bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective uptake of fexofenadine by Caco-2 cells as model intestinal epithelial cells
Authors: Togami Kohei , Tosaki Yuka , Chono Sumio , Morimoto Kazuhiro , Hayasaka Masataka , Tada Hitoshi
Published: October 2012

Objectives

Fexofenadine contains a chiral carbon in its chemical structure and is orally administered as a racemic mixture. This study evaluated the selective uptake of fexofenadine enantiomers by Caco-2 cells as a model of intestinal epithelial cells.

Methods

R(+)-fexofenadine or S(−)-fexofenadine was applied to Caco-2 cells, followed by incubation. After incubation, the amounts of fexofenadine enantiomers in cells were determined. The kinetic parameters for the uptake of fexofenadine enantiomers by Caco-2 cells were estimated using the Michaelis–Menten equation.

Key findings

The transporter-mediated uptake rate of R(+)-fexofenadine was 1.7-fold higher than that of S(−)-fexofenadine. The difference in transporter-mediated R(+)-fexofenadine and S(−)-fexofenadine uptake was completely diminished under ATP-depleted conditions and in the presence of organic anion transporter peptide (OATP) inhibitors. Also, a Dixon plot showed that each fexofenadine enantiomer was competitively inhibited by the other enantiomer. The ratio of R(+)-fexofenadine uptake to S(−)-fexofenadine uptake in the case of a racemic mixture was higher than that in the case of a single enantiomer.

Conclusion

This study suggested that the selective absorption of fexofenadine enantiomers by intestinal epithelial cells might have been due to the selective uptake mediated by OATPs and that the difference in intestinal absorption was enhanced with a racemic mixture.
Importance of Sinus Rhythm as Endpoint of Persistent Atrial Fibrillation Ablation
Authors: AMMAR SONIA , HESSLING GABRIELE , REENTS TILKO , PAULIK MARIA , FICHTNER STEPHANIE , SCHÖN PATRICK , DILLIER ROGER , KATHAN SUSANNE , JILEK CLEMENS , KOLB CHRISTOF , HALLER BERNHARD , DEISENHOFER ISABEL
Published: October 2012

Endpoint of Persistent AF Ablation. Background: The endpoint of persistent atrial fibrillation (AF) ablation is still a matter of debate. The purpose of this study was to evaluate if sinus rhythm (SR) as endpoint of persistent AF ablation has a better long‐term outcome compared to atrial tachycardia (AT) or AF at the end of the procedure.

Methods and Results: Between 2008 and 2011, 191 consecutive patients undergoing de novo catheter ablation for symptomatic persistent and long‐standing persistent AF using a sequential ablation approach (including pulmonary vein isolation, ablation of complex fractionated electrograms and linear lesions) were included in the study.

According to the result at the end of ablation procedure, patients were classified into 3 groups: patients with termination of AF into SR (Group 1, n = 62), patients with AT undergoing cardioversion (CV) (Group 2, n = 47), or patients with AF undergoing CV (Group 3, n = 82).

The primary endpoint was freedom from any atrial tachyarrhythmia off antiarrhythmic drugs at 12 months.

At 12 months, estimated proportions of patients free from any arrhythmia recurrence were 42% for Group 1, 13% for Group 2, and 25% for Group 3 (P = 0.002).

In a Cox regression analysis only termination into SR was associated with a lower risk of arrhythmia recurrence (HR: 0.62; P = 0.04).

Conclusion: If SR is achieved as endpoint of persistent and long‐standing persistent AF ablation using a sequential ablation approach it is associated with the highest long‐term single procedure success rate compared to AT or AF at the end of the procedure. (J Cardiovasc Electrophysiol, Vol. 24, pp. 388‐395, April 2013)
Neuroprotection by urate on 6‐OHDA‐lesioned rat model of Parkinson's disease: linking to Akt/GSK3β signaling pathway
Authors: Gong Li , Zhang Qi‐Lin , Zhang Ning , Hua Wen‐Yan , Huang Yi‐Xian , Di Ping‐Wei , Huang Tingting , Xu Xing‐Shun , Liu Chun‐Feng , Hu Li‐Fang , Luo Wei‐Feng
Published: October 2012

Higher plasma urate level is reported to be associated with a reduced risk and slower progression of Parkinson's disease (PD). In this study, we explored the effects of urate on dopaminergic neurons in nigrostriatal pathway in the 6‐hydroxydopamine (6‐OHDA) unilaterally lesioned rats. Uric acid (UA), when given twice daily at 200 mg/kg intraperitoneally for 10 consecutive days, elevated urate (the anionic form of UA) in plasma and striatum by 55% and 36.8%, respectively, as compared with vehicle group. This regimen of UA was found to ameliorate the behavioral deficits, dopaminergic neuron loss as well as dopamine depletion in the nigrostriatal system. Moreover, UA administration was capable of increasing glutathione level and superoxide dismutase activity while decreasing malondialdehyde accumulation in striatum. In addition, the phosphorylation of both protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) in the lesioned striata of 6‐OHDA‐lesioned rats was dramatically reduced as compared with sham‐operated rats. This reduction was attenuated in the Parkinsonian rats receiving UA treatment. Similarly, in vitro findings showed that UA alleviated the decrease in Akt activation and the increase in GSK3β activity caused by 6‐OHDA. Furthermore, neuroprotection by urate and its regulation on GSK3β phosphorylation at Ser9 was found to be abolished in the presence of PI3K inhibitor. Therefore, our findings demonstrated that urate was able to protect dopaminergic neurons in rat nigrostriatal pathway against the neurotoxicity of 6‐OHDA, and showed that its beneficial effects may be related to its regulation on Akt/GSK3β signaling.
Omega‐3 fatty acid eicospentaenoic acid attenuates MPP+‐induced neurodegeneration in fully differentiated human SH‐SY5Y and primary mesencephalic cells
Authors: Luchtman Dirk W. , Meng Qingjia , Wang Xiaofeng , Shao Di , Song Cai
Published: October 2012

Eicosapentaenoic acid (EPA), a neuroactive omega‐3 fatty acid, has been demonstrated to exert neuroprotective effects in experimental models of Parkinson's disease (PD), but the cellular mechanisms of protection are unknown. Here, we studied the effects of EPA in fully differentiated human SH‐SY5Y cells and primary mesencephalic neurons treated with MPP+. In both in‐vitro models of PD, EPA attenuated an MPP+‐induced reduction in cell viability. EPA also prevented the presence of electron‐dense cytoplasmic inclusions in SH‐SY5Y cells. Then, possible mechanisms of the neuroprotection were studied. In primary neurons, EPA attenuated an MPP+‐induced increase in Tyrosine‐related kinase B (TrkB) receptors. In SH‐SY5Y cells, EPA down‐regulated reactive oxygen species and nitric oxide. This antioxidant effect of EPA may have been mediated by its inhibition of neuronal NADPH oxidase and cyclo‐oxygenase‐2 (COX‐2), as MPP+ increased the expression of these enzymes. Furthermore, EPA prevented an increase in cytosolic phospholipase A2 (cPLA2), an enzyme linked with COX‐2 in the potentially pro‐inflammatory arachidonic acid cascade. Lastly, EPA attenuated an increase in the bax:bcl‐2 ratio, and cytochrome c release. However, EPA did not prevent mitochondrial enlargement or a decrease in mitochondrial membrane potential. This study demonstrated cellular mechanisms by which EPA provided neuroprotective effects in experimental PD.
Consumer‐Based Optimization of Blackberry, Blueberry and Concord Juice Blends
Authors: Lawless Lydia J. R. , Threlfall Renee T. , Meullenet Jean‐François , Howard Luke R.
Published: October 2012

The constant fight against aging increases the demand for products that have the potential to promote health. Dark‐pigmented fruits such as blackberries, blueberries and Concord grapes show potential to fulfill this demand. Four techniques (response surface, ideal point, desirability function and intuition) were used to optimize a mixture of blackberry, blueberry and Concord grape juice based on sensory and potential health properties. Participants (n = 108) evaluated 10 blending treatments for overall impression on the 9‐point verbal hedonic scale and ideal intensities of attributes on the ideal point scale. In a validation study (n = 78), the juice blend formulated using the desirability function solution (87% Concord + 13% blackberry) had the highest overall liking mean (7.6), although it was not statistically different from the ideal point solution (9% blackberry + 20% blueberry + 71% Concord) (7.0), the intuitive optimum (66% Concord + 34% blueberry) (6.9) or 100% Concord (7.3). When consumers were informed about the anthocyanin content of the juices, they were more likely to buy the three juice samples highest in anthocyanins and less likely to buy the two juice samples lowest in anthocyanins. This suggests that pursuing research that validates the health information and informing consumers of this information could have positive results in the marketplace.

Practical Applications

During product development, sensory properties are heavily emphasized as important factors in the final product. However, the impact of potential health properties on purchase intent and consumer liking should be considered. Approaches that investigated the role of both sensory properties and presence of potentially health beneficial compounds in product optimization are presented.
High gene flow on a continental scale in the polyandrous Kentish plover Charadrius alexandrinus
Authors: Küpper Clemens , Edwards Scott V. , Kosztolányi András , Alrashidi Monif , Burke Terry , Herrmann Philipp , Argüelles‐Tico Araceli , Amat Juan A. , Amezian Mohamed , Rocha Afonso , Hötker Hermann , Ivanov Anton , Chernicko Joseph , Székely Tamás
Published: October 2012

Gene flow promotes genetic homogeneity of species in time and space. Gene flow can be modulated by sex‐biased dispersal that links population genetics to mating systems. We investigated the phylogeography of the widely distributed Kentish plover Charadrius alexandrinus. This small shorebird has a large breeding range spanning from Western Europe to Japan and exhibits an unusually flexible mating system with high female breeding dispersal. We analysed genetic structure and gene flow using a 427‐bp fragment of the mitochondrial (mtDNA) control region, 21 autosomal microsatellite markers and a Z microsatellite marker in 397 unrelated individuals from 21 locations. We found no structure or isolation‐by‐distance over the continental range. However, island populations had low genetic diversity and were moderately differentiated from mainland locations. Genetic differentiation based on autosomal markers was positively correlated with distance between mainland and each island. Comparisons of uniparentally and biparentally inherited markers were consistent with female‐biased gene flow. Maternally inherited mtDNA was less structured, whereas the Z‐chromosomal marker was more structured than autosomal microsatellites. Adult males were more related than females within genetic clusters. Taken together, our results suggest a prominent role for polyandrous females in maintaining genetic homogeneity across large geographic distances.
Clinical and mycological features of onychomycosis in central Tunisia: a 22 years retrospective study (1986–2007)
Authors: Dhib I. , Fathallah A. , Yaacoub A. , Zemni R. , Gaha R. , Said M. B.
Published: October 2012

Onychomycosis is the most frequently encountered nail disease and may be difficult to diagnose and treat. The objective of this study was to determine the prevalence, the clinical and mycological characteristics of onychomycosis in central Tunisia. It is a retrospective study performed over a 22‐year period (1986–2007). It included 7151 patients (4709 women and 2442 men) with suspected fingernails and/or toenails onychomycosis. The patients were referred to the Mycology‐Parasitology Laboratory of Farhat Hached hospital in Sousse for mycological examination. Both direct microscopy and culture of the nail material were performed to diagnose and identify the causative fungal species. Onychomycosis was confirmed in 78.6% of investigated patients (5624/7151). The positivity rate was higher in women as compared with men. In both men and women, fingernails were most frequently involved than toenails. No significant relation was found between gender and toenails onychomycosis, whereas fingernails were frequently involved in women. As far as aetiological agents are considered, dermatophytes, yeast and moulds were responsible for 49.9%, 47.4% and 2.7% of onyxis cases respectively. In fingernail infections, yeast were the most frequent fungi (83.6%), Candida albicans being the leading species (51.6%). In contrast, in toenail infections, dermatophytes were more frequent (74.1%). Trichophyton rubrum was by far the dominant species (88.1%). Yeast were observed more frequently in women whereas dermatophytes were more common in men. Moulds were involved in 4.2% of cases. The most frequent species were Aspergillus sp. and Chrysosporium sp. Onychomycosis is a frequent disease in central Tunisia. T. rubrum is the predominant agent in toenails infection and yeast, mainly C. albicans, in fingernails onychomycosis.
Insincerity
Authors: Stokke Andreas
Published: October 2012

This paper argues for an account of insincerity in speech according to which an utterance is insincere if and only if it communicates something that does not correspond to the speaker's conscious attitudes. Two main topics are addressed: the relation between insincerity and the saying‐meaning distinction, and the mental attitude underlying insincere speech. The account is applied to both assertoric and non‐assertoric utterances of declarative sentences, and to utterances of non‐declarative sentences. It is shown how the account gives the right results for a range of cases.
Psychological morbidity in chronic orofacial pain and headaches
Authors: Yazdi M. , Yilmaz Z. , Renton T. , Page L.
Published: October 2012

Aims

The study aims to investigate the levels of anxiety and depression in patients experiencing orofacial pain and to explore similarities in psychological morbidity between patients experiencing chronic orofacial pain and those with chronic daily headaches. The study also aims to gain insight into the interference with functionality in chronic orofacial pain patients.

Materials and methods

The sample consisted of 150 new patients with chronic orofacial pain, 112 female and 38 male. Patients completed a retrospective facial pain questionnaire that included the Hospital Anxiety and Depression Scale (HADS), as well as the Brief Pain Inventory (BPI), to assess functionality interference. The chronic orofacial pain HADS were compared with HADS normative data and existing HADS data from a sample with chronic daily headache.

Results

Temporomandibular joint dysfunction was the most common diagnosis for chronic orofacial pain, affecting 75 patients. According to the BPI scores, patients mostly complained that the pain interfered with their enjoyment of life (49%), mood (44%) and sleep (44%), followed by general activity (39%), relationships with other people (35%) and work (34%). Both clinical HADS groups scored significantly higher than the normative group on the HADS (P < 0.001), while there were no statistical differences between the clinical groups.

Conclusion

Chronic orofacial pain can have a considerable detrimental effect on daily life and is associated with significantly greater levels of anxiety and depression than seen in general population samples. The levels of anxiety and depression seen in chronic orofacial pain patients were similar to the psychological morbidity found in patients with chronic daily headache.
SULTR3;1 is a chloroplast‐localized sulfate transporter in Arabidopsis thaliana
Authors: Cao Min‐Jie , Wang Zhen , Wirtz Markus , Hell Ruediger , Oliver David J. , Xiang Cheng‐Bin
Published: October 2012

Plants play a prominent role as sulfur reducers in the global sulfur cycle. Sulfate, the major form of inorganic sulfur utilized by plants, is absorbed and transported by specific sulfate transporters into plastids, especially chloroplasts, where it is reduced and assimilated into cysteine before entering other metabolic processes. How sulfate is transported into the chloroplast, however, remains unresolved; no plastid‐localized sulfate transporters have been previously identified in higher plants. Here we report that SULTR3;1 is localized in the chloroplast, which was demonstrated by SULTR3;1‐GFP localization, Western blot analysis, protein import as well as comparative analysis of sulfate uptake by chloroplasts between knockout mutants, complemented transgenic plants, and the wild type. Loss of SULTR3;1 significantly decreases the sulfate uptake of the chloroplast. Complementation of the sultr3;1 mutant phenotypes by expression of a 35S‐SULTR3;1 construct further confirms that SULTR3;1 is one of the transporters responsible for sulfate transport into chloroplasts.
Fluid Dynamics of a Transverse Jet Reactor for Zinc Aerosol Hydrolysis
Authors: Haltiwanger Nicodemus Julia , Davidson Jane H.
Published: October 2012

A new concept for control of the flow field, and thus particle yield, in an aerosol reactor designed for the hydrolysis of Zn in the two-step Zn/ZnO solar thermochemical cycle for hydrogen production is described and evaluated. For the hydrolysis step, much attention has been given to Zn nanoscale reacting aerosols for their potential to increase conversion to ZnO and because they enable a continuous, controllable process. The success of this continuous process depends on achieving high particle yields in the reactor. A key challenge is to control the flow field in aerosol reactors to keep the particles entrained in the flow without deposition on the reactor wall. The ability of a new reactor concept based on transverse jet fluid dynamics to control the flow field and rapidly cool the Zn vapor is investigated. In the transverse jet reactor, evaporated Zn entrained in an Ar carrier gas issues vertically into the horizontal tubular reactor through which cooler H2O and Ar flow. Particles are formed in the presence of steam at ~450 K. The trajectory of the jet is controlled via the effective velocity ratio, R, which is the square root of the ratio of the kinetic energy of the jet to that of the cross-flow. A computational fluid dynamics (CFD) model indicates that the trajectory of the jet can be controlled so that the majority of the Zn mass is directed down the center of the reactor, not near the reactor walls for R = 4.25 to R = 4.5. Experimentally, maximum particle yields of 93% of the mass entering the reactor are obtained at R = 4.5.
Two-Dimensional Mode I Crack Propagation in Saturated Ionized Porous Media Using Partition of Unity Finite Elements
Authors: Kraaijeveld F. , Huyghe J. M. , Remmers J. J. C. , de Borst R.
Published: October 2012

Shales, clays, hydrogels, and tissues swell and shrink under changing osmotic conditions, which may lead to failure. The relationship between the presence of cracks and fluid flow has had little attention. The relationship between failure and osmotic conditions has had even less attention. The aim of this research is to study the effect of osmotic conditions on propagating discontinuities under different types of loads for saturated ionized porous media using the finite element method (FEM). Discontinuous functions are introduced in the shape functions of the FEM by partition of unity method, independently of the underlying mesh. Damage ahead of the crack-tip is introduced by a cohesive zone model. Tensile loading of a crack in an osmoelastic medium results in opening of the crack and high pressure gradients between the crack and the formation. The fluid flow in the crack is approximated by Couette flow. Results show that failure behavior depends highly on the load, permeability, (osmotic) prestress and the stiffness of the material. In some cases it is seen that when the crack propagation initiates, fluid is attracted to the crack-tip from the crack rather than from the surrounding medium causing the crack to close. The results show reasonable mesh-independent crack propagation for materials with a high stiffness. Stepwise crack propagation through the medium is seen due to consolidation, i.e., crack propagation alternates with pauses in which the fluid redistributes. This physical phenomenon challenges the numerical scheme. Furthermore, propagation is shown to depend on the osmotic prestressing of the medium. This mechanism may explain the tears observed in intervertebral disks as degeneration progresses.
On the Shrinkage and Stiffening of a Cellulose Sponge Upon Drying
Authors: Rey Justine , Vandamme Matthieu
Published: October 2012

Everyone can observe the peculiar effect of water on a sponge: upon drying, a sponge shrinks and stiffens; it swells and softens upon wetting. In this work, we aim to explain and model this behavior by using the Biot–Coussy poromechanical framework. We measure the volume and the bulk modulus of sponges at different water contents. Upon drying, the volume of the sponge decreases by more than half and its bulk modulus increases by almost two orders of magnitude. We develop a partially saturated microporomechanical model of the sponge undergoing finite transformations. The model compares well with the experimental data. We show that about half of the stiffening of the sponge upon drying is due to geometrical nonlinearities induced by a closing of the pores under the action of capillary pressure. The other half of the stiffening can be explained by the nonlinear elastic properties of the cellulose material itself.
Modeling Hydroionic Transport in Cement-Based Porous Materials Under Drying-Wetting Actions
Authors: Li Kefei , Li Chunqiu
Published: October 2012

This paper investigates the hydroionic transport processes at the near surface of cement-based porous materials under external drying-wetting (D-W) actions. A basic multiphase model is retained and reviewed critically for moisture transport under D-W actions. The multiphase model fails to account for the substantial difference between moisture diffusivities during drying and wetting. The multiphase model is adapted for moisture transport under D-W actions through the respective mechanisms of moisture transport during drying and wetting. Together with the associated ionic transport, a global hydroionic model is established and the corresponding numerical scheme is developed to solve the near surface transport problem. Then, systematic experiments are performed on two concretes with high and low porosities for transport properties and hydroionic transport under D-W actions with pure water and salt solution. Experimental data validate the global model, while some fundamental aspects of hydroionic modeling are discussed.
Tortuosity and the Averaging of Microvelocity Fields in Poroelasticity
Authors: Souzanchi M. F. , Cardoso L. , Cowin S. C.
Published: October 2012

The relationship between the macro- and microvelocity fields in a poroelastic representative volume element (RVE) has not being fully investigated. This relationship is considered to be a function of the tortuosity: a quantitative measure of the effect of the deviation of the pore fluid streamlines from straight (not tortuous) paths in fluid-saturated porous media. There are different expressions for tortuosity based on the deviation from straight pores, harmonic wave excitation, or from a kinetic energy loss analysis. The objective of the work presented is to determine the best expression for tortuosity of a multiply interconnected open pore architecture in an anisotropic porous media. The procedures for averaging the pore microvelocity over the RVE of poroelastic media by Coussy and by Biot were reviewed as part of this study, and the significant connection between these two procedures was established. Success was achieved in identifying the Coussy kinetic energy loss in the pore fluid approach as the most attractive expression for the tortuosity of porous media based on pore fluid viscosity, porosity, and the pore architecture. The fabric tensor, a 3D measure of the architecture of pore structure, was introduced in the expression of the tortuosity tensor for anisotropic porous media. Practical considerations for the measurement of the key parameters in the models of Coussy and Biot are discussed. In this study, we used cancellous bone as an example of interconnected pores and as a motivator for this study, but the results achieved are much more general and have a far broader application than just to cancellous bone.
Measuring Dynamic In-Vivo Elbow Kinematics: Description of Technique and Estimation of Accuracy
Authors: McDonald Colin P. , Moutzouros Vasilios , Bey Michael J.
Published: October 2012

Background: The objectives of this study were to characterize the translational and rotational accuracy of a model-based tracking technique for quantifying elbow kinematics and to demonstrate its in vivo application. Method of Approach: The accuracy of a model-based tracking technique for quantifying elbow kinematics was determined in an in vitro experiment. Biplane X-ray images of a cadaveric elbow were acquired as it was manually moved through flexion-extension. The 3D position and orientation of each bone was determined using model-based tracking. For comparison, the position and orientation of each bone was also determined by tracking the position of implanted beads with dynamic radiostereometric analysis. Translations and rotations were calculated for both the ulnohumeral and radiohumeral joints, and compared between measurement techniques. To demonstrate the in vivo application of this technique, biplane X-ray images were acquired as a human subject extended their elbow from full flexion to full extension. Results: The in vitro validation demonstrated that the model-based tracking technique is capable of accurately measuring elbow motion, with reported errors averaging less than ±1.0 mm and ±1.0 deg. For the in vivo application, the carrying angle changed from an 8.3 ± 0.5 deg varus position in full flexion to an 8.4 ± 0.5 deg valgus position in full extension. Conclusions: Model-based tracking is an accurate technique for measuring in vivo, 3D, dynamic elbow motion. It is anticipated that this experimental approach will enhance our understanding of elbow motion under normal and pathologic conditions.
Negative oxygen ion formation in reactive magnetron sputtering processes for transparent conductive oxides
Authors: Welzel Thomas , Ellmer Klaus
Published: October 2012

Reactive d.c. magnetron sputtering in Ar/O2 gas mixtures has been investigated with energy-resolved mass spectrometry. Different metal targets (Mg, Ti, Zn, In, InSn, and Sn), which are of importance for transparent conductive oxide thin film deposition, have been used to study the formation of negative ions, mainly high-energetic O−, which are supposed to induce radiation damage in thin films. Besides their energy distribution, the ions have been particularly investigated with respect to their intensity in comparison of the different target materials. To realize the comparability, various calibration factors had to be introduced. After their application, major differences in the negative ion production have been observed for the target materials. The intensity, especially of O−, differs by about two orders of magnitude. It is shown that this difference results almost exclusively from ions that gain their energy in the target sheath. Those may gain additional energy from the sputtering process or reflection at the target. Low-energetic negative ions are, however, less affected by changes of the target material. The results concerning O− formation are discussed in term of the sputtering rate from the target and are compared to models for negative ion formation.
Cross-linking control during imprint for hybrid lithography
Authors: Dhima Khalid , Steinberg Christian , Möllenbeck Saskia , Mayer Andre , Wang Si , Scheer Hella-Christin
Published: October 2012

Hybrid lithography combining thermal nanoimprint with optical lithography is an effective means to prepare structures with differing geometries (nanometer, micrometer) over large areas, e.g., for sensor applications. For the realization of this technique, the suitability of photoresists for this process has to be investigated. In case of negative tone resists, the cross-linking induced or provided by exposure may be amplified in the imprint step due to heating times in the minute range. As cross-linking may impede the imprint, a subtle adjustment of the exposure dose with respect to the imprint temperature envisaged is required for successful processing. With an imprint temperature of 100 °C, good results for hybrid lithography could be obtained with two commercially available negative tone resists: ma-N 405 and ARN 4410. The latter could successfully be used for a subsequent liftoff. The best results were obtained when the resists were exposed before the imprint step.
Content‐based retrieval of brain tumor in contrast‐enhanced MRI images using tumor margin information and learned distance metric
Authors: Yang Wei , Feng Qianjin , Yu Mei , Lu Zhentai , Gao Yang , Xu Yikai , Chen Wufan
Published: October 2012

Purpose:

A content‐based image retrieval (CBIR) method for T1‐weighted contrast‐enhanced MRI (CE‐MRI) images of brain tumors is presented for diagnosis aid. The method is thoroughly evaluated on a large image dataset.

Methods:

Using the tumor region as a query, the authors’ CBIR system attempts to retrieve tumors of the same pathological category. Aside from commonly used features such as intensity, texture, and shape features, the authors use a margin information descriptor (MID), which is capable of describing the characteristics of tissue surrounding a tumor, for representing image contents. In addition, the authors designed a distance metric learning algorithm calledMaximum mean average Precision Projection (MPP) to maximize the smooth approximated mean average precision (mAP) to optimize retrieval performance.

Results:

The effectiveness of MID and MPP algorithms was evaluated using a brain CE‐MRI dataset consisting of 3108 2D scans acquired from 235 patients with three categories of brain tumors (meningioma, glioma, and pituitary tumor). By combining MID and other features, the mAP of retrieval increased by more than 6% with the learned distance metrics. The distance metric learned by MPP significantly outperformed the other two existing distance metric learning methods in terms of mAP. The CBIR system using the proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10 images were returned by the system. Compared with scale‐invariant feature transform, the MID, which uses the intensity profile as descriptor, achieves better retrieval performance.

Conclusions:

Incorporating tumor margin information represented by MID with the distance metric learned by the MPP algorithm can substantially improve the retrieval performance for brain tumors in CE‐MRI.
4D cone beam CT via spatiotemporal tensor framelet
Authors: Gao Hao , Li Ruijiang , Lin Yuting , Xing Lei
Published: October 2012

Purpose:

On‐board 4D cone beam CT (4DCBCT) offers respiratory phase‐resolved volumetric imaging, and improves the accuracy of target localization in image guided radiation therapy. However, the clinical utility of this technique has been greatly impeded by its degraded image quality, prolonged imaging time, and increased imaging dose. The purpose of this letter is to develop a novel iterative 4DCBCT reconstruction method for improved image quality, increased imaging speed, and reduced imaging dose.

Methods:

The essence of this work is to introduce the spatiotemporal tensor framelet (STF), a high‐dimensional tensor generalization of the 1D framelet for 4DCBCT, to effectively take into account of highly correlated and redundant features of the patient anatomy during respiration, in a multilevel fashion with multibasis sparsifying transform. The STF‐based algorithm is implemented on a GPU platform for improved computational efficiency. To evaluate the method, 4DCBCT full‐fan scans were acquired within 30 s, with a gantry rotation of 200°; STF is also compared with a state‐of‐art reconstruction method via spatiotemporal total variation regularization.

Results:

Both the simulation and experimental results demonstrate that STF‐based reconstruction achieved superior image quality. The reconstruction of 20 respiratory phases took less than 10 min on an NVIDIA Tesla C2070 GPU card. The STF codes are available athttps://sites.google.com/site/spatiotemporaltensorframelet.

Conclusions:

By effectively utilizing the spatiotemporal coherence of the patient anatomy among different respiratory phases in a multilevel fashion with multibasis sparsifying transform, the proposed STF method potentially enables fast and low‐dose 4DCBCT with improved image quality.
Impact of the number of discrete angles used during dose computation for TomoTherapy treatments
Authors: Sterpin E. , Verboomen C. , Vynckier S.
Published: October 2012

Purpose:

To quantify systematically the effect on accuracy of discretizing gantry rotation during the dose calculation process of TomoTherapy treatments.

Methods:

Up to version 4.0.x included, TomoTherapy treatment planning system (TPS) approximates gantry rotation by computing dose from 51 discrete angles corresponding to the center of the projections used to control the binary multileaf collimator. Potential effects on dose computation accuracy for off‐axis targets and low modulation factors have been shown previously for a few treatment configurations. In versions 4.1.x and later, TomoTherapy oversamples the projections to better account for gantry rotation, but only during full scatter optimization and final calculation (i.e., not during optimization in “beamlet” mode). The effect on accuracy of changing the number of angles was quantified with the following framework: (1) predict the impact of the discretization of gantry rotation for various modulation factors, target sizes, and off‐axis positions using a simplified analytical algorithm; (2) perform regular quality assurance using measurements with EDR2 radiographic films; (3) isolating the effect of changing the number of discretized angles only (51, 153, and 459) using a previously validated Monte Carlo model (TomoPen). The diameters of the targets were 2, 3, and 5 cm; off‐axis central positions of target volumes were 5, 10 and 15, and 17 cm (when accepted by the treatment unit); planned modulation factors were 1.3 and 2.0.

Results:

For extreme configurations (3 cm tumor, 1.3 modulation factor, 15 cm off‐axis position), effects on dose distributions were significant with 89.3% and 95.4% of the points passing gamma tests with 2%/2 mm and 3%/3 mm criteria, respectively, for TPS software version 4.0.x (51 gantry angles). The passing rate was 100% for both gamma criteria for the 4.1.x version (153 gantry angles). Those differences could be attributed almost completely to gantry motion discretization using TomoPen. Using 51 gantry angles for dose computation, TomoPen reproduced within statistical uncertainties (<1% standard deviation) dose distributions computed with version 4.0.x. Using 153 and 459 gantry angles, TomoPen reproduced within statistical uncertainties measurements and dose distributions computed with version 4.1.x.

Conclusions:

When low modulation factors and significant off‐axis positions are used, accounting for gantry rotation during dose computation using at least 153 gantry angles is required to ensure optimal accuracy.
Student-Directed Discovery of the Plant Microbiome and Its Products
Authors: Bascom-Slack Carol A. , Arnold A. Elizabeth , Strobel Scott A.
Published: October 2012

Endophyte Discovery, an IBI Prize–winning module, allows novice scientists to engage in meaningful discovery through inquiry-based research experiences.
Glial Progenitor Cell–Based Treatment and Modeling of Neurological Disease
Authors: Goldman Steven A. , Nedergaard Maiken , Windrem Martha S.
Published: October 2012

The diseases of myelin are among the most prevalent and disabling conditions in neurology. These diseases include both the vascular and inflammatory demyelinating disorders of adulthood, as well as the childhood leukodystrophies and cerebral palsy. These fundamentally glial disorders may be amenable to treatment by glial progenitor cells (GPCs), which give rise to astroglia and myelin-producing oligodendrocytes. Given the development of new methods for generating and isolating human GPCs, the myelin disorders may now be compelling targets for cell-based therapy. In addition, the efficient engraftment and expansion of human GPCs in murine hosts has led to the development of human glial chimeric mouse brains, which provides new opportunities for studying the species-specific roles of human glia in cognition, as well as in disease pathogenesis.
Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C–H Activation
Authors: Hyster Todd K. , Knörr Livia , Ward Thomas R. , Rovis Tomislav
Published: October 2012

Forced Asymmetry in Cp

The cyclopentadienyl (Cp) ligand—a pentagon of carbons—is a common feature in transition metal catalysts, but chiral variants of the structure have rarely been applied to asymmetric reactions. Two studies now demonstrate distinct approaches to rendering a Cp-derived rhodium catalyst enantioselective in a tandem carbon-hydrogen activation-ring closure reaction that couples olefins with benzamides (see the Perspective by

Wang and Glorius
). Hyster
et al.

(p.
500
) tethered a biotin derivative to the Cp ligand to enable docking in a chiral streptavidin protein cavity, which in turn was engineered to further optimize catalytic performance.
Ye and Cramer
(p.
504
) appended chiral substituents on the Cp framework to bias the rest of the coordination environment around the metal center.
Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy
Authors: Chojnacki Jakub , Staudt Thorsten , Glass Bärbel , Bingen Pit , Engelhardt Johann , Anders Maria , Schneider Jale , Müller Barbara , Hell Stefan W. , Kräusslich Hans-Georg
Published: October 2012

Switching on HIV

Newly assembled human immunodeficiency virus (HIV) virions bud from the host cell as immature particles. Proteolysis of the Gag protein, which forms a structural lattice below the viral membrane, leads to the formation of mature infectious HIV. Fusion of mature HIV virions with a target cell is mediated by viral envelope (Env) proteins that occur in trimeric “spikes” on the surface of the virion.

Chojnacki
et al.

(p.
524
) used subdiffraction microscopy to show that the spikes were dispersed on the immature virion but clustered into a single focus on the mature virion. The clustering was important for infectivity. Coupling Gag proteolysis with clustering may ensure that only particles whose interior has switched to the entry mode are competent for membrane fusion.
Vasopressin/Oxytocin-Related Signaling Regulates Gustatory Associative Learning in
C. elegans
Authors: Beets Isabel , Janssen Tom , Meelkop Ellen , Temmerman Liesbet , Suetens Nick , Rademakers Suzanne , Jansen Gert , Schoofs Liliane
Published: October 2012

Social Neuropeptides in Nematodes

The neuropeptides oxytocin and vasopressin stimulate maternal, reproductive, aggressive, and affiliative behaviors in mammals. They are implicated in behaviors ranging from ewe-lamb bonding in sheep to pair bonding in voles (see the Perspective by

Emmons

). Now,

Garrison
et al.

(p.
540
) and

Beets
et al.

(p.
543
) extend the evolutionary reach of these social neuropeptides to the invertebrate nematode worm,
Caenorhabditis elegans
. A similar neuropeptide was found to function in mating and also to modulate salt-taste preference, based on prior experience, suggesting an ancient role in associative learning.
Australopithecus afarensisScapular Ontogeny, Function, and the Role of Climbing in Human Evolution
Authors: Green David J. , Alemseged Zeresenay
Published: October 2012

Climbing Like an Ape

Recently, studies of several early human leg and foot fossils have implied that in some early species—even after humans became bipedal—climbing may have still been important. Shoulder bones, which would provide i mportant complementary information, are scarce, however. One of the few examples is fromAustralopithecus afarensisskeleton (DIK-1-1), which includes both scapula.Green and Alemseged(p.514; see the Perspective ofLarson) provide an analysis of the fossil's shoulders and show that, unlike modern humans, they retain several traits that are common in climbing apes, which may indicate thatA. afarensiswas an active climber.
Fishing for Answers off Fukushima
Authors: Buesseler Ken O.
Published: October 2012

Radionuclide levels in fish off Fukushima are highly variable but remain elevated, indicating a continuing source of radiation.
Lending Handedness to the Cyclopentadienyl Ligand
Authors: Wang Honggen , Glorius Frank
Published: October 2012

Chemical and biochemical modifications of the Cp ligand have allowed for the stereoselective formation of organic reaction products.
When a Brain Scan Bears Bad News
Authors: Underwood Emily
Published: October 2012

Experts gathered last week to hash out new guidance on so-called incidental findings: MRI scans performed for research that turn up abnormalities that have nothing to do with the study.
Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes
Authors: Senbagavalli P. , Hilda J. Nancy , Ramanathan V. D. , Kumaraswami V. , Nutman Thomas B. , Babu Subash
Published: October 2012

Circulating immune complexes (ICs) are associated with the pathogenesis of several diseases. Very little is known about the effect of ICs on the host immune response in patients with tuberculosis (TB). The effects of ICs isolated from patients with TB in modulating the release of calcium, cytokines, and granular proteins were studied in normal granulocytes, as were their chemotactic, phagocytic, and oxidative burst processes. ICs from TB patients induced decreased production of cytokines and platelet-activating factor (PAF) from normal granulocytes. ICs from TB patients also induced enhanced chemotaxis and phagocytosis but caused diminished oxidative burst. This was accompanied by an increased release in intracellular calcium. On the other hand, ICs from TB patients induced increased release of the granular proteins human neutrophil peptides 1 to 3 (HNP1–3). Thus, ICs from patients with TB exhibit a profound effect on granulocyte function with activation of certain effector mechanisms and dampening of others.
Quantitative Estimation of the Stability of Methicillin-Resistant Staphylococcus aureus Strain-Typing Systems by Use of Kaplan-Meier Survival Analysis
Authors: O'Sullivan Matthew V. N. , Sintchenko Vitali , Gilbert Gwendolyn L.
Published: October 2012

Knowledge concerning stability is important in the development and assessment of microbial molecular typing systems and is critical for the interpretation of their results. Typing system stability is usually measured as the fraction of isolates that change type after several
in vivo
passages, but this does not necessarily reflect
in vivo
stability. The aim of this study was to utilize survival analysis to provide an informative quantitative measure of
in vivo
stability and to compare the stabilities of various techniques employed in typing methicillin-resistant
Staphylococcus aureus
(MRSA). We identified 100 MRSA pairs (isolated from the same patient ≥1 month apart) and typed them using multilocus sequence typing (MLST), phage-derived open reading frame (PDORF) typing, toxin gene profiling (TGP), staphylococcal cassette chromosome
mec
(SCC
mec
) subtyping, pulsed-field gel electrophoresis (PFGE), and
spa
sequence typing. Discordant isolate pairs, belonging to different MLST clonal complexes, were excluded, leaving 81 pairs for analysis. The stabilities of these methods were examined using Kaplan-Meier survival analysis, and discriminatory power was measured by Simpson's index of diversity. The probability percentages that the type remained unchanged at 6 months for
spa
sequence typing, TGP, multilocus variable number of tandem repeats analysis (MLVA), SCC
mec
subtyping, PDORF typing, and PFGE were 95, 95, 88, 82, 71, and 58, respectively, while the Simpson's indices of diversity were 0.48, 0.47, 0.70, 0.72, 0.89, and 0.88, respectively. Survival analysis using sequential clinical isolates adds an important quantitative dimension to the measurement of stability of a microbial typing system. Of the methods compared here, PDORF typing provides high discriminatory power, comparable with that of PFGE, and a level of stability suitable for MRSA surveillance and outbreak investigations.
Candida guilliermondii and Other Species of Candida Misidentified as Candida famata: Assessment by Vitek 2, DNA Sequencing Analysis, and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry in Two Global Antifungal Surveillance Programs
Authors: Castanheira Mariana , Woosley Leah N. , Diekema Daniel J. , Jones Ronald N. , Pfaller Michael A.
Published: October 2012

Candida famata
(teleomorph
Debaryomyces hansenii
) has been described as a medically relevant yeast, and this species has been included in many commercial identification systems that are currently used in clinical laboratories. Among 53 strains collected during the SENTRY and ARTEMIS surveillance programs and previously identified as
C. famata
(includes all submitted strains with this identification) by a variety of commercial methods (Vitek, MicroScan, API, and AuxaColor), DNA sequencing methods demonstrated that 19 strains were
C. guilliermondii
, 14 were
C. parapsilosis
, 5 were
C. lusitaniae
, 4 were
C. albicans
, and 3 were
C. tropicalis
, and five isolates belonged to other
Candida
species (two
C. fermentati
and one each
C. intermedia
,
C. pelliculosa
, and
Pichia fabianni
). Additionally, three misidentified
C. famata
strains were correctly identified as
Kodomaea ohmeri
,
Debaryomyces nepalensis
, and
Debaryomyces fabryi
using intergenic transcribed spacer (ITS) and/or intergenic spacer (IGS) sequencing. The Vitek 2 system identified three isolates with high confidence to be
C. famata
and another 15 with low confidence between
C. famata
and
C. guilliermondii
or
C. parapsilosis
, displaying only 56.6% agreement with DNA sequencing results. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) results displayed 81.1% agreement with DNA sequencing. One strain each of
C. metapsilosis
,
C. fermentati
, and
C. intermedia
demonstrated a low score for identification (<2.0) in the MALDI Biotyper.
K. ohmeri
,
D. nepalensis
, and
D. fabryi
identified by DNA sequencing in this study were not in the current database for the MALDI Biotyper. These results suggest that the occurrence of
C. famata
in fungal infections is much lower than previously appreciated and that commercial systems do not produce accurate identifications except for the newly introduced MALDI-TOF instruments.