did not show a reaction with anti‐neurofilament antibodies and stained moderately using anti‐calbindin antibodies. In the immature neonatal retina the somas of all the horizontal cells seemed to be similar with regard to general morphology, but two populations could be distinguished on the basis of immunostaining. Some, identified as A‐type horizontal cells (by comparison with mature retina), were stained using either antibody. Interspersed among these were similar cells with no detectable immunoreactivity, identified as B‐type horizontal cells. By the end of the first postnatal week, faint reactivity to anti‐calbindin‐D was present in the somas of B‐type horizontal cells; they stained moderately throughout the rest of the period studied.

Thus differences in immunostaining indicate that the two horizontal cell subpopulations are established early in the rabbit, though some other distinguishing characteristics emerge only gradually as the retina matures. These results suggest that in mammals the determination of phenotypic subtype occurs early, possibly at the time that the cell is specified as a horizontal neuron, or shortly thereafter.
Persistence of heterotypical synapses in transplanted cerebellar cultures in the absence of functional glia
Authors: Seil Fredrick J.
Published: April 2003

Neonatal mouse cerebellar cultures depleted of granule cells and functional glia by exposure to cytosine arabinoside were transplanted with either granule cells and glia or with granule cells in the absence of functional glia. Myelination was evident in cultures transplanted with granule cells and glia, excess sprouted cortical neurites were reduced, Purkinje cells acquired astrocytic sheaths and had a near normal complement of axosomatic synapses, and homotypical parallel fiber‐Purkinje cell dendritic spine synapses were present in a 2.4:1 ratio to heterotypical recurrent axon collateral‐Purkinje cell dendritic spine synapses. Cultures transplanted with granule cells were not myelinated, sprouted cortical neurites were not reduced, Purkinje cells lacked astrocytic sheaths and their somata remained hyperinnervated, and the ratio of homotypical to heterotypical dendritic spine synapses was 1.4:1. In the absence of functional glia there was a greater persistence of heterotypical recurrent axon collateral‐Purkinje cell dendritic spine synapses. These results are consistent with a previously described astrocytic role in the regulation of axosomatic synapse density on glially ensheathed neurons, and suggest astrocytic participation in the reduction of heterotypical axospinous synapses. Astrocyte‐mediated synapse reduction may be an important mechanism for circuit reorganization after transplantation or during development.
Acute effects of capsaicin on the postnatal spiral ganglion
Authors: Simmons D.D. , Rogers M.S. , Woody D.
Published: April 2003

Capsaicin exerts both excitatory and desensitizing effects on a subset of sensory neurons during development in the dorsal root ganglion, but it is not known how widespread these effects are in other sensory ganglia especially those not known to have any pain sensitivity. The capsaicin sensitivity of auditory neurons in the spiral ganglion was investigated in acute preparations from three postnatal age groups in the hamster: postnatal days 6–8 (group 1), postnatal days 13–15 (group 2) and postnatal days 20–22 (group 3). Morphologically, capsaicin altered the shape, size, and staining characteristics of spiral ganglion cells (SGCs) across all age groups and this effect was apparently not selective for any identifiable subpopulation. However, SGCs from the youngest age groups were particularly sensitive to capsaicin neurotoxicity. When incubated in media that contained cobalt, capsaicin stimulated cobalt uptake within SGCs. KCl depolarization was able to produce the same level of cobalt uptake as capsaicin treatment. Our data suggest that the extent of capsaicin neurotoxicity in the spiral ganglion is strongly age dependent, involves the entry of calcium ions and is relatively nonspecific.
Changes in metabolic activity in the hyperstriatum of the chick before and after hatching
Authors: Rogers L.J. , Bell G.A.
Published: April 2003

Changes in metabolic activity in the hyperstriatal regions of the chick forebrain have been assessed just prior to and after hatching using 14C 2‐deoxyglucose (2‐DG) autoradiography. Embryos were injected on day E19, followed by either exposure to light for 30 min or being held in darkness. Other embryos were injected on day E20, after pipping of the egg shell had occurred, and chicks were injected on day 1 (D1) after hatching, followed by light exposure. In the E19 groups metabolic activity in visual regions of the hyperstriatum accessorium (HA) was significantly higher than that in the hyperstriatum dorsale (HD), the region which receives the thalamofugal visual projections. The result was the same in both the light and dark exposed embryos, indicating that the high level of activity in HA on day E19 is not visually driven and that HA may be processing inputs from other sensory modalities. At stage E20 the activities of HA and HD did not differ and by day 1 post‐hatching HD activity exceeded that of HA. Activity in HA fell between E19 and E20, while in HD activity rose between E20 and D1. The developmental sequence of metabolic activity levels in the intermediate medial hyperstriatum ventrale (IMHV), a region involved with imprinting memory formation, was higher on E19 and D1 than on E20. E20 is thus a quiescent period of neural activity in the hyperstriatum prior to hatching. Although a small number of the embryos showed distinct hemispheric asymmetries in metabolic activity, overall there was no significant asymmetry in the embryo groups. The implications of these results for imprinting and early perceptual processing are discussed: it appears that HA activity may be inhibited or limited during the sensitive period for visual imprinting, thereby temporarily diminishing the importance of the thalamofugal visual pathway relative to the tectofugal pathway in the imprinting process.
Impaired neurogenesis by methylazoxymethanol in newborn rats results in transient reduction of ornithine decarboxylase and polyamines in the cerebellum, but not in the olfactory bulbs
Authors: Facchinetti F. , Ciani E. , Sparapani M. , Barnabei O. , Contestabile A.
Published: April 2003

Polyamines and the key enzyme for their biosynthesis, ornithine decarboxylase (ODC) play an important role in the control of neuronal proliferation and differentiation. Exposure to agents that interfere with normal cell maturation is expected to result in alteration of neuronal ODC developmental pattern. We have administered to newborn rats, about 6 and 30 hr after birth, 20 mg/kg of methylazoxymethanol acetate (MAM), an agent able to selectively kill dividing cells and we have evaluated ODC activity and polyamine levels in the cerebellum and ODC activity in the olfactory bulbs at various developmental stages starting from postnatal day 4 (PD 4) until PD 28. Cerebellar weight decreased by 22–50% at the different developmental stages in MAM‐treated animals. A decline in ODC specific activity was observed at PD 4 and a decrease of putrescine levels at PD 4 and PD 6 in the cerebellum. At PD 10, however, both ODC activity and putrescine level were increased in MAM‐treated animals. Spermidine levels were never affected by the treatment, while spermine was significantly decreased at PD 6 and PD 8. These results demonstrate that altered ontogenetic patterns of ODC activity and polyamine levels are the consequence of disturbance of the normal process of brain maturation. No significant differences in specific ODC activity were noticed in the olfactory bulbs of MAM‐treated rats. This may be related to the more widespread time‐span of neurogenesis in this region, a fact that is also revealed by the higher ODC activity constitutively expressed at times in which neurogenesis has ended in the rest of the brain.
Thyroidal stimulation of tubulin and actin in rat brain cytoskeleton
Authors: De Arunangsu , Das Sumantra , Chaudhury Sukanya , Sarkar Pranab Kumar
Published: April 2003

In cultures of neonatal rat brain cells, labeled with 35S‐methionine in the presence or absence of triiodothyronine (T3), the hormone promoted a significant enhancement of labeled tubulin and actin in the insoluble fraction (30,000 g pellet) of cell homogenate. To identify the specific sub‐cellular fraction associated with this induction, organ cultures of 1 day rat cerebra were labelled with 35S‐methionine in the presence and absence of T3 and the insoluble fraction (30,000 g pellet) was subfractionated into mitochondria, plasma membrane and cytoskeleton. Analysis of the labeled proteins by SDS‐PAGE, autoradiography and densitometry revealed a T3‐induced increase of 50–80% for both tubulin and actin, only in the cytoskeleton fraction without any significant effect on the other fractions. Similar results were obtained when plasma membrane or cytoskeleton were isolated directly from labeled cerebrum by conventional methods instead of fractionating from the 30,000 g pellet. Analysis of relative stimulation of labeled tubulin and actin by T3 in cytoskeleton fraction derived from primary cultures of neuronal (N) and glial (G) cells labeled with 35‐methionine show that the stimulatory effect is predominantly on the N cells. Studies on the kinetics of induction of labeled tubulin and actin by T3 in the cytoskeleton fraction prepared from cerebra labeled with 35S‐methionine for 2, 8 and 18 hrs revealed no significant difference at 2 hrs; at 8 hrs, an increased incorporation into both tubulin and actin was reproducibly seen in the controls relative to T3‐treated samples. However by 18 hrs, this pattern reversed and an enhanced accumulation of both labeled tubulin and actin was observed under the influence of T3. The mechanism of this apparently intriguing effect of T3 on the kinetics of association of tubulin and actin with the cytoskeleton has been discussed in the light of the dual effect of the hormone on tubulin viz. enhancing its stability as well as rate of synthesis. The overall results indicate that the thyroid hormones play a major role in the cytoskeletal transport of tubulin and actin from their site of synthesis to that of assembly thus facilitating axodendritic outgrowth and morphological differentiation.
Duration of senescent cell survival in vitro as a characteristic of organism longevity, an additional to the proliferative potential of fibroblasts
Authors: Yegorov Yegor E , Zelenin Alexander V
Published: April 2003

More than 40 years have passed since the original publication by Hayflick and Moorhead led to the concept of the ‘Hayflick limit’ of the maximum number of divisions which somatic cells undergo in vitro. This concept is still regarded as a fundamental characteristic of species longevity. Here we want to emphasize another characteristic of somatic cells, namely, the duration of their survival in vitro in the non‐dividing state after cessation of proliferation. This is suggested on the basis of results of recent experiments with so‐called Japanese accelerated senescent mice. Results of these experiments reveal a good correlation between the longevity of the mice, the number of duplications of their fibroblasts in vitro, and the survival time of these cells in the non‐dividing state. In routine culture conditions, cell survival time may be very long, as much as a few years. However, when the cells are grown under conditions of oxidative stress, cellular longevity is markedly shortened. This new test may serve as an additional marker of organismic longevity. The comparative value of both tests, the classical ‘Hayflick limit’ and the new test, is discussed.
A structure‐based site‐directed mutagenesis study on the neurolysin (EC 3.4.24.16) and thimet oligopeptidase (EC 3.4.24.15) catalysis
Authors: Oliveira Vitor , Araújo Maurı́cio C , Rioli Vanessa , de Camargo Antonio C.M , Tersariol Ivarne L.S , Juliano Maria A , Juliano Luiz , Ferro Emer S
Published: April 2003

Neurolysin (EP24.16) and thimet oligopeptidase (EP24.15) are closely related metalloendopeptidases. Site‐directed mutagenesis of Tyr613(EP24.16) or Tyr612(EP24.15) to either Phe or Ala promoted a strong reduction ofkcat/KMfor both enzymes. These data suggest the importance of both hydroxyl group and aromatic ring at this specific position during substrate hydrolysis by these peptidases. Furthermore, the EP24.15 A607G mutant showed akcat/KMof 2×105M−1s−1for the Abz‐GFSIFRQ‐EDDnp substrate, similar to that of EP24.16 (kcat/KM=3×105M−1s−1) which contains Gly at the corresponding position; the wild type EP24.15 has akcat/KMof 2.5×104M−1s−1for this substrate.
Bafilomycin A1 induces apoptosis in PC12 cells independently of intracellular pH
Authors: Kinoshita Kuninori , Waritani Takaki , Noto Masahiko , Takizawa Kaori , Minemoto Yuzuru , Nishikawa Yasuko , Ohkuma Shoji
Published: April 2003

PC12 cells growth‐arrested with bafilomycin A1 died showing apoptotic chromatin condensation in the nuclei. The bafilomycin A1‐induced chromatin condensation was preceded by neurite outgrowth (NOG), required higher concentrations of bafilomycin A1 than NOG, and was suppressed by cycloheximide and aurintricarboxylic acid. NH4Cl (10 mM), another acidotropic pH perturbing agent, neither induced apoptotic chromatin condensation by itself nor suppressed that induced by bafilomycin A1, suggesting that bafilomycin A1‐induced apoptosis occurs independently of intracellular pH in PC12 cells.
Inhibition of protein phosphatases induces IGF‐1‐blocked neurotrophin‐insensitive neuronal apoptosis
Authors: Fernández-Sánchez María-Teresa , García-Rodríguez Armando , Díaz-Trelles Ramón , Novelli Antonello
Published: April 2003

We have previously described the marine toxin okadaic acid (OKA) to be a potent neurotoxin for cultured rat cerebellar neurons. Here we show that OKA‐induced neurodegeneration involves the DNA fragmentation characteristic of apoptosis and is protein synthesis‐dependent. DNA fragmentation and neurotoxicity correlated with inhibition of protein phosphatase (PP) 2A rather than PP1 activity. Neurotrophins NT‐3 and BDNF failed to protect from OKA‐induced apoptotic neurotoxicity that was, however, totally prevented by insulin‐like growth factor‐1. Neuronal death by OKA was significantly reduced by protein kinase C inhibitors and by the L‐type calcium channel agonist Bay K8644, while it was potentiated by the reduction of free extracellular calcium concentrations.
A clarification on conceptual and methodological issues related to the Job Characteristics Model
Authors: Rungtusanatham Manus , Anderson John C.
Published: April 2003

We provide a comment on ‘Comparing the effects of cellular and functional manufacturing on employees' perceptions and attitudes’ by Shafer, Tepper, Meredith, and Marsh (Journal of Operations Management, 1995, 12, 63–74). We identify and explicate three conceptual concerns related to their description of the Job Characteristics Model, as well as two methodological concerns with using the Job Diagnostic Survey to measure the five job characteristics and the Motivating Potential Score as an aggregate index of a job's ‘motivating potential’. We intend this explication to serve as a clarification and guidance for further conceptual and empirical research in operations management involving the Job Characteristics Model, the Job Diagnostic Survey, and the Motivating Potential Score. Our remarks are intended to be constructive and are offered in the spirit of scholarly advancement.
Unlocking the potential of advanced manufacturing technologies
Authors: Boyer Kenneth K. , Leong G.Keong , Ward Peter T. , Krajewski Lee J.
Published: April 2003

This research examines whether investments in advanced manufacturing technologies (AMTs) such as flexible manufacturing systems (FMS), computer aided design (CAD), computer aided manufacturing (CAM), robotics, etc., are more likely to lead to improved performance if they are supported by improvements in the manufacturing infrastructure of the company. This question is evaluated using data gathered from 202 manufacturing plants chosen from industries generally considered to have relatively high investments in technology.

Multiple item scales are developed and adapted from sources in the literature to measure investments in technology, infrastructure, and the performance of the plant. Evidence supporting the reliability and validity of these scales is provided. Hierarchical regression is used to analyze the relationship between technology, infrastructure, and performance. The results suggest that there is an important interaction between the adoption of advanced manufacturing technologies and investments in infrastructure. Firms that invest in both AMTs and infrastructure perform better than firms which only invest in one or the other. Separate analyses on sub‐samples of firms with the highest and lowest investments in AMTs show that infrastructural investments have a stronger relationship with performance in the high investment group. Thus, the data indicate that infrastructural investments provide a key to unlocking the potential of advanced manufacturing technologies.
Alternative methods of learning and process improvement in manufacturing
Authors: Upton David M. , Kim Bowon
Published: April 2003

This exploratory paper examines one class of decision related to learning and operations improvement: how and where to develop new manufacturing technologies as part of a program of continuous improvement. We examine the reasons for both the selection and the relative effectiveness of two methods for manufacturing improvement: learning by doing (in‐process learning) on the shop floor and learning by development and experimentation away from the shop floor (off‐line learning). We then explore how the development strategy selected affects the subsequent decision‐making process, and how strongly initial choices about improvement methods affect later ones. Empirical data are presented from two Korean shipbuilding companies. While the structural characteristics of a plant, such as its layout and equipment, do appear to influence the improvement method it selects, we find that other factors, such as corporate philosophy and plant history also play an important role in the initial selection of improvement method. However, these determining factors fade in importance sharply over time, as the plant develops its ability to improve using that particular method. The fact the plant has practised improvement by one method (and, therefore, has often become relatively better at that mode of learning), begins to dominate the selection of future improvement techniques. Although this process is quite rational at each planning step, it can result in improvement processes in which small changes in initial circumstances and managerial choices cause large changes in the overall improvement path. The results also suggest that when managers choose any improvement methodology, they are not only learning about their manufacturing systems—they are choosing how their operation will learn, and indeed may lock themselves into that mode of learning for a longer duration than that of the current set of improvement projects.
Macroeconomic influences on optimal asset allocation
Authors: Flavin T.J. , Wickens M.R.
Published: April 2003

We develop a tactical asset allocation strategy that incorporates the effects of macroeconomic variables. The joint distribution of financial asset returns and the macroeconomic variables is modelled using a VAR with a multivariate GARCH (M‐GARCH) error structure. As a result, the portfolio frontier is time varying and subject to contagion from the macroeconomic variable. Optimal asset allocation requires that this be taken into account. We illustrate how to do this using three risky UK assets and inflation as a macroeconomic factor. Taking account of inflation generates portfolio frontiers that lie closer to the origin and offers investors superior risk–return combinations.
Neurogenin3 triggers beta-cell differentiation of retinoic acid-derived endoderm cells
Authors: VETERE Amedeo , MARSICH Eleonora , DI PIAZZA Matteo , KONCAN Raffaella , MICALI Fulvio , PAOLETTI Sergio
Published: April 2003

Neurogenin3 is a member of the basic helix-loop-helix ('bHLH') family of transcription factors. It plays a crucial role in the commitment of embryonic endoderm into the pancreatic differentiation programme. This factor is considered to act upstream of a cascade of other transcription factors, leading to the fully differentiated endocrine phenotype. Direct observation of the sequential activation of these factors starting from Neurogenin3 had never been demonstrated. By using retinoic acid-derived-endoderm F9 cells as a model, the present study indicates that the ectopic expression of Neurogenin3 is able to start the differentiation pathway of endocrine pancreas. Neurogenin3 triggers the expression of several pancreatic transcription factors following a well defined temporal activation sequence. By reverse transcriptase PCR, immunohistochemistry and RIA, it is shown that stable transfected cells are able to form embryod bodies that produce insulin in response to glucose stimulation. This is the first report of a differentiation event induced by the ectopic expression of a transcription factor in embryonic pluripotent stem cells.
Haem oxygenase 1 gene induction by glucose deprivation is mediated by reactive oxygen species via the mitochondrial electron-transport chain
Authors: CHANG Se-Ho , GARCIA Jairo , MELENDEZ J. Andres , KILBERG Michael S. , AGARWAL Anupam
Published: April 2003

Glucose depletion results in cellular stress and reactive oxygen species (ROS) production, which evokes adaptive and protective responses. One such protective response is the induction of haem oxygenase 1 (HO-1), which catalyses the rate-limiting step in haem degradation, liberating iron, CO and biliverdin. The present study evaluated the role of ROS and the mitochondrial electron-transport chain in the induction of HO-1 by glucose deprivation in HepG2 hepatoma cells. Either N-acetylcysteine, an antioxidant, or deferoxamine, an iron chelator, resulted in a dose-dependent inhibition of HO-1 mRNA and protein induction during glucose deprivation, suggesting a redox- and iron-dependent mechanism. Inhibitors of electron-transport chain complex III, antimycin A and myxothiazol, the ATP synthase inhibitor oligomycin and ATP depletion with 2-deoxyglucose or glucosamine also blocked HO-1 induction. To address the involvement of ROS further, specifically H2O2, we showed that overexpression of catalase completely blocked HO-1 activation by glucose deprivation. In contrast, inhibition of nuclear factor κB, mitogen-activated protein kinase (MAPK), protein kinase A, protein kinase C, phosphoinositide 3-kinase, cyclo-oxygenase or cytosolic phospholipase A2, did not prevent HO-1 induction. These results demonstrate that activation of the HO-1 gene by glucose deprivation is mediated by a ‘glucose metabolic response’ pathway via generation of ROS and that the pathway requires a functional electron-transport chain.
Electron diffraction study of the rms displacements of the atoms in free clusters of krypton
Authors: Eremenko V. V. , Kovalenko S. I. , Solnyshkin D. D.
Published: April 2003

The size dependence of the rms amplitude 〈u2〉1/2 of the atoms in free clusters of krypton is determined for the first time, by an electron diffraction technique. The mean size N̄ of the clusters formed in supersonic jets of krypton varied from 1×103 to 2×104 atoms/cluster. It is found that 〈u2〉1/2 increases with decreasing cluster size. A comparison of the dependence observed in experiment with that calculated with allowance for the fractional contribution of surface atoms shows that for clusters with N̄⩾4×103 atoms/cluster the increase of 〈u2〉1/2 with decreasing N̄ is due solely to the growth of the relative number of surface atoms. The correlation between the calculation and experiment vanishes when N̄⩽4×103 atoms/cluster. In that case the experimental values are considerably higher than the calculated value, a circumstance which indicates that in small aggregations there are other factors besides the surface which contribute to the growth of 〈u2〉1/2.
Radiation symmetry control for inertial confinement fusion capsule implosions in double Z-pinch hohlraums on Z
Authors: Vesey Roger A. , Cuneo Michael E. , Porter John L. , Adams Richard G. , Aragon Rafael A. , Rambo Patrick K. , Ruggles Laurence E. , Simpson Walter W. , Smith Ian C. , Bennett Guy R.
Published: April 2003

The double Z-pinch hohlraum high-yield concept [Hammer et al., Phys. Plasmas 6, 2129 (1999)] utilizes two 63-MA Z pinches to heat separate primary hohlraums at either end of a secondary hohlraum containing the cryogenic fusion capsule. Recent experiments on the Z accelerator [Spielman et al., Phys. Plasmas 5, 2105 (1998)] at Sandia National Laboratories have developed an advanced single-sided power feed, double Z-pinch load to study radiation symmetry and pinch power balance using implosion capsules [Cuneo et al., Phys. Rev. Lett. 88, 215004 (2002)]. Point-projection x-ray imaging with the Z-Beamlet Laser mapped the trajectory and distortion of 2-mm diameter plastic ablator capsules. Using the backlit capsule distortion as a symmetry diagnostic, the ability to predictably tune symmetry at the <10% level in fluence by modifying the hohlraum geometry has been demonstrated. Systematic control of the time-integrated P2 Legendre mode asymmetry coefficient over a range of ±6% (±2% considering points nearest the optimum) was achieved by varying the length of the cylindrical secondary hohlraum containing the capsule, in agreement with viewfactor and radiation-hydrodynamics simulations.
Long pulse enhanced confinement discharges in the HT-7 superconducting tokamak by ion Bernstein wave heating and lower hybrid wave current drive
Authors: Li J. , Wan B. N. , Luo J. R. , Kuang G. L. , Zhao Y. P. , Zhao J. Y. , Zhang X. D. , Liu X. N. , Fu P. , Xie J. K. , Zhang C. , Gu X. M. , Mao J. S. , Shan J. F. , Bai H. Y. ,   HT-7 team, Gentle K. , Rowan B. , Philippe P. , Huang H. , Lao L. , Chan V. , Watari T. , Seki T. , Nakamura N.
Published: April 2003

Significant progress has been made on the HT-7 superconducting tokamak (R=1.22 m, a=0.27 m) in the past year toward obtaining advanced operating modes in steady state. By combining ion Bernstein wave and lower hybrid current drive edge-localized-mode-free limiter H-mode discharges with H89∼2, βN*H89>3 have been obtained that lasted for 53 τE. A well-boronized wall prevented further impurity accumulation and the large pumping kept the recycling at a very low level. The density was kept almost constant with the feedback control. The noninductive driven current fraction is about 60% and bootstrap fraction is about 18%. The central electron temperature is about 2.6 keV and density above 2×1019 m−3. With reduced plasma parameters of central Te∼1.5 keV and ne0∼2×1019 m−3, H89∼1.45, βN∼1.1, the improved confinement phase lasts for more than 100 τE with the noninductive driven current fraction ∼70%.
Sheared flow stabilization experiments in the ZaP flow Z pinch
Authors: Shumlak U. , Nelson B. A. , Golingo R. P. , Jackson S. L. , Crawford E. A. , Den Hartog D. J.
Published: April 2003

The stabilizing effect of a sheared axial flow on the m=1 kink instability in Z pinches has been studied numerically with a linearized ideal magnetohydrodynamic model to reveal that a sheared axial flow stabilizes the kink mode when the shear exceeds a threshold. The sheared flow stabilizing effect is investigated with the ZaP (Z-Pinch) Flow Z-pinch experiment at the University of Washington. An axially flowing Z pinch is generated with a 1 m coaxial accelerator coupled to a pinch assembly chamber. The plasma assembles into a pinch 50 cm long with a radius of approximately 1 cm. An azimuthal array of surface mounted magnetic probes located at the midplane of the pinch measures the fluctuation levels of the azimuthal modes m=1, 2, and 3. After the pinch assembles a quiescent period is found where the mode activity is significantly reduced. Optical images from a fast framing camera and a ruby holographic interferometer indicate a stable, discrete pinch plasma during this time. Multichord Doppler shift measurements of impurity lines show a large, sheared flow during the quiescent period and low, uniform flow profiles during periods of high mode activity. Z-pinch plasmas have been produced that are globally stable for over 700 times the theoretically predicted growth time for the kink mode of a static Z pinch. The plasma has a sheared axial flow that exceeds the theoretical threshold for stability during the quiescent period and is lower than the threshold during periods of high mode activity.
Toward solving the inhomogeneous Bloch equation
Authors: Kobayashi M.
Published: April 2003

The homogeneous Bloch equation reduces to the Riccati equation. By linearizing the Riccati equation, a set of three solutions of the homogeneous Bloch equation is found. The fundamental matrix becomes singular. We clarify the utility and limitation of our approach to solve the homogeneous Bloch equation.
Laboratory investigation of boundary layer processes due to strong spatial inhomogeneity
Authors: Amatucci W. E. , Ganguli G. , Walker D. N. , Gatling G. , Balkey M. , McCulloch T.
Published: April 2003

Laboratory experiments have been conducted to simulate the dynamics of highly localized magnetospheric boundary layers. These regions, such as the plasma sheet boundary layer and the magnetopause, are primary regions of solar wind mass, energy, and momentum transport into the near-Earth space environment. During periods of solar activity, the boundary layers can become compressed to scale lengths less than an ion gyroradius. Theoretical predictions indicate that the plasma can respond to relax these highly stressed conditions through the generation of instabilities in the lower hybrid frequency range. The experiments reported here document the characteristics of waves associated with these instabilities.
Thermal versus deformation-induced relaxation in a glass-forming fluid
Authors: Nandagopal Magesh , Utz Marcel
Published: April 2003

Plastic yielding in glassy solids has been interpreted as a strain-biased relaxation process, or, equivalently, as a strain-induced glass transition. The similarity between the structural relaxation induced by plastic deformation and thermal equilibrium of glasses has led to the formulation of the strain-temperature superposition principle. In the present work, the atomic motions caused by athermal plastic deformation of a binary Lennard-Jones glass are compared to thermal motion in the liquid in terms of the self part of the intermediate structure factor. A new approach is presented that allows to study the interplay of deformation-induced and thermal relaxation. It is found that these two processes occur independently of each other over a wide range of strain rates.
Trapped particles and asymmetry-induced transport
Authors: Kabantsev A. A. , Yu J. H. , Lynch R. B. , Driscoll C. F.
Published: April 2003

Trapped particle modes and the associated asymmetry-induced transport are characterized experimentally in cylindrical electron plasmas. Axial variations in the electric or magnetic confinement fields cause the particle trapping, and enable the E×B drift trapped-particle modes. Collisional diffusion across the trapping separatrix causes the modes to damp, and causes bulk radial transport when the confinement fields also have θ asymmetries. The measured asymmetry-induced transport rates are directly proportional to the measured mode damping rates, with simple scalings for all other plasma parameters. Significant transport is observed for even weak trapping fields (δB/B∼10−3), possibly explaining the “anomalous” background transport observed so ubiquitously in single species plasmas.
Currents and shear Alfvén wave radiation generated by an exploding laser-produced plasma: Perpendicular incidence
Authors: VanZeeland M. , Gekelman W. , Vincena S. , Maggs J.
Published: April 2003

Examples of one plasma expanding into another and the consequent radiation of wave energy are abundant in both nature and the laboratory. This work is an experimental study of the expansion of a dense laser-produced plasma (initially, nlpp/n0≫1) into a magnetized background plasma (n0=2×1012 cm−3) capable of supporting Alfvén waves. The experiments are carried out on the upgraded Large Plasma Device (LAPD) at UCLA [W. Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)]. It has been observed that the presence of a background plasma allows laser-plasma charge separation to occur that would otherwise be limited by large ambipolar fields. This charge separation results in the creation of current structures which radiate shear Alfvén waves. The waves propagate away from the target and are observed to become plasma column resonances. Conditions for increased current amplitude and wave coupling are investigated.
A propagation toolkit to design quantum controls
Authors: Yip Frank , Mazziotti David , Rabitz Herschel
Published: April 2003

A toolkit of time-propagation operators, to be stored and recalled as needed, is incorporated into the algorithms for the optimal control of quantum systems. Typically, the control field ε(t) revisits the same values many times during the full time evolution. This repetition may be utilized to enhance efficiency through a convenient toolkit of propagators where the propagators are computed and stored only at a small number of discrete electric-field values in the dynamic range εmin⩽ε(t)⩽εmax. At each time step of the controlled evolution a specific member of the pre-calculated toolkit is selected as dictated by the local control field value. The toolkit can reduce the cost of control field design by a factor scaling as ∼N for quantum systems described in a basis set of N states. Optimal control with the toolkit is demonstrated for systems up to dimension N=30.
Formation of enrichment layers in thin polymer films: The influence of single chain dynamics
Authors: Reister Ellen , Müller Marcus
Published: April 2003

We study the influence of single-chain dynamics on the collective dynamics during the formation of enrichment layers near walls that attract one species of polymers in a binary blend. This is done by using different dynamic extensions of self-consistent field theory for polymer blends confined between two hard walls. In dynamic self-consistent field theory the densities are evolved in time and the use of an Onsager coefficient proportional to the monomer densities represents the dynamics of pointlike particles. The method of the external potential dynamics makes use of the temporal propagation of the effective external fields. A constant Onsager coefficient in this method implies nonlocal dynamics of polymers. The comparison between the nonlocal dynamics and the local dynamics of pointlike particles shows distinct differences in the density profiles during the formation of enrichment layers: local dynamics leads to a quick process and a narrow depletion layer, whereas the nonlocal dynamics leads to a slower enrichment and wider depletion layers. To validate the self-consistent field results we employ corresponding Monte Carlo simulations using the bond fluctuation model that maps the polymer chains on a coarse-grained lattice. A quantitative comparison of the density profiles reveals better agreement of the simulation results with those achieved with the external potential dynamics method.
Statistical mechanical refinement of protein structure prediction schemes. II. Mayer cluster expansion approach
Authors: Eastwood Michael P. , Hardin Corey , Luthey-Schulten Zaida , Wolynes Peter G.
Published: April 2003

We investigate the use of a Mayer cluster expansion to quantify changes to the energy landscape of an ab initio protein structure prediction Hamiltonian as side-chain excluded volume radii are increased. The expansion is generalized so that the effect of other changes in the Hamiltonian, which would alone be best treated with a cumulant expansion, can be evaluated simultaneously. The effect of changing the excluded volume radii on various thermodynamic quantities, in particular the free energy and glass transition temperature, is calculated with the expansion and compared to results from simulation. The expansion is found to be sufficiently accurate at the second-order level to be useful for calculating values of the excluded volume radii that refine the energy landscape for structure prediction. This is explicitly checked by a free energy profile analysis and examining the quality of predictions before and after the optimization. A useful method to test whether equilibrium has been attained during molecular dynamics sampling is also described.