bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Regional Model Simulations with Precipitation Assimilation
Authors: Nunes Ana M. B. , Roads John O.
Published: October 2005

Although large-scale atmospheric reanalyses are now providing physical, realistic fields for many variables, precipitation remains problematic. As shown in recent studies, using a regional model to downscale the global reanalysis only marginally alleviates the precipitation simulation problems. For this reason, later-generation analyses, including the recent National Centers for Environmental Prediction regional reanalysis, are using precipitation assimilation as a methodology to provide superior precipitation fields. This methodology can also be applied to regional model simulations to substantially improve the precipitation fields downscaled from global reanalysis. As an illustration of the regional model precipitation assimilation impact, the authors describe here an extended-range simulation comparison over South America. The numerical experiments cover the beginning of the Large-Scale Biosphere–Atmosphere wet season campaign of January 1999. Evaluations using radiosonde datasets obtained during this campaign are provided as well. As will be shown, rain-rate assimilation not only increases the regional model precipitation simulation skill but also provides improvements in other fields influenced by the precipitation. Because of the potential impact on land surface features, the authors believe they will ultimately be able to show improvements in monthly to seasonal forecasts when precipitation assimilation is used to generate more accurate land surface initial conditions.
Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy? – A systematic review
Authors: Scharplatz Madlaina , Puhan Milo A , Steurer Johann , Perna Annalisa , Bachmann Lucas M
Published: October 2005

Background

Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D) polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease.

Methods

Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives) responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality.

Results

Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes.

Conclusion

Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.
A method of precise mRNA/DNA homology-based gene structure prediction
Authors: Churbanov Alexander , Pauley Mark , Quest Daniel , Ali Hesham
Published: October 2005

Background

Accurate and automatic gene finding and structural prediction is a common problem in bioinformatics, and applications need to be capable of handling non-canonical splice sites, micro-exons and partial gene structure predictions that span across several genomic clones.

Results

We present a mRNA/DNA homology based gene structure prediction tool, GIGOgene. We use a new affine gap penalty splice-enhanced global alignment algorithm running in linear memory for a high quality annotation of splice sites. Our tool includes a novel algorithm to assemble partial gene structure predictions using interval graphs. GIGOgene exhibited a sensitivity of 99.08% and a specificity of 99.98% on the Genie learning set, and demonstrated a higher quality of gene structural prediction when compared to Sim4, est2genome, Spidey, Galahad and BLAT, including when genes contained micro-exons and non-canonical splice sites. GIGOgene showed an acceptable loss of prediction quality when confronted with a noisy Genie learning set simulating ESTs.

Conclusion

GIGOgene shows a higher quality of gene structure prediction for mRNA/DNA spliced alignment when compared to other available tools.
Satisfaction is not all – patients' perceptions of outcome of general practice consultations, a qualitative study
Authors: Andén Annika , Andersson Sven-Olof , Rudebeck Carl-Edvard
Published: October 2005

Background

Evaluation of outcome in general practice can be seen from different viewpoints. In this study we focus on the concepts patients use to describe the outcome of a consultation with a GP.

Method

Patients were interviewed within a week after a consultation with a GP. The interviews were made with 20 patients in 5 focus groups and 8 individually. They were analysed with a phenomenographic research approach.

Results

From the patient's perspective, the outcome of a consultation is about cure or symptom relief, understanding, confirmation, reassurance, change in self-perception and satisfaction.

Conclusion

General practice consultations are often more important for patients than generally supposed. Understanding is the most basic concept.
Short- and long-term cause-specific survival of patients with inflammatory breast cancer
Authors: Tai Patricia , Yu Edward , Shiels Ross , Pacella Juan , Jones Kurian , Sadikov Evgeny , Mahmood Shazia
Published: October 2005

Background

Inflammatory breast cancer (IBC) had been perceived to have a poor prognosis. Oncologists were not enthusiastic in the past to give aggressive treatment. Single institution studies tend to have small patient numbers and limited years of follow-up. Most studies do not report 10-, 15- or 20-year results.

Methods

Data was obtained from the population-based database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1975–1995 using SEER*Stat5.0 software. This period of 21 years was divided into 7 periods of 3 years each. The years were chosen so that there was adequate follow-up information to 2000. ICD-O-2 histology 8530/3 was used to define IBC. The lognormal model was used for statistical analysis.

Results

A total of 1684 patients were analyzed, of which 84% were white, 11% were African Americans, and 5% belonged to other races. Age distribution was < 30 years in 1%, 30–40 in 11%, 40–50 in 22%, 50–60 in 24%, 60–70 in 21%, and > 70 in 21%. The lognormal model was validated for 1975–77 and for 1978–80, since the 10-, 15- and 20-year cause-specific survival (CSS) rates, could be calculated using the Kaplan-Meier method with data available in 2000. The data were then used to estimate the 10-, 15- and 20-year CSS rates for the more recent years, and to study the trend of improvement in survival. There were increasing incidences of IBC: 134 patients in the 1975–77 period to 416 patients in the 1993–95 period. The corresponding 20-year CSS increased from 9% to 20% respectively with standard errors of less than 4%.

Conclusion

The improvement of survival during the study period may be due to introduction of more aggressive treatments. However, there seem to be no further increase of long-term CSS, which should encourage oncologists to find even more effective treatments. Because of small numbers of patients, randomized studies will be difficult to conduct. The SEER population-based database will yield the best possible estimate of the trend in improvement of survival for patients with IBC.
Expression of POU-domain transcription factor, Oct-6, in schizophrenia, bipolar disorder and major depression
Authors: Ubhi Kirenjeet , Price Jack
Published: October 2005

Background

The POU-domain transcription factor Oct-6 has been reported to be differentially expressed between schizophrenic and control post-mortem brains. In this study, we attempted to replicate this finding and to discover whether Oct-6 was also dysregulated in bipolar disorder and major depression.

Methods

Oct-6 mRNA and protein expression were determined by in-situ hybridization and immunohistochemistry respectively in sections of post-mortem brain.

Results

We did not observe any differences in Oct-6 expression between any of the groups under study. Oct-6 mRNA and protein was identically expressed in the hippocampal and cortical regions of most specimens in all groups, including controls.

Conclusion

Oct-6 is, therefore, unlikely to be a specific marker for any psychological disorder; rather its expression in controls suggests that it is normally expressed in most adult brains.
Geographical variation of cerebrovascular disease in New York State: the correlation with income
Authors: Han Daikwon , Carrow Shannon S , Rogerson Peter A , Munschauer Frederick E
Published: October 2005

Background

Income is known to be associated with cerebrovascular disease; however, little is known about the more detailed relationship between cerebrovascular disease and income. We examined the hypothesis that the geographical distribution of cerebrovascular disease in New York State may be predicted by a nonlinear model using income as a surrogate socioeconomic risk factor.

Results

We used spatial clustering methods to identify areas with high and low prevalence of cerebrovascular disease at the ZIP code level after smoothing rates and correcting for edge effects; geographic locations of high and low clusters of cerebrovascular disease in New York State were identified with and without income adjustment. To examine effects of income, we calculated the excess number of cases using a non-linear regression with cerebrovascular disease rates taken as the dependent variable and income and income squared taken as independent variables. The resulting regression equation was: excess rate = 32.075 - 1.22*10-4(income) + 8.068*10-10(income
2), and both income and income squared variables were significant at the 0.01 level. When income was included as a covariate in the non-linear regression, the number and size of clusters of high cerebrovascular disease prevalence decreased. Some 87 ZIP codes exceeded the critical value of the local statistic yielding a relative risk of 1.2. The majority of low cerebrovascular disease prevalence geographic clusters disappeared when the non-linear income effect was included. For linear regression, the excess rate of cerebrovascular disease falls with income; each $10,000 increase in median income of each ZIP code resulted in an average reduction of 3.83 observed cases. The significant nonlinear effect indicates a lessening of this income effect with increasing income.

Conclusion

Income is a non-linear predictor of excess cerebrovascular disease rates, with both low and high observed cerebrovascular disease rate areas associated with higher income. Income alone explains a significant amount of the geographical variance in cerebrovascular disease across New York State since both high and low clusters of cerebrovascular disease dissipate or disappear with income adjustment. Geographical modeling, including non-linear effects of income, may allow for better identification of other non-traditional risk factors.
Heat shock protein and heat shock factor 1 expression and localization in vaccinia virus infected human monocyte derived macrophages
Authors: Kowalczyk Aleksandra , Guzik Krzysztof , Slezak Kinga , Dziedzic Jakub , Rokita Hanna
Published: October 2005

Background

Viruses remain one of the inducers of the stress response in the infected cells. Heat shock response induced by vaccinia virus (VV) infection was studied in vitro in human blood monocyte derived macrophages (MDMs) as blood cells usually constitute the primary site of the infection.

Methods

Human blood monocytes were cultured for 12 – 14 days. The transcripts of heat shock factor 1 (HSF1), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and two viral genes (E3L and F17R) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), and the corresponding proteins measured by Western blot. Heat shock factor 1 DNA binding activities were estimated by electrophoretic mobility shift assay (EMSA) and its subcellular localization analyzed by immunocytofluorescence.

Results

It appeared that infection with vaccinia virus leads to activation of the heat shock factor 1. Activation of HSF1 causes increased synthesis of an inducible form of the HSP70 both at the mRNA and the protein level. Although HSP90 mRNA was enhanced in vaccinia virus infected cells, the HSP90 protein content remained unchanged. At the time of maximum vaccinia virus gene expression, an inhibitory effect of the infection on the heat shock protein and the heat shock factor 1 was most pronounced. Moreover, at the early phase of the infection translocation of HSP70 and HSP90 from the cytoplasm to the nucleus of the infected cells was observed.

Conclusion

Preferential nuclear accumulation of HSP70, the major stress-inducible chaperone protein, suggests that VV employs this particular mechanism of cytoprotection to protect the infected cell rather than to help viral replication. The results taken together with our previuos data on monocytes or MDMs infected with VV orS. aureusstrongly argue that VV employs multiple cellular antiapoptotic/cytoprotective mechanisms to prolong viability and proinflammatory activity of the cells of monocytic-macrophage lineage.
Wnt5 signaling in vertebrate pancreas development
Authors: Kim Hyon J , Schleiffarth Jack R , Jessurun Jose , Sumanas Saulius , Petryk Anna , Lin Shuo , Ekker Stephen C
Published: October 2005

Background

Signaling by the Wnt family of secreted glycoproteins through their receptors, the frizzled (Fz) family of seven-pass transmembrane proteins, is critical for numerous cell fate and tissue polarity decisions during development.

Results

We report a novel role of Wnt signaling in organogenesis using the formation of the islet during pancreatic development as a model tissue. We used the advantages of the zebrafish to visualize and document this process in living embryos and demonstrated thatinsulin-positive cells actively migrate to form an islet. We used morpholinos (MOs), sequence-specific translational inhibitors, and time-lapse imaging analysis to show that the Wnt-5 ligand and the Fz-2 receptor are required for properinsulin-cell migration in zebrafish. Histological analyses of islets inWnt5a-/-mouse embryos showed that Wnt5a signaling is also critical for murine pancreaticinsulin-cell migration.

Conclusion

Our results implicate a conserved role of a Wnt5/Fz2 signaling pathway in islet formation during pancreatic development. This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease.
Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms
Authors: Taniguchi Yuko , Nosaka Kisato , Yasunaga Jun-ichirou , Maeda Michiyuki , Mueller Nancy , Okayama Akihiko , Matsuoka Masao
Published: October 2005

Background

Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome.

Results

The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells.

Conclusion

These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.
Targeting energy metabolism in brain cancer: review and hypothesis
Authors: Seyfried Thomas N , Mukherjee Purna
Published: October 2005

Malignant brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate) for energyin vivowhen glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet.
Contrasting Phenotypes of Putative Proprioceptive and Nociceptive Trigeminal Neurons Innervating Jaw Muscle in Rat
Authors: Connor Mark , Naves Ligia A , McCleskey Edwin W
Published: October 2005

Background:

Despite the clinical significance of muscle pain, and the extensive investigation of the properties of muscle afferent fibers, there has been little study of the ion channels on sensory neurons that innervate muscle. In this study, we have fluorescently tagged sensory neurons that innervate the masseter muscle, which is unique because cell bodies for its muscle spindles are in a brainstem nucleus (mesencephalic nucleus of the 5th cranial nerve, MeV) while all its other sensory afferents are in the trigeminal ganglion (TG). We examine the hypothesis that certain molecules proposed to be used selectively by nociceptors fail to express on muscle spindles afferents but appear on other afferents from the same muscle.

Results:

MeV muscle afferents perfectly fit expectations of cells with a non-nociceptive sensory modality: Opiates failed to inhibit calcium channel currents ( ICa) in 90% of MeV neurons, although ICa were inhibited by GABAB receptor activation. All MeV afferents had brief (1 msec) action potentials driven solely by tetrodotoxin (TTX)-sensitive Na channels and no MeV afferent expressed either of three ion channels (TRPV1, P2X3, and ASIC3) thought to be transducers for nociceptive stimuli, although they did express other ATP and acid-sensing channels. Trigeminal masseter afferents were much more diverse. Virtually all of them expressed at least one, and often several, of the three putative nociceptive transducer channels, but the mix varied from cell to cell. Calcium currents in 80% of the neurons were measurably inhibited by μ-opioids, but the extent of inhibition varied greatly. Almost all TG masseter afferents expressed some TTX-insensitive sodium currents, but the amount compared to TTX sensitive sodium current varied, as did the duration of action potentials.

Conclusion:

Most masseter muscle afferents that are not muscle spindle afferents express molecules that are considered characteristic of nociceptors, but these putative muscle nociceptors are molecularly diverse. This heterogeneity may reflect the mixture of metabosensitive afferents which can also signal noxious stimuli and purely nociceptive afferents characteristic of muscle.
Non-Linear Stability Analysis of a Thin Newtonian Film Flowing Down an Infinite Vertical Rotating Cylinder
Authors: Chen C-I , Chen C-K , Yang Y-T
Published: October 2005

Non-linear stability theories for the characterization of Newtonian film flow down an infinite vertical rotating cylinder is given. A generalized non-linear kinematic model is derived to represent the physical system and is solved by the long-wave perturbation method in a two-step procedure. In the first step, the normal mode method is used to characterize the linear behaviours. In the second step, an elaborated non-linear film flow model is solved by using the method of multiple scales to characterize flow behaviours at various states of subcritical stability, subcritical instability, supercritical stability, and supercritical explosion. The modelling results indicate that by increasing the rotation speed, ω, and decreasing the radius of cylinder, R, the film flow becomes less stable, generally.
Pattern Recognition on Diesel Engine Working Conditions by Wavelet Kullback-Leibler Distance Method
Authors: Zhou P , Li H , Clelland D
Published: October 2005

This article introduces a novel pattern recognition and fault diagnosis method for diesel engines. The method is developed from engine vibration signal analysis in combination with wavelet and Kullback-Leibler distance (KLD) approaches. The new approach is termed wavelet Kullback-Leibler distance (WKLD). Experimental data relating to piston and cylinder liner wear obtained from a production diesel engine are used to evaluate the newly developed method. A good agreement between the experimental data and the WKLD estimation is found. The results of this article suggest that WKLD is an advancement on the methods which have been currently developed for pattern recognition and fault diagnosis of diesel engines.
Kinematic Analysis and Synthesis of the Knotting Mechanisms Can be Used in the Production of Handmade Carpet: A Case Study
Authors: Topalbekiroğlu M
Published: October 2005

The weaving process in a handmade carpet contains independent knots, which have a complex structure. A new production method, mechanism, or machine for producing knots in handmade carpets has not been developed since thousands of years. They are still woven by human hand. Two different types of knots are used to form handmade carpets, which are called as the Turkish (Gördes knot) and the Persian (Sehna knot) knots. In this article, the conceptual design and dimensional synthesis for mechanisms used to produce these knots are studied. To generate all-acceptable one-degree of freedom (DOF) and two-DOF planar knotting mechanism, a systematic methodology is presented. First, the functional requirements of the knotting mechanism are established according to the problem statement. Some of the functional requirements of the knotting mechanism are then translated into the structural characteristics of mechanism. On the basis of the requirements and the structural considerations, the unwanted mechanism is screened out. Finally, two different mechanisms are developed for the knotting mechanism and their dimensions are determined by dimensional synthesis method.
Dynamic Response Simulations of Flexible Beams Using the Energy Wave Scattering Method
Authors: Chen T
Published: October 2005

The dynamic response of a flexible beam is simulated using the energy wave scattering method. A new topology is demonstrated to model the flexible beam and it can distinguish the displacements contributed by kinetic energy and potential energy. Experiments are conducted using both a highly distributed model and a lumped-distributed model. Numerical procedures and examples are presented. The experimental results are compared with the simulated ones and a good comparison is shown.
Optimal Design of Laminated Composite Plates for Maximum Buckling Load Using Genetic Algorithm
Authors: Kim C. W. , Lee J. S.
Published: October 2005

An optimization procedure using a genetic algorithm (GA) is proposed to determine the optimal stacking sequence of laminated composite plates for the maximum buckling load under several different loadings, such as uniaxial compression, shear, biaxial compression, and the combination of shear and biaxial loadings. A series of optimal design is conducted for composite laminates having different aspect ratios, load conditions, and number of plies. Critical buckling load is taken as fitness function and fibre orientations are taken as design variables. A performance index is introduced to represent the effectiveness of optimal design with respect to worst case design. Then, for uniaxial compression loading, postbuckling behaviour is analysed numerically for the optimally designed composite plates as well as the worst case design composite plate. It shows the outstanding postbuckling performance of one of the optimally designed composite plates against the worst case design composite plate. Also, a GA finds the global solution without requiring auxiliary information such as derivatives of the objective function.
A Model of Magnetic Force for Thrust Bearings of Permanent Magnets
Authors: Qingchang T , Zunquan K , Wei L , Yongchen P
Published: October 2005

In this work, non-uniform magnetization of magnetic rings of the thrust bearings constructed from permanent magnets are experimentally measured and analysed. Effects of the non-uniform magnetization and the soft-magnetic material on magnetic force of the thrust bearings are investigated using the theory of magnetic charges, and a model for predicting magnetic force of the thrust bearings is established. The model is verified experimentally. From this model, the magnetic force fluctuations caused by the non-uniform magnetization are calculated and analysed.
A Combined Experimental and Computational Fluid Dynamics Analysis of the Dynamics of Drop Formation
Authors: Fawehinmi O. B. , Gaskell P. H. , Jimack P. K. , Kapur N , Thompson H. M.
Published: October 2005

This article presents a complementary experimental and computational investigation of the effect of viscosity and flowrate on the dynamics of drop formation in the dripping mode. In contrast to previous studies, numerical simulations are performed with two popular commercial computational fluid dynamics (CFD) packages, CFX and FLOW-3D, both of which employ the volume of fluid (VOF) method. Comparison with previously published experimental and computational data and new experimental results reported here highlight the capabilities and limitations of the aforementioned packages.
Simulation of Bulk Metal Forming by Means of Finite Integral Mesh Free Methods
Authors: Li C. S. , Xiong S. W. , Rodrigues J. M. C. , Martins P. A. F.
Published: October 2005

This paper draws from the fundamentals of the finite integral mesh free representation methods and of the rigid-plastic formulation for slightly compressible materials to the main aspects of computer implementation and modelling of bulk-metal forming processes. Fundamental research and development is based on the reproducing kernel particle method (RKPM) and the corrected smoothed particle hydrodynamics (CSPH) method. Special emphasis is placed on a wide range of theoretical and numerical subjects such as discretization procedures, numerical integration of the system matrices derived from the weak form, relief of volumetric locking, geometrical update of the deforming workpiece, and treatment of the frictional contact interface between the workpiece and tooling.
A Novel Technique for Steam Turbine Exhaust Pressure Limitation Using Dynamic Pressure Sensors
Authors: Riaz M. S. , Barb K. J. , Engeda A
Published: October 2005

In this paper, a novel approach is presented to increase the operational flexibility of steam turbines. Exhaust pressure at the exit of the last-stage blades is one of the most important parameters that limit the operation of a steam turbine, especially on days with hot ambient conditions. The main concern in these off-design high-exhaust pressure operating conditions is that it can result in flow separation, which can lead to aeromechanics instabilities and thus to blade failure because of high-cycle fatigue. In the method proposed in this paper, dynamic pressure transducers are placed around the perimeter of the last-stage blade to measure the pressure variations caused by vibrating last-stage blades. This approach, which is applicable to condensing turbines only, will provide increased exhaust pressure limits through realtime monitoring of the pressure signal and thereby enable the power plant to produce more power during times of peak demand. Finite elements analysis was performed to predict the natural frequencies of the row of blades to distinguish between the synchronous and nonsynchronous modes of vibration. Strain gauges were placed on the blades to obtain the experimental frequency information of the system. Response from the dynamic pressure transducers was compared with responses from the strain gauges. An excellent agreement between the two sets of results proved the validity of the proposed method.
Dynamic Response of Toroidal Drive to Mesh Parametric Excitations
Authors: Xu L , Jin H , Hao X
Published: October 2005

In this article, a three-dimensional dynamic model of the toroidal drive is given. By the model, equations of the relative displacements between different components and the dynamic equations for the drive are obtained. Changes of the mesh stiffness are analysed and the equation of periodical time-varying mesh stiffness is presented in Fourier series form. Under neglecting nonlinear items, time-varying mesh stiffness is changed into equivalent exciting load and linear dynamic equations of the drive are obtained. Then, the analytical equations of the forced response for the drive to mesh stiffness excitation are obtained, and the equations of the dynamic factors between a planet and worm or stator are given as well. By aforementioned equations, the forced frequency responses of the drive system to mesh stiffness variation are given, the variations of dynamic response for the worm as functions of the main parameters are presented, and the dynamic factor between a planet and worm is given as a function of operating speed.
Three-Dimensional Characterization of Engineering Surfaces Using Triangular Motifs
Authors: Kumar J , Shunmugam M. S.
Published: October 2005

The functional behaviour of manufactured surfaces is influenced by the surface topography. Encouraged by the results obtained in the implementation of two-dimensional motifs for practical profiles, a few attempts have been made to arrive at areal motifs for characterization of the surfaces. In this paper, an approach for establishing three-dimensional motifs based on triangular motif is presented. The triangular motif is formed with three peaks and a deep valley between them. To represent the surface by significant motifs, initial motifs are combined using four rules that are extended from the rules defined in ISO 12085 for combining two-dimensional motifs. Application of this technique to practical surfaces shows interesting results for characterizing the manufactured surfaces.
The Dynamic Analysis of a 2-PRR Planar Parallel Mechanism
Authors: Wang L-P , Wang J-S , Chen J
Published: October 2005

The article presents the inverse dynamics of a two-degrees-of-freedom planar parallel manipulator by the Newton-Euler approach. On the basis of the inverse dynamic model, the driving forces of actuators are simulated in different motion parameters. Further, the effects of inertia of each moving component to the driving forces are computed through the numerical method.
Analysis and Fabrication Process of an Electro-Magnetically Actuated Valveless Micropump with Two Parallel Flexible Diaphragms
Authors: Su Y , Chen W , Cui F , Zhang W
Published: October 2005

This article presents a parallel dynamic passive valveless micropump, which consists of three layers - valveless pump body, diaphragm, and electromagnetic coil. The valveless pump body is wetly etched in a silicon wafer, the diaphragm is a polydimethyl siloxane (PDMS) film spun on a silicon wafer with embedded permanent magnet posts, and the coil is electroplated on a silicon substrate. Under the actuation of the magnetic field of the coil, the flexible diaphragm can be displaced upwards and downwards. In this article, after analysing magnetic and mechanical characteristics of the flexible membrane and direction dependence of the nozzle, a micropump is designed. In addition, the relative length ( L/d) of the micropump's nozzle is 4. A 7×7 array of permanent magnetic posts is embedded in the PDMS film. The two diaphragms work in an anti-step mode, which can relieve the liquid shock and increase the discharge of the micropump. ANSYS® and Matlab® are adopted to analyse the actuation effect of the coil and the flow characteristic of the micropump. Results show that when actuated under a 0.3 A, 100 Hz current, the displacement of the diaphragm is >30 μm and the discharge of the micropump is ε6 μ1/s.
Development of a method for the measurement of dehydroepiandrosterone sulphate by liquid chromatography-tandem mass spectrometry
Authors: Chadwick C A , Owen L J , Keevil B G
Published: October 2005

Background: Dehydroepiandrosterone sulphate (DHEAS) is a steroid that is increasingly being recognized as a potential drug of abuse in many countries. This is due to its reputation as a hormone that may be able to retard the ageing process.

The measurement of DHEAS is useful in the diagnosis of medical conditions such as congenital adrenal hyperplasia and polycystic ovary syndrome. Thus, a liquid chromatography-tandem mass spectrometry method has been developed to determine DHEAS concentrations in human serum.

Method: The chromatography was performed using a WatersTM 2795 Alliance HT LC system coupled to a Mercury Fusion-RP column fitted with a SecurityGuardTM column.

Results: DHEAS and the internal standard, deuterated DHEAS, both had a retention time of 1.5 min. The transition determined by the Micromass QuattroTM tandem mass spectrometer for DHEAS was m/z 367.3>96.7 and for the internal standard m/z 369.3>96.6.

The method was linear up to 20 µmol/L; the lower limit of detection and the lower limit of quantitation were both 1 µmol/L. The intra- and interassay imprecision were <11% over a concentration range of 1-18 µmol/L for the in-house quality control and <12% for the intra- and interassay imprecision for the Bio-Rad Lyphocheck QC.

Conclusion: The measurement of DHEAS by liquid chromatography-tandem mass spectrometry is robust and has a simple sample preparation procedure with a rapid cycle time of only 4 min.
Erythrocyte zinc in hospital patients
Authors: Batchat L , Vaja S , Treacher D , Kinerons M , Swaminathan R
Published: October 2005

Background: Abnormal thyroid function tests (serum thyrotropin [TSH], free thyroxine [T4] and free triiodothyronine [T3]) are frequently seen in hospitalized patients. Assessment of thyroid function in these patients is difficult. It has been suggested that acutely ill patients may be hypothyroid at the tissue level. Erythrocyte zinc (EZn) has been shown to be increased in hypothyroidism. The aim of this study was to examine EZn as an index of thyroid status of hospital patients.

Methods: In order to assess the thyroid status at tissue level, we measured EZn in 26 healthy subjects, 39 critically ill patients and 19 hospitalized geriatric patients. EZn was measured in young cells, as the effect of illness is likely to be seen in the newly formed cells.

Result: TSH and free T3 were lower in critically ill patients and serum free T3 was lower in geriatric patients. EZn in young cells was higher in both patient groups (by 13% and 23%, respectively). EZn in old cells was also higher in the geriatric group.

Conclusion: We conclude that EZn is higher in hospitalized patients, suggesting that these patients may be hypothyroid at the tissue level.
Do we need lipid clinics? Shifting the balance between secondary and primary care
Authors: Stuart W , Smellie A
Published: October 2005

Background: Increasing activity in cholesterol lowering is placing increasing demands on lipid clinics to be able to cope with the increase in demand. A combination of interventions has been used to improve laboratory testing, focus interpretative results and provide educational and advisory facilities for general practitioners in order to increase shared care of many potential clinic patients.

Methods: Retrospective study of clinic waiting times, results in patients managed on a shared care basis, and overall clinical activity over a three-and-a-half-year intervention period between March 2001 and August 2004 in a single-consultant, single-centre secondary care clinic serving three primary care trusts, covering a population of approximately 270,000 people. The interventions involved a change to the laboratory request form, outreach educational meetings and promotion of use of 'written advice only' for certain patients as an alternative to direct clinic referral. The main outcome measures were percentages of patients followed up in primary care, change in cholesterol and triglyceride results after advice, and clinic waiting time.

Results: A total of 520 patients were referred over three and a half years, either to be seen or for written advice only. About 291 of these were handled by advisory letters. In all, 90% of these patients were already receiving or had received lipid-lowering therapy at the time of referral. 98% of patients were followed up by their general practice post-advice. Cholesterol and triglyceride concentrations fell by 23% and 39%, respectively, post-advice. Waiting times fell from a peak of 35 weeks before the interventions to an average of three weeks after. This fall has been maintained over the three-and-a-half years the intervention has run.

Conclusions: The interventions have resulted in a large fall in clinic waiting times, improvement in lipid results, and high rate of general practice follow-up, all of which have been sustained in the long term.
Detection assessment and monitoring of hepatic fibrosis: biochemistry or biopsy?
Authors: Mardini H , Record C
Published: October 2005

Hepatic fibrosis is an important consequence of inflammatory disorders affecting the liver, and ultimately progresses to cirrhosis. Here we explore methods for the detection and monitoring of hepatic fibrosis, particularly in hepatitis C, alcoholic liver disease, non-alcoholic fatty liver disease and during methotrexate therapy, in all of which progressive fibrosis can develop over a number of years in a minority of patients.

Liver biopsy currently remains the gold standard to assess fibrosis. However, it has several limitations, including manpower issues, cost, risk of patient injury, including mortality and morbidity, observer variability and sampling variation. Several non-invasive diagnostic tests for fibrosis and cirrhosis have therefore been evaluated. The usefulness of a laboratory test for screening for a pathological abnormality such as fibrosis is critically dependent on the prevalence of the pathology in the population under investigation. When the prevalence is expected to be low, screening tests should have a high negative predictive value so that large numbers of patients can be spared the next diagnostic step, namely liver biopsy. For the moment, clinical chemistry laboratories should offer the aspartate aminotransferase alanine aminotransferase ratio, AST/platelet ratio and the Rosenberg fibrosis index as part of their routine service for monitoring the development of hepatic fibrosis.
Caspase and calpain function in cell death: bridging the gap between apoptosis and necrosis
Authors: Harwood Steven M , Yaqoob Muhammad M , Allen David A
Published: October 2005

Calpain and caspase are families of cysteine proteases that have important roles in the initiation, regulation and execution of cell death. The function of both groups of proteases in the progression of apoptotic and necrotic pathways is presented here in the context of a concise overview of regulated cell death. Many of the morphological differences between apoptotic and necrotic processes are thought to be as a consequence of the action of cysteine proteases. Recent studies suggest that caspase and calpain cascades are tightly interrelated and an appreciation of how these proteases cross-talk should enable a greater understanding of how the boundaries between apoptotic and necrotic cell death have become blurred. Furthermore, an assessment of the contribution that caspase and calpain make to human physiology and pathology is provided, with a description of how these proteases can be detected and quantified. Lastly, an evaluation is made of how caspase and calpain activation might be exploited diagnostically.
The influence of genetic and environmental factors on plasma homocysteine concentrations in a population at high risk for coronary artery disease
Authors: Bowron Ann , Scott Jeff , Stansbie David
Published: October 2005

Background: Elevated plasma total homocysteine (tHcy) predisposes to vascular disease and results from interactions between genetic and nutritional factors. MTHFR C677T increases tHcy in association with low folate. CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C677T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease. This study examines the effect on plasma tHcy of interactions between these polymorphisms in an at-risk group.

Methods: Blood samples were collected from 376 subjects at increased risk of coronary artery disease. Plasma tHcy and vitamin B6 were measured by HPLC and red cell folate and serum vitamin B12 were measured by immuno-luminometric assay. MTHFR C677T and CBS 844ins68 status was established by standard PCR techniques.

Results: MTHFR TT predisposed to hyperhomocysteinaemia; this was increased in the presence of low folate ( P<0.05) and vitamin B12 ( P<0.01). An inverse relationship was found between tHcy and folate ( r= -0.42, P<0.0001), vitamin B12 ( r= -0.26, P<0.0005) and vitamin B6 ( r= -0.25, P<0.01). There was no interaction between plasma tHcy, vitamins or MTHFR C677T and CBS 844ins68.

Discussion: In this population at high risk of coronary artery disease, plasma tHcy was determined by vitamin status. This was exacerbated by the MTHFR C677T mutation. CBS 844ins68 did not influence tHcy and did not negate the tHcy-raising effect of MTHFR C677T.
Interference of ascorbic acid with chemical analytes
Authors: Meng Qing H , Irwin William C , Fesser Jennifer , Massey K Lorne
Published: October 2005

Background: Ascorbic acid can interfere with methodologies involving redox reactions, while comprehensive studies on main chemistry analysers have not been reported. We therefore attempted to determine the interference of ascorbic acid with analytes on the Beckman Synchron LX20®.

Methods: Various concentrations of ascorbic acid were added to serum, and the serum analytes were measured on the LX20.

Results: With a serum ascorbic acid concentration of 12.0 mmol/L, the values for sodium, potassium, calcium and creatinine increased by 43%, 58%, 103% and 26%, respectively ( P<0.01). With a serum ascorbic acid concentration of 12.0 mmol/L, the values for chloride, total bilirubin and uric acid decreased by 33%, 62% and 83%, respectively ( P<0.01), and were undetectable for total cholesterol, triglyceride, ammonia and lactate. There was no definite influence of ascorbic acid on analytical values for total CO2, urea, glucose, phosphate, total protein, albumin, amylase, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total iron, unbound iron-binding capacity or magnesium.

Conclusions: Ascorbic acid causes a false increase in sodium, potassium, calcium and creatinine results and a false decrease in chloride, total bilirubin, uric acid, total cholesterol, triglyceride, ammonia and lactate results.
Potential pitfalls in intraoperative parathyroid hormone measurements during parathyroid surgery
Authors: Phillips IJ , Kurzawinski TR , Honour JW
Published: October 2005

Background: The outcome of parathyroid surgery is often not clear for at least 24 h after the operation. A frozen section does not always distinguish between an adenoma and hyperplasia. Minimally invasive surgical techniques are being refined, so the need for perioperative assurance about the completeness of surgery has increased. The value of intraoperative parathyroid hormone (PTH) measurements in 26 surgical cases undergoing parathyroidectomy has been evaluated.

Methods: Twenty-one patients were diagnosed as having primary hyperparathyroidism, including two patients with multiple endocrine neoplasia type I (MEN I). Five patients had tertiary hyperparathyroidism, including one patient with X-linked hypophosphataemia and four with renal hyperparathyroidism (RHPT).

Blood samples were taken at the onset of surgery, at the time of tumour resection and at 5-min intervals following removal of the tumour. PTH was measured using a PTH Turbo assay on the DPC Immulite analyser.

Results: Current practice suggests that the PTH concentration should fall to less than 50% of the pre-incision value or to less than 50% of the level at the time of tumour resection (time equals zero). PTH levels were therefore monitored at 5-min intervals following removal of the tumour. In most of the case studies PTH followed the suggested pattern, but not when further exploration was warranted to determine if another adenoma was present. In some cases the PTH levels fell by the appropriate margin to deem the procedure a success but at 10 min post-gland excision the PTH began to rise again. Further exploration was required to confirm the continued source of PTH.

Conclusion: We recommend that intraoperative PTH measurements continue until at least 15 min post-gland removal in cases of suspected single-gland disease. A decline in PTH concentration to at least 50% of the pre-incision or time of gland resection levels should be observed. If the PTH remains elevated or rises again after an appropriate decrease in levels, then multigland disease or ectopic sources should be considered.

Caution is recommended in interpreting intraoperative PTH measurements to ensure complete success of the surgical procedure.
Natriuretic peptides and the heart: current and future implications for clinical biochemistry
Authors: Penney M D
Published: October 2005

The measurement of B-type natriuretic peptides in plasma is under intense promotion as a method of screening for heart failure. This article provides a historical context for this contention, and attempts to highlight what practical problems may be encountered in establishing a screening service from a clinical biochemistry standpoint. B-type natriuretic peptide measurements may also prove, in future, to have a significant role in the objective monitoring of treatment for heart failure, and to be a valuable prognostic indicator in patients suffering from acute coronary syndrome.