bluuebunny/crossref_metadata_2025 huggingface dataset:
ALE formulation of Reynolds fluid film equation
Authors: Schweizer B.
Published: September 2008

The pressure distribution in hydrodynamic journal bearings is usually calculated by the Reynolds fluid film equation, a linear elliptical partial differential equation. Applying appropriate boundary conditions, e.g., Reynolds boundary conditions, the governing boundary value problem becomes nonlinear. For solving this nonlinear boundary value problem, there exist several established methods. The paper at hand presents an alternative approach using an ALE (Arbitrary Lagrangian Eulerian) formulation.
The effect of the boundary slip on the stability of shear flow
Authors: He Qiaolin , Wang Xiao‐Ping
Published: September 2008

We study the linearized stability of shear flow satisfying Navier slip boundary conditions. The Orr‐Sommerfeld equation for the plane Poiseuille flow with Navier slip boundary conditions is solved numerically by the Chebyshev collocation method. Our numerical results show that slip at the boundary increases the critical Reynolds number Rc for instability. The dependence of the this critical Reynolds number on the slip length ls is found to be Rc(ls)‐ Rc(0) ≈ C ls2.
Thermoviscoplasticity at small strains
Authors: Bartels S. , Roubíček T.
Published: September 2008

A viscoelastic solid in Kelvin‐Voigt rheology involving plasticity coupled with a heat‐transfer equation through a temperature‐dependent yield stress is investigated. No hardening is studied but the evolution of the plastic strain is considered to be rate‐dependent. A numerical scheme which is semi‐implicit in time and employs lowest order finite elements on weakly acute triangulations in space is devised and its convergence is proved by careful subsequent limit passage. Computational studies underline robustness and efficiency of the method and illustrate physical effects such as the softening of a material due to dissipated energy that causes a rise in temperature and a local decrease of the yield stress.
Prospective Outcomes of Selective Lymph Node Dissection for Papillary Thyroid Carcinoma Based on Preoperative Ultrasonography
Authors: Sugitani Iwao , Fujimoto Yoshihide , Yamada Keiko , Yamamoto Noriko
Published: September 2008

Background

Although many patients with papillary thyroid carcinoma (PTC) display associated cervical lymph node metastases (LNM), the optimal extent of lymph node dissection (LND) remains a matter of debate. Since 1993, we have performed cervical LND based on the preoperative suspicion of LNM by ultrasonography (US). We prospectively analyzed the outcomes of our “selective” LND to determine when prophylactic lateral neck dissection is advisable.

Methods

Prospective analysis was conducted for 361 consecutive patients with PTC who received initial surgery between 1993 and 2001. Mean duration of follow‐up was 8.1 years. Dissection of the central compartment only was performed for patients with LNM in the central zone only and for patients with no LNM detected by US (Group A). Modified radical lateral neck dissection (MND; combined with central compartment dissection) was performed for patients diagnosed with lateral neck LNM (Group B).

Results

Pathological LNM was found in 136 of 231 patients in Group A (59%). As for the accuracy of US diagnosis, positive predictive value was 82%. Nodal recurrences, occurring all in the lateral cervical region associated with one case of contralateral paratracheal region, was seen in 18 patients (8%) and 10‐year nodal disease‐free survival was 91%. Univariate analysis revealed true positive diagnosis by US, large primary tumor (≥4 cm), primary tumor located in the upper part of the thyroid lobe, presence of distant metastasis, extrathyroidal invasion of the primary tumor, and a poorly differentiated component of the primary tumor as significant risk factors for nodal recurrence. Among the risk factors that could be diagnosed preoperatively, distant metastasis (risk ratio, 46; p = 0.01) and large primary tumor (risk ratio, 3.6; p = 0.03) were the most important factors under multivariate analysis. Of the other 130 patients in Group B, only 3 patients had no pathological LNM (positive predictive value, 98%). Twenty‐six patients (20%) developed nodal recurrence, with a 10‐year nodal disease‐free survival of 76%. Age (50 years or older), large nodal metastasis (≥3 cm), extrathyroidal invasion, and higher serum thyroglobulin level (≥320 ng/ml) represented significant factors for nodal recurrence.

Conclusions

When preoperative US shows no LNM or indicates only LNM in the central compartment, dissection of the central compartment alone offers a sufficient alternative to routine prophylactic MND. However, patients with PTC demonstrating large primary tumor and/or distant metastasis were high‐risk for recurrence in the lateral cervical compartment. We recommend prophylactic MND to reduce nodal recurrence for those patients.
A test of the latitudinal defense hypothesis: herbivory, tannins and total phenolics in four North American tree species
Authors: Adams Jonathan M. , Rehill Brian , Zhang Yangjian , Gower Jonathan
Published: September 2008

It is widely believed that insect herbivory is less intense at higher latitudes, due to winter mortality which would tend to keep insect herbivores from reaching density‐limitation of their populations. One prediction of this theory is that plants should tend to be better defended at lower latitudes. Here we investigated latitudinal trends in herbivory and tannins, in four species of common North American trees. Our comparisons spanned 15° of latitude in Acer rubrum, Fagus grandifolia, and Quercus alba, and 10° latitude in Liquidambar styraciflua. Sun leaves on forest edges were sampled, at phenologically equivalent times of year. Analysis revealed significant differences between populations, including those at similar latitudes, but no significant latitudinal trend in herbivory, condensed and hydrolyzable tannins, or total phenolics measured as Folin–Denis reactives in any of the four species. Our findings contradict the theory that low latitude plants are better defended, in that lower latitude populations of the four tree species showed no greater amounts of phenolics. The possible implications for community ecology are discussed.
Sesamin Increases Alpha‐Linolenic Acid Conversion to Docosahexaenoic Acid in Atlantic Salmon (Salmo salar L.) Hepatocytes: Role of Altered Gene Expression
Authors: Trattner Sofia , Ruyter B. , Østbye T. K. , Gjøen T. , Zlabek V. , Kamal‐Eldin A. , Pickova J.
Published: September 2008

In vitro cultivated Atlantic salmon (Salmo salar L.), hepatocytes were incubated without or with a mixture of sesamin and episesamin in order to test for possible effects on lipid metabolism. Sesamin/episesamin exposure (0.05 mM, final concentration) led to increased elongation and desaturation of 14C 18:3n‐3 to docosahexaenoic acid (14C 22:6n‐3, DHA, P < 0.01) and down regulated gene expression of Δ6 and Δ5 desaturases compared to control treatment. Sesamin/episesamin further increased the hepatocytes capacity for fatty acid β‐oxidation of 14C 18:3n‐3 (P < 0.01) to the 14C acid soluble products, acetate, malate and oxaloacetate, in agreement with an increased gene expression of carnitine palmitoyltransferase I. Also the gene expression of cluster of differentiation 36 was upregulated and the expression of scavenger receptor type B, peroxisome proliferator‐activated receptors α and γ were downregulated. The amount of triacylglycerols secreted by the cells tended to be lower in the sesamin/episesamin incubated hepatocytes than the control cells. This study shows that sesamin has favourable effects on lipid metabolism leading to increased level of DHA, which may be of interest for aquaculture use.
Advanced imaging of the cervical spine and spinal cord in 22q11.2 deletion syndrome: Age-matched, double-cohort, controlled study
Authors: Ricchetti Eric T. , Hosalkar Harish S. , Gholve Purushottam A. , Cameron Danielle B. , Drummond Denis S.
Published: September 2008

Purpose

The 22q11.2 deletion syndrome is a common genetic syndrome with a wide spectrum of abnormalities. We have previously described multiple anomalies of the upper cervical spine in this disorder. The objective of this study was to use advanced imaging to further define the morphology of the cervical spine and spinal cord in the 22q11.2 deletion syndrome, with a comparison to age-matched controls.

Methods

A total of 32 patients with a 22q11.2 deletion underwent advanced imaging (computed tomography/magnetic resonance imaging; CT/MRI) of the cervical spine. In 27 patients, space available for the cord (SAC); the sagittal diameter of the vertebral body, spinal canal, cerebrospinal fluid (CSF), and spinal cord; and the cross sectional area of the spinal canal, CSF, and spinal cord were measured at each cervical level and compared to 29 age-matched controls. Statistical analysis was performed and potential implications were hypothesized.

Results

In 22q11.2 patients, advanced imaging identified 40 pathologies not evident on plain radiographs with potential mechanical and/or neurological implications. These patients also had significantly smaller values ( P ≤ 0.05) of the following parameters at one or more cervical levels, relative to age-matched controls: width of the vertebral body, spinal canal, CSF, and spinal cord; area of the spinal canal, CSF, and spinal cord. Neurologic symptoms were observed in 4/32 patients, with one patient requiring surgical intervention.

Conclusions

Advanced imaging of the cervical spine can detect findings not evident on plain radiographs in the 22q11.2 deletion syndrome. CT and/or MRI may be indicated when there is a high index of suspicion for clinical instability or neurologic compromise in order to rule out dynamic encroachment or impending neurologic sequelae. Spinal canal and spinal cord dimensions are reduced in these patients relative to controls with currently unknown clinical significance.
Existence of minimizers of free autonomous variational problems via solvability of constrained ones
Authors: Cupini Giovanni , Guidorzi Marcello , Marcelli Cristina
Published: September 2008

We consider the following autonomous variational problem

\text{minimize }\left\{\:\int \limits_{a}^{b}f\left(v(x),v^{′}(x)\right)\:\mathrm{d}x:\:v∊W^{1,1}(a,b),\:v(a) = \alpha ,\:v(b) = \beta \right\}

where the Lagrangian

f

is assumed to be continuous, but not necessarily coercive, nor convex. We show that the existence of the minimum is linked to the solvability of certain constrained variational problems. This allows us to derive existence theorems covering a wide class of nonconvex noncoercive problems.

On considère la classe des problèmes variationels autonomes ci-dessous :

\text{minimiser }\left\{\:\int \limits_{a}^{b}f\left(v(x),v^{′}(x)\right)\:\mathrm{d}x:\:v∊W^{1,1}(a,b),\:v(a) = \alpha ,\:v(b) = \beta \right\}

où le lagrangien

f

est une fonction continue sans hypothèse de coercivité ou de convexité. On démontre que l'existence de solutions pour ces problèmes est liée à l'existence de solutions de certains problèmes variationels sous contraintes. Ce résultat permet d'obtenir des théorèmes d'existence pour une classe étendue de problèmes variationels ni coercifs ni convexes.
High-electric-field limit for the Vlasov–Maxwell–Fokker–Planck system
Authors: Bostan Mihai , Goudon Thierry
Published: September 2008

In this paper we derive the high-electric-field limit of the three-dimensional Vlasov–Maxwell–Fokker–Planck system. We use the relative entropy method which requires the smoothness of the solution of the limit problem. We obtain convergences of the electro-magnetic field, charge and current densities.
Perioperative ketamine does not prevent chronic pain after thoracotomy
Authors: Dualé Christian , Sibaud Fabrice , Guastella Virginie , Vallet Laurent , Gimbert Yves‐Alain , Taheri Hammou , Filaire Marc , Schoeffler Pierre , Dubray Claude
Published: September 2008

Thoracotomy is often responsible for chronic pain, possibly of neuropathic origin. To confirm preclinical studies, the preventive effects of perioperative ketamine were tested in a randomized, double‐blind, placebo‐controlled clinical trial on persistent neuropathic pain after thoracotomy. Eighty‐six patients scheduled for thoracotomy under standardised general anaesthesia were randomised to receive either ketamine (1mgkg−1 at the induction, 1mgkg−1h−1 during surgery, then 1mgkg−1 during 24h; n=42) or normal saline (n=44). Postoperative analgesia included a single dose of intrapleural ropivacaine, intravenous paracetamol and nefopam, and patient‐controlled intravenous morphine. Vital parameters and analgesia were recorded during the 48 first postoperative hours. Seventy‐three patients were followed up. The patient's chest was examined 1–2 weeks, 6 weeks and 4 months after surgery. At the last two observations, spontaneous pain score over a one‐week period (visual analogue scale), neuropathic pain score (NPSI), and intake of analgesics, were assessed. No drug affecting neuropathic pain (except opiates) was given during the follow‐up. Two patients in each group were lost to follow‐up after the 6 week visit. Ketamine improved immediate postoperative pain, but the groups were similar in terms of neuropathic pain and intake of analgesics, 6 weeks (NPSI score: ketamine: 1.25 [0–4.125]; placebo: 1 [0–4]) and 4 months after surgery. Thus, ketamine given in 24‐h infusion failed to prevent chronic neuropathic pain after thoracotomy. Other perioperative preventive long‐lasting treatments or techniques could be tested in this context.
Prospects for the classification of mental disorders of children and adolescents
Authors: Schmidt M.H. , Sinzig J.
Published: September 2008

Suggestions for classification of mental disorders of children and adolescents in DSM-V and ICD-11 have been made, which differ strongly from the current descriptive approach of dimensional classification.

These suggestions even comprise a dichotomized system for health care as well as for scientific purposes.

Nevertheless it is obvious that we are far behind an “etiological” classification, so that trade-offs have necessarily to be made in DSM-V and ICD-11.

Appropriate proposals concern the strict separation of disorders that are typical for children and adolescents as well as for adults.

Furthermore a differentiation of diagnosis for infants, toddlers and preschool children is required in both classification systems. As far as it is relevant for treatment, combined diagnosis in DSM-V and subthreshold diagnosis as well as coding-possibilities for findings in molecular biology should be permitted.

As personality disorders should only be diagnosed after the age of 16, it is recommended to dimensionally classify personality traits that are pathognomonic for specific symptom patterns and of prognostic relevance.

DSM-V and ICD-11 should allow age-specific information on axis-IV. The article discusses the general question of how relational disorders respectively disturbances should be classified and include furthermore special recommendations concerning ICD and DSM categories.
Study of the interaction of the Ig2 module of the fibroblast growth factor receptor, FGFR Ig2, with the fibroblast growth factor 1, FGF1, by means of NMR spectroscopy
Authors: Kochoyan Artur , Poulsen Flemming M. , Berezin Vladimir , Bock Elisabeth , Kiselyov Vladislav V.
Published: September 2008

Fibroblast growth factor (FGF) receptor (FGFR) consists extracellularly of three immunoglobulin (Ig) modules (Ig1–3). Currently, there are two competing models (symmetric and asymmetric) of the FGF–FGFR–heparin complex based on crystal structures. Indirect evidence exists in support of both models. However, it is not clear which model is physiologically relevant. Our aim was to obtain direct, non‐crystallographic evidence in support of them. We found by nuclear magnetic resonance that Ig2 could bind to FGF1 not only via the primary site (present in both models), but also via the secondary site (present only in the symmetric model). Thus, our data support the symmetric model.
Merging Microfluidics with Microtitre Technology for More Efficient Drug Discovery
Authors: Tolan Nicole V. , Genes Luiza I. , Spence Dana M.
Published: September 2008

Detecting multiple components from a single red blood cell (RBC) sample within a flow-based system in less than 20 min will enable improved in vitro determinations of drug efficacy and cellular response to administered drugs. Here, an example of an improved in vitro measurement involving iloprost, a pharmaceutical reported to improve blood flow, has been determined by incorporating multiple cell types onto a single device. The method allows fluid flow to address individual rows of wells contained within an 18-well microfluidic array that serves as a precursor to a 96-well microtitre plate device. The ability to better mimic the in vivo circulation by incorporating the flow of blood components, coupled with simultaneous detection and laboratory automation in place for microtitre plates, suggests that the microfluidic array presented here will allow for improved mechanistic drug research studies. Using fluorescence microscopy, concentrations of multiple metabolites present within the RBC can also be determined using the microfluidic array. The current progress toward using this device for personalized medicine is presented here.
The Race for Data: Compound Distribution at AstraZeneca R&D Boston
Authors: Hvezda Karen , Boeckeler Matthew
Published: September 2008

AstraZeneca R&D Boston's Compound Management Group (CMG) underwent an extensive workflow redesign project in May 2007. The primary goal of this project was to shift from a solid compound distribution platform to a more robust and efficient liquid compound delivery platform. As a result of the project, there were substantial time savings and efficiency gains in both solid and liquid compound preparation and distribution. Due to the inherent benefits of distributing liquids instead of solid samples, CMG was able to provide assay-ready plates through the use of custom robotics and software tools developed in-house. The implementation of these new platforms drove down upstream processing (solubilization) time by 85%, and allowed internal compound requests to be processed and plated within 24 h. In addition, these compounds are now available for testing at all the AstraZeneca (AZ) sites globally, within one week of compound submission to CMG. Due to the efficiency improvements, CMG was able to not only continue to meet internal customers' demands for solid samples, but also to decrease turnaround time for order delivery, which increases the speed at which a research team can test compounds and subsequently receive project-driving data.
Biomek-3000 and GenPlex SNP Genotyping in Forensic Genetics
Authors: Stangegaard Michael , Tomas Carmen , Hansen Anders J. , Frank-Hansen Rune , Børsting Claus , Morling Niels
Published: September 2008

Single nucleotide polymorphism genotyping provides a supplement for conventional short tandem repeats-based kits currently used for human identification. GenPlex (Applied Biosystems (AB), Foster City, CA) is an SNP-genotyping kit based on a multiplex of 48 informative, autosomal SNPs from the SNP forID Consortium. Our objective was to setup, implement, and validate a small and affordable automated liquid-handling robot for forensic casework samples (buccal swaps on FTA-paper and Qiagen purified blood).

The reaction scheme consisted of numerous steps and was cumbersome to perform consistently manually. Automation was accomplished with a Biomek-3000 (Beckmann Coulter) laboratory-automated workstation using five in-house-developed methods. All methods allowed the user to select the number of subsequent injections to the capillary electrophoresis instrument (ABI 3130 xl, AB) enabling processing of both partial and full plates.

A total of 286 samples were analyzed in duplicates with the GenPlex reaction using the Biomek-3000. The results were compared with those obtained from the same samples using the SNaPshot(AB) single-base extension system. Full concordance of the results was obtained in all but one sample. The results demonstrate that the Biomek-3000 can perform a series of complex reactions leading to highly consistent forensic genetic SNP-typing results.
Automation of Sample Dispensing Using Pocket Tips for Evaluation of CYP2C9 Isoenzyme Reversible Inhibition in an Evolution Precision Pipetting Platform
Authors: Ramírez Manuel , Tudela Consuelo , Crespo Juan B. , Rubles Alicia , Jiménez Antonio , Tarazona Guillermo , Fernández Laura , Sánchez Pilar , Kroncke Doug , Tabanera Noemí , Pérez Joseé , Sánchez Manuel , Tormo José R. , Peláez Fernando
Published: September 2008

Most of the medicinal chemistry compounds received from other Merck Research Laboratories (MRL) for evaluation in our in vitro counterscreenings are in pure DMSO solution. This solvent has shown to be a key interference factor in the radiometric evaluation of cytochrome P-450 (CYP) inhibition. To avoid this problem, we have been using a ternary solvent solution that keeps DMSO concentration to a minimum during the titration of the compounds.

The equipment used at our laboratory to perform the dose—response titration of the compounds in the CYP assays is PerkinElmer Evolution Precision Pipetting Platform (EP3) robots with limited microliter capabilities using disposable tips. The need for a nanoliter dispensing technique that keeps the percentage of DMSO at levels that do not affect the assay, and the need to use pure DMSO solutions at high concentrations to avoid solubility issues of the compounds, moved us to design a new automated sample management process for all compounds that were requested to be tested in these assays.

The PocketTips system (nAscent BioSciences Inc., Wellesley Hills, MA) seemed to be a good option for pipetting very low volumes without acquiring new expensive nanoliter liquid handling equipment. Apparent difficulties with implementation were the unavailability of PocketTips for the 96-tips head of the EP3 (PerkinElmer, Waltham, MA) and the need for testing several CYP isoenzymes (up to four) by using the same rack of tips to save run time and reduce costs.

In this article, we discuss the entire process to introduce and validate a new dispensing process for sampling of compounds with multiple nanoliters dispensing at the assay level, indicating in detail how we implemented the use of recycled PocketTips in our PerkinElmer EP3 workstations.
Fully Automated Laboratory Robotic System for Automating Sample Preparation and Analysis to Reduce Cost and Time in Drug Development Process
Authors: Saitoh Satoshi , Yoshimori Takayuki
Published: September 2008

We have developed a fully automated laboratory robotic system (FA-LAS) capable of conducting most of routine experiments. Main objectives for developing this novel robotic system are to streamline the analytical tasks by automating sample preparations and analytical procedures, and to ensure the safety of analysts by assigning risk-involving procedures, such as handling of highly active substances.

FA-LAS integrates numbers of unique functional devices and is highly competent for analyses of various research and development products.

Comparative evaluations of FA-LAS with conventional manual preparation for drug substances and pharmaceutical products' real quantitative high performance liquid chromatography (HPLC) tests fulfilled this study's targeted criteria, which are 100 ± 5% for accuracy and coefficient of variation (%CV) ≤ 3% for repeatability for both HPLC analyses of drug substances and pharmaceutical products. In addition, several advantages over conventional manual methods were confirmed, such as reducing “working hour” for analysts, eliminating “working-hour” restriction, and decreasing drastically lag time for each prepared sample toward HPLC analysis.

FA-LAS's unique features will work as a bridge between the sample management system and automatic documentation system, and it will reduce drastically in human resources, budgets, and time frame for development of pharmaceutical products.
Label-Free Detection of a Biomarker with Piezoelectric Micro Cantilever Based on Mass Micro Balancing
Authors: Lee Yeolho , Lee Sangkyu , Seo Hyejung , Jeon Sangmin , Moon Wonkyu
Published: September 2008

With a piezoelectric micro cantilever sensor, a biomarker for various cancers is detected up to the concentration level required to determine a disease by using the mass micro balancing whose principle is that change of mechanical vibrant frequency is measured due to a target material attached on a sensor structure. The used piezoelectric micro cantilever sensor is designed so as to have the sufficient values of mass sensitivity and reliability. The used piezoelectric film, which acts as both sensor and actuator, is a plumbum zirconate titanate (PZT). Geometrical dimension of the micro cantilever is 100 μm (length) by 30 μm (width) by 5 μm (thickness). The 50-μm-long PZT film with thickness of 2.5 μm is covered from its root to its middle. Carcinoembryonic antigen (CEA), the biomarker for testing the sensor as label-free detection for pathological tests, is known as a biomarker for various cancers. The critical value of CEA concentration is known as 30 pM (5 ng/mL), and it is detected by the binding of antigen and antibody from high concentration to the critical concentration. From the results, the sensor could be applied to label-free detection sensors for pathological tests.
A Method for Fabrication of Polycarbonate-Based Bioactive Platforms
Authors: Najmabadi Peyman , Ko Kwang-Seuk , Clair James J. La , Burkart Michael D.
Published: September 2008

Surface-based assays have been used extensively for the functional and structural analysis of biomolecules such as DNA or proteins. These experiments are established by the analysis of binding between acceptor molecules and immobilized receptors on a platform. Site-specific printing of receptor molecules on gold, glass, or polycarbonate (PC) surfaces is conventionally performed by the chemical derivatization of a surface, priming it to covalently bind to subsequently deposited receptor molecules. Unlike conventional methods, we have developed a new fabrication method for bioactive PC surfaces by directly molding PC granules doped with receptor molecules. PC-based receptor molecules were synthesized and commercially available PC granules were doped with these synthesized molecules. In our proof-of-concept study, PC doped with dye 1 ( Fig. 1 ) was used as the receptor molecule. Using an aluminum mold and a hot press machine, PC-based objects were manufactured through compression molding using doped PC granules. Affinity analysis was evaluated by monitoring the localization of a monoclonal antibody elicited against dye 1 to the surface of the molded platforms by fluorescence microscopy. The results illustrated effective binding of an anti-dye 1 monoclonal antibody to the surface, substantiating successful display of assemblies of molecular receptors on the surface through compression molding. Although conventional surface functionalization methods impose limited applications and alter desired opto-mechanical properties of the polymer, our investigation provides a versatile means for the fabrication of bioactive PC-based platforms. It can also be used for engineering and imbedding receptor arrays within three-dimensional objects with applications to the production of opto-medical devices or biosensors.
Haem and folate transport by proton-coupled folate transporter/haem carrier protein 1 (SLC46A1)
Authors: Laftah Abas H. , Latunde-Dada Gladys O. , Fakih Sarah , Hider Robert C. , Simpson Robert J. , McKie Andrew T.
Published: September 2008

Haem carrier protein 1 (HCP1) was originally identified and characterised as a mammalian haem transporter. However, recent evidence has shown that it is also a proton-coupled folate transporter (PCFT) and mutations in the gene cause hereditary folate deficiency in humans. We therefore investigated haem and folate transport characteristics of PCFT/HCP1 bothin vivoandin vitroin CD-1 mice and in the presence or absence of a blocking antibody for PCFT/HCP1, and also in cultured cells (which express PCFT/HCP1 endogenously) to elucidate the specificity and selectivity of PCFT/HCP1. Thein vivostudy showed that the addition of folic acid inhibited59Fe-labelled haem transport in hypoxic mice but had no effect in normal mice. Usingin vitromethods, the results showed increased [3H]folate uptake into everted duodenum from hypoxic mice but uptake was reduced by the addition of haem or PCFT/HCP1 antibodies to the medium. Caco-2 cells transiently transfected with small interfering RNA (siRNA) PCFT/HCP1 duplex oligos resulted in a 69 % reduction in PCFT/HCP1 mRNA when compared with the control siRNA. Both haem and folate uptake were significantly (P < 0·05) reduced in cells transfected with PCFT/HCP1 siRNA; however, the magnitude of reduction with folic acid uptake was greater (48 %) than that of haem (22·5 %). Overall the data support PCFT/HCP1 as a primary folate transporter with a lower affinity for haem. PCFT/HCP1 could therefore play a physiological role in Fe nutrition and the data highlight the potential for the interaction of folate and haem at the level of intestinal absorption.
Maternal undernutrition programmes atherosclerosis in the ApoE*3-Leiden mouse
Authors: Yates Zoe , Tarling Elizabeth J. , Langley-Evans Simon C. , Salter Andrew M.
Published: September 2008

Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher;P < 0·001) and TAG (39 % higher;P < 0·001) relative to offspring exposed to a control dietin utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2·61-fold greater lesion area;P < 0·001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease.
Late Neoproterozoic amphibolite-facies metamorphism of a pre-Caledonian basement block in southwest Wedel Jarlsberg Land, Spitsbergen: new evidence from U–Th–Pb dating of monazite
Authors: MAJKA JAROSLAW , MAZUR STANISLAW , MANECKI MACIEJ , CZERNY JERZY , HOLM DANIEL K.
Published: September 2008

Southwest Spitsbergen, Wedel Jarlsberg Land, consists of two Proterozoic crustal blocks with differing metamorphic histories. Both blocks experienced Caledonian greenschist-facies metamorphism, but only the southern block records an earlier pervasive M1 amphibolite-facies metamorphism and strong deformational fabric. In situ EMPA total-Pb monazite geochronology from both matrix and porphyroblast inclusion results indicate that the older M1 metamorphism occurred at 643 ± 9 Ma, consistent with published cooling ages of c. 620 Ma (hornblende) and 580 Ma (mica) obtained from these same rocks. This region thus contains a lithostratigraphic profile and metamorphic history which are unique within the Svalbard Archipelago. Documentation of a pervasive late Neoproterozoic Barrovian metamorphism is difficult to reconcile with a quiescent non-tectonic regime typically inferred for this region, based on the occurrence of rift-drift sequences on the Baltic and Laurentian passive margins. Instead, our new metamorphic age implies an exotic origin of the pre-Devonian basement exposed in SW Spitsbergen and supports models of terrane assembly postulated for the Svalbard Archipelago.
Hanukkah in the Narrative Chronology of the Fourth Gospel
Authors: POIRIER JOHN C.
Published: September 2008

It is almost universally supposed that the narrative chronology of the Fourth Gospel does not turn to Hanukkah until 10.22, but the first explicit reference to ‘the feast of Dedication’ need not represent the point at which the narrative first turns to that feast. This article argues, in turn, for a Hanukkah setting throughout John 10, then throughout chap. 9, and finally throughout chap. 8 (minus vv. 1–11). Thus Jesus' claim to be ‘the light of the world’ (8.12) invokes the symbolism of Hanukkah rather than of Sukkoth.
Alius Paulus: Paul's Promise to Send Timothy at Philippians 2.19–24
Authors: HOLLOWAY PAUL A.
Published: September 2008

Interpreters of Paul's letter to the Philippians continue to struggle to understand the place of Paul's promise to send Timothy (Phil 2.19–24) in the overall rhetoric of the letter. However, if one reads Philippians as a letter of consolation the problems associated with this text can be solved. In particular, it becomes evident that the imprisoned and possibly soon-to-be-executed Paul offers Timothy to his anxious readers as his replacement, as another Paul or alius Paulus, according to the topos ‘consolation by means of a replacement’ for which there are many pertinent ancient parallels. This reading also explains why Paul describes Timothy as his ‘child’ (τεκνον) in the gospel ministry – children were often seen as replacements for dead parents – and why he insists that Timothy is ‘of like soul/mind’ (ισοψυχον) to himself.
Seven ‘deadly’ assumptions: unravelling the implications of HIV/AIDS among grandmothers in South Africa and beyond
Authors: CHAZAN MAY
Published: September 2008

Over the past few years, the pivotal roles older women play in responding to the unprecedented HIV/AIDS epidemic in southern Africa has received increasing recognition by academics, governments, funding agencies, non-governmental organisations, and citizens around the world. Yet, discourses surrounding AIDS and ‘grandmotherhood’ are laden with a number of ungrounded assumptions that have important implications for researchers, advocates and decision-makers. Drawing on ethnographic and survey data predominantly from South Africa, this paper challenges seven such assumptions. The paper illustrates how certain prevailing ‘wisdoms’ about grandmothers and AIDS in southern Africa are not entirely accurate and may mask many women's struggles and vulnerabilities, perpetuate stereotypes and misguide well-meaning policies. It also suggests that the societal impacts of AIDS in the region are, at present, not as dramatic as often portrayed, largely because the strength and resilience of many older women have cushioned some of the negative consequences. The paper thus calls for more nuanced and forward-looking analyses and interventions – ones that recognise grandmothers as central to the society's thin safety net and that grapple with older women's complex and diverse vulnerabilities.
Financial strain, negative social interaction, and self-rated health: evidence from two United States nationwide longitudinal surveys
Authors: KRAUSE NEAL , NEWSOM JASON T. , ROOK KAREN S.
Published: September 2008

Three hypotheses concerning negative social interaction in later life were evaluated in this study. First, it was predicted that greater personal economic difficulty is associated with more frequent negative social interaction with social network members in general. Secondly, it was proposed that more frequent negative social interaction exacerbates the undesirable effect of personal financial strain on change in self-rated health during late life. Thirdly, an effort was made to see if some types of negative social interaction, but not others, accentuate the undesirable effects of personal economic problems on self-rated health. Data from two nationwide longitudinal surveys that were conducted in the United States revealed that greater personal financial difficulty is associated with more interpersonal conflict. The findings further indicate that the undesirable effects of personal economic difficulty on change in self-rated health are more pronounced at progressively higher levels of negative social interaction. Finally, the data suggest that one form of negative social interaction (not getting help when it is expected) is more likely to intensify the unwanted effects of personal financial strain on self-rated health than other types of negative social interaction.
An on-line task modification method for singularity avoidance of robot manipulators
Authors: Qiu Changwu , Cao Qixin , Miao Shouhong
Published: September 2008

In this paper, we present an on-line task modification method (OTMM) to realize singularity avoidance for nonredundant and redundant manipulators at the velocity level. The method introduces a correction vector, constructed from the task velocity and the singular vector corresponding to the minimum singular value, into the task velocity. The performance is simply affected by the choice of the lower limit of the minimum singular value and a scalar adjusting function, which is monotone with respect to the minimum singular value. The method makes unnecessary avoiding the singularity point by off-line path planning for nonredundant or redundant manipulators, and the effort to check whether the singularity is escapable for redundant manipulators. The simulation results show the effectiveness of the OTMM for on-line singularity avoidance in manipulator motion control.
Game theoretic applications to environmental and natural resource problems
Authors: SUMAILA USSIF RASHID , DINAR ARIEL , ALBIAC JOSE
Published: September 2008

Game theory has been useful as an analytical framework for assessing environmental and resource regulations and policies. The papers in this volume provide the latest methodological and applied works in game theory to a wide range of natural and environmental resource problems such as fishing, grazing, pollution, climate change, water allocation, and stochastic production processes. The findings in the papers suggest that game theory is an effective tool for the analysis of the efficient use of shared natural resources; it can be used to identify stable agreements between parties to a resource conflict, and show how non-cooperation over global public goods/bads has a high social cost tag.
Bedeutung der Tumorzytogenetik in der Tumordiagnostik
Authors: Wenzel Friedel , Röthlisberger Benno
Published: September 2008

Tumorerkrankungen werden meist durch erworbene genetische Veränderungen verursacht. Seit einem halben Jahrhundert beschäftigt sich die klassische Tumorzytogenetik mit dem Nachweis von lichtmikroskopisch erkennbaren Chromosomenanomalien bei hämatologischen Neoplasien und in deutlich geringerem Ausmaß auch bei soliden Tumoren. Ganz generell kann festgehalten werden, dass die Bedeutung von genetischen Faktoren zur Klassifikation von Tumoren stetig zunimmt. Dabei werden vor allem bei hämatologischen Neoplasien neben den «klassischen» zytogenetischen Parametern zunehmend neu auch molekulargenetische Faktoren berücksichtigt. Für die Routineuntersuchung von soliden Tumoren spielt die konventionelle Zytogenetik aufgrund technischer und analytischer Probleme kaum eine Rolle. Hingegen werden bekannte Chromosomenaberrationen zunehmend mittels Fluoreszenz-in-situ Hybridisierung (FISH) oder mittels molekulargenetischer Methoden gesucht. In Zukunft werden auch Microarray-basierte Methoden in der Diagnostik von Tumoren zunehmend an Bedeutung gewinnen.
Laboruntersuchungen in der Gesundheitsvorsorge
Authors: Risch Lorenz , Saely Christoph H. , Drexel Heinz
Published: September 2008

Vorsorge hat zum Ziel, dass Personen gesünder älter werden. Vorsorgeuntersuchungen sollen Krankheiten an der Entstehung hindern oder sie früh erkennen, damit rechtzeitig interveniert werden kann. Für die Anforderungen an Vorsorgeuntersuchungen existieren Kriterien. Neben Anamnese und körperlicher Untersuchung kommen im Rahmen von Vorsorgeprogrammen auch Labortests zur Anwendung. Dazu gehören die Bestimmung von Blutglucose, Lipiden sowie der Testung von okkultem Blut im Stuhl. Weitere Parameter (TSH, PSA, Kreatinin, Albumin/Kreatinin Ratio) kommen in speziellen Situationen in Betracht. Zurzeit existiert für diese letztgenannten Tests noch keine solide Indikation für einen breiten Einsatz im Rahmen eines Massenscreenings. Der vorliegende Artikel stellt die Rolle von Labortests im Rahmen von Vorsorgeuntersuchungen vor und beleuchtet insbesondere auch Empfehlungen zu deren Einsatz in der Schweiz und in Österreich.
Einsatz von Metabolomics zur Diagnose von Stoffwechselkrankheiten
Authors: Weinberger Klaus M.
Published: September 2008

Metabolomics, also die systematische Identifizierung und Quantifizierung der niedermolekularen Stoffwechselprodukte in einer bestimmten Zelle, einem Gewebe oder einer Körperflüssigkeit, wird zunehmend als die aussagekräftigste Disziplin innerhalb der funktionellen Genomanalyse erkannt. Langjährige positive Erfahrungen in der Routinediagnostik angeborener Stoffwechselstörungen sowie verbesserte Empfindlichkeit und Reproduzierbarkeit quantitativer multiparametrischer Assays durch instrumentelle und experimentelle Innovationen lassen viele zusätzliche diagnostische Anwendungen in greifbare Nähe rücken. Dieser Artikel fasst die wissenschaftlichen und technologischen Hintergründe zusammen, die zum rasanten Aufschwung von Metabolomics in den vergangenen Jahren geführt haben, und beleuchtet anhand einiger Beispiele das Potential der hochauflösenden Stoffwechselanalytik für die Labormedizin der Zukunft.
Alte und neue Eisenparameter – Bedeutung im Eisenstoffwechsel und in der Diagnostik
Authors: Graf Lukas , Herklotz Roberto , Huber Andreas R. , Korte Wolfgang
Published: September 2008

Eisen ist ein essentielles Element, welches zudem auch potentiell toxisch ist. Im menschlichen Organismus existieren deshalb ausgeklügelte Mechanismen für die Aufnahme, den Transport sowie die Lagerung von Eisen. Erst seit einigen wenigen Jahren ist das Hepcidin bekannt, welches der wichtigste Regulator der intestinalen Eisenaufnahme zu sein scheint. Die Expression von Hepcidin wird aber nicht nur durch den Eisenstatus selber gesteuert, sondern auch durch Entzündungsmediatoren und Wachstumsfaktoren der Erythropoiese. Hepcidin spielt deshalb auch eine wichtige Rolle in der Entstehung der Anämie der chronischen Erkrankung und bei der Eisenüberladung bei ineffektiver Erythropoiese. Das Serumferritin ist der zuverlässigste Parameter, um das vorhandene Speichereisen abzuschätzen. Ferritin ist ein Akutphaseprotein, welches zum Beispiel im Rahmen ablaufender Infekte oder Entzündungen erhöht sein kann. Um in diesen Situationen zwischen einem Eisenmangel und einer Anämie der chronischen Erkrankung zu unterscheiden, ist die Bestimmung des löslichen Transferrinrezeptors hilfreich. Neuere Parameter wie das Zinkprotoporphyrin oder der Anteil hypochromer Erythrozyten (%HYPO) eignen sich gut zur Diagnose eines funktionellen Eisenmangels. Zur Vermeidung von Organschäden ist die rechtzeitige Diagnose einer Eisenüberladung wichtig. Als Screeningparameter haben sich hierfür die Transferrinsättigung und das Serumferritin bewährt. Falls nicht klar eine sekundäre Eisenüberladung vorliegt, muss nach einer primären, hereditär bedingten Eisenüberladung gesucht werden. Der Großteil dieser hereditären Hämochromatosen (homozygotes Vorliegen von Cys282Tyr oder Compound-Heterozygotie für Cys282Tyr/His63Asp) sind durch Mutationen im HFE-Gen bedingt, welche mittels PCR-Technik einfach gefunden werden können. Zur Quantifizierung des Speichereisens ist nach wie vor die Leberbiopsie der Goldstandard; neue kernspintomographische Methoden wie zum Beispiel T2* scheinen sich allerdings ebenfalls gut zur Bestimmung der Eisenüberladung einzelner Organe zu eignen.
Diagnostik der Autoimmunerkrankungen
Authors: Beleznay Zsuzsanna , Regenass Stephan
Published: September 2008

Autoantikörper spielen eine zentrale Rolle in der Labordiagnostik von Autoimmunerkrankungen. Neben der diagnostischen Verwendbarkeit sind diverse biologische Wirkungen von Autoantikörpern bekannt, die vom protektiven Effekt natürlicher Autoantikörpern vom Typ IgM gegen neoplastische Zellen, respektive deren Vorläufer, bis zur direkten Pathogenizität bei Myasthenia gravis oder dem Goodpasture Syndrome reichen. Autoantikörper gegen SSA Ro52 sind verantwortlich für den kongenitalen AV Block dritten Grades bei neonatalem Lupus erythematodes. Protektive Autoantikörper können im Krankheitsverlauf neurologische paraneoplastische Symptome auslösen, wenn die gegen Tumorantigene gerichteten Antikörper die Bluthirnschranke passieren und Zugang zu im Gehirn exprimierten Epitopen finden. Für die Verlaufsbeurteilung von Autoimmunerkrankungen spielen Autoantikörper eine geringe Rolle, mit den wichtigen Ausnahmen des Lupus erythematodes und ANCA – positiven Kleingefäßvaskulitiden. Verschiedene Autoantikörper, z.B. gegen Mitochondrien und gegen zitrullierte Autoantigene, sind wichtige prognostische Indikatoren. Kentnisse über das von Antikörpern erkannte Epitop sind Voraussetzung für die Wahl aussagekräftiger diagnostischer Methoden. Klassische Methoden, insbesondere die Immunfluoreszenzmikroskopie, stellen auch heute wertvolle Bestätigungsmethoden dar, und ermöglichen den Nachweis verschiedener Autoantikörper, die aktuell von Analyseautomaten nicht erfasst werden. Die Standardisation der Autoimmundiagnostik ist nicht abgeschlossen und erfordert den Einsatz von Laboratorien, Klinikern und der Industrie.
Die Bedeutung der Präanalytik
Authors: Hagemann Peter
Published: September 2008

Die bisherige Qualitätssicherung in der Labormedizin hat sich hauptsächlich auf die analytische Qualität konzentriert. Präanalytische Fehler haben mit etwa zwei Dritteln indessen den größten Anteil an allen Laborfehlern. Mängel einer optimalen Indikationsstellung tragen dazu bei, dass die Labormedizin nicht immer effektiv genutzt wird. Mängel im Bereich der übrigen Präanalytik bewirken eine reduzierte Effizienz der Labormedizin. Nicht selten wird das Potential einer sorgfältig evaluierten neuen Methode auf dem Weg zur «convenience» der täglichen Nutzung vergeudet. Gelingt es, durch bessere Beherrschung von Einflussgrößen und Störfaktoren sowie einen insgesamt standardisierteren präanalytischen Ablauf zuverlässigere Laborbefunde zu ermitteln, werden wir bei gleichen Kosten mehr Wert erzeugen. Entscheidende Voraussetzung dafür ist die Bewusstheit des Problems. Die Mittel sind weitgehend vorhanden, und das Ziel ist erreichbar.
Laboratoriumsmedizinische Strategien in der endokrinologischen Diagnostik ovarieller Störungen
Authors: Luppa Peter B. , Seifert-Klauss Vanadin
Published: September 2008

Labordiagnostik ist für die adäquate Beratung und Behandlung vieler ovarieller Störungen unverzichtbar. Dies wird im nachfolgenden Beitrag schlaglichtartig für vier häufige Problemfelder der gynäkologischen Endokrinologie dargestellt. Die Strategien bei der sekundären Amenorrhoe, bei weiblicher Infertilität inklusive des PCO-Syndroms, sowie die endokrinologische Diagnostik in der Perimenopause und bei hormonell aktiven Ovarialtumoren werden in ihren wesentlichen Grundzügen aufgezeigt.