bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic Neuroendocrine Tumor with Ectopic Adrenocorticotropin Production upon Second Recurrence
Authors: Miehle Konstanze , Tannapfel Andrea , Lamesch Peter , Borte Gudrun , Schenker Eva , Kluge Regine , Ott Rudolf A. , Wiechmann Volker , Koch Martin , Kassahun Woubet , Paschke Ralf , Koch Christian A.
Published: August 2004

We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing’s syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with 111In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing’s syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.
Expression of SHOX in Human Fetal and Childhood Growth Plate
Authors: Munns C. J. F. , Haase H. R. , Crowther L. M. , Hayes M. T. , Blaschke R. , Rappold G. , Glass I. A. , Batch J. A.
Published: August 2004

Abnormalities in the growth plate may lead to short stature and skeletal deformity including Leri Weil syndrome, which has been shown to result from deletions or mutations in the SHOX gene, a homeobox gene located at the pseudoautosomal region of the X and Y chromosome. We studied the expression of SHOX protein, by immunohistochemistry, in human fetal and childhood growth plates and mRNA by in situ hybridization in childhood normal and Leri Weil growth plate. SHOX protein was found in reserve, proliferative, and hypertrophic zones of fetal growth plate from 12 wk to term and childhood control and Leri Weil growth plates. The pattern of immunostaining in the proliferative zone of childhood growth plate was patchy, with more intense uniform immunostaining in the hypertrophic zone. In situ hybridization studies of childhood growth plate demonstrated SHOX mRNA expression throughout the growth plate. No difference in the pattern of SHOX protein or mRNA expression was seen between the control and Leri Weil growth plate. These findings suggest that SHOX plays a role in chondrocyte function in the growth plate.
The −514 C→T Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis
Authors: Isaacs Aaron , Sayed-Tabatabaei Fakhredin A. , Njajou Omer T. , Witteman Jacqueline C. M. , van Duijn Cornelia M.
Published: August 2004

Investigations of the −514 C→T single nucleotide polymorphism (SNP) in the hepatic lipase (HL) gene promoter region (LIPC) have yielded contradictory results regarding its association with changes in plasma lipids. The current study is a meta-analysis of 25 publications on this SNP, comprising over 24,000 individuals, and its relationship with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides, and HL activity. Significant decreases were observed in HL activity for both the CT and TT genotypes compared with the CC genotype [weighted mean difference (WMD), −5.83 mmol/liter·h (95% confidence interval, −8.48, −3.17) and −11.05 mmol/liter·h (95% confidence interval, −14.74, −7.36), respectively]. Moreover, significant increases in HDL were found; the CT to CC comparison showed an increase in WMD of 0.04 mmol/liter (95% confidence interval, 0.02, 0.05) mmol/liter, and the increase in the TT vs. CC difference was WMD of 0.09 mmol/liter (95% confidence interval, 0.07, 0.12). These changes appear to be stepwise, implying an allele dosage effect. All P values for these associations were less than 0.001. This meta-analysis demonstrates the importance of the −514C→T SNP in determining HL activity and plasma HDL concentration and helps quantify the role that hepatic lipase plays in the metabolism of HDL.
Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels
Authors: Böttner Antje , Kratzsch Jürgen , Müller Grit , Kapellen Thomas M. , Blüher Susann , Keller Eberhard , Blüher Matthias , Kiess Wieland
Published: August 2004

Adiponectin is an adipocytokine with profound antidiabetic and antiatherogenic effects that is decreased in obesity. With the increasing prevalence of obesity and the emergence of related disorders, including type 2 diabetes in children, the regulation of adiponectin and its relationship to childhood obesity is of great interest. In this study we aimed to elucidate the impact of gender, pubertal development, and obesity on adiponectin levels in children. We investigated two phenotypically characterized cohorts of 200 normal weight and 135 obese children and adolescents covering a wide range of age (3.4–17.9 yr) and body mass index (−2.1 to +4.8 sd score). In healthy lean boys, adiponectin levels significantly declined in parallel with physical and pubertal development, subsequently leading to significantly reduced adiponectin levels in adolescent boys compared with girls (5.6 ± 0.5 vs. 7.1 ± 0.5 mg/liter; P = 0.03). This decline was inversely related to testosterone (r = −0.42; P < 0.0001) and dehydroepiandrosterone sulfate (r = −0.20; P = 0.0068) serum concentrations and may account for the gender differences seen in adults. Using a stepwise forward multiple regression model, pubertal stage was the strongest independent predictor of adiponectin (r2 = 0.206; P < 0.0001), with additional influences of body mass index sd score and testosterone. Adiponectin levels were decreased in obese children and adolescents compared with lean peers of corresponding age and pubertal stage (5.18 vs. 7.13 mg/liter; P = 0.015). In obese children, adiponectin levels were closely associated with parameters related to the metabolic syndrome, such as insulin resistance, hyperinsulinemia, blood pressure, and uric acid, in univariate and multivariate analyses, with the insulin sensitivity index being the strongest independent parameter identified by stepwise forward multiple regression (r2 = 0.226; P < 0.0001). Hence, there is a strong association of adiponectin serum concentrations with obesity, pubertal development, and metabolic parameters in children indicating epidemiological and pathophysiological relevance already in childhood.
Morning Preprandial Plasma Ghrelin and Catecholamine Concentrations in Patients with Phenylketonuria and Normal Controls: Evidence for Catecholamine-Mediated Ghrelin Regulation
Authors: Schulpis Kleopatra H. , Papassotiriou Ioannis , Vounatsou Maria , Karikas George A. , Tsakiris Stylianos , Chrousos George P.
Published: August 2004

Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine. Poor diet control results in high plasma Phe and low plasma Tyr and catecholamine concentrations. Ghrelin, a recently described gastrointestinal hormone that is elevated in the fasting state and low in the fed state, is considered a major appetite-stimulating hormone, possibly involved in the generation of obesity and insulin resistance. We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake. Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer. The ghrelin concentration (744 ± 25 ng/liter) in diet-controlled patients did not differ from that in controls (802 ± 26 ng/liter; P > 0.05). On the contrary, the ghrelin concentration was significantly reduced in poorly controlled patients (353 ± 23 ng/liter; P < 0.0001). Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls. We conclude that ghrelin secretion may receive positive direct or indirect input from catecholamines. The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system.
Functional Characterization of Melanocortin-3 Receptor Variants Identify a Loss-of-Function Mutation Involving an Amino Acid Critical for G Protein-Coupled Receptor Activation
Authors: Tao Ya-Xiong , Segaloff Deborah L.
Published: August 2004

Although melanocortin-4 receptor mutations are the cause of the most common monogenic form of obesity, the involvement of the melanocortin-3 receptor (MC3R) in the pathogenesis of obesity is unknown. Earlier studies failed to identify any mutations in obese patients except for the identification of two variants (K6T and I81V) that likely represent polymorphisms. However, a potential mutation (I183N) was recently reported from patients having high-fat contents. We report here the functional characterization of these variants. We show that K6T and I81V have ligand binding and signaling properties similar to wild-type (wt) MC3R, indicating that they are indeed polymorphisms. However, the other variant, I183N, completely lacks signaling in response to agonist stimulation, although it binds ligand with normal affinity and with only slightly decreased capacity. Coexpression of the wt and I183N MC3Rs showed that I183N does not exert dominant-negative activity on wt MC3R. These results provide supporting evidence for the hypothesis proposed in the original case report that MC3R mutation might be a genetic factor that confers susceptibility to obesity, likely due to haploinsufficiency. Further mutations at I183 revealed a discrete requirement for I183 in agonist-induced MC3R activation. The corresponding residue is also important for agonist-induced human melanocortin-4 receptor and lutropin receptor activation. In summary, we identify a residue that is critical for activation of G protein-coupled receptors.
Increased Expression of Regulator of G Protein Signaling-2 (RGS-2) in Bartter’s/Gitelman’s Syndrome. A Role in the Control of Vascular Tone and Implication for Hypertension
Authors: Calò Lorenzo A. , Pagnin Elisa , Davis Paul A. , Sartori Michelangelo , Ceolotto Giulio , Pessina Achille C. , Semplicini Andrea
Published: August 2004

Regulator of G protein signaling-2 (RGS-2) plays a key role in the G protein-coupled receptor (GPCR) angiotensin II (Ang II) signaling. NO and cGMP exert a vasodilating action also through activation and binding to RGS-2 of cGMP dependent protein kinase 1-α, which phosphorylates RGS-2 and dephosphorylates myosin light chain. In Bartter’s/Gitelman’s patients (BS/GS) Ang II related signaling and vasomotor tone are blunted. Experiments were planned to explore whether RGS-2 may play a role in BS/GS vascular hyporeactivity. NO metabolites and cGMP urinary excretion were also measured. Mononuclear cells (PBM) from six BS/GS patients and six healthy controls were used. PBM RGS-2 mRNA and RGS-2 protein were increased in BS/GS: 0.47 ± 0.06 d.u. vs 0.32 ± 0.04, (p < 0.006) (RGS-2 mRNA), and 0.692 ± 0.02 vs 0.363 ± 0.06 (p < 0.0001) (RGS2 protein). Incubation of PBM with Ang II increased RGS-2 protein in controls (from 0.363 ± 0.06 d.u. to 0.602 ± 0.05; p < 0.0001) but not in BS/GS (from 0.692 ± 0.02 to 0.711 ± 0.02). NO2-/NO3- and cGMP urinary excretion were increased in BS/GS (0.46 ± 0.13 vs 0.26 ± 0.05 μmol/μmol of urinary creatinine, p < 0.005, and 0.060 ± 0.030 vs 0.020 ± 0.01 p < 0.009, respectively). These results demonstrate that RGS-2 is increased and maximally stimulated in BS/GS and human RGS-2 system reacts as predicted by knockout mice experiments. This is the first report of RGS-2 level in a human clinical condition characterized by altered vascular tone, underlines the importance of RGS-2 as a key regulator element for Ang II signaling and provides insight into the links between BS/GS genetic abnormalities and abnormal vascular tone regulation.
Integration of anteroposterior and dorsoventral regulation ofPhox2btranscription in cranial motoneuron progenitors by homeodomain proteins
Authors: Samad Omar Abdel , Geisen Marc J. , Caronia Giuliana , Varlet Isabelle , Zappavigna Vincenzo , Ericson Johan , Goridis Christo , Rijli Filippo M.
Published: August 2004

Little is known about the molecular mechanisms that integrate anteroposterior (AP) and dorsoventral (DV) positional information in neural progenitors that specify distinct neuronal types within the vertebrate neural tube. We have previously shown that in ventral rhombomere (r)4 of Hoxb1 and Hoxb2 mutant mouse embryos, Phox2bexpression is not properly maintained in the visceral motoneuron progenitor domain (pMNv), resulting in a switch to serotonergic fate. Here, we show that Phox2b is a direct target of Hoxb1 and Hoxb2. We found a highly conserved Phox2b proximal enhancer that mediates rhombomere-restricted expression and contains separate Pbx-Hox (PH) and Prep/Meis (P/M) binding sites. We further show that both the PH and P/M sites are essential for Hox-Pbx-Prep ternary complex formation and regulation of the Phox2b enhancer activity in ventral r4. Moreover, the DV factor Nkx2.2 enhances Hox-mediated transactivation via a derepression mechanism. Finally, we show that induction of ectopic Phox2b-expressing visceral motoneurons in the chick hindbrain requires the combined activities of Hox and Nkx2 homeodomain proteins. This study takes an important first step to understand how activators and repressors, induced along the AP and DV axes in response to signaling pathways, interact to regulate specific target gene promoters, leading to neuronal fate specification in the appropriate developmental context.
Control ofArabidopsisflowering: the chill before the bloom
Authors: Henderson Ian R. , Dean Caroline
Published: August 2004

The timing of the floral transition has significant consequences for reproductive success in plants. Plants gauge both environmental and endogenous signals before switching to reproductive development. Many temperate species only flower after they have experienced a prolonged period of cold, a process known as vernalization, which aligns flowering with the favourable conditions of spring. Considerable progress has been made in understanding the molecular basis of vernalization in Arabidopsis. A central player in this process is FLC, which blocks flowering by inhibiting genes required to switch the meristem from vegetative to floral development. Recent data shows that many regulators of FLC alter chromatin structure or are involved in RNA processing.
A multivariate gait data analysis technique: Application to knee osteoarthritis
Authors: Astephen J L , Deluzio K J
Published: August 2004

Modern gait analysis is a powerful non-invasive tool for calculating the mechanical factors involved in pathological processes such as knee osteoarthritis (OA). Although very accurate measurements can be made, the clinical applicability and widespread use of gait analysis have been hindered by a lack of appropriate data analysis techniques for reducing and analysing the resulting large volumes of highly correlated gait data. This paper introduces a multidimensional galt data analysis technique that simultaneously considers multiple time-varying and discrete measures, exploiting the correlation structure between and within the measures. The multidimensional analysis technique was used to detect discriminatory mechanical features of knee OA gait patterns that involved interacting changes in several gait measures, at specific time portions of the gait cycle. The two most discriminatory features described a dynamic alignment difference and a loading response difference with knee OA.
The effect of acetabular cup size on the short-term stability of revision hip arthroplasty: A finite element investigation
Authors: Phillips A.T.M. , Pankaj  , Usmani A S , Howie C R
Published: August 2004

The study uses idealized two-dimensional finite element models to examine the behaviour of the acetabular construct following revision hip arthroplasty, carried out using the Slooff-Ling impaction grafting technique. The behaviour of bone graft was considered in detail, with non-linear elasticity and non-associated plasticity being adopted. Load was applied to the acetabular construct through a femoral head using smooth sliding surfaces. In particular, four models were subjected to two idealized cyclic load cases to investigate the effect of acetabular cup size on the short-term stability of the acetabular construct. The study suggests that benefits may be gained by using the largest practical size of acetabular cup.
A novel test method for evaluation of the abrasive wear behaviour of total hip stems at the interface between implant surface and bone cement
Authors: Bader R , Steinhauser E , Holzwarth U , Schmitt M , Mittelmeier W
Published: August 2004

After total hip replacement, some cemented titanium stems show above-average early loosening rates. Increased release of wear particles and resulting reaction of the peri-prosthetic tissue were considered responsible. The objective was to develop a test method for analysing the abrasive wear behaviour of cemented stems and for generating wear particles at the interface with the bone cement.

By means of the novel test device, cemented hip stems with different designs, surface topographies and material compositions using various bone cements could be investigated. Before testing, the cemented stems were disconnected from the cement mantle to simulate the situation of stem loosening (debonding). Subsequently, constant radial contact pressures were applied on to the stem surface by a force-controlled hydraulic cylinder. Oscillating micromotions of the stem (± 250 μm; 3 × 106cycles; 5 Hz) were carried out at the cement interface initiating the wear process.

The usability of the method was demonstrated by testing geometrically identical Ti-6A1-7Nb and Co-28Cr-6Mo hip stems ( n = 12) with definite rough and smooth surfaces, combined with commercially available bone cement containing zirconium oxide particles. Under identical frictional conditions with the rough shot-blasted stems, clearly more wear particles were generated than with the smooth stems, whereas the material composition of the hip stems had less impact on the wear behaviour.
Muscle forces analysis in the shoulder mechanism during wheelchair propulsion
Authors: Lin Hwai-Ting , Su Fong-Chin , Wu Hong-Wen , An Kai-Nan
Published: August 2004

This study combines an ergometric wheelchair, a six-camera video motion capture system and a prototype computer graphics based musculoskeletal model (CGMM) to predict shoulder joint loading, muscle contraction force per muscle and the sequence of muscular actions during wheelchair propulsion, and also to provide an animated computer graphics model of the relative interactions. Five healthy male subjects with no history of upper extremity injury participated. A conventional manual wheelchair was equipped with a six-component load cell to collect three-dimensional forces and moments experienced by the wheel, allowing real-time measurement of hand/rim force applied by subjects during normal wheelchair operation. An Expert Vision™ six-camera video motion capture system collected trajectory data of markers attached on anatomical positions. The CGMM was used to simulate and animate muscle action by using an optimization technique combining observed muscular motions with physiological constraints to estimate muscle contraction forces during wheelchair propulsion. The CGMM provides results that satisfactorily match the predictions of previous work, disregarding minor differences which presumably result from differing experimental conditions, measurement technologies and subjects. Specifically, the CGMM shows that the supraspinatus, infraspinatus, anterior deltoid, pectoralis major and biceps long head are the prime movers during the propulsion phase. The middle and posterior deltoid and supraspinatus muscles are responsible for arm return during the recovery phase. CGMM modelling shows that the rotator cuff and pectoralis major play an important role during wheelchair propulsion, confirming the known risk of injury for these muscles during wheelchair propulsion. The CGMM successfully transforms six-camera video motion capture data into a technically useful and visually interesting animated video model of the shoulder musculoskeletal system. The CGMM further yields accurate estimates of muscular forces during motion, indicating that this prototype modelling and analysis technique will aid in study, analysis and therapy of the mechanics and underlying pathomechanics involved in various musculoskeletal overuse syndromes.
Evaluation of three pose estimation algorithms for model-based Roentgen stereophotogrammetric analysis
Authors: Kaptein B L , R Valstar E , Stoel B C , Rozing P M , Reiber J H C
Published: August 2004

Model-based roentgen stereophotogrammetric analysis (RSA) uses a three-dimensional surface model of an implant in order to estimate accurately the pose of that implant from a stereo pair of roentgen images. The technique is based on minimization of the difference between the actually projected contour of an implant and the virtually projected contour of a model of that same implant. The advantage of model-based RSA over conventional marker-based RSA is that it is not necessary to attach markers to the implant. In this paper, three pose estimation algorithms for model-based RSA are evaluated. The algorithms were assessed on the basis of their sensitivities to noise in the actual contour, to the amount of drop-outs in the actual contour, to the number of points in the actual contour and to shrinkage or expansion of the actual contour. The algorithms that were studied are the iterative inverse perspective matching (IIPM) algorithm, an algorithm based on minimization of the difference (DIF) between the actual contour and the virtual contour, and an algorithm based on minimization of the non-overlapping area (NOA) between the actual and virtual contour. The results of the simulation and phantom experiments show that the NOA algorithm does not fulfil the high accuracy that is necessary for model-based RSA. The IIPM and DIF algorithms are robust to the different distortions, making model-based RSA a possible replacement for marker-based RSA.
Steady-state elastohydrodynamic lubrication analysis of a metal-on-metal hip implant employing a metallic cup with an ultra-high molecular weight polyethylene backing
Authors: Liu F , Wang F C , Jin Z M , Hirt F , Rieker C , Grigoris P
Published: August 2004

The elastohydrodynamic lubrication (EHL) analysis was carried out in this study for a 28 mm diameter metal-on-metal hip prosthesis employing a metallic cup with an ultra-high molecular weight polyethylene (UHMWPE) backing under a simple steady state rotation representing the flexion/extension during walking. Both Reynolds and elasticity equations were coupled and solved numerically by the finite difference method. The elastic deformation was determined by means of the fast Fourier transform (FFT) technique using the displacement coefficients obtained from the finite element method. Excellent agreement of the predicted elastic deformation was obtained between the FFT technique and the conventional direct summation method. The number of grid points used in the lubrication analysis was found to be important in predicting accurate film thicknesses, particularly at low viscosities representative of physiological lubricants. The effect of the clearance between the femoral head and the acetabular cup on the predicted lubricant film thickness was shown to be significant, while the effect of load was found to be negligible. Overall, the UHMWPE backing was found not only to reduce the contact pressure as identified in a previous study by the authors (Liu et al., 2003) but also significantly to increase the lubricant film thickness for the 28mm diameter metal-on-metal hip implant, as compared with a metallic mono-block cup.
Pebble-bed modular reactor: A generation IV high-temperature gas-cooled reactor
Authors: Koster A , Matzie R , Matzner D
Published: August 2004

Most of the development in nuclear power in the past 30 years has gone into water-cooled reactors. As government funding has dwindled, development of promising alternative systems has lapsed in most countries. Although gas-cooled reactors have had a very good safety record, many have not been able to compete on economic grounds, mainly because of poor operating records and/or high infrastructure costs. Since broad-based construction has not been achieved, gas-cooled reactors have not benefited from cost reductions in the learning curve. The realization that nuclear energy will need to contribute to future power production expansion and the reduction of greenhouse gases has led to the resurgence of interest in safer and more economical ways to produce nuclear energy. One of these alternatives is the high-temperature gas-cooled reactor, as exemplified by the pebble-bed modular reactor (PBMR) being developed in South Africa. This direct-cycle, low power density design is based on clustering modules of modest power output into flexible power plants. Economic targets can be met through simplification by dispensing with the need for extensive back-up safety systems and high plant availability due to on-power refuelling and low-maintenance equipment.
RAPID-L and RAPID operator-free fast reactors combined with a thermoelectric power conversion system
Authors: Kambe M , Tsunoda H , Nakajima K , Iwamura T
Published: August 2004

The 200 kWe, uranium nitride fuelled, lithium-cooled, fast reactor concept “RAPID-L” for a lunar base power system, and the 1000 kWe, U-Pu-Zr metal fuelled, sodium-cooled, fast reactor concept “RAPID” for a terrestrial power system have been demonstrated. These reactors are characterized by the RAPID (Refuelling by All Pins Integrated Design) refuelling concept, which enables quick and simplified refuelling. The essential feature of the RAPID concept is that the reactor core consists of an integrated fuel assembly (IFA) instead of conventional fuel subassemblies. In this small-size reactor core, all the fuel pins are integrated altogether and encased in a fuel cartridge. Refuelling is conducted by replacing an IFA. The reactor can be operated without refuelling for up to 10 years. Unique challenges in reactivity control system design have been addressed in these reactors. They have no control rod, but involve the following innovative reactivity control systems: lithium expansion modules (LEMs) for inherent reactivity feedback, lithium injection modules (LIMs) for inherent ultimate shutdown and lithium release modules (LRMs) for automated reactor start-up. All these systems adopt lithium-6 as a liquid poison instead of B4C rods. In combination with LEMs, LIMs and LRMs, RAPID-L and RAPID can be operated without an operator. Another characteristic of RAPID-L and RAPID is a thermoelectric (TE) power conversion system instead of the conventional steam turbine generator. In this paper, design characteristics of RAPID-L and RAPID power system concepts are discussed.
Evidence for nuclear emissions during acoustic cavitation revisited
Authors: Nigmatulin R. I. , Taleyarkhan R. P. , Lahey R. T.
Published: August 2004

This paper extends the experimental and numerical results presented previously and addresses the major criticisms raised. In addition, the most recent results are discussed. In acoustic cavitation experiments with chilled (ɛ0 °C) deuterated acetone (C3D6O), the production of tritium and 2.45 MeV neutrons [which are characteristic of deuterium-deuterium (D-D) fusion] was observed during vapour bubble implosions in an acoustic pressure field. Similar experiments with deuterated acetone at room temperature (ɛ20 °C) and control experiments with normal acetone (C3H6O), at both 0 and 20 °C, showed no statistically significant increases in either tritium level or neutron emissions. Numerical simulations of the processes that account for the shock waves generated in the liquid and within the collapsing bubbles supported these experimental observations and showed that high densities and temperatures (° 108 K) may be achieved during bubble cloud implosions, yielding the conditions required for D-D nuclear fusion reactions. The present paper treats the bubble fusion experiments and theoretical results in greater detail than was possible in the previous publications, contains some refinements, addresses some important questions raised by reviewers and critics and discusses possible applications of this interesting phenomenon.
Where next for nuclear power?
Authors: Rippon S. E.
Published: August 2004

There is no doubt in the author's mind that nuclear power will be needed in the future to provide plentiful supplies of environmentally clean and low-cost electrical power. However, in North America and Western Europe there has been a politically motivated pause in new ordering of nuclear plant. In this period a great deal of development work has gone into new generations of nuclear reactor design. Most rely heavily on a wealth of experience from well over 400 commercial units operating successfully around the world. These plants offer an exceptional level of safety and preclude the need for any emergency planning for local populations. Some of the evolutionary designs are already starting to be built and put into operation in Southeast Asia and Russia. More radical new designs have also been developed with passive features that offer comparable levels of safety. These new reactor designs are generally smaller and greatly simplified. Most are at a point where they are ready for commercial exploitation. The electricity utility market has a wide choice in the coming years. It is by no means certain, but it looks as if large evolutionary designs will be adopted in countries with powerful electricity grid systems, while there is a huge potential for the smaller units in new markets.
Modular integral water reactors: The ultimate in safety and simplicity
Authors: Carelli M. D. , Matzie R. A. , Crump M. W.
Published: August 2004

The integral water reactor design (i.e. a design where all primary system components—steam generators, pumps, pressurizer and even control rod drive mechanisms-are within the reactor vessel) is presented here. A background discussion of how integral designs were introduced in the 1990s is provided, followed by a description of one of those designs, the safe integral reactor (SIR). The rest of the article is then devoted to the international reactor innovative and secure (IRIS) which is currently being developed by an international consortium led by Westinghouse and including 20 + members from 10 nations. In discussing how IRIS has furthered the integral reactor concept, the design characteristics of IRIS are described along with its unique approach to safety, which focuses on exploiting the integral configuration to eliminate by design the occurrence of accidents in lieu of coping with their consequences. The IRIS safety approach is so successful that seven of eight class IV accidents (the accidents that could eventually lead to a radioactive release to the environment) typical of loop PWRs are either eliminated or downgraded, and thus it is being considered to pursue the licensing of IRIS without the requirement for off-site emergency response. The main characteristics of the IRIS safety by design are provided along with a discussion of its licensing approach.
‘Fit for purpose’ nuclear energy
Authors: Ion S. E. , Franklin K. C.
Published: August 2004

The demand for energy is increasing worldwide. Countries need to ensure their energy future while decreasing their carbon emissions. Nuclear power is flexible enough to meet these demands in terms of carbon-free electricity and security of supply. A range of options for nuclear generated electricity are summarized in this paper, which suit both the developed and the developing world, and the factors involved in which option to choose are outlined.
Progress in permanent geologic disposal of spent nuclear fuel and high-level radioactive waste in the United States
Authors: Dyer J. R. , Peters M. T.
Published: August 2004

The mission of the Office of Civilian Radioactive Waste Management (OCRWM) of the US Department of Energy (DOE) is to manage and dispose of spent nuclear fuel and high-level radioactive waste in a manner that protects health, safety and the environment, enhances national and energy security and merits public confidence. Consolidation of spent nuclear fuel and high-level radioactive waste from 126 sites in 39 states and safe disposal at Yucca Mountain are vital to the US national interests. The US geologic repository programme's key objective remains to begin receiving spent nuclear fuel and high-level radioactive waste at the US Nuclear Regulatory Commission (NRC) licensed Yucca Mountain repository in 2010. To achieve this objective, the DOE must, in less than 7 years, seek and secure authorization to construct the repository from the NRC, begin constructing the repository and receive a license amendment allowing receipt of radioactive materials and operation of the repository. DOE must also develop a transportation system to ship spent nuclear fuel and high-level radioactive waste from civilian and defence storage sites to the repository. This paper describes near-term efforts in developing the license application and transportation system. Successfully licensing, constructing and operating a repository will rely on information gained from more than two decades of scientific investigations at the Yucca Mountain site, all of which contribute to the technical basis for understanding the repository system. This paper also summarizes ongoing and completed in situ testing in the exploratory studies facility (ESF) and cross-drift. The ESF, a U-shaped tunnel approximately 7.9 km long and about 300 m below the crest of Yucca Mountain, has been used extensively to conduct tests in 13 alcoves and niches and to access a smaller cross-drift, 5 m in diameter and 2.7 km long.
Catalyst warm-up to light-off by pulsating engine exhaust: Two-dimensional studies
Authors: Benjamin S F , Roberts C A
Published: August 2004

This paper presents the results of two-dimensional studies on a range of different catalyst substrates warmed by exhaust from a four-cylinder gasoline engine. Engine speeds investigated were 2000 and 3000 r/min, corresponding to frequencies of 67 and 100 Hz. Of the nine substrates investigated, four were washcoated but non-reactive and four were washcoated and reactive. The ninth substrate was a hybrid sample with its front end inactive and its downstream end active: this is analogous to an aged catalyst. The temperatures at 16 locations within the substrates were measured. All the substrates were warmed by the pulsating exhaust flow from an engine running lean of stoichiometric. Thereactive substratates were warmed through light-off and both substrate temperatures and hydrocarbon conversion were monitored. The latter was measured with very high response time fast flame ionization detectors. Predicted temperatures and conversion were obtained from a two-dimensional computational fluid dynamics (CFD) model. The model was based on the porous medium approach and incorporated a simple chemical scheme for oxidation under lean conditions. Standard values for reaction rate constants were found to be accurate for the lean conditions studied. Comparison was made of measurements of temperature and conversion fraction with predictions, with particular reference to the time taken to achieve light-off. Steady flow CFD predictions were found to be in good overall agreement with engine test data. Pulsing flow CFD predictions were found, however, to improve on the degree of agreement for warm-up of non-reactive samples, but at the expense of increased computation time. The performance of the reactive hybrid sample was accurately predicted by adjustment of the parameter for active area per unit volume, providing the basis for a technique for prediction of performance for aged catalysts.
High-pressure multicomponent liquid sprays: Departure from ideal behaviour
Authors: Trujillo M F , Torres D J , O'Rourke P J
Published: August 2004

An investigation is performed to determine quantitatively the departures from ideal behaviour that can be expected in pressure-volume-temperature (P-V-T) relationships, internal energy departures, relevant thermo-dynamic partial derivatives, droplet vaporization and spray development in high-pressure environments typical of diesel engine conditions. All of the necessary modifications have been added to the KIVA-3V code. The equation of state employed is the Peng-Robinson equation. Results show that as the fraction of air increases in a fuel/air mixture the departure from ideal behaviour in P-V-T relationships is lessened. The largest deviation from ideal predictions in spray development is attributed to a significant underprediction of the vaporization rate at high pressures (P ≫ Pc) and relatively low temperatures (T ≈ Tc). Thermodynamic partial derivatives can also show deviations from ideal behaviour even when the compressibility factor Z is equal to one.
Development and validation of a control-oriented library for the simulation of automotive engines
Authors: Canova M
Published: August 2004

The evolution of automotive engines has led to the introduction of electronic control systems, capable of optimizing engine performance to improve fuel consumption and pollutant emissions. Theoretical models play an important role in the design of engine control and diagnostic systems, allowing a reductionin development time and costs. The paper describes the development of a control-oriented submodels library for engine components and subsystems. Library blocks were assembled together to build a mean value engine model (MVEM) for the simulation of a diesel engine, fitted with a common rail injection system, waste-gated turbine and exhaust gas recirculation (EGR). Simulation results were compared with experimental data, both in steady and transient conditions. The model satisfactorily estimated engine behaviour with very short calculation times.
Identifying a critical time for mixing in a direct injection diesel engine through the study of increased in-cylinder mixing and its effect on emissions
Authors: Kurtz E M , Foster D E
Published: August 2004

An experimental study aimed at understanding the effect of in-cylinder mixing on direct injection diesel combustion was conducted in which an auxiliary gas injector was installed on to a single-cylinder diesel engine. The gas injector was used to inject air and nitrogen, thereby enhancing in-cylinder mixing at a specific time in the combustion cycle. The phasing of that gas injection event with respect to the fuel injection event was changed. The results suggest that it is primarily the fuel injected at the tail end of the fuel injection event that has difficulty mixing. Prior to the end of fuel injection, the kinetic energy input during fuel injection is sufficient to mix the fuel with air. However, near the end of fuel injection the kinetic energy is low and the fuel is not followed by any kinetic energy inputs that could help bring about mixing, which causes that fuel to produce large amounts of soot that ultimately have trouble oxidizing. It was also found that in-cylinder turbulence had no effect on NOx emissions when it occurred after +20° ATDC (after top dead centre), just after the end of fuel injection in these experiments. It was believed that, by that time, the NOx chemistry was frozen. However, NOx emissions were affected by early gas injection such that injecting air brought about an increase in NOx emissions while injecting nitrogen reduced NOx emissions. This finding suggests that early and prolonged injection of diluents could be used as a soot-friendly form of exhaust gas recirculation, provided that the injection overlaps the end of fuel injection.
An investigation of using various diesel-type fuels in homogeneous charge compression ignition engines and their effects on operational and controlling issues
Authors: Milovanovic N , Chen R , Dowden R , Turner J
Published: August 2004

Homogeneous charge compression ignition (HCCI) engines appear to be a future alternative to diesel and spark-ignited engines. The HCCI engine has the potential to deliver high efficiency and very low NOx and particulate matter emissions. There are, however, problems with the control of ignition and heat release range over the entire load and speed range which limits the practical application of this technology.

The aim of this paper is to analyse the use of different types of diesel fuels in an HCCI engine and hence to find the most suitable with respect to operational and control issues. The single-zone combustion model with convective heat transfer loss is used to simulate the HCCI engine environment. n-Heptane, dimethyl ether and bio-diesel (methyl butanoate and methyl formate) fuels are investigated. Methyl butanoate and methyl formate represent surrogates of heavy and light bio-diesel fuel respectively. The effects of different engine parameters such as equivalence ratio and engine speed on the ignition timing are investigated. The use of internal exhaust gas recirculation is investigated as a potential strategy for controlling the ignition timing.

The results indicate that the use of bio-diesel fuels will result in lower sensitivity of ignition timing to changes in operational parameters and in a better control of the ignition process when compared with the use of n-heptane and dimethyl ether.
Excitation Wavelength Dependence of Solvation Dynamics in a Water Pool of a Reversed Micelle
Authors: Satoh Taku , Okuno Hiroaki , Tominaga Keisuke , Bhattacharyya Kankan
Published: August 2004

We have investigated the excitation wavelength dependence of solvation dynamics in the water pool of a reversed micelle using dynamic Stokes shift method. The solvation dynamics displays nanosecond and subnanosecond components, which are almost independent of the excitation wavelength. On the other hand, the total dynamics Stoke shift decreases with increasing the excitation wavelength.
Novel Silver(I) and Copper(II) Complexes of Tetrakis(2-pyridyl)methane
Authors: Matsumoto Kouzou , Kannami Masaki , Oda Masaji
Published: August 2004

Tetrakis(2-pyridyl)methane forms a novel one dimensional coordination polymer complex with Ag(I) ion and two kinds of complexes different in coordination modes with Cu(II) ion, indicating its versatile ability as a symmetric tetradentate ligand.
Molecular Design and Crystal Structures of Chiral Macrotricyclic Cage Amines
Authors: Yoshida Haruki , Izumi Mitsunori , Ito Naohito , Ichikawa Kazuhiko , Shiro Motoo
Published: August 2004

Chiral macrotricyclic cage amines have been synthesized; their X-ray structures have revealed that the asymmetric framework has been formed by adding a single chiral carbon into methylene skeleton of cage amine. The 1H NMR spectra have shown the stable and rigid conformation in solution.
Preparation of H2Ti4O9 with High Specific Surface Area
Authors: Wang Jinshu , Yin Shu , Sato Tsugio
Published: August 2004

H2Ti4O9 nanocrystals with high specific surface areas were prepared by exfoliation and reassembly process through a novel way of ball milling and ion-exchange reaction. The specific surface area of H2Ti4O9 nanocrystals depends on solution pH value and ball milling time. H2Ti4O9 nanocrystals precipitated by milling K2Ti4O9 for 2 h and exfoliating in 1 M HCl followed by adjusting solution pH at 8 has the specific surface area of 328.2 m2/g.
Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?
Authors: Sanderson Jeremy , Ansari Azhar , Marinaki Tony , Duley John
Published: August 2004

Thiopurines [azathioprine (AZA), 6-mercaptopurine (6-MP) and thioguanine (6-TG)] have a well-established role as immunosuppressive agents in a variety of chronic inflammatory conditions, haematological neoplasia and in transplant rejection. Despite good overall clinical response rates, particularly when used as steroid sparing agents, adverse effects are a limiting problem leading to withdrawal in up to a quarter of patients. Severe myelosuppression is the most serious toxicity occurring early or occasionally later during treatment.

An understanding of the competing pathways involved in the metabolism of thiopurines has important implications for predicting some of the more severe toxicity seen with these drugs. Thiopurine methyl transferase (TPMT) is an enzyme catalysing the methylation of 6-MP, competing with xanthine oxidase (XO) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) to determine the amount of 6-MP metabolised to cytotoxic thioguanine nucleotides. Allelic polymorphisms in the TPMT gene predict the activity of the enzyme such that 1 in 10 of the population are heterozygous and have approximately 50% of normal activity, whilst 1 in 300 are completely deficient. As a result, these individuals are at high risk of severe myelosuppression. Conversely, individuals with very high levels of TPMT activity are hyper-methylators in whom clinical response is less likely. Prior knowledge of TPMT status avoids exposure of individuals with zero TPMT to potentially fatal treatment with AZA or 6-MP and provides one of the best examples of predictive pharmacogenetics in therapeutics. This article reviews literature on the role of TPMT measurement prior to treatment with thiopurines and provides some guidance to the use of TPMT as a guide to tailoring thiopurine therapy.