bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Lipoprotein Production Is Stimulated by an Acute Elevation of Plasma Free Fatty Acids in the Fasting State: Studies in Insulin-Resistant and Insulin-Sensitized Syrian Golden Hamsters
Authors: Lewis Gary F. , Naples Mark , Uffelman Kristine , Leung Nathalie , Szeto Linda , Adeli Khosrow
Published: July 2004

It is not known whether intestinal lipoprotein production is stimulated by an acute elevation of plasma free fatty acids (FFA). We examined the effect of an intralipid and heparin infusion on the intestinal lipoprotein production rate (PR) in insulin-sensitive [chow-fed (CHOW)], insulin-resistant [60% fructose (FRUC) or 60% fat-fed (FAT)], and insulin-sensitized [FRUC or FAT plus rosiglitazone (RSG)-treated] Syrian Golden hamsters. After 5 wk of treatment, overnight-fasted hamsters underwent in vivo Triton WR-1339 studies for measurement of apolipoprotein B48 (apoB48) PR in large (Svedberg unit, >400) and small (Svedberg unit, 100–400) lipoprotein fractions, with an antecedent 90-min infusion of 20% intralipid and heparin (IH) to raise plasma FFA levels approximately 5- to 8-fold vs. those in the saline control study. IH markedly increased apoB48 PR in CHOW by 3- to 5-fold, which was confirmed ex vivo in pulse-chase experiments in primary cultured hamster enterocytes. Oleate, but not glycerol, infusion was associated with a similar elevation of apoB48 PR as IH. In FRUC and FAT, basal (saline control) apoB48 PR was approximately 4-fold greater than that in CHOW; there was no additional stimulation with IH in vivo and only minimal additional stimulation ex vivo. RSG partially normalized basal apoB48 PR in FAT and FRUC, and PR was markedly stimulated with IH. We conclude that intestinal lipoprotein production is markedly stimulated by an acute elevation of plasma FFAs in insulin-sensitive hamsters, in which basal production is low, but minimally in insulin-resistant hamsters, in which basal production is already elevated. With RSG treatment, basal PR is partially normalized, and they become more susceptible to the acute FFA stimulatory effect.
Interleukin (IL)-6, But Not IL-1, Induction in the Brain Downstream of Cyclooxygenase-2 Is Essential for the Induction of Febrile Response against Peripheral IL-1α
Authors: Kagiwada Kyoko , Chida Dai , Sakatani Tomoya , Asano Masahide , Nambu Aya , Kakuta Shigeru , Iwakura Yoichiro
Published: July 2004

IL-1 is an endogenous pyrogen produced upon inflammation or infection. Previously, we showed that, upon injection with turpentine, IL-1 is induced in the brain in association with the development of fever. The role of endogenous IL-1 in the brain and the signaling cascade to activate thermosensitive neurons, however, remain to be elucidated. In this report, febrile response was analyzed after peripheral injection of IL-1α. We found that a normal febrile response was induced even in IL-1α/β-deficient mice, indicating that production of IL-1 in the brain is not necessarily required for the response. In contrast, IL-6-deficient mice did not exhibit a febrile response. Cyclooxygenase (Cox)-2 expression in the brain was strongly induced 1.5 h after injection of IL-1α, whereas IL-6 expression was observed 3 h after the injection. Cox-2 expression in the brain was not influenced by IL-6 deficiency, whereas indomethacin, an inhibitor of cyclooxygenases, completely inhibited induction of IL-6. These observations suggest a mechanism of IL-1-induced febrile response in which IL-1 in the blood activates Cox-2, with the resulting prostaglandin E2 inducing IL-6 in the brain, leading to the development of fever.
Progesterone Receptor and the Cell Cycle Modulate Apoptosis in Granulosa Cells
Authors: Quirk Susan M. , Cowan Robert G. , Harman Rebecca M.
Published: July 2004

Our previous studies showed that exposure of bovine preovulatory follicles to the LH surge-induced resistance of granulosa cells, but not theca cells, to apoptosis. Here, the temporal development of resistance to apoptosis and potential roles of progesterone receptor (PR) and alterations in the cell cycle in mediating this effect were examined. Injection of cows with GnRH induced an LH surge within 2 h. Granulosa cells isolated 0, 6, and 10 h after GnRH were sensitive to Fas ligand-induced apoptosis, but cells isolated at 14 h were resistant. PR was first detectable in granulosa cells at 10 and 14 h and was not detectable in theca. Treatment of granulosa cells isolated 14 h after GnRH with the PR antagonist, RU486, induced susceptibility to apoptosis, an effect mediated by PR and not glucocorticoid receptor. After GnRH treatment, granulosa cells, but not theca cells, exited the cell cycle, expression of cyclin D2 was reduced, and p27Kip1 was elevated. Treatment of granulosa cells isolated from small antral follicles with the G1 phase blocker, mimosine, reduced Fas ligand-induced killing, suggesting that nonproliferating cells are resistant to apoptosis. Treatment of granulosa cells isolated 14 h after GnRH with RU486 induced reentry of some cells into the cell cycle and reversed resistance to apoptosis, suggesting that cycling cells became susceptible to apoptosis. Treatment with mimosine prevented the ability of RU486 to promote susceptibility to apoptosis. In summary, the LH surge induces expression of PR by granulosa cells and withdrawal from the cell cycle, and these events promote resistance to apoptosis.
Involvement of Brainstem Catecholaminergic Inputs to the Hypothalamic Paraventricular Nucleus in Estrogen Receptor α Expression in this Nucleus during Different Stress Conditions in Female Rats
Authors: Estacio Maria Amelita C. , Tsukamura Hiroko , Reyes Beverly A. S. , Uenoyama Yoshihisa , I’Anson Helen , Maeda Kei-Ichiro
Published: July 2004

In the present study, we determined the involvement of brainstem catecholaminergic inputs to the paraventricular nucleus (PVN) on estrogen receptor α (ERα) expression in this nucleus during conditions of 48-h fasting, 2-deoxy-d-glucose (2DG)-induced acute glucoprivation and 1-h immobilization, in ovariectomized rats. Our approach was to examine the effect of lesioning catecholaminergic inputs to the PVN using DSAP [saporin-conjugated anti-DBH (dopamine-β-hydroxylase)]. Bilateral injection of DSAP into the PVN, 2 wk before stress, prevented fasting-, glucoprivation-, and immobilization-induced increase in ERα-immunopositive cells in the PVN. The DBH-immunoreactive (ir) terminals in the PVN were severely depleted by DSAP injection in all experimental groups. Among the brainstem noradreneregic cell groups examined, DBH-ir cell bodies were significantly reduced in the A2 region of all experimental groups treated with DSAP compared with the saporin- and vehicle-injected controls. PVN DSAP injection caused a small, but not significant, decrease in A1 DBH-ir cell bodies in fasted and immobilized rats, and a significant, but slight, reduction in A1 DBH-ir cell bodies of iv 2DG- injected rats compared with PVN vehicle-injected or PVN saporin-injected controls. The A6 DBH-ir cell bodies in all experimental groups treated with DSAP, saporin, or vehicle did not show any significant difference. These results suggest that the brainstem catecholaminergic inputs to the PVN, especially from the A2 cell group, may play a major role in mediating the induction of ERα expression in the PVN by metabolic stressors such as fasting, acute glucoprivation, and less specific stressors, such as immobilization, in female rats.
Metabolic Consequences of Hypoxia from Birth and Dexamethasone Treatment in the Neonatal Rat: Comprehensive Hepatic Lipid and Fatty Acid Profiling
Authors: Bruder Eric D. , Lee Ping C. , Raff Hershel
Published: July 2004

Neonatal hypoxia is a common condition resulting from pulmonary and/or cardiac dysfunction. Dexamethasone therapy is a common treatment for many causes of neonatal distress, including hypoxia. The present study examined the effects of dexamethasone treatment on both normoxic and hypoxic neonatal rats. We performed comprehensive hepatic fatty acid/lipid profiling and evaluated changes in pertinent plasma hormones and lipids and a functional hepatic correlate, i.e. hepatic lipase activity. Rats were exposed to hypoxia from birth to 7 d of age. A 4-d tapering dose regimen of dexamethasone was administered on: postnatal day (PD)3 (0.5 mg/kg), PD4 (0.25 mg/kg), PD5 (0.125 mg/kg), and PD6 (0.05 mg/kg). The most significant finding was that dexamethasone attenuated nearly all hypoxia-induced changes in hepatic lipid profiles. Hypoxia increased the concentration of hepatic triacylglyceride and free fatty acids and, more specifically, increased a number of fatty acid metabolites within these lipid classes. Administration of dexamethasone blocked these increases. Hypoxia alone increased the plasma concentration of cholesterol and triacylglyceride, had no effect on plasma glucose, and only tended to increase plasma insulin. Dexamethasone administration to hypoxic pups resulted in an additional increase in plasma lipid concentrations, an increase in insulin, and a decrease in plasma glucose. Hypoxia and dexamethasone treatment each decreased total hepatic lipase activity. Normoxic pups treated with dexamethasone displayed increased plasma lipids and insulin. The effects of dexamethasone on hepatic function in the hypoxic neonate are dramatic and have significant implications in the assessment and treatment of metabolic dysfunction in the newborn.
Regulation of the Follicle-Stimulating Hormone β Gene by the LHX3 LIM-Homeodomain Transcription Factor
Authors: West Brooke E. , Parker Gretchen E. , Savage Jesse J. , Kiratipranon Parinda , Toomey Katherine S. , Beach Lisa R. , Colvin Stephanie C. , Sloop Kyle W. , Rhodes Simon J.
Published: July 2004

FSH is a critical hormone regulator of gonadal function that is secreted from the pituitary gonadotrope cell. Human patients and animal models with mutations in the LHX3 LIM-homeodomain transcription factor gene exhibit complex endocrine diseases, including reproductive disorders with loss of FSH. We demonstrate that in both heterologous and pituitary gonadotrope cells, specific LHX3 isoforms activate the FSH β-subunit promoter, but not the proximal LHβ promoter. The related LHX4 mammalian transcription factor can also induce FSHβ promoter transcription, but the homologous Drosophila protein LIM3 cannot. The actions of LHX3 are specifically blocked by a dominant negative LHX3 protein containing a Krüppel-associated box domain. Six LHX3-binding sites were characterized within the FSHβ promoter, including three within a proximal region that also mediates gene regulation by other transcription factors and activin. Mutations of the proximal binding sites demonstrate their importance for LHX3 induction of the FSHβ promoter and basal promoter activity in gonadotrope cells. Using quantitative methods, we show that the responses of the FSHβ promoter to activin do not require induction of the LHX3 gene. By comparative genomics using the human FSHβ promoter, we demonstrate structural and functional conservation of promoter induction by LHX3. We conclude that the LHX3 LIM homeodomain transcription factor is involved in activation of the FSH β-subunit gene in the pituitary gonadotrope cell.
In Vivo and in Vitro Inhibition of cyp19 Gene Expression by Prostaglandin F2α in Murine Luteal Cells: Implication of GATA-4
Authors: Stocco Carlos
Published: July 2004

A major function of the corpus luteum (CL) is to secrete progesterone. In rats, this gland also produces significant amounts of 17β-estradiol. Progesterone and 17β-estradiol are important regulators of rat luteal cell function. Estrogen biosynthesis is catalyzed by P450aromatase (P450arom), which is encoded by the cyp19 gene. In the rat CL, P450arom is expressed throughout pregnancy until the day before parturition, when it rapidly decreases. The mechanisms that control P450arom expression in luteal cells, particularly, the one or more factors that cause its rapid fall before parturition, are not known. Inasmuch as prostaglandin (PG) F2α plays a key role in the regulation of luteal function at the end of pregnancy, the purpose of this investigation was to determine whether PGF2α affect the expression of P450arom in the CL before parturition. PGF2α decreased luteal P450arom mRNA and protein levels in vivo and in vitro. A decrease in P450arom mRNA was also observed in mice CL just before parturition, but this change did not take place in PGF2α receptor knockout mice. The time course of the decrease in P450arom mRNA by PGF2α reflected the P450arom mRNA half-life determined by actinomycin D. Moreover, nuclear run-on assay showed that PGF2α attenuates P450arom gene transcription. Gel shift assays revealed that GATA-4 binds to the P450aromatase promoter, and that such binding is increased by PGF2α. It is concluded that PGF2α decreases luteal P450arom mRNA levels at the end of pregnancy in rodents by inhibiting cyp19 expression.
Grape Seed-Derived Procyanidins Have an Antihyperglycemic Effect in Streptozotocin-Induced Diabetic Rats and Insulinomimetic Activity in Insulin-Sensitive Cell Lines
Authors: Pinent M. , Blay M. , Bladé M. C. , Salvadó M. J. , Arola L. , Ardévol A.
Published: July 2004

Flavonoids are functional constituents of many fruits and vegetables. Some flavonoids have antidiabetic properties because they improve altered glucose and oxidative metabolisms of diabetic states. Procyanidins are flavonoids with an oligomeric structure, and it has been shown that they can improve the pathological oxidative state of a diabetic situation. To evaluate their effects on glucose metabolism, we administered an extract of grape seed procyanidins (PE) orally to streptozotocin-induced diabetic rats. This had an antihyperglycemic effect, which was significantly increased if PE administration was accompanied by a low insulin dose. The antihyperglycemic effect of PE may be partially due to the insulinomimetic activity of procyanidins on insulin-sensitive cell lines. PE stimulated glucose uptake in L6E9 myotubes and 3T3-L1 adipocytes in a dose-dependent manner. Like insulin action, the effect of PE on glucose uptake was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase and to SB203580, an inhibitor of p38 MAPK. PE action also stimulated glucose transporter-4 translocation to the plasma membrane. In summary, procyanidins have insulin-like effects in insulin-sensitive cells that could help to explain their antihyperglycemic effect in vivo. These effects must be added to their antioxidant activity to explain why they can improve diabetic situations.
The Vitamin D Receptor Is Present in Caveolae-Enriched Plasma Membranes and Binds 1α,25(OH)2-Vitamin D3in Vivo and in Vitro
Authors: Huhtakangas Johanna A. , Olivera Christopher J. , Bishop June E. , Zanello Laura P. , Norman Anthony W.
Published: July 2004

The steroid hormone 1α,25(OH)2-vitamin D3 (1,25D) regulates gene transcription through a nuclear receptor [vitamin D receptor (VDR)] and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). This study characterized the VDRmem present in a caveolae-enriched membrane fraction (CMF), a site of accumulation of signal transduction agents. Saturable and specific [3H]-1,25D binding in vitro was found in CMF of chick, rat, and mouse intestine; mouse lung and kidney; and human NB4 leukemia and rat ROS 17/2.8 osteoblast-like cells; in all cases the 1,25D KD binding dissociation constant = 1–3 nm. Our data collectively support the classical VDR being the VDRmem in caveolae: 1) VDR antibody immunoreactivity was detected in CMF of all tissues tested; 2) competitive binding of [3H]-1,25D by eight analogs of 1,25D was significantly correlated between nuclei and CMF (r2 = 0.95) but not between vitamin D binding protein (has a different ligand binding specificity) and CMF; 3) confocal immunofluorescence microscopy of ROS 17/2.8 cells showed VDR in close association with the caveolae marker protein, caveolin-1, in the plasma membrane region; 4) in vivo 1,25D pretreatment reduced in vitro [3H]-1,25D binding by 30% in chick and rat intestinal CMF demonstrating in vivo occupancy of the CMF receptor by 1,25D; and 5) comparison of [3H]-1,25D binding in VDR KO and WT mouse kidney tissue showed 85% reduction in VDR KO CMF and 95% reduction in VDR KO nuclear fraction. This study supports the presence of VDR as the 1,25D-binding protein associated with plasma membrane caveolae.
Design with uncertain qualitative variables under imperfect knowledge
Authors: Pons D. J. , Raine J. K.
Published: July 2004

To support early design and design under risk, it is necessary to have methodologies to process the various forms of uncertainties. Three independent dimensions of uncertainty are identified in the paper as certainty of analysis (epistemic uncertainty), random variability (stochastic variability and design indecision) and type of variable. The type of variable is further categorized into six scales that are broadly grouped into quantitative and qualitative. Common engineering modelling tools used for design do not operate well on combinations of random variables, qualitative variables and imperfect knowledge. The hypothesis of this paper is that a modelling system could be developed to accommodate the multiple types of uncertainty that can exist during engineering design. This is worth doing as accommodating design uncertainty is an important part of risk management in engineering. The paper then proceeds to describe the way in which the design for system integrity (DSI) methodology meets these objectives. DSI may be used to create models with uncertain variables (including textual and non-ordered), given subjective and imperfect knowledge (including uncertain opinion). Consequently, DSI supports risk management in engineering design.
Dynamic performance of shoe centreless grinding
Authors: Zhang H , Lieh J , Yen D
Published: July 2004

The dynamic performance of shoe centreless grinding is presented in this paper. A model with a single-mass system was developed and used to evaluate the system response in the time and the frequency domains. Based on the model, stability and critical parameters of the grinding process were studied. Numerical simulations were conducted in MATLAB. The model was verified by experiments from real grinding trials.
Assembly and task planning using Petri nets: A survey
Authors: Rosell J
Published: July 2004

The automatic synthesis of a plan to perform a robotized assembly task from a high-level description of the product to be assembled is a difficult issue which involves assembly planning and task planning. This paper summarizes the problems that an autonomous robotic assembly system must tackle both regarding assembly planning and task planning and reviews the approaches that use Petri nets as a formalism to develop the corresponding planners. The need for integration of both assembly and task planning is made evident, and approaches covering that are described.
Tool wear monitoring—an intelligent approach
Authors: Rao Ch Srinivasa , Srikant R. R.
Published: July 2004

Tool wear monitoring is one of the most crucial and inevitable processes in present-day manufacturing systems. With the growth of unmanned factories, the need for on-line monitoring systems is well recognized. Artificial intelligence techniques such as artificial neural networks, fuzzy logic and the neuro-fuzzy technique have proved their potential in monitoring the manufacturing processes. In shop-floor control, the condition of the cutting tool is of more concern than the actual tool wear value but, in research activities, the estimation of the actual value of the tool wear occupies a prominent place. The present work is concerned with the assessment of the tool condition and also the estimation of the tool wear value. In the present paper, artificial intelligence techniques are applied to estimate the tool condition and tool wear value on line. Kohonen's self-organizing map is applied in neural networks for estimating the tool condition. Fuzzy logic and the neuro-fuzzy technique are implemented by triangular membership functions. To assess the tool wear value, a back-propagation neural network is applied. In fuzzy logic and neuro-fuzzy techniques, the centroid method of defuzzification is applied to obtain the flank wear value. Experimental data are generated by machining EN-8 steel with a high-speed steel cutting tool. The obtained data are used to train and test the networks. To make the monitoring system user friendly, a user interface is developed using Microsoft Visual Basic 6.0.
Generating optimal T-shape cutting patterns for rectangular blanks
Authors: Cui Y
Published: July 2004

Both the material usage and the complexity of the cutting process should be considered in generating cutting patterns. This paper presents an algorithm for generating guillotine-cutting patterns for rectangular blanks. It simplifies the cutting process by allowing only one size of blanks to appear in a strip. The direction of a strip is either in the sheet length direction or in the sheet width direction. The algorithm uses an implicit enumeration method and the knapsack algorithm to determine the optimal combination of strips and strip directions to make the material usage reach its maximum. The algorithm is compared with the well-known two-stage algorithm through experimental computations. The computational results indicate that the algorithm is efficient both in computation time and in material usage, and it is able to simplify the cutting process greatly. Finally, the solution to an example is given.
Optimization of computer numerical control set-up parameters to manufacture rapid prototypes
Authors: Relvas C , Simóes J. A.
Published: July 2004

This paper describes the study performed to determine the influence and optimize computer numerical control (CNC) set-up parameters to manufacture rapid prototype parts. The competitiveness of CNC was assessed relative to conventional rapid prototyping techniques by comparing dimensional precision, quality of the prototype, execution times and costs. CNC machine set-up parameters were first optimized using specimens of part of a hand dorsum model. Based on these findings, a CNC hand model was manufactured and compared with others manufactured by laminated object manufacturing (LOM), selective layer sintering (SLS) and stereolithography (SLA) rapid prototyping (RP) techniques. Overall, the study evidenced that CNC milling can be more or as competitive as the RP techniques tested. In fact, the CNC prototype was manufactured in significantly less time, was less expensive and presented excellent quality of dimensional control and surface texture. However, the quality of the CNC prototype is subject to expertise of the computer aided design/manufacture (CAD/CAM) operator.
An investigation of the tool-chip contact length and wear in high-speed turning of EN19 steel
Authors: Abukhshim N. A. , Mativenga P. T. , Sheikh M. A.
Published: July 2004

In this paper, existing models for the tool-chip contact length are reviewed with regards to high-speed machining theory. Results of an investigation into the tool-chip contact length and tool wear of uncoated tungsten-based cemented carbide tools for dry high-speed turning of EN19 alloy steel are presented. The tests were conducted at cutting speeds ranging between 200 and 1200m/min with feed rates of 0.14 and 0.2 mm/rev and a constant depth of cut of 0.1 mm. From measurements, the effect of cutting speed on contact length and tool life has been determined and several important relationships established. It was found that the contact length changes according to the contact phenomena in the tool-chip interface zone, which is predominantly affected by the cutting speed. Moreover, the influence of the cutting speed on the contact length changes significantly from conventional to high-speed cutting environments. The study concludes that existing models are quantitatively inadequate for predicting tool-chip contact lengths in high speed turning.
Improving wood surface form by modification of the rotary machining process
Authors: Hynek P , Jackson M , Parkin R , Brown N
Published: July 2004

This paper describes a way of improving surface quality of rotary-machined surfaces by introducing additional vertical cutterhead movement. It is shown through simulation that vertical cutterhead movement reduces surface waviness height, if synchronized with the angular position of the knife tips. A discussion on the vertical cutterhead movement implementation is presented. A new algorithm for surface waviness simulation of rotary-machined surfaces is also presented. The algorithm is used to investigate the influence of vertical cutterhead movement on the machined surface.
Variation in flowmeter manufacture: Some observations and lessons
Authors: Baker R. C.
Published: July 2004

This paper discusses two concepts essential to high-quality manufacture, in particular, of flowmeters. The first is the understanding, control and reduction of variation so that high quality in the product can be achieved. The second is consideration of the need for good housekeeping and how this is an essential for documentation of the meter's manufacture to allow the product to be verified through its working life and to be withdrawn if it fails to meet its specification. The theoretical basis is reviewed and examples are then given from a particular industrial group—flowmeter manufacturers—for evidence of the effects of manufacturing variation, its control and the resultant high quality that can be achieved. This is done by reviewing relevant theoretical and experimental work on various flowmeters so as to understand the causes of variation. Lessons can be learned from this relating to design for production, manufacturing, alternatives to calibration and the importance of software. This is illustrated by a simplified case study of one type of flowmeter, the electromagnetic flowmeter. This leads to conclusions on the possible lessons for companies on design, variation/quality and measuring on line, verification and customer communications.
A Combined DFMA and TRIZ approach to the simplification of product structure
Authors: Bariani P. F. , Berti G. A. , Lucchetta G
Published: July 2004

In order to tackle the problem of part count reduction more effectively, an approach that combines the design for manufacture and assembly (DFMA) method with the theory of inventive problem solving (TRIZ) is presented in this paper. This new approach was developed by merging the common characteristics and connecting the complementary aspects of the two methods, which were then applied to the redesign of a satellite antenna.
Real-time fault detection and isolation in industrial machines using learning vector quantization
Authors: Marzi H
Published: July 2004

This paper presents a real-time approach to the problem of fault detection in industrial machines. In this study learning vector quantization (LVQ) of adaptive neural networks has been used to identify faults by relating patterns of fault signatures to their causes. The fault detection system is designed to operate based on steady state and transient responses obtained by monitoring sensitive parameters of an industrial machine. The steady state signal acts as a stimulus. When the signal exceeds a predetermined threshold it will initiate a non-destructive test on the machine during which a transient response of a second sensitive parameter will be captured. This transient pattern will be compared with the database of the patterns of fault signatures. The closest match will determine the cause of fault.

The technique has been applied to a computer numerically controlled (CNC) machining centre. The diagnostic system is shown to be capable of first deciding whether the system is healthy or faulty; if faulty, it then decides whether one of the known faults or a novel fault, not seen before, is occurring. Having made the decision that one of the common faults is occurring it is then capable of deciding, from four different levels, the approximate severity level of the fault. In this approach, the use of LVQ significantly reduces the training time period of the network by about 90 per cent as compared to other learning methods such as back propagation (BP).
Incremental simulation modelling for Internet collaborative design
Authors: Qin S. F. , Wright D. K.
Published: July 2004

In order to support Web-based collaborative design in terms of transferring or updating models dynamically and efficiently, new incremental modelling and local updating strategies have been developed for simulation modelling application. Three-dimensional simulation models are utilized to visualize behaviour of production control systems by simulating motions and state changes of controls. During an early design stage where details of mechanical parts might be not available, simulation is more focused on visualization effects of motion and state changes than on geometry details such as rounds or chamfers. Based on an assembly connection concept, a drag-and-drop assembly method has also been proposed in simulation assembly. An assembly connection making assembly easier is defined as a group of assembly constraints. A case study example is given to illustrate application context of the proposed research.
On the possibility of using laser technology for diamond tool manufacturing
Authors: Kovalenko V. S. , Golovko L. F. , Novikov N. V. , Shepelev A. A. , Sorochenko V. G.
Published: July 2004

An analysis of ways to increase the quality and productivity of diamond tool manufacturing is given. Study results of opportunities given to solve this problem by the application of laser technology are offered. It is shown that laser heating can be applied to increase the dispersivity and uniformity of structure of a diamond-containing layer, for sintering previously prepared briquettes of a diamond-containing mixture and for manufacturing one-row multilayer diamond tools using strong and wear-resistant binders.
Analysis of key parameters in sheet hydroforming combined with stretching forming and deep drawing
Authors: Lang L. H. , Danckert J , Nielsen K. B.
Published: July 2004

Sheet hydroforming has proven to be an effective method for manufacturing complicated parts. To explore sheet deformation under complex strain conditions, the forming process of a conical cup was studied on the basis of the proposed hydromechanical deep drawing with uniform pressure on to the blank. The failure types including fracture and wrinkling were analysed in detail. The process windows for the pressure in the die cavity were drawn out using the different roughness of the punch surface in local areas. The forming process of the conical cup was explored using pure aluminium and soft steel. Effects of the key process parameters including the punch surface roughness and the pressure variation on the finally formed parts were investigated in both experiment and simulation. It was shown that the results from the simulation were in reasonable agreement with those from the experiment.
Development of an improved voltage and current measurement system for studying spark characteristics with application to electrodischarge machining
Authors: Guha A , Roy S , Mishra P. K.
Published: July 2004

An on-line measurement system for voltage and current has been developed with application to wire electrodischarge machining. It uses the Hall effect sensor for current measurement. This measurement system was tested to count the actual number of pulses taking place during machining and to capture the spark characteristics during several unstable machining conditions.
Real-time compensatory control of thermal errors for high-speed machine tools
Authors: Kim K-D , Kim M-S , Chung S-C
Published: July 2004

This paper proposes a developmental procedure of a real-time thermal error compensator for a high-speed machine tool (HSMT). A vertical-type HSMT having a slant column with lightweight moving slides is used to investigate thermal characteristics. Since spindle speed is very fast in the HSMT, a large amount of thermal drift error occurs within a few minutes of operation. Owing to tooling problems of the high-speed spindle, axial offset errors also appear on the machined surfaces. If-then rules and thermal mode approaches are applied to remove defects of the machined surfaces. An infinite impulse response filter is used to compensate for surface roughness of the machine surface. A personal-computer-based error compensation scheme has been developed for the real-time thermal error compensation. Compensation interval of the developed compensator is selected to satisfy correction requirement of thermal errors of the HSMT. Experimental results confirm the validity of the developed compensator and show that the accuracy of machined surface is dramatically improved.
The yeast Apq12 protein affects nucleocytoplasmic mRNA transport
Authors: BAKER KRISTIAN E. , COLLER JEFF , PARKER ROY
Published: July 2004

An important step in mRNA biogenesis is the export of mRNA from the nucleus to the cytoplasm. In this work, we provide evidence that the previously uncharacterized gene APQ12 functions in nucleocytoplasmic mRNA transport in Saccharomyces cerevisiae. First, apq12Δ strains manifest 3′ hyperadenylated mRNA similar to other previously characterized RNA export mutants. Second, bulk poly(A)+ RNA is retained in the nucleus in apq12Δ cells. Third, an Apq12p–GFP chimeric protein is localized to the nuclear periphery. Fourth, mRNA in apq12Δ cells is stabilized, consistent with a defect in the rate of nuclear export. Interestingly, apq12Δ mutants are severely compromised for growth and display atypical cell morphology. Because this aberrant cell morphology is not seen with other viable export mutants, Apq12p must have either an additional cellular function, or preferentially impinge on the export of mRNAs regulating cell growth. Together, these findings support a role for APQ12 in nucleocytoplasmic transport of mRNA.
Solution structure of an RNA stem–loop derived from the 3′ conserved region of eel LINE UnaL2
Authors: BABA SEIKI , KAJIKAWA MASAKI , OKADA NORIHIRO , KAWAI GOTA
Published: July 2004

The eel long interspersed element (LINE) UnaL2 and its partner short interspersed element (SINE) share a conserved 3′ tail containing a stem–loop that is critical for their retrotransposition. Presumably, the first step of retrotransposition is the recognition of their 3′ tails by UnaL2-encoded reverse transcriptase. The solution structure of a 17-nucleotide RNA derived from the 3′ tail of UnaL2 was determined by NMR. The GGAUA loop forms a specific structure in which the uridine is exposed to solvent with the third and fifth adenosines stacked. A sharp turn in the phosphodiester backbone occurs between the second guanosine and third adenosine. When the uridine is mutated (but not deleted), all mutants form the loop structure, indicating that the loop structure requires an exposed fourth residue. The retrotransposition assay in HeLa cells revealed that retrotransposition requires the second guanosine, although any nucleoside functions at the fourth position, suggesting that UnaL2 reverse transcriptase specifically recognizes the 5′ side of the GGANA loop.
Optimization of apolipoprotein B mRNA editing by APOBEC1 apoenzyme and the role of its auxiliary factor, ACF
Authors: CHESTER ANN , WEINREB VIOLETTA , CARTER CHARLES W. , NAVARATNAM NAVEENAN
Published: July 2004

Expression and purification to homogeneity of the apolipoprotein B mRNA editing subunit, APOBEC1, has allowed the demonstration that this apoenzyme has considerable residual enzymatic activity on a minimal apoB mRNA substrate, even in the absence of any auxiliary factors. Assay of this activity as a function of various experimental conditions has led to substantial optimization of assay conditions through the use of incomplete factorial and response surface experiments. Surprisingly, the apoenzyme is thermostable, and has a temperature optimum near 45°C. We have used these optimized conditions, to assess steady-state kinetic parameters for APOBEC1 mRNA editing activity with and without the auxiliary factor, ACF. An important effect of the auxiliary factor is to broaden the temperature range of APOBEC1 activity, lowering the optimal temperature and enabling it to function optimally at lower temperatures. A model consistent with this observation is that at lower temperatures ACF promotes a conformational transition in the RNA substrate that occurs spontaneously at higher temperature. Notably, the substantial RNA editing activity of APOBEC1 alone may be responsible for the “hyperediting” observed upon overexpression of APOBEC1 in transgenic mice.
Chemical synthesis and binding activity of the trypanosomatid cap-4 structure
Authors: LEWDOROWICZ MAGDALENA , YOFFE YAEL , ZUBEREK JOANNA , JEMIELITY JACEK , STEPINSKI JANUSZ , KIERZEK RYSZARD , STOLARSKI RYSZARD , SHAPIRA MICHAL , DARZYNKIEWICZ EDWARD
Published: July 2004

Leishmaniaand other trypanosomatids are early eukaryotes that possess unusual molecular features, including polycistronic transcription andtrans-splicing of pre-mRNAs. The spliced leader RNA (SL RNA) is joined to the 5′ end of all mRNAs, thus donating a 5′ cap that is characterized by complex modifications. In addition to the conserved m7GTP, linked via a 5′-5′-triphosphate bound to the first nucleoside of the mRNA, the trypanosomatid 5′ cap includes 2′-Omethylations on the first four ribose moieties and unique base methylations on the first adenine and the fourth uracil, resulting in the cap-4 structure, m7Gpppm36,6,2′Apm2′Apm2′Cpm23,2′U, as reported elsewhere previously. A library of analogs that mimic the cap structure to different degrees has been synthesized. Their differential affinities to the cap binding proteins make them attractive compounds for studying the molecular basis of cap recognition, and in turn, they may have potential therapeutic significance. The interactions between cap analogs and eIF4E, a cap-binding protein that plays a key role in initiation of translation, can be monitored by measuring intrinsic fluorescence quenching of the tryptophan residues. In the present communication we describe the multistep synthesis of the trypanosomatid cap-4 structure. The 5′ terminal mRNA tetranucleotide fragment (pm36,6,2′Apm2′Apm2′Cpm23,2′U) was synthesized by the phosphoramidite solid phase method. After deprotection and purification, the 5′-phosphorylated tetranucleotide was chemically coupled with m7GDP to yield the cap-4 structure. Biological activity of this newly synthesized compound was confirmed in binding studies with eIF4E fromLeishmaniathat we recently cloned (LeishIF4E-1), using the fluorescence time-synchronized titration method.
Ligand-induced changes in 2-aminopurine fluorescence as a probe for small molecule binding to HIV-1 TAR RNA
Authors: BRADRICK THOMAS D. , MARINO JOHN P.
Published: July 2004

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated in part through an interaction between the virally encoded trans-activator protein Tat and the trans-activator responsive region (TAR) of the viral RNA genome. Because TAR is highly conserved and its interaction with Tat is required for efficient viral replication, it has received much attention as an antiviral drug target. Here, we report a 2-aminopurine (2-AP) fluorescence-based assay for evaluating potential TAR inhibitors. Through selective incorporation of 2-AP within the bulge (C23 or U24) of a truncated form of the TAR sequence (Δ TAR-ap23 and Δ TAR-ap24), binding of argininamide, a 24-residue arginine-rich peptide derived from Tat, and Neomycin has been characterized using steady-state fluorescence. Binding of argininamide to the 2-AP ΔTAR constructs results in a four- to 11-fold increase in fluorescence intensity, thus providing a sensitive reporter of that interaction (KD ~ 1 mM). Similarly, binding of the Tat peptide results in an initial 14-fold increase in fluorescence (KD ~ 25 nM), but is then followed by a slight decrease that is attributed to an additional, lower-affinity association(s). Using the ΔTAR-ap23 and TAR-ap24 constructs, two classes of Neomycin binding sites are detected; the first molecule of antibiotic binds as a noncompetitive inhibitor of Tat/argininamide (KD ~ 200 nM), whereas the second, more weakly bound molecule(s) becomes associated in a presumably nonspecific manner (KD ~ 4 μM). Taken together, the results demonstrate that the 2-AP fluorescence-detected binding assays provide accurate and general methods for quantitatively assessing TAR interactions.
Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence
Authors: SIMMONDS PETER , TUPLIN ANDREW , EVANS DAVID J.
Published: July 2004

Discrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. Irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts.
Functional analysis of mRNA scavenger decapping enzymes
Authors: LIU SHIN-WU , JIAO XINFU , LIU HUDAN , GU MEIGANG , LIMA CHRISTOPHER D. , KILEDJIAN MEGERDITCH
Published: July 2004

Eukaryotic cells primarily utilize exoribonucleases and decapping enzymes to degrade their mRNA. Two major decapping enzymes have been identified. The hDcp2 protein catalyzes hydrolysis of the 5′ cap linked to an RNA moiety, whereas the scavenger decapping enzyme, DcpS, functions on a cap structure lacking the RNA moiety. DcpS is a member of the histidine triad (HIT) family of hydrolases and catalyzes the cleavage of m7GpppN. HIT proteins are homodimeric and contain two conserved 100-aminoacid HIT fold domains with independent active sites that are each sufficient to bind and hydrolyze cognate substrates. We carried out a functional characterization of the DcpS enzyme and demonstrate that unlike previously described HIT proteins, DcpS is a modular protein that requires both the core HIT fold at the carboxylterminus and sequences at the amino-terminus of the protein for cap binding and hydrolysis. Interestingly, DcpS can efficiently compete for and hydrolyze the cap structure even in the presence of excess eIF4E, implying that DcpS could function to alleviate the accumulation of complexes between eIF4E and cap structure that would otherwise accumulate following mRNA decay. Using immunofluorescence microscopy, we demonstrate that DcpS is predominantly a nuclear protein, with low levels of detected protein in the cytoplasm. Furthermore, analysis of the endogenous hDcp2 protein reveals that in addition to the cytoplasmic foci, it is also present in the nucleus. These data reveal that both decapping enzymes are contained in the nuclear compartment, indicating that they may fulfill a greater function in the nucleus than previously appreciated.
Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination
Authors: RYDER SEAN P. , WILLIAMSON JAMES R.
Published: July 2004

Inadequate formation and maintenance of myelin is the basis for several neurodegenerative disorders, including leukodystrophy and multiple sclerosis. In mice, oligodendrocyte differentiation and subsequent formation of myelin requires the Quaking gene. Mutation of this gene leads to embryonic lethality or to a trembling phenotype characteristic of dysmyelination. Quaking encodes Qk1, a member of the highly conserved STAR/GSG family of RNA-binding proteins that function as master developmental regulators in higher eukaryotes. Qk1 has been implicated in the regulation of alternative splicing, stability, and translation control of mRNAs that code for myelin structural components in glial cells. We have used quantitative gel mobility shift and fluorescence polarization assays to define the nucleotide sequence specificity of the Qk1 STAR/GSG domain, and to probe the interaction between Qk1 and the 3′-untranslated region (UTR) of myelin basic protein (MBP) mRNA. The results show that Qk1 recognizes a hexanucleotide consensus element that is similar although not identical to the specificity determinant recognized by the Caenorhabditis elegans STAR/GSG protein GLD-1. Several consensus sites are present in the 3′-UTR of MBP mRNA. The highest affinity site is located within the RNA localization region, suggesting a possible role for Qk1 in restricting MBP mRNA to the myelin compartment.
Procrastination and counterfactual thinking: Avoiding what might have been
Authors: Sirois Fuschia M.
Published: July 2004

The possible negative consequences of counterfactuals were explored in the current study by examining the relationship between counterfactual direction and trait procrastination, a self‐defeating behavioural style. Eighty participants generated counterfactuals in response to two experimental anxiety inductions. Trait procrastination was overall related to avoiding thoughts about how things could have been better (making more downward and relatively fewer upward counterfactuals) in response to the two anxiety‐provoking scenarios, suggesting the involvement of a self‐enhancement motive (mood repair). Evidence for the involvement of this self‐motive in procrastinating behaviour also emerged, as procrastination was more related to making more downward counterfactuals for a delay‐specific anxiety scenario than for a general anxiety scenario. The pattern of results supports the proposal that downward counterfactuals may be associated with negative behavioural styles such as procrastination and implicates self‐enhancement motives in this relationship. The behavioural and motivational consequences of downward counterfactuals are discussed and possible connections between downward counterfactuals and other self‐defeating behaviours are presented.
Why are men more likely to support group‐based dominance than women? The mediating role of gender identification
Authors: Dambrun Michaël , Duarte Sandra , Guimond Serge
Published: July 2004

Arguing from a sociobiological perspective, Sidanius and Pratto (1999) have shown that the male/female difference in social dominance orientation (SDO) is largely invariant across cultural, situational and contextual boundaries. The main objective of this study was to test the validity of Social Dominance Theory (SDT) by contrasting it with a model derived from Social Identity Theory (SIT). More specifically, while SIT predicts that gender identification mediates the effect of gender on SDO, SDT predicts the reverse. According to SDT, the degree to which men and women endorse status legitimizing ideology should determine to what extent they identify with their gender group. Using structural equation modelling, the results provide strong support for the SIT model and no support for SDT predictions. Implications of these results for social dominance theory and its sociobiologically based invariance hypothesis are discussed.