bluuebunny/crossref_metadata_2025 huggingface dataset:
The behaviour of REFEL SiC under electrodischarge machining
Authors: Mahdavinejad R , Mehraban M , Mahdavinejad D
Published: December 2006

Electrodischarge machining (EDM) is an important manufacturing technology for machining difficult-to-cut materials and/or shaping complicated contours and profiles with a high material removal rate, low tool wear, and good tolerances. REFEL silicon carbide (SiC) is a ceramic material that is used increasingly as a substitute for metals in modern technology. Machining of this material is very difficult owing to its high hardness and resistance to wear. EDM appears to be the best and perhaps the only nonconventional method for machining SiC parts. Unfortunately, it shows high instability and tendency to arcing, as compared to machining of steel. In this paper, REFEL SiC is machined under 15 different pulse durations. The results show that arcing has the highest level of occurrence among four complete distinct pulses in EDM. The main output parameters (such as stock removal rate and tool wear ratio) do not change appreciably with increasing pulse times and currents. Scanning electron microscope (SEM) pictures show that increasing pulse current (contrary to ED machining of steel) has almost no effect on the integrity of the machined surface. Finite difference analysis of heat transfer on a SiC body shows that the heat is generated mainly near the workpiece surface and close to the plasma channel contact. Results show that an increase in discharge current increases the voltage drop and heat generation within the workpiece body while affecting deeper areas.
Prediction of cutting force and temperature rise in the end-milling operation
Authors: Palanisamy P , Rajendran I , Shanmugasundaram S , Saravanan R
Published: December 2006

The cutting force has a significant influence on the dimensional accuracy because of tool and workpiece deflection in milling. Force modelling in metal cutting is important for a multitude of purposes, including thermal analysis, tool life estimation, chatter prediction, and tool condition monitoring. In this paper, the dynamic cutting force model for end milling is developed to predict the tangential cutting force and the thrust force. The model prediction is validated with the experimental cutting forces during the machining of AISI 1020 steel using a three-axis milling tool dynamometer. The tool-chip interface temperatures for different machining conditions are determined using Oxley's energy partition function and Rapier's equation to study the thermal effect on the cutting force. Experiments have been conducted to validate the predicted temperature using a K-type thermocouple and an infrared pyrometer. The maximum temperature in the tool increased from 459 to 944 °C as the cutting speed is increased from 20 to 200 m/min when machining at a depth of cut of 2.5mm. The surface plots have been drawn using MATLAB to indicate the variation in the cutting temperature in shear and friction zone with the cutting parameters. Knowledge of the force acting on the cutter and tool-chip interface temperature may help the operator to select suitable cutting parameters in order to limit the tool-chip interface temperature.
Three-dimensional finite element analysis simulations of the fused deposition modelling process
Authors: Zhang Y , Chou Y K
Published: December 2006

Fused deposition modelling (FDM) is a layer-manufacturing technology that has been widely used for rapid prototyping applications in product design and development. Owing to the intensive energy, rapid cooling, and phase changes, parts made by FDM and other layer-manufacturing processes deviate from the designed geometry, and some require laborious post-processing. Most severe form inaccuracies such as curl, warping, and delamination are attributed to the residual stress accumulations during prototype fabrications.

This study investigates the FDM process, which consists of complicated heat and mass transfer phenomena coupled with mechanical loading and phase changes. A finite element analysis model using element activations has been developed to simulate the mechanical and thermal phenomena in FDM and further used for residual stress and part distortion simulations. The model has also been used to study the tool-path effects on the FDM process. Tool-path patterns affect the residual stresses in not only the magnitude but also the distribution which shows stress concentrations aligned with the primary direction of the tool path. Measured prototypes from the experiment show that the part distortion centre shifts distinctly owing to different tool-path patterns, which is consistent with the residual stress characteristics in the simulations. From the simulations, it is also shown that the short-raster tool path results in higher residual stresses, and thus possibly larger distortions, than the long-raster and alternate-raster patterns, both having similar stress distributions and distortion features.
On the effect of fixture layout on part stability and flatness during machining: A finite element analysis
Authors: Deiab I M
Published: December 2006

Deflection during machining can potentially introduce inaccuracies into the machined part geometry ultimately reducing its functionality. The traditional approach used in industry for fixture layout and configuration is mainly a trial and error scheme, which involves online examination of different combinations of fixture positions and clamping force magnitudes based on previous experience. Thus to be relevant, physics-based simulations of cutting processes must include the dynamics of the machine tool, fixture element, and part. In the current paper a developed simulation system is used to analyse and modify the fixture layout a priori to the metal removal process. This work analyses the effect of cutting forces, part features, and location of the fixture elements on the flatness and stability of the part. A typical industrial flexible part is used as a case study and its dynamic behaviour is analysed under different fixturing scenarios. The cutting forces are modelled using a mechanistic approach. The finite element method is used to model and analyse the dynamic behaviour of the fixtured part. Modal analysis was carried out using the finite element method and then results were verified experimentally.
Micromilling: Material microstructure effects
Authors: Popov K B , Dimov S S , Pham D T , Minev R M , Rosochowski A , Olejnik L
Published: December 2006

Micromilling is one of the technologies that is currently widely used for the production of microcomponents and tooling inserts. To improve the quality and surface finish of machined microstructures the factors affecting the process dynamic stability should be studied systematically. This paper investigates the machining response of a metallurgically and mechanically modified material. The results of micromilling workpieces of an Al 5000 series alloy with different grain microstructures are reported. In particular, the machining response of three Al 5083 workpieces whose microstructure was modified through a severe plastic deformation was studied when milling thin features in microcomponents. The effects of the material microstructure on the resulting part quality and surface integrity are discussed and conclusions made about its importance in micromilling. The investigation has shown that through a refinement of material microstructure it is possible to improve significantly the surface integrity of the microcomponents and tooling cavities produced by micromilling.
Experimental and theoretical analysis of freight wagon link suspension
Authors: Jönsson P-A , Andersson E , Stichel S
Published: December 2006

Link suspension is the most prevailing suspension system for two-axle freight wagons and still frequently used for four-axle freight wagons in central and western Europe. The system design is simple and has existed for more than 100 years. However, still, the characteristics are not fully understood. This article focuses on the lateral characteristics of the link suspension. First, results from stationary measurements on freight wagons and laboratory tests on single links are presented. Then, a simulation mathematical model is proposed. Finally, the influence of various parameters on the link characteristics is investigated. With the developed simulation model, many of the stability problems of link suspension running gears can be explained, but further research is needed to fully understand the characteristics and to be able to recommend improvements. From the tests, it also becomes obvious that the characteristics of different links can vary significantly from each other depending on age and maintenance status.
Relation between the geometry of rail welds and the dynamic wheel - rail response: Numerical simulations for measured welds
Authors: Steenbergen M J M M , Esveld C
Published: December 2006

The primary mechanisms playing a role in the dynamic wheel-rail response to rail weld irregularities in a ballasted track are pointed out. The concept of P1 and P2 forces for metallurgical rail welds, introduced in a first paper [1] concerning the present research, is further elaborated. The dynamic wheel-rail response is simulated for a number of geometrical rail weld measurements. Results show a good correlation between the gradient of the rail weld geometry and the maximum dynamic wheel-rail contact forces, whereas the correlation with vertical peak deviations is shown to be very poor. Therefore, an assessment method based on the gradient (introducing a speed-dependent quality index [1]) is more consistent than a method based on vertical tolerances. An approximate formula is presented to calculate the maximum dynamic wheel-rail contact force as a function of the train velocity and the maximum gradient of the weld geometry, in analogy to Jenkins' formulae for calculating P1 and P2 forces at dipped rail joints.
Modelling and robust μ-synthesis control of an intelligent self balancing two-wheel vehicle
Authors: Karkoub M A
Published: December 2006

A non-linear dynamic model is developed for a new type of two-wheel vehicles (B2). The B2 has two wheels side by side actuated via two DC motors and commanded through a controller card using a joystick. The vehicle can carry up to two passengers at a time. A first effort has been made to formulate a suitable set of requirements to be followed during the design phase. On the basis of such requirements, a reference linear dynamic model of the B2 has been derived. Then, a model matching H∞ control problem has been solved via the μ-synthesis approach, which allows disturbance rejection and robustness specifications to be taken into account. Finally, the designed control laws have been evaluated numerically both for the loaded and unloaded vehicle cases. The controller performed well even under maximum uncertainty and perturbation conditions.
Spatial revolute joints with clearances for dynamic analysis of multi-body systems
Authors: Flores P , Ambrósio J , Claro J C P , Lankarani H M
Published: December 2006

This paper presents a new technique for assessing the influence that clearance of spatial joints has on the kinematics and dynamics of multi-body systems. The technique is developed for the revolute joint in which the basic elements are the journal and bearing. Under certain working conditions, these two mechanical elements collide with each other being the contact treated as coupled forces. The forces between each pair of contacting bodies are equal and opposite, and the magnitude and direction are calculated based on the positions and velocities of the bodies, as well as on the geometry of the joint. A continuous contact force model is used to evaluate the contact-impact force. The proposed methodology is developed in the framework of the multi-body systems formulation; therefore, the forces developed during the contact between the joint elements are introduced into the systems' equations of motion as external forces. A double pendulum is used as a numerical example to show the application of the proposed methodology, being the efficiency of the developed methodologies discussed in the process of the results obtained.
HPLC–Tandem Mass Spectrometric Method to Characterize Resveratrol Metabolism in Humans
Authors: Urpi-Sarda Mireia , Zamora-Ros Raul , Lamuela-Raventos Rosa , Cherubini Antonio , Jauregui Olga , de la Torre Rafael , Covas Maria Isabel , Estruch Ramon , Jaeger Walter , Andres-Lacueva Cristina
Published: December 2006

Background: Nutritional biomarkers are alternatives to traditional dietary assessment tools. We sought to develop a method for nutritional analysis of resveratrol, a phenolic compound with purported health-promoting properties, and to determine all resveratrol metabolites.

Methods: We obtained LDL and urine samples from 11 healthy male volunteers who had consumed 250 mL of Merlot red wine. We measured resveratrol and its metabolites with 96-well solid-phase extraction plates coupled with HPLC-tandem mass spectrometry. Hexestrol was used as the internal standard. Gradient chromatography in multiple reaction monitoring mode was performed on a Luna C18 column, maintained at 40 °C; m/z transitions were as follows: resveratrol, 227/185; resveratrol glucosides, 389/227; resveratrol glucuronides, 403/227; resveratrol sulfates, 307/227; taxifolin, 303/285; and hexestrol, 269/134.

Results: Standard calibration curves were linear at 4.4–3289.5 nmol/L. Residual analyses were 100% (3.2) for trans-resveratrol and 100% (11.1) for trans-piceid. In both matrices, imprecision (CV) was <10.8% at all concentrations. Detection limits for resveratrol were 0.2 nmol/L (LDL), 0.3 nmol/L (synthetic urine), and 4.0 nmol/L (blank urine). Resveratrol and metabolites were checked for stability, and no degradation was observed.

Conclusions: The HPLC–tandem mass spectrometry method enabled us to identify resveratrol sulfates in human LDL and to characterize the complete profile of resveratrol metabolism in human LDL and urine. This method provides an accurate index of exposure to resveratrol and its metabolites, which can be used as nutritional biomarkers for evaluating the biological effects of moderate wine intake on human health.
Persistent Dopamine Functions of Neurons Derived from Embryonic Stem Cells in a Rodent Model of Parkinson Disease
Authors: Rodríguez-Gómez Jose A. , Lu Jian-Qiang , Velasco Iván , Rivera Seth , Zoghbi Sami S. , Liow Jeih-San , Musachio John L. , Chin Frederick T. , Toyama Hiroshi , Seidel Jurgen , Green Michael V. , Thanos Panayotis K. , Ichise Masanori , Pike Victor W. , Innis Robert B. , McKay Ron D. G.
Published: December 2006

The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

Disclosure of potential conflicts of interest is found at the end of this article.
Control of high molecular weight disinfection byproducts in drinking water by coagulation
Authors: Zhang X.R. , Minear R.A.
Published: December 2006

A major portion of the total organic halogen formed during chlorination is likely attributable to high molecular weight (MW) DBPs (above 500 Da), which may have potential adverse health effects. In this work, highly dosed chlorinated Suwannee River fulvic acid samples with and without coagulation pretreatment were separated and fractionated by using ultrafiltration (UF) and size exclusion chromatography (SEC) techniques. The SEC fractions corresponding to the high MW region were concentrated with nitrogen sparging and characterized by negative ion electrospray ionization/mass spectrometry (ESI-MS). The SEC–UV chromatograms and SEC–ESI-MS spectra show that coagulation greatly reduced the formation of high MW DBPs. It is of note that phosphate from the buffer could affect the ESI-MS characterization in 2–3 SEC fractions although most of the phosphate had been removed by UF.
Mechanism investigation of virus removal in a membrane bioreactor
Authors: Zheng X. , Liu J.X.
Published: December 2006

Virus removal in a membrane bioreactor (MBR) by gravity drain was studied. Coliphage f2 (mean size of 25 nm), which is similar in size to human enteric pathogenic viruses, was selected as a model virus. Two microfiltration membrane modules with pore sizes of 0.22 μm and 0.1 μm were applied to investigate the effects of membrane pore size on the virus rejection. The MBR with these modules could reject virus in a range of 2.6–5.1 logs. The experimental results showed that the mechanisms of virus removal in the MBR involved rejection and inactivation. The virus rejection depended mainly on the dynamic layer on the membrane surface (not membrane itself) because virus rejection by the membrane modules with pore sizes of 0.1 μm and 0.22 μm were similar. The microbial activity and the aeration oxidation were the two important factors for the virus inactivation. It was found that the inactivation of coliphage f2 was much more rapidly in activated sludge mixed liquor than in clean water, and the effect of aeration was significant.
Role of carboxylic and phenolic groups in NOM adsorption on minerals: a review
Authors: Guan X.H. , Li D.L. , Shang C. , Chen G.H.
Published: December 2006

This paper presented the current state of our understanding of the roles of carboxylic and phenolic groups in NOM adsorption and reviewed the contradictory opinions in the literatures. Previous studies carried out by other researchers indicated that aromatic carboxylates were adsorbed onto metal (hydr)oxides via outer-sphere complexes under most conditions and phenolic groups were very crucial for formation of inner-sphere complexes between organic acids and metal (hydr)oxides. Adsorption test with in-situ ATR-FTIR spectroscopic investigation were carried out to verify the role of aromatic carboxylic and phenolic groups in the NOM adsorption onto aluminium hydroxide surfaces by using a series of aromatic carboxylic acids and dihydroxybenzoic acids as the surrogate of NOM. Our studies suggested that the formation of outer-sphere complexes dominated the adsorption of most of the aromatic carboxylates over the pH range of 5–9; inner-sphere complexes were only detected at some pH levels for some aromatic carboxylates adsorption; and the aromatic carboxylates were most likely to be adsorbed to the first surface layer of hydroxyl groups and water molecules without forming coordinative bonds with the aluminium hydroxide surfaces but strong hydrogen bonds were formed in this process. Our study also revealed that (1) the presence of phenolic groups can increase the interaction strength of carboxylate groups with aluminium hydroxide; (2) chelate formation involving a carboxylate oxygen atom and ortho-phenolic-oxygen is important for the adsorption of organic matter on aluminium hydroxide at acidic pH; and 3) the phenolic groups adjacent to each other are more important than the carboxylic groups at alkaline pH for organic matter adsorption.
Ultrasound pre-treatment of waste activated sludge
Authors: (Hans) van Leeuwen J , Akin Beril , Khanal Samir Kumar , Sung Shihwu , Grewell David , (Hans) van Leeuwen J
Published: December 2006

Waste activated sludge (WAS) is more difficult to digest than primary sludge due to rate limiting cell hydrolysis. High-power ultrasound can effectively disintegrate the bacterial cells and thus enhance the subsequent digestion. This research examines the effectiveness of ultrasound pretreatment on WAS disintegration at different specific energy inputs, ultrasonic densities and total solids (TS) contents. The results show that the cut diameter (d50) for WAS with 2% TS content declined nearly 6.5-fold at an ultrasonic density of 0.67 W/ml. For higher TS contents of 4 and 6%, higher densities of 1.03 and 0.86 W/ml, respectively, were needed to achieve the same degree of particle size reduction. The efficacy of ultrasonic disintegration measured as soluble chemical oxygen demand (SCOD) release was primarily governed by ultrasonic density (W/ml); whereas ultrasonic density did not show a significant effect on protein release at all TS levels. SCOD release of about 320 mg SCOD/g TS was obtained at a TS content of 2% and specific energy input of 5 kWs/gTS. The SCOD release, however, decreased to 160 and 90 mgSCOD/gTS at 4 and 6% TS contents, respectively. The highest protein release of 73 mg/gTS was obtained at a TS content of 2% and specific energy input of 10 kWs/gTS. The sludge disintegration efficiency declined significantly at higher TS content. Thus, there is a limiting TS concentration that could be effectively disintegrated by ultrasound, and this is governed by the capability of an ultrasonic unit in producing cavitation. The degree of disintegration also depends on types of ultrasonic unit used.
Agreement between computed tomography, magnetic resonance imaging, and surgical findings in dogs with degenerative lumbosacral stenosis
Authors: Suwankong Niyada , Voorhout George , Hazewinkel Herman A. W. , Meij Björn P.
Published: December 2006

Objective—To assess the extent of agreement between computed tomography (CT), magnetic resonance imaging (MRI), and surgical findings in dogs with degenerative lumbosacral stenosis.

Design—Observational study.

Animals—35 dogs with degenerative lumbosacral stenosis.

Procedures—Results of preoperative CT and MRI were compared with surgical findings with respect to degree and location of disk protrusion, position of the dural sac, amount of epidural fat, and swelling of spinal nerve roots.

Results—A lumbosacral step was seen on radiographic images from 22 of 32 (69%) dogs, on CT images from 23 of 35 (66%) dogs, and on MR images from 21 of 35 (60%) dogs. Most dogs had slight or moderate disk protrusion that was centrally located. There was substantial or near perfect agreement between CT and MRI findings in regard to degree of disk protrusion (kappa, 0.88), location of disk protrusion (0.63), position of the dural sac (0.89), amount of epidural fat (0.72), and swelling of spinal nerve roots (0.60). The degree of agreement between CT and surgical findings and between MRI and surgical findings was moderate in regard to degree and location of disk protrusion (kappa, 0.44 to 0.56) and swelling of spinal nerve roots (0.40 and 0.50).

Conclusions and Clinical Relevance—Results indicate that there is a high degree of agreement between CT and MRI findings in dogs with degenerative lumbosacral stenosis but that the degree of agreement between diagnostic imaging findings and surgical findings is lower.
Idiopathic primary chylopericardium in a dog
Authors: Boston Sarah E. , Moens Noël M. , Martin Dawn M.
Published: December 2006

Case Description—A 7-year-old spayed female Labrador Retriever was evaluated because of pericardial effusion.

Clinical Findings—The dog had a history of decreased appetite and exercise intolerance of 3 days' duration. Thoracic radiography performed by the referring veterinarian revealed a large cardiac silhouette. Heart sounds were muffled. Echocardiographic findings were indicative of severe pericardial effusion with cardiac tamponade; no pleural effusion was identified. Pericardiocentesis yielded a considerable amount of chylous fluid. A diagnosis of chylopericardium in the absence of pleural effusion was made.

Treatment and Outcome—Conservative management was not effective, and subtotal pericardectomy and thoracic duct ligation were recommended. Surgery was postponed by the owners for 25 days, at which time the dog had both chylopericardium and chylothorax. The dog underwent subtotal pericardectomy and thoracic duct ligation; to delineate the thoracic duct, intraoperative lymphangiography was performed by injection of a radiopaque contrast agent directly into a mesenteric lymph node and subsequent injection of methylene blue solution into another mesenteric lymph node. Surgical treatment resulted in complete resolution of the clinical signs and pleural effusion.

Clinical Relevance—To the authors' knowledge, this is the first report of the development of chylopericardium prior to development of chylothorax in a dog. Treatment with thoracic duct ligation and pericardectomy resulted in complete resolution of the effusion and clinical signs.
Iridium‐Catalysed Asymmetric Hydrogenation of Vinylsilanes as a Route to Optically Active Silanes
Authors: Källström Klas , Munslow Ian J. , Hedberg Christian , Andersson Pher G.
Published: December 2006

The first use of vinylsilanes as substrates in the asymmetric iridium‐catalysed hydrogenation is reported, providing products with enantioselectivities of up to 98 %.
Microwave‐Accelerated Coupling‐Isomerization Reaction (MACIR) – A General Coupling‐Isomerization Synthesis of 1,3‐Diarylprop‐2‐en‐1‐ones
Authors: Schramm (née Dediu) Oana G. , Müller Thomas J. J.
Published: December 2006

The microwave‐accelerated coupling‐isomerization reaction (MACIR) of (hetero)aryl halides and propargyl alcohols represents a general Pd/Cu and base‐catalyzed process for the synthesis of 3‐arylprop‐2‐en‐1‐ones in good yields.
Rhesus macaques (Macaca mulatta) are not neophobic toward novel food with a high sugar content
Authors: Johnson Elizabeth C.
Published: December 2006

While we know that food neophobia in nonhuman primates is affected by social factors, little is known about how palatability, and specifically sugar content, might ameliorate a monkey's hesitancy to eat a novel food. It is likely that an innate preference for sweet substances would alter an animal's typical neophobic response. To test this, I presented nine male rhesus macaques with novel foods that contained a low, high, or no amount of sugar. As expected, the monkeys exhibited a neophobic response to the no‐sugar novel foods but not to the high‐sugar novel foods. Previous research on food neophobia may need to be reevaluated in light of the effects of sugar content on the neophobic response. Am. J. Primatol. 69:591–596, 2007.© 2006 Wiley‐Liss, Inc.
Simulation of β‐depsipeptides: The effect of missing hydrogen‐bond donors on their folding equilibria
Authors: Gattin Zrinka , Glättli Alice , Jaun Bernhard , van Gunsteren Wilfred F.
Published: December 2006

β‐Depsipeptides are β‐peptides in which one or more peptide linkages are replaced by ester linkages, resulting in a loss of a hydrogen‐bond donor (NH) and weakening of the corresponding carbonyl hydrogen‐bond acceptor moiety. The effects of three of such peptide by ester substitutions in a hepta‐β‐peptide upon its (un)folding equilibrium in methanol solution are investigated using molecular dynamics simulations and compared to experimental data from NMR spectroscopy. The simulated conformational ensembles largely reproduce the experimentally measured NOE and 3J‐coupling constant data for the three different hepta‐β‐peptides, and confirm the relative stabilities of the 314‐helical conformation, which is most weakened by substitution of the 4th peptide linkage and least by substitution of the 6th peptide linkage. The simulations are complementary to the experimental data by providing detailed insight into the conformational distributions that are compatible with the experimentally measured average values of observables. © 2006 Wiley Periodicals, Inc. Biopolymers 85:318–332, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Decreased pCO2 accumulation by eliminating bicarbonate addition to high cell‐density cultures
Authors: Goudar Chetan T. , Matanguihan Ricaredo , Long Edward , Cruz Christopher , Zhang Chun , Piret James M. , Konstantinov Konstantin B.
Published: December 2006

High‐density perfusion cultivation of mammalian cells can result in elevated bioreactor CO2 partial pressure (pCO2), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 × 106 cells/mL, the bioreactor pCO2 exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO3, and 40% from NaHCO3 added for pH control. Recognizing the limitations to the practicality of gas sparging for CO2 removal in perfusion systems, a strategy based on CO2 reduction at the source was investigated. The NaHCO3 in the medium was replaced with a MOPS–Histidine buffer, while Na2CO3 replaced NaHCO3 for pH control. These changes resulted in 63–70% pCO2 reductions in multiple 15 L perfusion bioreactors, and were reproducible at the manufacturing‐scale. Bioreactor pCO2 values after these modifications were in the 68–85 mm Hg range, pCO2 reductions consistent with those theoretically expected. Low bioreactor pCO2 was accompanied by both 68–123% increased growth rates and 58–92% increased specific productivity. Bioreactor pCO2 reduction and the resulting positive implications for cell growth and productivity were brought about by process changes that were readily implemented and robust. This philosophy of pCO2 reduction at the source through medium and base modification should be readily applicable to large‐scale fed‐batch cultivation of mammalian cells. Biotechnol. Bioeng. 2007;96:1107–1117. © 2006 Wiley Periodicals, Inc.
Enhanced protein production by engineered zinc finger proteins
Authors: Reik Andreas , Zhou Yuanyue , Collingwood Trevor N. , Warfe Lyndon , Bartsevich Victor , Kong Yanhong , Henning Karla A. , Fallentine Barrett K. , Zhang Lei , Zhong Xiaohong , Jouvenot Yann , Jamieson Andrew C. , Rebar Edward J. , Case Casey C. , Korman Alan , Li Xiao‐Yong , Black Amelia , King David J. , Gregory Philip D.
Published: December 2006

Increasing the yield of therapeutic proteins from mammalian production cell lines reduces costs and decreases the time to market. To this end, we engineered a zinc finger protein transcription factor (ZFP TF) that binds a DNA sequence within the promoter driving transgene expression. This ZFP TF enabled >100% increase in protein yield from CHO cells in transient, stable, and fermentor production run settings. Expression vectors engineered to carry up to 10 ZFP binding sites further enhanced ZFP‐mediated increases in protein production up to ∼500%. The multimerized ZFP binding sites function independently of the promoter, and therefore across vector platforms. CHO cell lines stably expressing ZFP TFs demonstrated growth characteristics similar to parental cell lines. ZFP TF expression and gains in protein production were stable over >30 generations in the absence of antibiotic selection. Our results demonstrate that ZFP TFs can rapidly and stably increase protein production in mammalian cells. Biotechnol. Bioeng. 2007; 97: 1180–1189. © 2006 Wiley Periodicals, Inc.
Development of a 3D cell culture system for investigating cell interactions with electrospun fibers
Authors: Sun Tao , Norton David , McKean Robert J. , Haycock John W. , Ryan Anthony J. , MacNeil Sheila
Published: December 2006

There are many variables to be considered in studying how cells interact with 3D scaffolds used in tissue engineering. In this study we investigated the influence of the fiber diameter and interfiber spaces of 3D electrospun fiber scaffolds on the behavior of human dermal fibroblasts. Fibers of two dissimilar model materials, polystyrene and poly‐L‐lactic acid, with a broad range of diameters were constructed in a specifically developed 3D cell culture system. When fibroblasts were introduced to freestanding fibers, and encouraged to “walk the plank,” a minimum fiber diameter of 10 µm was observed for cell adhesion and migration, irrespective of fiber material chemistry. A distance between fibers of up to 200 µm was also observed to be the maximum gap that could be bridged by cell aggregates—a behavior not seen in conventional 2D culture. This approach has identified some basic micro‐architectural parameters for electrospun scaffold design and some key differences in fibroblast growth in 3D. We suggest the findings will be of value for optimizing the integration of cells in these scaffolds for skin tissue engineering. Biotechnol. Bioeng. 2007; 97: 1318–1328. © 2006 Wiley Periodicals, Inc.
Outcome of patients rehabilitated through a New Zealand forensic psychiatry service: a 7.5 year retrospective study
Authors: Simpson Alexander I. F. , Jones Roland M. , Evans Ceri , McKenna Brian
Published: December 2006

This paper describes a 7.5 year retrospective study of all patients discharged from inpatient forensic services to forensic community team (FCT) follow‐up from the Auckland Regional Forensic Psychiatry Service. Patients' files were studied for clinical, criminal, and risk data, type of service delivered, and final level of function achieved in the community. Rearrest, re‐hospitalization, and reimprisonment data were obtained from clinical, court, and prison records.

105 patients were included. The most common diagnosis was a psychotic disorder, and index offending behaviour was typically violent. The median period of inpatient stay was 36 months and mean subsequent FCT follow‐up 21.7 months (SD 17.8). The majority of patients were from Maori and Pacific Island ethnic groups. At the end of the study, half were in independent living, half were in some form of employment, and 19% were readmitted to a forensic hospital.

One patient was rearrested but not reimprisoned whilst under forensic community team care. However, 9 of the 48 who were discharged to general mental health services were rearrested and 5 reimprisoned. Only two offences were as serious as the original index offence.

Broad based assertive, mandated, and committed forensic rehabilitation can achieve high quality outcomes. These levels of function may not be sustained under less assertive care. Copyright © 2006 John Wiley & Sons, Ltd.
Integrating children's services to promote children's welfare: early findings from the implementation of children's trusts in England
Authors: O'Brien Margaret , Bachmann Max , Husbands Chris , Shreeve Ann , Jones Natalia , Watson Jacqueline , Shemilt Ian
Published: December 2006

As part of the reform of English children's services, children's trust pathfinders were launched in 2003 by the British government to promote greater inter‐agency co‐operation between children's services and professionals. This paper reports on early findings from a multi‐method, longitudinal national evaluation of the implementation and impact of all 35 children's trust pathfinders. Using data from a 2004 survey of 35 children's trusts managers and in‐depth interviews with 107 professionals conducted in 2005, results show strong endorsement of an integrated children's service vision. However, arrangements for co‐operation on governance and strategic developments were more advanced than for procedural or frontline professional practice. In this transitional period, professionals were negotiating a balance between targeted and universal service provision and, concurrently, establishing the scope of formal strategic partnership bodies (including local safeguarding children boards) with potentially overlapping remits. Copyright © 2006 John Wiley & Sons, Ltd.
A Resonance Energy Transfer Immunoassay Based on a Thiol‐Reactive Ruthenium Donor Dye and a Longwave‐Emitting Acceptor
Authors: Weh Jochen , Duerkop Axel , Wolfbeis Otto S.
Published: December 2006

A novel immunoassay is described that applies a thiol‐reactive ruthenium metal–ligand complex as the donor dye in a luminescence energy transfer (LET) detection scheme. Unlike amine‐reactive labels, the LET with a thiol label allows improved specificity and better reproducibility of labelling positions on proteins, because the number of reactive thiol groups of proteins is distinctly smaller. This helps to reduce the risk of over‐labelling and self‐quenching of the fluorophore. The synthesis of the thiol label was significantly improved, resulting in almost quantitative yields of pure product. The absorption and emission maxima of the ruthenium donor dye are at 460 nm and 600 nm, respectively, and a Stokes' shift of 140 nm warrants distinct separation of excitation and emission wavelengths even in turbid samples. A cyanine dye with an absorption maximum at 642 nm was chosen as the acceptor label because it has good overlap with the emission spectrum of the donor label. The emission of the acceptor peaks at 660 nm, thus further increasing the Stokes' shift (to an overall 200 nm). The quantification of anti‐HSA with the LET immunoassay is possible with this new approach at concentrations as low as 220 pmol L−1.
Hydrogencyanamide‐Bridged One‐Dimensional Polymers Built on MnIII–Schiff Base Fragments: Synthesis, Structure, and Magnetism
Authors: Yuan Mei , Zhao Fei , Zhang Wen , Pan Feng , Wang Zhe‐Ming , Gao Song
Published: December 2006

The ability of NCNH− to construct transition metal coordination polymers and to transmit magnetic coupling was investigated. By introduction of various tetradentate Schiff base ligands (L) and different solvents (S), nine NCNH−‐bridged manganese(III) coordination complexes were obtained. Their structures can be divided into three types: I) NCNH‐bridged chains built on mononuclear [MnIII(L)] units, [MnIII(L)(μ1,3‐NCNH)]n (L=5‐Brsalen (1), 5‐Clsalen (2)); II) NCNH‐bridged chains built on dinuclear [MnIII2(L)2] units, complexes 3–8, [MnIII2(L)2(μ1,3‐NCNH)]ClO4⋅S (L=salen, 5‐Fsalen, 5‐Clsalen, 5‐OCH3salen; S=CH3OH or C2H5OH); III) NCNH‐bridged MnIII dimers linked by hydrogen bonds into a 1D polymer, {[MnIII(3‐OCH3salen)(H2O)]2(μ1,3‐NCNH)}ClO4⋅0.5 H2O (9, salen=N,N′‐bis(salicylidene)‐1,2‐diaminoethane). In these complexes, the NCNH− resonance structure dominates the bonding mode of the NCNH− ligand adopting the μ1,3‐bridging mode. Magnetic characterization shows that the asymmetric NCNH− bridge transmits antiferromagnetic interaction between MnIII ions and often favors the weak ferromagnetism caused by spin canting in these one‐dimensional chains. However, these complexes exhibit different magnetic behaviors at low temperatures.
Experiences with psychotherapy for depression in routine care: a naturalistic patient survey in Germany
Authors: Hoyer Jürgen , Helbig Sylvia , Wittchen Hans‐Ulrich
Published: December 2006

The present survey assessed consumer satisfaction of patients having undergone psychotherapy for depression as well as service characteristics including treatment access, communication of diagnosis and treatment rationale, quality assurance and adverse events. The study was conducted in the form of a 15‐item questionnaire that was published in one of Germany's leading health magazines. 473 persons responded (81.5% women, age range 17–83). 49.8% of the respondents reported substantial or reasonable improvement; two out of three patients stated they had been satisfied with their therapy. Improvement and satisfaction were greater in those patients who had been informed about diagnosis and treatment; they were lower when unpleasant experiences were reported. Methodological restrictions of the study are outlined and hypotheses about potential strengths and deficits in the delivery of psychotherapy for depression in Germany are proposed. Copyright © 2006 John Wiley & Sons, Ltd.
Mechanistic Analysis of Nucleophilic Substrates Oxidation by Functional Models of Vanadium‐Dependent Haloperoxidases: A Density Functional Theory Study
Authors: Schneider Curtis J. , Zampella Giuseppe , Greco Claudio , Pecoraro Vincent L. , De Gioia Luca
Published: December 2006

Density functional theory has been used to investigate the structural, electronic, and reactivity properties of an established functional model for vanadium‐dependent haloperoxidases, K[VO(O2)Hheida] (Hheida2– = 2,2′‐[(2‐hydroxyethyl)imino]diacetate). Possible solution species were determined on the basis of potential exogenous donors present under the conditions necessary for reactivity. The energetically favored solution‐state species is a 1:1 complex of Hheida and vanadium with a coordinated hydroxyethyl donor trans to the vanadium–oxido bond which is in agreement with the reported solid‐state structure for K[VO(O2)Hheida]. Transition states of the oxidation reaction were located for four substrates: chloride, bromide, iodide, and dimethyl sulfide. The role of protonation and its effects on reactivity were examined for each substrate. Protonation of the peroxido moiety leads to a significant drop in the activation barrier for oxidation. In contrast no transition states could be located for an oxido‐transfer process involving the oxido ligand. Barriers of activation calculated for halide oxidation were similar, providing support to the hypothesis that the pKa of the halide in acetonitrile is responsible for the decrease in reactivity between I–, Br–, and Cl–. The results presented herein provide a mechanistic correlation between a functional model and the enzyme, making K[VO(O2)Hheida] a “complete” functional model for vanadium‐dependent haloperoxidase.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Pyropheophytin a – Determination of thermal degradation products of chlorophyll a in virgin olive oil
Authors: Gertz Christian , Fiebig Hans‐Jochen
Published: December 2006

The “Joint Committee for the Analysis of Fats, Oils, Fatty Products, Related Products and Raw Materials (GA Fett)” has developed the following method for the determination of Pyropheophytin a in virgin olive oils to detect a possible thermal treatment. It is intended to include this method in Section C, Chapter VI of the German Standard Methods.*
Mycothiazole: Synthesis of the C8–C18 Subunit and Further Evidence of the (Z)‐Δ14 Double Bond Configuration
Authors: Rega Miriam , Candal Paloma , Jiménez Carlos , Rodríguez Jaime
Published: December 2006

The synthesis of mycothiazole derivatives was undertaken in order to have further evidence of the C14–C15 double bond configuration. The recently revised (Z) configuration in the natural compound is consistent with the data found for our synthetic analogs. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Chiral Macrocyclic Bis(oxazoline) CuI Complexes – Structure/Stereoselectivity Relationships in Catalytic Cyclopropanations
Authors: Portada Tomislav , Roje Marin , Raza Zlata , Čaplar Vesna , Žinić Mladen , Šunjić Vitomir
Published: December 2006

The design and synthesis of 18 chiral macrocycles with built in C2‐symmetric bis(oxazoline) units is described and the catalytic properties of their copper(I) complexes in cyclopropanations of styrene with ethyl diazoacetate are assessed. The bridging of two homochiral centers in the bis(oxazoline) unit gives a macrocyclic ligand, which upon binding of CuI is transformed into a macrocyclic catalytic complex containing a chiral cavity. Such a complex represents a conceptually new type of supramolecular organometallic catalyst, possessing a chiral reaction cavity. A clear relationship between catalyst structures and the stereoselectivity outcome in the catalytic cyclopropanations has been established and it is demonstrated that both the enantioselectivity and the diastereoselectivity can be independently modified by variation of the ligand structural parameters. The CuI complex of the ligand 3b gave a trans/cis diastereomeric ratio of 94:6 (de = 88 %), representing the highest diastereoselectivity obtained to date for cyclopropanations catalyzed by the bis(oxazoline) class of complexes. An explanation of the observed relationship between stereochemical outcome and ligand structure is proposed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Evaluation of the home help service and its impact on the informal caregiver's burden of dependent elders
Authors: Carretero Stephanie , Garcés Jorge , Ródenas Francisco
Published: December 2006

Aim

This study looks at the objective and subjective characteristics of home respite service provision and its impact on the informal care burden of dependent elders.

Method

A sample of 296 dependent people and their informal caregivers was randomly selected among users and non‐users of the Home Help Service (HHS) in an autonomous Spanish region (Comunidad Valenciana). An experimental design was used and a field study was carrying out that collected information on sociodemographic variables of the dependent person and his/her caregiver, HHS characteristics and the assessment of the services delivered by this resource as well as the informal caregivers'burden.

Results

The results show that the services of this resource are very limited, with low cover and frequency, and they do not address the real dependency needs in specific activities of daily living. However, users and caregivers are satisfied with this care and experience a higher quality of life since it was implemented, although the HHS does not alleviate informal caregivers' stress.

Conclusion

These data show the need to extend the services delivered by the HHS and the duration of care, address the caregiver's need for psychological care, and look at potentially modifiable variables in the care context when designing prevention and psychosocial intervention programmes to lessen the informal caregiver's burden. Copyright © 2006 John Wiley & Sons, Ltd.
Oligonucleotide Analogues with Integrated Bases and Backbone. Part 13
Authors: Zhang Xiaomin , Bernet Bruno , Vasella Andrea
Published: December 2006

The self‐complementary UA and AU dinucleotide analogues 41–45, 47, 48, and 51–60 were prepared by Sonogashira coupling of 6‐iodouridines with C(5′)‐ethynylated adenosines and of 8‐iodoadenosines with C(5′)‐ethynylated uridines. The dinucleotide analogues associate in CDCl3 solution. The C(6/I)‐unsubstituted AU dimers 51 and 54 prefer an anti‐oriented uracilyl group and form stretched linear duplexes. The UA propargyl alcohols 41 and 43–45 possess a persistent intramolecular O(5′/I)H⋅⋅⋅N(3/I) H‐bond and, thus, a syn‐oriented adeninyl and a gt‐ or tg‐oriented ethynyl moiety; they form corrugated linear duplexes. All other dimers form cyclic duplexes characterized by syn‐oriented nucleobases. The preferred orientation of the ethynyl moiety (the C(4′),C(5′) torsion angle) defines a conformation between gg and one where the ethynyl group eclipses O(4′/I). The UA dimers 42, 47, and 48 form Watson–Crick H‐bonds, the AU dimers 56 and 58–60 H‐bonds of the Watson–Crick‐type, the AU dimers 53 and 55 reverse‐Hoogsteen, and 57 Hoogsteen H‐bonds. The pairing mode depends on the substituent of C(5′/I) (H, OSiiPr3; OH) and on the H‐bonds of HOC(5′/I) in the AU dimers. Association constants were derived from the concentration‐dependent chemical shift for HN(3) of the uracilyl moiety; they vary from 45–104 M−1 for linear duplexes to 197–2307 M−1 for cyclic duplexes. The thermodynamic parameters were determined by van't Hoff analysis of the temperature‐dependence of the (concentration‐dependent) chemical shift for HN(3) of the uracilyl moiety. Neglecting stacking energies, one finds an average energy of 3.5–4.0 kcal/mol per intermolecular H‐bond. Base stacking is evidenced by the temperature‐dependent CD spectra. The crystal structure of 54 shows two antiparallel chains of dimers connected by Watson‐Crick H‐bonds. The chains are bridged by a strong H‐bond between the propargylic OH and OC(4) and by weak reverse A ⋅ A Hoogsteen H‐bonds.