bluuebunny/crossref_metadata_2025 huggingface dataset:
Tools and ingredients for the biocatalytic synthesis of metabolites
Authors: Wohlgemuth Roland
Published: September 2009

Metabolic networks have been an interesting starting point not only for the design of synthetic routes in a similar sequence of reactions, e.g., in biomimetic syntheses, but also for assembling a number of biocatalytic steps by preparing the required enzymes and auxiliary reagents. Retrosynthetic analysis involving multiple biocatalytic reactions steps therefore needs to consider the practically realized biocatalytic single steps. The opportunities for route selection are enlarged if novel synthetic reactions connecting easily available starting materials and products are found, and/or both biocatalytic and classical reactions of organic chemistry are utilized. Tools and ingredients for biocatalytic synthesis are of special interest for reactions difficult to achieve by classical organic synthesis. Densely and differentially functionalized small molecules do not allow much space for protecting or activating groups. Biocatalytic reactions have therefore performed well for a number of useful metabolites in enantiopure form to achieve full functionality. Although many well‐known metabolites from classical biochemistry have only been prepared in racemic form, it is of fundamental interest to have these available in enantiomerically pure form. Biocatalytic reactions with nature's privileged chiral catalysts appear to be a promising synthetic strategy towards these metabolites, especially when sensitive or stable‐isotope‐labeled metabolites are to be prepared. The main applications for these metabolites are as references materials in metabolomics, as enzyme substrates for the characterization of metabolic enzyme activities and as potential pharmaceuticals in biomedical research. The use of stable‐isotope‐labeled metabolites can thereby simplify in vivo applications and metabolic flux analyses.
BAK and BAX deletion using zinc‐finger nucleases yields apoptosis‐resistant CHO cells
Authors: Cost Gregory J. , Freyvert Yevgeniy , Vafiadis Annamaria , Santiago Yolanda , Miller Jeffrey C. , Rebar Edward , Collingwood Trevor N. , Snowden Andrew , Gregory Philip D.
Published: September 2009

Anoxic and metabolic stresses in large‐scale cell culture during biopharmaceutical production can induce apoptosis. Strategies designed to ameliorate the problem of apoptosis in cell culture have focused on mRNA knockdown of pro‐apoptotic proteins and over‐expression of anti‐apoptotic ones. Apoptosis in cell culture involves mitochondrial permeabilization by the pro‐apoptotic Bak and Bax proteins; activity of either protein is sufficient to permit apoptosis. We demonstrate here the complete and permanent elimination of both the Bak and Bax proteins in combination in Chinese hamster ovary (CHO) cells using zinc‐finger nuclease‐mediated gene disruption. Zinc‐finger nuclease cleavage of BAX and BAK followed by inaccurate DNA repair resulted in knockout of both genes. Cells lacking Bax and Bak grow normally but fail to activate caspases in response to apoptotic stimuli. When grown using scale‐down systems under conditions that mimic growth in large‐scale bioreactors they are significantly more resistant to apoptosis induced by starvation, staurosporine, and sodium butyrate. When grown under starvation conditions, BAX‐ and BAK‐deleted cells produce two‐ to fivefold more IgG than wild‐type CHO cells. Under normal growth conditions in suspension culture in shake flasks, double‐knockout cultures achieve equal or higher cell densities than unmodified wild‐type cultures and reach viable cell densities relevant for large‐scale industrial protein production. Biotechnol. Bioeng. 2010; 105: 330–340. © 2009 Wiley Periodicals, Inc.
Computational study of the drag and oscillatory movement of biofilm streamers in fast flows
Authors: Taherzadeh Danial , Picioreanu Cristian , Küttler Ulrich , Simone Angelo , Wall Wolfgang A. , Horn Harald
Published: September 2009

Hydrodynamic conditions have a significant impact on the biofilm lifecycle. Not well understood is the fact that biofilms, in return, also affect the flow pattern. A decade ago, it was already shown experimentally that under fast flows, biofilm streamers form and oscillate with large amplitudes. This work is a first attempt to answer the questions on the mechanisms behind the oscillatory movement of the streamers, and whether this movement together with the special streamlined form of the streamers, have both a physical and biological benefit for biofilms. In this study, a state of the art two‐dimensional fluid–structure interaction model of biofilm streamers is developed, which implements a transient coupling between the fluid and biofilm mechanics. Hereby, it is clearly shown that formation of a Kármán vortex street behind the streamer body is the main source of the periodic oscillation of the streamers. Additionally it is shown that the formation of streamers reduces the fluid forces which biofilm surface experiences. Biotechnol. Bioeng. 2010; 105: 600–610. © 2009 Wiley Periodicals, Inc.
Comparison of Micromixing Models for Calculation of the Chemical Reaction Rate in Homogeneous Turbulent Flow
Authors: Chorny A.
Published: September 2009

Turbulent mixing with a single second‐order isothermal reaction in a homogeneous flow is considered. A mixing model is stated using the probability density function (PDF) equation method and the concepts of mixture fraction and progress variable. Different micromixing models are compared. With the interaction exchange mean/linear square mean estimation (IEM/LSME) model, the time variation of the mixture fraction PDF contradicts the physical representation of mixing. The Langevin model describes mixing from the segregating state to the homogeneous state of a mixture. The PDF model proves to be two‐mode at intermediate mixing stages. This is also true for the multi‐zone PDF model. As compared to the multi‐zone PDF model, others reveal higher averaged progress variables over the entire time range and at all Damköhler number values. Such a difference is made by the approximations for the averaged reaction rate that should be allowed for in the modeling of turbulent mixing with chemical reaction.
A Microfluidic Approach for a Continuous Crystallization of Drug Carrier Nanoparticles
Authors: Jasch K. , Barth N. , Fehr S. , Bunjes H. , Augustin W. , Scholl S.
Published: September 2009

Solid lipid nanoparticles (SLN) as a new generation of drug carrier systems for pharmaceutical applications are currently under intensive investigation. They can be prepared by melt‐homogenization of a matrix lipid in surfactant‐containing aqueous media. In the corresponding production sequence, the crystallization of the resulting lipid droplets to solid nanoparticles is a crucial step for reproducible product properties. Hitherto, melt crystallization in these dispersions is usually performed in a batchwise process under poorly defined cooling conditions, without much regard to the well‐known aspects of heat transfer, homogeneity in the product mixture, and precise process control. In addition, these setups often only allow the application of low cooling rates. The use of high, well‐defined cooling rates would, however, offer very interesting new possibilities for the manufacturing of such drug carrier systems. Due to their small volumes and superior heat and mass transfer performance, microfluidic devices ensure a precise setting and control of the optimum process conditions. In this study, a microfluidic process for the continuous melt crystallization of SLN suspensions is established, allowing for high and well‐defined cooling rates. For various cooling rates, the crystallized SLN were analyzed by differential scanning calorimetry, X‐ray diffraction, laser diffraction, and photon correlation spectroscopy. The samples were also analyzed after well‐defined storage times in order to investigate the stability of the suspensions.
Modulation of Excited‐State Proton Transfer of 2‐(2′‐Hydroxyphenyl)benzimidazole in a Macrocyclic Cucurbit[7]uril Host Cavity: Dual Emission Behavior and pKa Shift
Authors: Shaikh Mhejabeen , Dutta Choudhury Sharmistha , Mohanty Jyotirmayee , Bhasikuttan Achikanath C. , Nau Werner M. , Pal Haridas
Published: September 2009

The effect of the macrocyclic host, cucurbit[7]uril (CB7), on the photophysical properties of the 2‐(2′‐hydroxyphenyl)benzimidazole (HPBI) dye have been investigated in aqueous solution by using ground‐state absorption and steady‐state and time‐resolved fluorescence measurements. All three prototropic forms of the dye (cationic, neutral, and anionic) form inclusion complexes with CB7, with the largest binding constant found for the cationic form (K≈2.4×106 M−1). At pH≈4, the appearance of a blue emission band upon excitation of the HPBI cation in the presence of CB7 indicates that encapsulation into the CB7 cavity retards the deprotonation process of the excited cation, and hence reduces its subsequent conversion to the keto form. Excitation of the neutral form (pH≈8.5), however, leads to an increase in the keto form fluorescence, indicating an enhanced excited‐state intramolecular proton‐transfer process for the encapsulated dye. In both the ground and excited states, the two pKa values of the HPBI dye show upward shifts in the presence of CB7. The prototropic equilibrium of the CB7‐complexed dye is represented by a six‐state model, and the pH‐dependent changes in the binding constants have been analyzed accordingly. It has been observed that the calculated pKa values using this six‐state model match well with the values obtained experimentally. The changes in the pKa values in the presence of CB7 have been corroborated with the modulation of the proton‐transfer process of the dye within the host cavity.
Theoretical Study of the Cycloaddition Reaction of a Tungsten‐Containing Carbonyl Ylide
Authors: Ito Kazuta , Hara Yoshihiro , Mori Seiji , Kusama Hiroyuki , Iwasawa Nobuharu
Published: September 2009

The [3+2] cycloaddition reaction of a tungsten‐containing carbonyl ylide with methyl vinyl ether and the insertion reactions of the nonstabilized carbene complex intermediates produced have been investigated through the use of B3LYP density functional theory. The [3+2] cycloaddition reaction of the tungsten‐containing carbonyl ylide has been proven to proceed concertedly, reversibly, and with high endo selectivity. The intermolecular SiH insertion reactions of the carbene complex intermediates have been proven to be favored over the intramolecular CH insertion, in good agreement with experimental results. Moreover, the kinetic endo/exo ratio of the [3+2] cycloaddition reaction has been shown to determine the endo/exo selectivity of the SiH insertion products. In addition, secondary orbital interactions involving the benzene ring and the carbonyl ligand on the metal center have turned out to strongly influence the high endo selectivity of the [3+2] cycloaddition reaction with methyl vinyl ether.
The Stereochemistry of 1,2,3‐Triols Revealed by 1H NMR Spectroscopy: Principles and Applications
Authors: Freire Félix , Lallana Enrique , Quiñoá Emilio , Riguera Ricardo
Published: September 2009

The conformational compositions of the tris(α‐methoxy‐α‐phenylacetic acid) ester derivatives of 1,2,3‐prim,sec,sec‐triols are presented. These conformations have been determined by theoretical and experimental data (i.e., energy‐ and chemical‐shift calculations, circular dichroism (CD) experiments, coupling‐constant analysis, enantioselective deuteration experiments, and low‐temperature NMR spectroscopic studies). A detailed analysis of the anisotropic effects due to the most significant conformers in the 1H NMR spectra supported the correlation between the 1H NMR spectra (ΔδRS value of H(3′) and |Δ(ΔδRS)| parameters) and the absolute configuration of the substrate. The study also allows the identification of the pro‐R and pro‐S methylene protons from their vicinal coupling constants and relative chemical shifts.
Influence of carbonisation on selected engineering properties of carbon resin electrodes for electrochemical treatment of wastewater
Authors: Oke Isaiah Adesola
Published: September 2009

In this study, effects of selected factors on selected properties of carbon resin electrodes (CRE) have been investigated. CRE were developed from used dry cells and resin using non‐heat‐treatment process. Selected properties (density, electrical resistance, microstructure, hygroscopy, stability moisture content, compressive and flexural strength) of the electrodes were monitored and effects of carbonisation temperature, carbon particle size, and compaction pressure on these properties were studied.

The study revealed that the density of CRE was in the range of 1.33 to 1.59 g/cm3, compressive strength ranged from 36.56 to 43.81 MN/m2, flexural strength, moisture content, and swelling were in the range of 6.76 to 8.10 MN/m2, 0.84–0.93%, and 6.04–9.30%, respectively. In all cases electrical resistance and density of CRE decreased with increasing carbonisation temperature at various operational factors (particle size, compacting pressure, and percentage of the resin used). Also, it was revealed that carbonisation of CRE from 30 to 220°C reduced specific electrical resistance and density from 1.85 to 1.29 × 10−1 Ω/cm and from 1.35 to 1.24 g/cm3, respectively, but carbonisation temperature had no significant effect on wetness, compressive and flexural strength, stability, and moisture content of the electrodes. Estimated costs revealed that cost of producing CRE was cheaper ($13.25/m) than that of heat‐treated electrodes ($33.33/m).

It was concluded that carbonisation temperature, particle size, compacting pressure, and percentage of the resin used are important factors in the development of CRE with lower specific electrical resistance.
Vibrational, optical and microhardness studies of trimethoprim DL ‐malate
Authors: Franklin S. , Bhuvana K. P. , Balasubramanian T.
Published: September 2009

Trimethoprim malate, an organic crystal, has been synthesized using slow evaporation method from its aqueous solution. Structural, optical and the mechanical properties of the grown crystal have been investigated by various characterization techniques which include FTIR spectra, single crystal XRD, UV‐Vis spectra and Vickers microhardness testing. The structure of the compound predicted by analysing the recorded FTIR spectrum compliments the structure determined using single crystal X‐ray diffraction. Single crystal X‐ray diffraction study reveals that the crystals are monoclinic [P21/c, a=12.9850 Å, b=9.3038 Å, c=15.6815 Å and β=111.065°]. The UV‐Vis spectrum exhibits maximum transparency (98%) for a wide range suggesting the suitability of the title compound for optical applications. The optical constants have been calculated and illustrated graphically. Microhardness tests have been performed on the cystal under study and the Vicker hardness number has been calculated. The work hardening coefficient is found to be 2.85 which suggest that the crystal belongs to the family of soft materials. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A simple glucose reduction route for the synthesis of sheet‐like copper dendrites
Authors: Ni Yonghong , Wang Biao , Liu Rong , Hong Jianming
Published: September 2009

In the current paper we designed a simple glucose reduction route for synthesis of sheet‐like Cu dendrites on a high yield, using CuSO4 as the starting material. The reaction was carried out at 180 °C for 18 h in the absence of any structure‐directing agent. The product was characterized by X‐ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and electron diffraction (ED). Some factors influencing the shapes of Cu microcrystals, including the reaction temperature, time, and the concentration of the starting CuSO4, were investigated. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Contribution to the study of elastic properties of KGd(WO4)2:Er3+ single crystals by Brillouin spectroscopy
Authors: Kasprowicz D. , Trzaskowska A. , Majchrowski A. , Michalski E. , Drozdowski M. , Mielcarek S.
Published: September 2009

In this paper we present the study of the acoustic phonons propagating in Er3+‐doped KGd(WO4)2 single crystals by Brillouin spectroscopy. For the investigated crystals the velocities of the longitudinal and transverse acoustic phonons [100], [010], [001], [101] and [110] have been determined. Moreover, the values of the elastic constants: C22, C44 and C66 of Er3+‐doped KGd(WO4)2 single crystals have been estimated. It was revealed that the presence of the Er3+‐ions in KGd(WO4)2 crystals, for the used doping concentration 1 at% does not influence their elastic properties. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Green fiber lasers: An alternative to traditional DPSS green lasers for flow cytometry
Authors: Telford William G. , Babin Sergey A. , Khorev Serge V. , Rowe Stephen H.
Published: September 2009

Green and yellow diode‐pumped solid‐state (DPSS) lasers (532 and 561 nm) have become common fixtures on flow cytometers, due to their efficient excitation of phycoerythrin (PE) and its tandems, and their ability to excite an expanding array of expressible red fluorescent proteins. Nevertheless, they have some disadvantages. DPSS 532‐nm lasers emit very close to the fluorescein bandwidth, necessitating optical modifications to permit detection of fluorescein and GFP. DPSS 561‐nm lasers likewise emit very close to the PE detection bandwidth and also cause unwanted excitation of APC and its tandems, requiring high levels of crossbeam compensation to reduce spectral overlap into the PE tandems. In this article, we report the development of a new generation of green fiber lasers that can be engineered to emit in the range between 532 and 561 nm. A 550‐nm green fiber laser was integrated into both a BD LSR II™ cuvette and FACSVantage DiVa™ jet‐in‐air cell sorter. This laser wavelength avoided both the fluorescein and PE bandwidths and provided better excitation of PE and the red fluorescent proteins DsRed and dTomato than a power‐matched 532 nm source. Excitation at 550 nm also caused less incidental excitation of APC and its tandems, reducing the need for crossbeam compensation. Excitation in the 550 nm range, therefore, proved to be a good compromise between 532‐ and 561‐nm sources. Fiber laser technology is, therefore, providing the flexibility necessary for precisely matching laser wavelengths to our flow cytometry applications. Published 2009 Wiley‐Liss, Inc.
Flow cytometry and the stability of phycoerythrin‐tandem dye conjugates
Authors: Hulspas Ruud , Dombkowski David , Preffer Frederic , Douglas Derick , Kildew‐Shah Brian , Gilbert John
Published: September 2009

Routine clinical flow cytometric procedures demand rigorous, simple, and reproducible procedures for spectral compensation. The current, often laborious, spectral compensation procedures are the result of variability in instrument settings, instrument performance, and variability in reagents. In particular, the use of tandem dye conjugates necessitates elaborate spectral compensation procedures that need to be applied frequently. Manufacturer, lot number, and handling procedures are considered the key aspects affecting the fluorescence characteristics of tandem dyes. A better understanding of how specific conditions affect the variability in emission spectra of tandem dyes can lead to a considerable increase in reliability of measurements and a potential simplification of setup procedures for routine, clinical flow cytometry. We investigated the effect of light exposure, handling, and storage conditions on the fluorescence characteristics of some common phycoerythrin tandem fluorochromes. In general, PE‐Cy5 showed the lowest degradation rates, whereas PE‐Cy7 showed the highest. During storage, long‐term degradation rates were lowest for reagents packaged using an extra light protective approach. Under these conditions, a degradation rate of 0.9%/month of a PE‐Cy7 conjugate decreased to 0.3%/month. As degradation rates were minimized, we studied the effect of slow degradation of a set of tandem dye conjugates on compensation matrix values over several months. Finally, we explored the effect of slow degradation on flow cytometric analysis using the same compensation settings for extended periods for an analysis template with preset regions and gating strategies. © 2009 International Society for Advancement of Cytometry
Selective interaction between Trf3 and Taf3 required for early development and hematopoiesis
Authors: Hart Daniel O. , Santra Manas K. , Raha Tamal , Green Michael R.
Published: September 2009

In zebrafish, TATA‐box‐binding protein (TBP)‐related factor 3, Trf3, is required for early development and initiation of hematopoiesis, and functions by promoting expression of a single target gene, mespa. Recent studies have shown that in murine muscle cells, TRF3 interacts with the TBP‐associated factor TAF3. Here we investigate the role of Taf3 in zebrafish embryogenesis. We find that like Trf3‐depleted zebrafish embryos, Taf3‐depleted embryos exhibit multiple developmental defects and fail to undergo hematopoiesis. Both Trf3 and Taf3 are selectively bound to the mespa promoter and are required for mespa expression. Significantly, Taf3 interacts with Trf3 but not Tbp, and a Trf3 mutant that disrupts this interaction fails to support mespa transcription, early development, and hematopoiesis. Thus, a selective interaction between Trf3 and Taf3 is required for early zebrafish development and initiation of hematopoiesis. Finally, we provide evidence that TRF3 and TAF3 are also required for hematopoiesis initiation in the mouse. Developmental Dynamics 238:2540–2549, 2009. © 2009 Wiley‐Liss, Inc.
A soft X‐ray and gamma‐ray source using laser and electron beams
Authors: Miyamoto Shuji , Amano Sho , Inoue Takahiro , Mochizuki Takayasu
Published: September 2009

Soft X‐ray and gamma‐ray beam sources are developed by using laser and high‐energy electron beams. Laser plasma soft X‐ray source is a cryogenic Xe target irradiated by a high average power (>100 W) and high peak power (30 MW, 0.3 J/10 ns) laser. A conversion efficiency from the laser energy to the soft X‐ray (70 to 200 eV) energy of 22% was achieved. Laser Compton gamma‐ray source on a synchrotron radiation facility, New SUBARU, is a new quasi‐monochromatic high‐energy photon beam. The world's highest class gamma‐ray flux of more than 106 photons/s is generated at a photon energy range of 6 to 17 MeV. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 92(10): 13–23, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10134
Counterion Effects on the Mesomorphic Properties of Chiral Imidazolium and Pyridinium Ionic Liquids
Authors: Kohnen Gilles , Tosoni Martin , Tussetschläger Stefan , Baro Angelika , Laschat Sabine
Published: September 2009

Novel calamitic N‐methylimidazolium and pyridinium salts with modified citronellyl side‐chains and various counterions 3–14 have been synthesised by utilising the commercially available (R)‐citronellol (15) as the starting material. Differential scanning calorimetry (DSC), polarising optical microscopy (POM) and temperature‐dependent X‐ray diffraction studies revealed smectic A (SmA) mesophases for all the series. 1H NMR studies of the N‐methylimidazolium salts have shown that there is a correlation between the mesophase dependence on the counterion and the counterion‐dependent chemical shifts of the acidic 2‐H proton.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthesis and Property Studies of Cyclotrisazobenzenes
Authors: Reuter Raphael , Hostettler Nik , Neuburger Markus , Wegner Hermann A.
Published: September 2009

Azobenzenophanes are fascinating macrocycles, which are of special interest due to their unique photochromic behavior. Cyclotrisazobenzenes2(R = H, Br,tBu) were prepared to probe how much strain the photoisomerization of the azobenzene motive can tolerate. The macrocycles were synthesized in an overall yield of 10–20 % fromortho‐phenylenediamine (6). Solid‐state structures of cyclotrisazobenzenes2aand2bwere obtained. Irradiation under various conditions did not induce any isomerization.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Fabrication of Nanoporous Copper Film for Electrochemical Detection of Glucose
Authors: Sattayasamitsathit Sirilak , Thavarungkul Panote , Thammakhet Chongdee , Limbut Warakorn , Numnuam Apon , Buranachai Chittanon , Kanatharana Proespichaya
Published: September 2009

A nanoporous copper film was fabricated on a copper wire by electrodeposition of copper/zinc alloy and chemically etching of zinc. The surface morphology was investigated by SEM. When applied to detect glucose in an amperometric flow injection system the porous copper electrode provided 12 times higher sensitivity than solid copper. It could be continuously used up to 50 times (%RSD=5.7). Different preparations of the porous film provided reproducible responses (P<0.05). Detection of glucose in E. coli cultivation medium compared well with spectrophotometric technique (P<0.05). This simple technique can produce a nanoporous electrode with good performances and can easily be applied to other metals and analytes.
A parametric study of seismic behavior of roller seismic isolation bearings for highway bridges
Authors: Ou Yu‐Chen , Song Jianwei , Lee George C.
Published: September 2009

A roller seismic isolation bearing is proposed for use in highway bridges. The bearing utilizes a rolling mechanism to achieve seismic isolation and has a zero post‐elastic stiffness under horizontal ground motions, a self‐centering capability, and unique friction devices for supplemental energy dissipation. The objectives of this research are to investigate the seismic behavior of the proposed bearing using parametric studies (1) with nonlinear response history analysis and (2) with equivalent linear analysis according to the AASHTO guide specifications, and by comparing the results from both analysis methods (3) to evaluate the accuracy of the AASHTO equivalent linear method for predicting the peak displacement of the proposed bearing during an earthquake. Twenty‐eight ground motions are used in the studies. The parameters examined are the sloping angle of the intermediate plate of the bearing, the amount of friction force for supplemental energy dissipation, and the peak ground acceleration levels of the ground motions. The peak displacement and base shear of the bearing are calculated. Results of the studies show that a larger sloping angle does not reduce the peak displacement for most of the parametric combinations without friction devices. However, for parametric combinations with friction devices, it allows for the use of a higher friction force, which effectively reduces the peak displacement, while keeping a self‐centering capability. The AASHTO equivalent linear method may underestimate the peak displacement by as much as 40%. Vertical ground motions have little effect on the peak displacement, but significantly increase the peak base shear. Copyright © 2009 John Wiley & Sons, Ltd.
Adjoint‐based design of shock mitigation devices
Authors: Stück Arthur , Camelli Fernando F. , Löhner Rainald
Published: September 2009

Unsteady Euler and adjoint Euler solvers have been combined in order to aid in the design of shock mitigation devices. The flowfield is integrated forward in time and stored. The adjoint is then integrated going backwards in time, restoring and interpolating the saved Euler solution to the current point in time. The gradient is obtained from a surface integral formulation during the adjoint run. Comparisons of adjoint‐based and finite‐differencing gradients for different verification cases show less than 10% deviation. The results obtained indicate that this is a very cost‐effective way to obtain the gradients of an objective function with respect to surface design changes. Moreover, as the sensitivity information is determined over a complete surface, the procedure provides considerable insight, and can efficiently facilitate the design of shock mitigation devices such as architecturally appealing blast walls. Copyright © 2009 John Wiley & Sons, Ltd.
Disorder‐specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention‐deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder
Authors: Rubia Katya , Cubillo Ana , Smith Anna B. , Woolley James , Heyman Isobel , Brammer Michael J.
Published: September 2009

Background:

Inhibitory dysfunction is a key behavioral and cognitive phenotype of attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). Both disorders show neuropsychological deficits and fronto‐striatal dysfunction during tasks of motor response inhibition and cognitive flexibility. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between adolescents with ADHD and those with OCD to identify disorder‐specific neurofunctional markers that distinguish these two inhibitory disorders.

Methods:

Event‐related fMRI was used to compare brain activation between 20 healthy boys, 18 (Stop task) or 12 boys (Switch task) with ADHD, and 10 boys with OCD during a tracking Stop task that measures inhibition and stopping failure and during a visual–spatial switching task measuring cognitive flexibility.

Results:

Both patient groups shared brain dysfunction compared to healthy controls in right orbitofrontal (successful inhibition) and left dorsolateral prefrontal cortices (failed inhibition). Right inferior prefrontal dysfunction, however, was disorder‐specific to ADHD during both tasks. Left inferior prefrontal dysfunction during the Switch task was significant in children with ADHD relative to controls, but only reached a trend in patients with OCD. Patients with ADHD furthermore showed disorder‐specific dysfunction in left basal ganglia and cingulate gyrus during the Switch task.

Conclusions:

Patients with ADHD compared to those with OCD have both common and distinct dysfunctions during inhibitory control. The most consistently reported functional abnormality in children with ADHD in right inferior prefrontal cortex during inhibitory control appears to be disorder‐specific when compared to patients with OCD and may be a specific neurofunctional biomarker of ADHD. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
The Iowa Gambling Task in fMRI images
Authors: Li Xiangrui , Lu Zhong‐Lin , D'Argembeau Arnaud , Ng Marie , Bechara Antoine
Published: September 2009

The Iowa Gambling Task (IGT) is a sensitive test for the detection of decision‐making impairments in several neurological and psychiatric populations. Very few studies have employed the IGT in functional magnetic resonance imaging (fMRI) investigations, in part, because the task is cognitively complex. Here we report a method for exploring brain activity using fMRI during performance of the IGT. Decision‐making during the IGT was associated with activity in several brain regions in a group of healthy individuals. The activated regions were consistent with the neural circuitry hypothesized to underlie somatic marker activation and decision‐making. Specifically, a neural circuitry involving the dorsolateral prefrontal cortex (for working memory), the insula and posterior cingulate cortex (for representations of emotional states), the mesial orbitofrontal and ventromedial prefrontal cortex (for coupling the two previous processes), the ventral striatum and anterior cingulate/SMA (supplementary motor area) for implementing behavioral decisions was engaged. These results have implications for using the IGT to study abnormal mechanisms of decision making in a variety of clinical populations. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Resting state and task‐induced deactivation: A methodological comparison in patients with schizophrenia and healthy controls
Authors: Mannell Maggie V. , Franco Alexandre R. , Calhoun Vince D. , Cañive Jose M. , Thoma Robert J. , Mayer Andrew R.
Published: September 2009

Changes in the default mode network (DMN) have been linked to multiple neurological disorders including schizophrenia. The anticorrelated relationship the DMN shares with task‐related networks permits the quantification of this network both during task (task‐induced deactivations: TID) and during periods of passive mental activity (extended rest). However, the effects of different methodologies (TID vs. extended rest) for quantifying the DMN in the same clinical population are currently not well understood. Moreover, several different analytic techniques, including independent component analyses (ICA) and seed‐based correlation analyses, exist for examining functional connectivity during extended resting states. The current study compared both methodologies and analytic techniques in a group of patients with schizophrenia (SP) and matched healthy controls. Results indicated that TID analyses, ICA, and seed‐based correlation all consistently identified the midline (anterior and posterior cingulate gyrus) and lateral parietal cortex as core regions of the DMN, as well as more variable involvement of temporal lobe structures. In addition, SP exhibited increased deactivation during task, as well as decreased functional connectivity with frontal regions and increased connectivity with posterior and subcortical areas during periods of extended rest. The increased posterior and reduced anterior connectivity may partially explain some of the cognitive dysfunction and clinical symptoms that are frequently associated with schizophrenia. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Real‐time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake subjects
Authors: Macefield Vaughan G. , Henderson Luke A.
Published: September 2009

To understand the central neural processes involved in blood pressure regulation we recorded muscle sympathetic nerve activity (MSNA) via a tungsten microelectrode in the common peroneal nerve while performing functional magnetic resonance imaging (fMRI) of the brainstem at 3T. Blood oxygen level dependent (BOLD) changes in signal intensity were measured over 4 s every 8 s (200) volumes; MSNA was recorded during the previous 4 s epoch, which takes into account peripheral conduction delays along unmyelinated axons and neurovascular coupling delays. Analysis of temporal coupling between BOLD signal intensity and nerve signal intensity revealed sites in which the two signals covaried, but only in the medulla. Because scans were conducted in a caudorostral direction, we could constrain the analysis to the medulla by only examining the first 1 s of the fMRI and nerve signals. Increases in MSNA were associated with robust bilateral increases in signal intensity in the dorsolateral region of the medulla that corresponds to the human equivalent of the rostal ventrolateral medulla (RVLM). Reciprocal decreases in signal intensity occurred in the regions of the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM). Group analysis also revealed increases in signal intensity in the caudal pressor area (CPA), medullary raphé (MR), and dorsal motor nucleus of the vagus (DMX). We have shown for the first time that this combined approach of recording sympathetic neural activity and fMRI provides real‐time imaging of the neural processes responsible for the generation of sympathetic nerve activity in awake human subjects. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Experimental hyperthyroidism in rats increases the expression of the ubiquitin ligases atrogin‐1 and MuRF1 and stimulates multiple proteolytic pathways in skeletal muscle
Authors: O'Neal Patrick , Alamdari Nima , Smith Ira , Poylin Vitaliy , Menconi Michael , Hasselgren Per‐Olof
Published: September 2009

Muscle wasting is commonly seen in patients with hyperthyroidism and is mainly caused by stimulated muscle proteolysis. Loss of muscle mass in several catabolic conditions is associated with increased expression of the muscle‐specific ubiquitin ligases atrogin‐1 and MuRF1 but it is not known if atrogin‐1 and MuRF1 are upregulated in hyperthyroidism. In addition, it is not known if thyroid hormone increases the activity of proteolytic mechanisms other than the ubiquitin–proteasome pathway. We tested the hypotheses that experimental hyperthyroidism in rats, induced by daily intraperitoneal injections of 100 µg/100 g body weight of triiodothyronine (T3), upregulates the expression of atrogin‐1 and MuRF1 in skeletal muscle and stimulates lysosomal, including cathepsin L, calpain‐, and caspase‐3‐dependent protein breakdown in addition to proteasome‐dependent protein breakdown. Treatment of rats with T3 for 3 days resulted in an approximately twofold increase in atrogin‐1 and MuRF1 mRNA levels. The same treatment increased proteasome‐, cathepsin L‐, and calpain‐dependent proteolytic rates by approximately 40% but did not influence caspase‐3‐dependent proteolysis. The expression of atrogin‐1 and MuRF1 remained elevated during a more prolonged period (7 days) of T3 treatment. The results provide support for a role of the ubiquitin–proteasome pathway in muscle wasting during hyperthyroidism and suggest that other proteolytic pathways as well may be activated in the hyperthyroid state. J. Cell. Biochem. 108: 963–973, 2009. © 2009 Wiley‐Liss, Inc.
Purification and characterization of heparan sulfate from human primary osteoblasts
Authors: Murali Sadasivam , Manton Kerry J. , Tjong Vinalia , Su Xiaodi , Haupt Larisa M. , Cool Simon M. , Nurcombe Victor
Published: September 2009

Heparan sulfate (HS) is a linear, highly variable, highly sulfated glycosaminoglycan sugar whose biological activity largely depends on internal sulfated domains that mediate specific binding to an extensive range of proteins. In this study we employed anion exchange chromatography, molecular sieving and enzymatic cleavage on HS fractions purified from three compartments of cultured osteoblasts—soluble conditioned media, cell surface, and extracellular matrix (ECM). We demonstrate that the composition of HS chains purified from the different compartments is structurally non‐identical by a number of parameters, and that these differences have significant ramifications for their ligand‐binding properties. The HS chains purified of conditioned medium had twice the binding affinity for FGF2 when compared with either cell surface or ECM HS. In contrast, similar binding of BMP2 to the three types of HS was observed. These results suggest that different biological compartments of cultured cells have structurally and functionally distinct HS species that help to modulate the flow of HS‐dependent factors between the ECM and the cell surface. J. Cell. Biochem. 108: 1132–1142, 2009. © 2009 Wiley‐Liss, Inc.
Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation
Authors: Yao Yu‐Hua , Dai Qi , Li Ling , Nan Xu‐Ying , He Ping‐An , Zhang Yao‐Zhou
Published: September 2009

A (two‐dimensional) 2D graphical representation of protein sequences based on six physicochemical properties of amino acids is outlined. The numerical characterization of protein graphs is given as descriptors of protein sequences. It is not only useful for comparative study of proteins but also for encoding innate information about the structure of proteins. The coefficient of determination is proposed as a new similarity/dissimilarity measure. Finally, a simple example is taken to highlight the behavior of the new similarity/dissimilarity measure on protein sequences taken from the ND6 (NADH dehydrogenase subunit 6) proteins for eight different species. The results demonstrate the approach is convenient, fast, and efficient. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Controlled systemic release of interleukin‐12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas
Authors: Tevz Gregor , Kranjc Simona , Cemazar Maja , Kamensek Urska , Coer Andrej , Krzan Mojca , Vidic Suzana , Pavlin Darja , Sersa Gregor
Published: September 2009

Background

The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)‐12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side‐effects of IL‐12 gene therapy, the objective was to achieve the controlled release of IL‐12 after intramuscular gene electrotransfer.

Methods

Gene electrotransfer of the plasmid pORF‐mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL‐12 was monitored in the serum of mice after carrying out two sets of intramuscular IL‐12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL‐12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X‐rays, was evaluated on subcutaneous SA‐1 and LPB tumors, as well as on lung metastases.

Results

A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL‐12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3‐fold was determined. The amount of circulating IL‐12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid.

Conclusions

The present study demonstrates the feasibility of treatment by IL‐12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.
An emerging research agenda for investigative interviewing: hypotheses from the narrative action system
Authors: Youngs Donna , Canter David
Published: September 2009

The present issue of JIP‐OP brings together an intriguing range of papers that cover a wide range of aspects of testimony and aspects of investigative interviewing. They show how the considerations of how testimony is obtained is broadening out from the memory improvement strategies that once dominated this area with attempts to detect deception, to cover many aspects of how testimony is obtained. This draws attention to the need for more careful examination of the variations in testimony eliciting processes that will be responsive to differences in context and crime. A research agenda is therefore proposed that draws on developments in the understanding of psychological differences between crimes. This research would study the relationship between the psychological processes underpinning offence actions and the interview behaviour of suspects or witnesses. With regard to suspects, recent developments in the modelling of offence style have indicated a narrative basis (narrative action system model) for understanding the patterns of offence actions and the perpetrator's psychological background and characteristics that can be inferred from these. It is therefore suggested that the Hero's Quest, Professional's Adventure, Revenger's Tragedy, and Victim's Irony offending narratives and the Object, Vehicle, and Person victim roles assigned within these, may provide a fruitful link to different patterns of interview behaviour, with consequent implications for approaches to interviewing. Copyright © 2009 John Wiley & Sons, Ltd.
Patellar tendon orientation and patellar tracking in male and female knees
Authors: Varadarajan Kartik M. , Gill Thomas J. , Freiberg Andrew A. , Rubash Harry E. , Li Guoan
Published: September 2009

Knowledge of patellofemoral joint biomechanics is important for understanding sex‐related dimorphism in patellofemoral pathologies and advancement of related treatments. We evaluated the hypotheses that sex differences exist in patellar tendon (PT) orientation and patellar tracking during weight‐bearing knee flexion and that they relate to differences in tibiofemoral rotation. The PT orientation and patellar tracking were measured in healthy subjects (18 male, 13 female) during weight‐bearing knee flexion, using magnetic resonance and dual fluoroscopic imaging. These data were analyzed for sex differences and correlation with previously reported tibiofemoral rotation data. The results indicated a significant effect of sex on PT orientation, particularly at low flexion angles. In females, the PT was oriented more anteriorly in the sagittal plane, more medially in the coronal plane, and showed greater external tilt in the transverse plane of the tibia (p < 0.05). Significant correlations between tibiofemoral rotation and PT orientation (p < 0.01) indicated that sex differences in coronal and transverse plane orientation of the PT relate to differences in tibiofemoral rotation. Patellar tracking did not show significant sex differences or correlation to tibiofemoral rotation. Further studies are warranted to determine implications for patellofemoral pathologies and treatments like total knee arthroplasty. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:322–328, 2010
Dermal fibroblast‐mediated BMP2 therapy to accelerate bone healing in an equine osteotomy model
Authors: Ishihara Akikazu , Zekas Lisa J. , Litsky Alan S. , Weisbrode Steven E. , Bertone Alicia L.
Published: September 2009

This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein‐2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb‐BMP2‐treated bone defects. On the histologic evaluation, the bone defects with DFb‐BMP2 implantation had greater formation of mature cartilage and bone nodules within the osteotomy gap and greater mineralization activity on osteotomy edges. Autologous DFbs were successfully isolated in high numbers by a skin biopsy, rapidly expanded without fastidious culture techniques, permissive to adenoviral vectors, and efficient at in vitro BMP2 protein production and BMP2‐induced osteogenic differentiation. This study demonstrated an efficacy and feasibility of DFb‐mediated BMP2 therapy to accelerate the healing of osteotomies. Skin cell‐mediated BMP2 therapy may be considered as a potential treatment for various types of fractures and bone defects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:403–411, 2010