bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid characterization of lipids by MALDI MS. Part 2: Artifacts, ion suppression, and TLC MALDI imaging
Authors: Lay Jackson O. , Gidden Jennifer , Liyanage Rohana , Emerson Beth , Durham Bill
Published: February 2012

Several new methods have been developed recently that allow the direct detection of lipids without resorting to derivatization or chromatographic separation. The simplest of these is direct MALDI (matrix‐assisted laser desorption/ionization) mass spectrometry. This approach is most useful for mixtures that contain minimal amounts of ion‐suppressing interfering components. However, when such components are present, their effects can often be minimized by using simple separation techniques beforehand, such as solid phase extraction or thin layer chromatography. For example, direct MALDI has been used for rapid screening of lipids and taxonomic identification of the source organisms with no sample pretreatment. Collecting fractions from solid phase extraction cartridges have also been used to avoid the most extreme effects of ion suppression from more complex lipid mixtures. More recently, direct MALDI has been applied to the analysis of TLC plates allowing the detection of TLC‐separated lipids from the complex lipidome. Herein, we briefly describe the application of rapid MALDI MS to some typical research problems involving the characterization of lipids. In Part 1 [1] we covered bacterial taxonomy by direct analysis of intact lipids and the analysis of food oil triacylglycerols . Part 2 will address ion suppression, spontaneous fragmentation, and coupling MALDI with chromatography. The spontaneous fragmentation of protonated lipids in oils by direct MALDI produces artifactual diacylglycerol‐like ions. An understanding of this process and its minimization facilitates monitoring the decomposition of lipids by direct analysis. Suppression also has an impact on direct analysis of lipids, especially when mixtures contain both polar and non‐polar lipids. We demonstrate the use of solid phase extraction and thin layer chromatography to produce fractions or substrates from complex biological samples in which lipids can be detected by direct and rapid MALDI MS analysis.
Resource implications of expanding the use of donation after circulatory determination of death in liver transplantation
Authors: Broomhead Robert Hayden , Patel Sanjiv , Fernando Bimbi , O'Beirne James , Mallett Susan
Published: February 2012

In the United Kingdom, liver transplantation using donation after circulatory determination of death (DCDD) organs has increased steadily over the last few years and now accounts for 20% of UK transplant activity. The procurement of DCDD livers is actively promoted as a means of increasing the donor pool and bridging the evolving disparity between the wait-list length and the number of transplants performed. The objective of this retrospective study of a cohort of patients who were matched for age, liver disease etiology, and Model for End-Stage Liver Disease score was to determine whether differences in perioperative costs and resource utilization are associated with the use of such organs. Our results showed an increased prevalence of reperfusion syndrome in the DCDD cohort (P < 0.001), a prolonged heparin effect (P = 0.01), a greater incidence of hyperfibrinolysis (P = 0.002), longer periods of postoperative ventilator use (P = 0.03) and vasopressor support (P = 0.002), and a prolonged length of stay in the intensive therapy unit (ITU; P = 0.02). The peak posttransplant aspartate aminotransferase level was higher in the DCDD group (P = 0.007), and there was significantly more graft failure at 12 months (P = 0.03). In conclusion, we have demonstrated different perioperative and early postoperative courses for DCDD and donation after brain death (DBD) liver transplants. The overall quality of DCDD grafts is poorer; as a result, the length of the ITU stay and the need for multiorgan support are increased, and this has significant financial and resource implications. We believe that these implications require a careful real-life consideration of benefits. It is essential for DCDD not to be seen as a like-for-like alternative to DBD and for every effort to be continued to be made to increase the number of donations from brain-dead patients as a first resort. Liver Transpl, 2012. © 2012 AASLD.
Immunoprophylaxis against and prevention of recurrent viral hepatitis after liver transplantation
Authors: Laryea Marie A. , Watt Kymberly D.
Published: February 2012

The reinfection of the hepatic allograft with hepatitis B virus and hepatitis C virus can have important sequelae that result in poor long-term patient and graft survival. Although a response to treatment with antiviral medications can improve these outcomes, not all patients tolerate these medications or experience viral eradication. Avoiding reinfection of the graft is the most effective means of improving the long-term outcomes for these patient populations. This review is focused on the prevention of viral hepatitis reinfection after liver transplantation. Liver Transpl, 2012. © 2012 AASLD.
Polymer Nanostructures Made by Scanning Probe Lithography: Recent Progress in Material Applications
Authors: Xie Zhuang , Zhou Xuechang , Tao Xiaoming , Zheng Zijian
Published: February 2012

Scanning probe lithography (SPL) is a series of techniques that utilizes a scanning probe or an array of probes for surface patterning. Recent developments of new material systems and patterning approaches have made SPL a promising, low‐cost, bench‐top, and versatile tool for fabricating various polymer nanostructures, with extraordinary importance in physical sciences, life sciences and nanotechnology. This feature article highlights the recent progress in four material applications: polymer resists, polymeric carriers for patterning functional materials, electronically active polymers and polymer brushes for tailoring surface morphology and functionality. An overview of future possibilities, with regard to challenges and opportunities in this field, is given at the end of the paper.
Anisotropic Ionic Mobility of Lithium Salts in Lamellar Liquid Crystalline Polymer Networks
Authors: Ramón‐Gimenez Laura , Storz Rebekka , Haberl Johannes , Finkelmann Heino , Hoffmann Anke
Published: February 2012

New mesogens presenting smectic A (SmA) phases and capable of hosting lithium salts are designed. The mesogens comprise a vinyl‐functionalized spacer to allow further reaction to the polymer backbone, an aromatic core and ethylene oxide chains, able to coordinate lithium ions. Copolymerizing these monomers with a suitable crosslinker yields the first lithium containing liquid crystalline elastomers (LCEs). The SmA structure where the ethylene oxide chains are microphase separated in layers is fixed by the crosslinking and permanent macroscopic orientation is obtained. Diffusion and conductivity measurements of the monomer sample show a large anisotropy of the ion mobility (100 for the cation and 400 for the anion). In the elastomer the anisotropy of the lithium mobility is comparable to that in the monomers.
Molecular Modelling of G Protein‐Coupled Receptors Through the Web
Authors: Rodríguez David , Bello Xabier , Gutiérrez‐de‐Terán Hugo
Published: February 2012

With the recent crystallization of several G Protein‐Coupled receptors (GPCRs), homology modelling and all atom molecular dynamics (MD) simulations have proven their usefulness for exploring the structure and function of this superfamily of membrane receptors. Subsequently, automated computational protocols have been implemented as web‐based servers in the recent years to produce reliable models of GPCRs, providing partial or global solutions for the structural characterization and molecular simulation of GPCRs. These dedicated modelling services represent an attractive tool for the broader community of public researchers and pharmaceutical companies, in order to assist in the structure‐based drug design of GPCRs. We here collect and analyze the existing web servers, among which a previously unreported service, GPCR‐ModSim, offers for the first time full atom MD simulations in the pipeline for GPCR molecular modelling.
Fish liver and seagull eggs, vitamin D‐rich foods with a shadow: Results from the Norwegian Fish and Game Study
Authors: Birgisdottir Bryndis E. , Brantsæter Anne L. , Kvalem Helen E. , Knutsen Helle K. , Haugen Margaretha , Alexander Jan , Hetland Ragna B. , Aksnes Lage , Meltzer Helle M.
Published: February 2012

Scope Fish liver, fish liver oil, oily fish and seagull eggs have been major sources of vitamin D for the coastal population of Norway. They also provide dioxin and polychlorinated dioxin‐like compounds (dl‐compounds), which may interfere with vitamin D homeostasis. We investigated whether serum 25‐hydroxyvitamin D (25(OH)D) might be compromised by concomitant intake of dl‐compounds.

Methods and results We studied 182 adults participating in the Norwegian Fish and Game Study. Participants who consumed fish liver and/or seagull eggs had higher dl‐compound intake and blood concentrations than non‐consumers (p < 0.001). Vitamin D intake was higher (p < 0.001), whereas serum 25(OH)D was lower (p = 0.029) in consumers than in non‐consumers. Among non‐consumers, vitamin D intake was associated with serum 25(OH)D (β=1.06; 95% CI: 0.48, 1.63). This association was weaker among consumers (β = 0.52; 95% CI: −0.05, 1.08), but strengthened when adjusted for retinol intake (β = 0.66; 95% CI: 0.12, 1.21). The association between vitamin D intake and serum 25(OH)D did not seem to be compromised by intake of dl‐compounds.

Conclusion To secure adequate vitamin D status while keeping the intake of dioxins and dl‐polychlorinated biphenyls low, a healthy diet should include both supplemental vitamin D and oily fish. Despite high nutrient content, dietary fish liver and seagull eggs should be restricted, due to dl‐compounds and possible vitamin A‐D antagonism.
Pre‐existent Hsp72 contributes to glutamine‐induced hepatic hsp72 gene activation during heat shock recovery period in rat
Authors: Wang Shu‐Jung , Chen Hsiang‐Wen , Yang Rei‐Cheng
Published: February 2012

Scope Functional maintenance of liver is very important at all times for personal health. Hsp induction is associated with the protection of the organ. Glutamine, a nutrient inducer of Hsps, enhances cellular survival via Hsp72 induction in several organs, but not in the liver. The present study showed a novel approach to facilitate glutamine‐induced hepatic Hsp72 synthesis and its possible mechanisms were discussed.

Methods and results Sprague‐Dawley rats were used as the experimental animals and the livers were the targets. Glutamine was administered via tail‐vein injection, and its effects on hsp72 gene activation, including Hsp72 expression, heat shock factor‐1 (HSF‐1) phosphorylation and DNA‐binding activation, were evaluated. The results showed that Hsp72 itself played a critical role in glutamine‐induced hepatic Hsp72 synthesis during HS recovery period in a dose‐dependent manner of preexistent Hsp72. The peak value of HSF‐1 phosphorylation, HSF‐1 DNA‐binding activity, hsp72 mRNA accumulation, and Hsp72 synthesis was detected at 8 h after glutamine administration.

Conclusion Glutamine switched on alteration pathway in inducing hsp72 gene activation. The existence of Hsp72 plays a critical role in the reactivation of hsp72 gene. Glutamine sustained the induction of intracellular Hsp72, which could be beneficial in protecting the liver from various injuries.
Synthesis of methoxybenzoflavones and assignments of their NMR data
Authors: Hwang Doseok , Jo Geunhyeong , Hyun Jiye , Lee Sung Dae , Koh Dongsoo , Lim Yoongho
Published: February 2012

A phytotoxic root exudate from Acroptilon repens was identified as 7,8‐benzoflavone, an inhibitor of cytochrome P450 1A2 and activator of cytochrome P450 3A4. The synthetic 5,6‐benzoflavone also is a potent phytotoxin. Six 7,8‐benzoflavones and eight 5,6‐benzoflavones were synthesized in this study. The NMR data for a few of these compounds have been previously reported; however, the NMR data for most of them have not been reported. For reference purposes, the complete NMR data for the 14 benzoflavones are described. Copyright © 2012 John Wiley & Sons, Ltd.
Hybrid FE‐DQ for dynamic analysis of multilayered half‐space subjected to concentrated point impulsive loading
Authors: Vosoughi A. R. , Banan Mo. R. , Banan Ma. R. , Malekzadeh P.
Published: February 2012

A hybrid finite element method and differential quadrature method (DQM) is developed to estimate the dynamic response of two‐dimensional multilayered half‐spaces subjected to impulsive point loading. Nonreflecting absorbing boundary conditions consist of appropriate springs, and dampers are considered. The capabilities of the finite element method for solving boundary value problems with general domain, loading and systematic boundary treatment are combined with accurate and stable time marching capabilities of the DQM to develop an accurate and efficient numerical technique. The capability, efficiency, robustness and convergence of the DQM for solving the dynamic problem are demonstrated through numerical simulations of various half‐spaces with different time increments and layer arrangement. Also, comparison study when using Newmark's time integration scheme for the same problem is done. It can be concluded that the DQM as an unconditionally stable method is suitable for solving such a problem. Also, parametric study is performed to show the effect of the absorbing boundary conditions on the dynamic response. Copyright © 2012 John Wiley & Sons, Ltd.
On the interface identification of free boundary problem by method of fundamental solution
Authors: Zhao Haifeng , Yan Liang , Liu Jijun
Published: February 2012

The Stefan problems with one phase have been studied thoroughly. For the numerical implementations of free‐boundary problems, the unknown free boundary makes the mesh generation process much difficult. The purpose of this paper is to give a meshless numerical scheme on the basis of the method of fundamental solution for solving a two‐phase Stefan problem with variable diffusion coefficients. By introducing some mathematical transform and artificial boundary, this problem is solved approximately by constructing an explicit solution with the superposition of finite number of source points, in terms of the fundamental solution to a standard heat equation. The superposition coefficients of solutions as well as the free boundary are solved by a least square solution for a nonlinear algebra system in terms of the initial and boundary value conditions. Our proposed scheme can be considered as a generalization of numerical linear algebra system applied to the PDEs by method of fundamental solution. Numerical examples are presented to show the validity of the proposed scheme. Copyright © 2012 John Wiley & Sons, Ltd.
A method for computation of discontinuous wave propagation in heterogeneous solids: basic algorithm description and application to one‐dimensional problems
Authors: Park K. C. , Lim S. J , Huh H.
Published: February 2012

An explicit integration algorithm for computations of discontinuous wave propagation in heterogeneous solids is presented, which is aimed at minimizing spurious oscillations when the wave fronts pass through several zones of different wave speeds. The essence of the present method is a combination of two wave capturing characteristics: a new integration formula that is obtained by pushforward–pullback operations in time designed to filter post‐shock oscillations, and the central difference method that intrinsically filters front‐shock oscillations. It is shown that a judicious combination of these two characteristics substantially reduces both spurious front‐shock and post‐shock oscillations. The performance of the new method is demonstrated as applied to wave propagation through a uniform bar with varying courant numbers, then to heterogeneous bars. Copyright © 2012 John Wiley & Sons, Ltd.
Understanding Living Skills: First Steps to Evidence‐based Practice. Lessons Learned from a Practice‐based Journey in the Netherlands
Authors: Ammeraal Marion A. , Coppers Jacqueline
Published: February 2012

Living skills training is a commonly used but sparsely described and researched – occupational therapy – intervention for people with severe mental health problems. A service improvement project was established in a mental health organization in the Netherlands starting in 2006 to design more effective living skills training courses for individuals and groups. The steps of the evidence‐based practice process underpinned the project. Theoretical and empirical evidence was derived from an extensive literature review. This was supplemented by the preferences of clients and their families as an equally valued source of evidence as is the experience and knowledge of a range of mental health professionals. Information from these three sources provided building blocks for the development of living skills training, resulting in an individual process guideline and two group courses. Implications for practice is that living skills training needs to be part of multidisciplinary treatment and can be best provided in the client's natural context. Limitations of this study are the lack of an evaluation of both the group courses and of the individual process guideline, also due to the continuous implementation in an ever‐changing context. There is further need for research into the clinical and cost effectiveness of living skills training, both for individuals and groups, to support evidence‐based decision making and service planning. Copyright © 2012 John Wiley & Sons, Ltd.
Depression is associated with some patient‐perceived cosmetic changes, but not with radiotherapy‐induced late toxicity, in long‐term breast cancer survivors
Authors: Brunault Paul , Suzanne Isabelle , Trzepidur‐Edom Magdalena , Garaud Pascal , Calais Gilles , Toledano Alain , Camus Vincent
Published: February 2012

Objective

Although depression is prevalent in long‐term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS.

Methods

In all, 214 patients recruited from the ARCOSEIN study were assessed for late radiotherapy toxicity (by using the LENT‐SOMA scale) and patient and doctor ratings of breast cosmetic outcomes (mean = 6.7 years since the end of treatment). We reassessed 120 of these patients for depression (HAD) during a second wave of long‐term assessment (mean = 8.1 years since the end of treatment). We used univariate analyses and polytomous logistic regression analyses to predict the HAD depression, which was defined as follows: normal, 0–7 points; and significant depression, ≥8 points (8–10 points, possible depression; ≥11 points, probable depression).

Results

The mean HAD depression score was 4.5 ± 3.6. 19. 2% of our population had significant depression, 6.7% with probable depression, and 12.5% with possible depression. Significant depression was not associated with late radiotherapy toxicity or initial cancer‐related variables. Patients with probable depression reported worse cosmetic outcomes than nondepressed patients in terms of perceived breast largeness (p = 0.04), breast deformation (p = 0.02), and changes in skin pigmentation (p = 0.03).

Conclusions

In LTBCS, depression seems to be more strongly associated with changes in some patients' perceived breast cosmetic outcome than late treatment toxicity or initial cancer‐related variables. Copyright © 2012 John Wiley & Sons, Ltd.
Multiscale modeling of cellular actin filaments: From atomistic molecular to coarse‐grained dynamics
Authors: Deriu Marco A. , Shkurti Ardita , Paciello Giulia , Bidone Tamara C. , Morbiducci Umberto , Ficarra Elisa , Audenino Alberto , Acquaviva Andrea
Published: February 2012

In this article, we present a computational multiscale model for the characterization of subcellular proteins. The model is encoded inside a simulation tool that builds coarse‐grained (CG) force fields from atomistic simulations. Equilibrium molecular dynamics simulations on an all‐atom model of the actin filament are performed. Then, using the statistical distribution of the distances between pairs of selected groups of atoms at the output of the MD simulations, the force field is parameterized using the Boltzmann inversion approach. This CG force field is further used to characterize the dynamics of the protein via Brownian dynamics simulations. This combination of methods into a single computational tool flow enables the simulation of actin filaments with length up to 400 nm, extending the time and length scales compared to state‐of‐the‐art approaches. Moreover, the proposed multiscale modeling approach allows to investigate the relationship between atomistic structure and changes on the overall dynamics and mechanics of the filament and can be easily (i) extended to the characterization of other subcellular structures and (ii) used to investigate the cellular effects of molecular alterations due to pathological conditions. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Three‐dimensional domain swapping in the protein structure space
Authors: Huang Yongqi , Cao Huaiqing , Liu Zhirong
Published: February 2012

Since the proposal of three‐dimensional (3D) domain swapping, many 3D domain‐swapped structures have been reported. However, when compared with the vast protein structure space, it is still unclear whether 3D domain swapping is a general mechanism for protein assembly. Here, we investigated this possibility by constructing a dataset consisting of more than 500 domain‐swapped structures. The domain‐swapped structures were mapped into the protein structure space. We found that about 10% of protein folds and 5% of protein families contain domain‐swapped structures. When comparing the domain‐swapped structures in a family/superfamily, we found that proteins within a family/superfamily can swap in different ways. Interface analysis revealed that the hinge loops contributed more than half of the open interface in 70% of bona fide domain‐swapped dimers, indicating that the hinge loops play an important role in stabilizing the domain‐swapped conformations. Our study supports the suggestion that domain swapping is a general property of all proteins and will facilitate further understanding the mechanism of 3D domain swapping. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Effect of Linalool on Morphine Tolerance and Dependence in Mice
Authors: Hosseinzadeh Hossein , Imenshahidi Mohsen , Hosseini Mohammadreza , Razavi Bibi Marjan
Published: February 2012

Linalool, a terpene alcohol, has been shown to interact with the opioid system and N‐methyl‐ d‐aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and100 mg/kg), clonidine (positive control), alpha‐2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail‐flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of Salvia miltiorrhiza Hydrophilic Extract on the Endothelial Biomarkers in Diabetic Patients with Chronic Artery Disease
Authors: Qian Shuhong , Wang Shijin , Fan Ping , Huo Dongxia , Dai Liping , Qian Qingwen
Published: February 2012

The aim of this pilot study was to investigate whether the administration of Salvia miltiorrhiza hydrophilic extract (SMHE) reduced the level of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and von Willebrand factor (vWF) in diabetic patients with coronary heart disease (CHD). Sixty‐two diabetic patients with CHD were recruited and randomly assigned into placebo and treatment groups. Patients were given SMHE for 60 days. Levels of sVCAM‐1, vWF and oxidative low density lipoprotein (oxLDL) were determined by using enzyme linked immunosorbent assay (ELISA). The results showed that the levels of VCAM‐1 and vWF positively correlated with the level of oxLDL in diabetic patients with CHD. Levels of sVCAM‐1 and vWF in serum were reduced significantly in patients receiving SMHE treatment at day 60 in comparison with the baseline. Administration of SMHE also led to a clear decrease in the levels of oxLDL in diabetic patients with CHD. In summary, this study suggests that SMHE has a potential protective effect on the development of diabetic cardiovascular disease. Copyright © 2012 John Wiley & Sons, Ltd.
In vitro Inhibition of CYP3A4 by the Multiherbal Commercial Product Sambucus Force and its Main Constituents Echinacea purpurea and Sambucus nigra
Authors: Schrøder‐Aasen Torstein , Molden Guri , Nilsen Odd Georg
Published: February 2012

The multiherbal product Sambucus Force contains Echinacea purpurea and Sambucus nigra as its main constituents. The aims of this study were to evaluate Sambucus Force's inhibition potential and inhibition mechanisms towards CYP3A4, and to evaluate the inhibitory co‐contribution of E. purpurea and S. nigra. Metabolic studies were performed with recombinant human CYP3A4, with testosterone as substrate. Sambucus Force inhibited CYP3A4 activity with a mean (95% confidence interval) half maximal inhibitory concentration (IC50) value of 1192 (1091–1302) µg/mL. The inhibitory potency seems exclusively to be exerted by E. purpurea, implicating an insignificant inhibition by S. nigra. The inhibition by E. purpurea as a single herb was in agreement with mechanism‐based inhibition with heterotropic positive cooperative effects. Echinacea purpurea acted differently in the multiherbal product, which showed a dual inhibition profile with both an uncompetitive (substrate‐dependent) inhibition and a time‐dependent (substrate‐independent) inhibitory mechanism. These mechanistic differences are suggested to be caused by herb–herb interactions in the multiherbal product. The CYP3A4 inhibition of Sambucus Force in vitro is considered relatively weak, but recommended high herbal dosages might enhance the potential for clinical interactions. Copyright © 2012 John Wiley & Sons, Ltd.
Are Mould Hepatotoxins Responsible for Kava Hepatotoxicity?
Authors: Rowe Anthony , Ramzan Iqbal
Published: February 2012

Previous studies with kava components such as kavalactones, pipermethystine and flavokavain B have demonstrated hepatotoxicity from these constituents. Regardless, there has recently been speculation that adulterants or impurities such as the mould hepatotoxin aflatoxin are a more likely cause of kava hepatotoxicity, despite a paucity of supporting evidence. Although there is limited similarity between acute kava hepatotoxicity and acute aflatoxicosis, and background levels of aflatoxin have been detected in kava samples, unless epidemiological investigations can uncover direct evidence implicating mould hepatotoxins, it remains more likely that chemical constituents of kava are the cause of the hepatotoxicity from kava. Copyright © 2012 John Wiley & Sons, Ltd.
High‐throughput screening for glutathione conjugates using stable‐isotope labeling and negative electrospray ionization precursor‐ion mass spectrometry
Authors: Liao Shengkai , Ewing Nigel P. , Boucher Brian , Materne Olivier , Brummel Christopher L.
Published: February 2012

RATIONALE

It has been proposed that the increase in the instances of idiosyncratic adverse drug reactions (IADRs) and black box warnings may be attributed to the occurrence of reactive metabolites. Consequently, a high‐throughput screen for reactive metabolites formed from liver microsome extracts with added glutathione (GSH) was developed for use in the early stages of drug discovery.

METHODS

To enhance sensitivity and specificity, as well as accelerate data processing, a mixture of a stable‐isotope probe consisting of natural GSH (light GSH) and stable‐isotope‐labeled [15 N,13 C2] GSH (heavy GSH) at a ratio of 1:1 was used. Any metabolite that reacted with the GSH results in the formation of light and heavy GSH conjugates with a 3 Da difference. Employing a precursor‐ion scan using negative ion electrospray ionization (ESI) corresponding to the expected fragments, signals with the appropriate ratio in the precursor ion scan are then further examined.

RESULTS

The new method greatly simplifies data collection by assuming molecules containing GSH will fragment to form specific ions. As such, this approach accelerates data processing (and collection) at the risk of missing compounds that do not fragment as expected. The assay was validated with 33 diverse drugs known to form GSH conjugates, 5 drugs known to not form GSH adducts and over 100 samples containing components of the normal in vitro matrix. In all cases data collected matched the expected result.

CONCLUSIONS

The observed sensitivity, specificity, and fast data processing make this assay an excellent fit for high‐throughput screening of reactive metabolites in the early stages of drug discovery. This method is not intended to eliminate compounds or terminate their development. Instead, it is to bring forward molecules with one less liability and thus a greater probability of ultimate success. Copyright © 2012 John Wiley & Sons, Ltd.
Ex vivo measurement reliability using two different cbct scanners for orthodontic purposes
Authors: Dalessandri Domenico , Bracco Pietro , Paganelli Corrado , Hernandez Soler Vicente , Martin Conchita
Published: February 2012

Background

There are many cone beam computed tomography (CBCT) scanners available on the market: detector technology, algorithm precision, and scanner settings influence image quality. The aim of this study was to compare the accuracy of linear measurements made on images of the same sample obtained using two different CBCT scanners.

Methods

Twenty‐eight linear measurements between orthodontic anatomical landmarks that were marked with gutta‐percha points on a fresh sacrificed lamb head were taken three times. The head was scanned with two CBCT scanners using different scanning parameters. Digital Imaging and Communications in Medicine (DICOM) images were reconstructed and the same measurements were taken three times by the same operator. Measurements were repeated 4 months later by two operators.

Results

There was minimal, clinically significant difference between the measurements taken with the digital caliper or CBCT scanners, but there was no difference between the two different scanners.

Conclusions

There is no clinically significant difference between these two scanners; a difference was found between the CBCT and real anatomical measurements in only a few cases. Copyright © 2012 John Wiley & Sons, Ltd.
Component structure of the vacant set induced by a random walk on a random graph
Authors: Cooper Colin , Frieze Alan
Published: February 2012

We consider random walks on several classes of graphs and explore the likely structure of the vacant set, i.e. the set of unvisited vertices. Let Γ(t) be the subgraph induced by the vacant set of the walk at step t. We show that for random graphs Gn,p (above the connectivity threshold) and for random regular graphs Gr,r ≥ 3, the graph Γ(t) undergoes a phase transition in the sense of the well‐known ErdJW‐RSAT1100590x.png ‐Renyi phase transition. Thus for t ≤ (1 ‐ ε)t*, there is a unique giant component, plus components of size O(log n), and for t ≥ (1 + ε)t* all components are of size O(log n). For Gn,p and Gr we give the value of t*, and the size of Γ(t). For Gr, we also give the degree sequence of Γ(t), the size of the giant component (if any) of Γ(t) and the number of tree components of Γ(t) of a given size k = O(log n). We also show that for random digraphs Dn,p above the strong connectivity threshold, there is a similar directed phase transition. Thus for t ≤ (1 ‐ ε)t*, there is a unique strongly connected giant component, plus strongly connected components of size O(log n), and for t ≥ (1 + ε)t* all strongly connected components are of size O(log n). © 2012 Wiley Periodicals, Inc. Random Struct. Alg., 2012
A secure mutual authentication scheme for session initiation protocol using elliptic curve cryptography
Authors: He Debiao , Chen Jianhua , Chen Yitao
Published: February 2012

The session initiation protocol (SIP) is one of the most important protocols supporting multimedia services. With the wide spread of the internet, the security of SIP is becoming more and more important. In 2009, Tsai proposed an efficient authentication scheme as an enhancement to SIP. However, Arshad et al. demonstrated that Tsai's scheme was vulnerable to the off‐line password‐guessing attack and the stolen‐verifier attack. They also pointed out that Tsai's scheme did not provide known‐key secrecy and perfect forward secrecy. To overcome the weaknesses, Arshad et al. also proposed an improved authentication scheme based on the elliptic curve discrete logarithm problem for SIP and claimed that their scheme can withstand various attacks. In this paper, we do a cryptanalysis of the scheme by Arshad et al., and we show that their scheme is vulnerable to the off‐line password‐guessing attack. We also propose an improved authentication scheme based on the elliptic curve cryptography for SIP which is immune to the presented attacks. Copyright © 2012 John Wiley & Sons, Ltd.
Exfoliation and Reassembly of Cobalt Oxide Nanosheets into a Reversible Lithium‐Ion Battery Cathode
Authors: Compton Owen C. , Abouimrane Ali , An Zhi , Palmeri Marc J. , Brinson L. Catherine , Amine Khalil , Nguyen SonBinh T.
Published: February 2012

An exfoliation–reassembly–activation (ERA) approach to lithium‐ion battery cathode fabrication is introduced, demonstrating that inactive HCoO2 powder can be converted into a reversible Li1‐xHxCoO2 thin‐film cathode. This strategy circumvents the inherent difficulties often associated with the powder processing of the layered solids typically employed as cathode materials. The delamination of HCoO2 via a combination of chemical and mechanical exfoliation generates a highly processable aqueous dispersion of [CoO2]− nanosheets that is critical to the ERA approach. Following vacuum‐assisted self‐assembly to yield a thin‐film cathode and ion exchange to activate this material, the generated cathodes exhibit excellent cyclability and discharge capacities approaching that of low‐temperature‐prepared LiCoO2 (~83 mAh g−1), with this good electrochemical performance attributable to the high degree of order in the reassembled cathode.
Experimental Design for the Mechanism Study of Lime Dissolution in Liquid Slag
Authors: Deng Tengfei , Glaser Björn , Sichen Du
Published: February 2012

The applicability of rotating rod technique in the study of lime dissolution in slag was investigated. Both computational fluid dynamic (CFD) and cold model experiments showed that the mass transfer due to radial velocity introduced by forced convection was zero if the rod was long. The mass transfer by forced convection was also less important in comparison with natural convection and diffusion when the rod was half length of the height of the bath. This finding was in accordance with the criteria put forward by the original work that the method could only be applicable when a thin disk (instead of rod) with big diameter and big liquid bath were used. To study the lime dissolution by forced convection a new experimental technique was developed. A cube was placed in the slag that was eccentrically stirred. The whole system, viz. the sample along with the slag could be quenched. The new technique could study the effect of forced convection on the dissolution. The microscopic study on the quenched slag‐lime samples could reveal the dissolution mechanism successfully.
Targeted therapy for biliary tract cancers
Authors: Faris Jason E. , Zhu Andrew X.
Published: February 2012

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies, with a historically poor prognosis as a whole. Until recently, the development of effective therapeutics was hampered by the relatively low incidence, heterogeneity in patients and tumors, and correspondingly poor clinical trial enrollments. With the publication of the landmark phase III ABC‐02 trial demonstrating the superiority of gemcitabine and cisplatin combination chemotherapy, the landscape changed for the development of new agents. Despite this progress, there are currently no approved targeted agents for BTC. This review will focus on recent developments in targeted therapeutics, directed against several key signaling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen‐activated protein kinase pathway. Data from recent phase I and II trials will be discussed, along with a preview of upcoming trials involving targeted therapies.
Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities
Authors: Cohen Roger B. , Oudard Stéphane
Published: February 2012

Treatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the last two decades as major pathways involved in pathogenesis have been elucidated. These include the vascular endothelial growth factor (VEGF) axis and mammalian target of rapamycin (mTOR). Therapies targeting the VEGF pathway include bevacizumab, sorafenib, sunitinib, pazopanib, and axitinib, whereas temsirolimus and everolimus inhibit the mTOR pathway. All of these novel therapies—VEGF and mTOR inhibitors—are associated with a variety of unique toxicities, some of which may necessitate expert medical management, treatment interruption, or dose reduction. Common adverse events with newer drugs include hypertension, skin reactions, gastrointestinal disturbances, thyroid dysfunction, and fatigue. Skilled management of these toxicities is vital to ensure optimal therapeutic dosing and maximize patient outcomes, including improved survival and quality of life. This review describes and compares the toxicity profiles of novel molecularly targeted agents used in the treatment of mRCC and presents guidance on how best to prevent and manage treatment-related toxicities. Particular attention is given to axitinib, the newest agent to enter the armamentarium. Axitinib is a second-generation receptor tyrosine kinase inhibitor with potent VEGF receptor inhibition that provides durable responses and superior progression-free survival in advanced RCC compared with sorafenib.
Long‐term hydrochemical monitoring in an Oyasan Experimental Forest Watershed comprised of two small forested watersheds of Japanese cedar and Japanese cypress
Authors: Urakawa Rieko , Toda Hiroto , Haibara Kikuo , Aiba Yoshinori
Published: February 2012

Forest ecosystems are self‐fertilizing systems, and development of forest stands depends on nutrient supply via biogeochemical cycling within the ecosystem. Therefore, it is important to clarify the nutrient cycle mediating growth and development. In addition, long‐term hydrochemical monitoring is needed to understand the influence of environmental changes on biogeochemical cycling in forest ecosystems. The Oyasan Experimental Forest Watershed (OEFW) is located in the Field Museum Oyasan, the university forest of Tokyo University of Agriculture and Technology, in Gunma prefecture, Japan. OEFW comprises two small adjacent forested watersheds—A‐watershed and B‐watershed—with respective areas of 1.3 and 1.8 ha. A‐watershed is a reestablished forest planted with sugi (Japanese cedar; Cryptomeria japonica) and hinoki (Japanese cypress; Chamaecyparis obtusa) in 1976, and has been managed intensively with fertilizer application. By contrast, B‐watershed is an established forest planted with sugi and hinoki in 1907. No forest practices have been carried out except for thinning of suppressed trees in 1983. However, the sugi plantation on the lowest slope (18% of the watershed area) was cut in 2000, and sugi was replanted the following year. In this data paper, we present data on the daily precipitation, discharge, pH, and concentrations of major nutrients (Ca2+, Mg2+, K+, Na+, NH4+, Cl−, NO3−, and SO42−) in rainwater and stream water since November 1978. The arithmetical mean pH of precipitation, stream water in A‐ and B‐watershed from the beginning of the monitoring to the present were 4.77 ± 0.67, 6.85 ± 0.41 and 6.88 ± 0.36 (average ± SD), respectively. The arithmetical mean concentrations in precipitation in mmolc L−1 were 0.030 ± 0.030 for Ca2+, 0.010 ± 0.011 for Mg2+, 0.009 ± 0.013 for K+, 0.020 ± 0.024 for Na+, 0.035 ± 0.041 for NH4+, 0.026 ± 0.029 for Cl−, 0.033 ± 0.038 for NO3−, and 0.046 ± 0.043 for SO42−. The mean concentrations in stream water in A‐watershed were 0.180 ± 0.032 for Ca2+, 0.073 ± 0.013 for Mg2+, 0.018 ± 0.009 for K+, 0.182 ± 0.024 for Na+, 0.010 ± 0.010 for NH4+, 0.060 ± 0.008 for Cl−, 0.111 ± 0.038 for NO3−, and 0.074 ± 0.012 for SO42−; whereas for B‐watershed the mean concentrations were 0.169 ± 0.025 for Ca2+, 0.079 ± 0.016 for Mg2+, 0.018 ± 0.005 for K+, 0.192 ± 0.026 for Na+, 0.010 ± 0.010 for NH4+, 0.065 ± 0.010 for Cl−, 0.093 ± 0.025 for NO3−, and 0.087 ± 0.011 for SO42−.
Nano-Mechanical Transduction of Polymer Micro-Cantilevers to Detect Bio-Molecular Interactions
Authors: Urwyler Prabitha , Köser Joachim , Schift Helmut , Gobrecht Jens , Müller Bert
Published: February 2012

Using variothermal polymer micro-injection molding, disposable arrays of eight polymer micro-cantilevers each 500 μm long, 100 μm wide and 25 μm thick were fabricated. The present study took advantage of an easy flow grade polypropylene. After gold coating for optical read-out and asymmetrical sensitization, the arrays were introduced into the Cantisens® Research system to perform mechanical and functional testing. We demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 μM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.
Dynamic Cellular Uptake of Mixed-Monolayer Protected Nanoparticles
Authors: Carney Randy P. , Carney Tamara M. , Mueller Marie , Stellacci Francesco
Published: February 2012

Nanoparticles (NPs) are gaining increasing attention for potential application in medicine; consequently, studying their interaction with cells is of central importance. We found that both ligand arrangement and composition on gold nanoparticles play a crucial role in their cellular internalization. In our previous investigation, we showed that 66-34OT nanoparticles coated with stripe-like domains of hydrophobic (octanethiol, OT, 34%) and hydrophilic (11-mercaptoundecane sulfonate, MUS, 66%) ligands permeated through the cellular lipid bilayer via passive diffusion, in addition to endo-/pino-cytosis. Here, we show an analysis of NP internalization by DC2.4, 3T3, and HeLa cells at two temperatures and multiple time points. We study four NPs that differ in their surface structures and ligand compositions and report on their cellular internalization by intracellular fluorescence quantification. Using confocal laser scanning microscopy we have found that all three cell types internalize the 66-34OT NPs more than particles coated only with MUS, or particles coated with a very similar coating but lacking any detectable ligand shell structure, or ‘striped’ particles but with a different composition (34-66OT) at multiple data points.
Multitransition kinks and pulses for fourth order equations with a bistable nonlinearity
Authors: Bonheure Denis
Published: February 2012

We study the existence of stationary solutions of a class of diffusion equations related to the so-called extended Fisher–Kolmogorov equation and the Swift–Hohenberg equation. We prove the existence of multitransition kinks and pulses. These solutions are obtained as local minima of the associated functional. For the Swift–Hohenberg equation, our result partially proves a numerical conjecture.

Nous étudions l’existence de solutions stationnaires d’une classe d’équations de diffusion incluant l’équation de Fisher–Kolmogorov généralisée et l’équation de Swift–Hohenberg. Nous démontrons l’existence de solutions hétéroclines et homoclines à transitions multiples. Ces solutions sont des minima locaux de la fonctionnelle associée. Nos résultats couvrent partiellement une conjecture numérique concernant l’équation de Swift–Hohenberg.
A Synthetic Biology Project – Developing a single‐molecule device for screening drug–target interactions
Authors: Firman Keith , Evans Luke , Youell James
Published: February 2012

This review describes a European‐funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug–target interactions at the single‐molecule level. Production of the proteins required for the system followed the principle of previously described “bioparts” concepts (a system where a database of biological parts – promoters, genes, terminators, linking tags and cleavage sequences – is used to construct novel gene assemblies) and cassette‐type assembly of gene expression systems (the concept of linking different “bioparts” to produce functional “cassettes”), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette‐system. Finally, micro‐engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti‐malarial drugs, but we also suggest other potential uses for the device.
Article Commentary: Cultural Differences in Hand Rehabilitation
Authors: Erlandsson Gard
Published: February 2012

The purpose of this paper is to compare and contrast Western hand therapy interventions and practices in Chinese hospitals. For the past 2 years, I have been providing hand therapy in two local Chinese hospitals in the more developed eastern part of China. One hospital is a public traditional Chinese hospital and the other a private hospital that integrates a traditional Chinese medicine approach with international methods. Hand therapists take great pride in our profession and constantly strive to improve clinical skills and seek innovative solutions to complex hand injuries. We are regularly challenged with traumatic injuries that require the use of our expertise, creativity, and problem-solving skills in order to enable clients to re-engage in their life roles and occupations. The opportunity to practice in different cultural settings generates a sense of excitement, adventure, challenges, and drama and requires a deep commitment to the practice of hand rehabilitation.