bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of upland open drains upon runoff generation: a numerical assessment of catchment‐scale impacts
Authors: Lane Stuart N. , Milledge David G.
Published: March 2012

Shallow upland drains, grips, have been hypothesized as responsible for increased downstream flow magnitudes. Observations provide counterfactual evidence, often relating to the difficulty of inferring conclusions from statistical correlation and paired catchment comparisons, and the complexity of designing field experiments to test grip impacts at the catchment scale. Drainage should provide drier antecedent moisture conditions, providing more storage at the start of an event; however, grips have higher flow velocities than overland flow, thus potentially delivering flow more rapidly to the drainage network. We develop and apply a model for assessing the impacts of grips on flow hydrographs. The model was calibrated on the gripped case, and then the gripped case was compared with the intact case by removing all grips. This comparison showed that even given parameter uncertainty, the intact case had significantly higher flood peaks and lower baseflows, mirroring field observations of the hydrological response of intact peat. The simulations suggest that this is because delivery effects may not translate into catchment‐scale impacts for three reasons. First, in our case, the proportions of flow path lengths that were hillslope were not changed significantly by gripping. Second, the structure of the grip network as compared with the structure of the drainage basin mitigated against grip‐related increases in the concentration of runoff in the drainage network, although it did marginally reduce the mean timing of that concentration at the catchment outlet. Third, the effect of the latter upon downstream flow magnitudes can only be assessed by reference to the peak timing of other tributary basins, emphasizing that drain effects are both relative and scale dependent. However, given the importance of hillslope flow paths, we show that if upland drainage causes significant changes in surface roughness on hillslopes, then critical and important feedbacks may impact upon the speed of hydrological response. Copyright © 2012 John Wiley & Sons, Ltd.
Ice jam modelling and field data collection for flood forecasting in the Saint John River, Canada
Authors: Beltaos Spyros , Tang Patrick , Rowsell Robert
Published: March 2012

Ice jams cause major flooding and severe damages to communities and infrastructure along the Saint John River. There is a growing need to develop capability in forecasting and analysing ice‐jam‐related flood events. This capability is also essential in anticipating the potential for increased ice jam damages as a result of a changing climate. The well‐known and user‐friendly Hydrologic Engineering Centre's River Analysis System (HEC‐RAS) model, which can simulate ice jam configuration under steady‐state conditions, has been calibrated for operational application along the international Saint John River from Dickey, Maine, USA, to Grand Falls, New Brunswick. Examples of model results are presented, and the modelling experience gained to date is outlined. Surprisingly, model output begins to deteriorate when the spacing of cross sections is less than a site‐specific threshold. Once calibrated, the model generates good results, but model parameters change from site to site. Inconsistencies relative to current ice jam understanding and potential improvements are identified. A dangerous consequence of jamming is the sharp wave (jave for short) that is generated upon ice jam release. At present, dynamic aspects of breakup can best be assessed by measurement. Specially designed portable loggers were deployed in 2009 to capture various javes as well as the spring flood that typically arrives after ice clearance. The results enabled a comprehensive comparison between the characteristics of javes and runoff waves, whereas the runoff data were also used to test the unsteady flow routine of HEC‐RAS, which can be used to develop forecasts for runoff floods. Copyright © 2012 Her Majesty the Queen in right of Canada. Published by John Wiley & Sons, Ltd.
Dimensionality reduction in drought modelling
Authors: Santos João Filipe , Portela Maria Manuela , Pulido‐Calvo Inmaculada
Published: March 2012

For monitoring hydrological events characterized by high spatial and temporal variability, the number and location of recording stations must be carefully selected to ensure that the necessary information is collected. Depending on the characteristics of each natural process, certain stations may be spurious or redundant, whereas others may provide most of the relevant data. With the objective of reducing the costs of the monitoring system and, at the same time, improving its operational effectiveness, three procedures were applied to identify the minimum network of rain gauge stations able to capture the characteristics of droughts in mainland Portugal. Drought severity is characterized by the standardized precipitation index applied to the timescales of 1, 3, 6 and 12 consecutive months. The three techniques used to reduce the dimensionality of the network of rain gauges were as follows: (i) artificial neural networks with sensitivity analysis, (ii) application of the mutual information criterion and (iii) K‐means cluster analysis using Euclidean distances. The results demonstrated that the best dimensionality reduction method was case dependent in the three regions of Portugal (northern, central and southern) previously identified by cluster analysis. All the reduction techniques lead to the selection of a subset of rain gauges capable of reproducing the original temporal patterns of drought. For specific severe drought events in Portugal in the past, the comparison between drought spatial patterns obtained with the original stations and the selected subset indicated that the subset produced statistically satisfactory results (correlation coefficients higher than 0.6 and efficiency coefficients higher than 0.5). Copyright © 2012 John Wiley & Sons, Ltd.
CONVERGENT READINGS OF GROUNDWATER GOVERNANCE? ENGAGING EXCHANGES BETWEEN DIFFERENT RESEARCH PERSPECTIVES
Authors: Faysse Nicolas , Petit Olivier
Published: March 2012

In the last 50 years, the study of groundwater governance has given rise to rich and differentiated analytical approaches. This article proposes an exchange between the main heuristic viewpoints, results and theses of three approaches which studied groundwater governance: the study of groundwater governance as collective action initiated by Ostrom, the analysis made by Shah on informal groundwater economies and the works of Prakash, Mukherji and Birkenholtz drawing on political ecology. The aquifers on which each approach originally built its analysis played a key role in the design of analytical frameworks which, in the case of the first two approaches, were later applied to a much larger set of cases. The three approaches share many commonalities in their heuristic methods. However, they differ in the content of governance systems recommended to achieve sustainable groundwater use, and especially in the benefits of involving water users in the implementation of governance. Therefore, they also differ on what should be the focus of academic analyses. It is thus of interest to organize joint readings of cases of groundwater governance and to discuss the contents of research programmes able to provide fruitful analyses of these cases, based on local specificities. Copyright © 2012 John Wiley & Sons, Ltd.
Nonclinical vaccine safety evaluation: advantages of continuous temperature monitoring using abdominally implanted data loggers
Authors: Kaaijk Patricia , van der Ark Arno A. J. , van Amerongen Geert , van den Dobbelsteen Germie P. J. M.
Published: March 2012

Fever has been reported as the most common adverse event after vaccination in infants and children. For this reason it is important that, prior to clinical testing of a new vaccine, change in body temperature following vaccination is tested carefully in nonclinical animal studies. Since both the timing and the height of the temperature peak after vaccination may differ from vaccine to vaccine, it is important that the time point for body temperature measurement should be chosen on a case‐by‐case basis with sufficient knowledge of the specific vaccine. In order to determine the best time point for rectal body temperature measurement after vaccination with a new vaccine candidate against N. meningitidis serogroup B, to be applied in a formal Good Laboratory Practice (GLP) toxicology study, miniature temperature data loggers were implanted into the peritoneal cavity of rabbits. The continuous body temperature monitoring appeared to give a complete picture of the entire body temperature kinetics after vaccination. The body temperature peaked at 4 h after vaccination, and this time point was subsequently applied in the toxicology study. Measured body temperature values at the selected time point of 4 h after vaccination were comparable in the continuous temperature setting and in the formal toxicology study, i.e. rectal temperature measurement at one time point. In the present study implanted temperature loggers were successfully used to define an adequate time point to be applied in determining rectal body temperature in a formal GLP toxicology study with a new vaccine candidate. Copyright © 2012 John Wiley & Sons, Ltd.
Methyl tert butyl ether is anti‐angiogenic in both in vitro and in vivo mammalian model systems
Authors: Kozlosky John , Bonventre Josephine , Cooper Keith
Published: March 2012

Methyl‐tertiary butyl ether (MTBE), a well known gasoline oxygenate, and US Food and Drug Administration approved gallstone treatment, has been previously shown to specifically target teleost embryonic angiogenesis. The studies reported here were to determine whether similar vascular disrupting effects occur in higher vertebrate models. Rat brain endothelial cells were isolated and allowed to form microcapillary‐like tubes on Matrigel. MTBE (0.34–34.0 mm) exposure resulted in a dose‐dependent reduction of tube formation, with the LOAEL at 0.34 mm, while MTBE's primary metabolite, tertiary butyl alcohol had no effect on tube formation. HUVECs, a primary cell line representing macrovascular cells, were able to form tubes on Matrigel in the presence of MTBE (1.25–80 mm), but the tubes were narrower than those formed in the absence of MTBE. In a mouse Matrigel plug implantation assay, 34.0 mm MTBE completely inhibited vessel invasion into plugs containing endothelial cell growth supplement (ECGS) compared with control plugs with ECGS alone. When timed‐pregnant Fisher 344 rats were gavaged with MTBE (500–1500 mg kg−1) from day 6 of organogenesis through 10 days post‐parturition, no organ toxicity or histological changes in pup vasculature were observed. Results of the in vitro cell culture studies show that MTBE is anti‐angiogenic at mm concentrations and has potential use as an anti‐angiogenic treatment for solid tumors with minimal toxicity. Copyright © 2012 John Wiley & Sons, Ltd.
Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer
Authors: Kwon Min J. , An Songhie , Choi Sunghyun , Nam Kihoon , Jung Hye S. , Yoon Chang S. , Ko Jung H. , Jun Hye J. , Kim Tae K. , Jung Soo J. , Park Jeong H. , Lee Yan , Park Jong‐Sang
Published: March 2012

Background

The development of an efficient method to improve the wound healing process is urgently required for diabetic patients suffering a threat of limb amputations. Various growth factors have been proposed for treatment; however, more research still has to be carried out to maintain their curative effect. In the present study, we describe a simple nonviral gene therapy method for improving wound healing.

Methods

Minicircle plasmid DNA encoding vascular endothelial growth factor (VEGF) was combined with an arginine‐grafted cationic dendrimer, PAM‐RG4. The formed complexes were injected subcutaneously into the skin wounds of diabetic mice.

Results

Actively proliferating cells in wound tissue were efficiently transfected, resulting in a high level of VEGF expression. Within 6 days after injection, skin wounds in the diabetic mice were generally healed and displayed a well‐ordered dermal structure, which was confirmed by histological staining.

Conclusions

This simple and effective gene therapy method may represent a powerful tool for the treatment of diabetic foot ulcers and other diseases that are refractory to treatment. Copyright © 2012 John Wiley & Sons, Ltd.
Mapping of discontinuous conformational epitopes by amide hydrogen/deuterium exchange mass spectrometry and computational docking
Authors: Pandit Deepangi , Tuske Steven J. , Coales Stephen J , E Sook Yen , Liu Anita , Lee Jessica E. , Morrow Jeffrey A. , Nemeth Jennifer F. , Hamuro Yoshitomo
Published: March 2012

Understanding antigen–antibody interactions at the sub‐molecular level is of particular interest for scientific, regulatory, and intellectual property reasons, especially with increasing demand for monoclonal antibody therapeutic agents. Although various techniques are available for the determination of an epitope, there is no widely applicable, high‐resolution, and reliable method available. Here, a combination approach using amide hydrogen/deuterium exchange coupled with proteolysis and mass spectrometry (HDX‐MS) and computational docking was applied to investigate antigen–antibody interactions. HDX‐MS is a widely applicable, medium‐resolution, medium‐throughput technology that can be applied to epitope identification. First, the epitopes of cytochrome c–E8, IL‐13–CNTO607, and IL‐17A–CAT‐2200 interactions identified using the HDX‐MS method were compared with those identified by X‐ray co‐crystal structures. The identified epitopes are in good agreement with those identified using high‐resolution X‐ray crystallography. Second, the HDX‐MS data were used as constraints for computational docking. More specifically, the non‐epitope residues of an antigen identified using HDX‐MS were designated as binding ineligible during computational docking. This approach, termed HDX‐DOCK, gave more tightly clustered docking poses than stand‐alone docking for all antigen–antibody interactions examined and improved docking results significantly for the cytochrome c–E8 interaction. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of neutralizing affinity‐matured human respiratory syncytial virus F binding antibodies in the sub‐picomolar affinity range
Authors: Canziani Gabriela A. , Melero Jose A. , Lacy Eilyn R.
Published: March 2012

In the human adaptation and optimization of a mouse anti–human respiratory syncytial virus neutralizing antibody, affinity assessment was crucial to distinguish among potential candidates and to evaluate whether this correlated with function in vitro and in vivo. This affinity assessment was complicated by the trimeric nature of the antigen target, respiratory syncytial virus F (RSV‐F) glycoprotein. In the initial affinity screen, surface plasmon resonance was used to determine the intrinsic binding affinities of anti‐RSV‐F Fab and immunoglobulin G (IgG) to the extracellular domain of RSV‐F. This assessment required minimal biotinylation of the RSV‐F protein and design of a capture strategy to minimize avidity effects. Approximately 30 Fabs were selected from three optimization phage display libraries on the basis of an initial ELISA screen. Surface plasmon resonance analysis demonstrated the success of optimization with some candidates from the screened libraries having low picomolar dissociation constants, more than 700‐fold tighter than the parental monoclonal antibody (B21M). The affinities of these antibodies were further evaluated by a kinetic exclusion assay, a solution binding technology. One IgG (monoclonal antibody 029) displayed a low picomolar KD comparable with that of motavizumab, an RSV antibody in clinical study. Kinetic exclusion assay showed that two other of the matured IgGs (011 and 019) had sub‐picomolar dissociation constants that could not be resolved further. We discuss the relevance of these interaction analysis results in the light of recently published data on the mechanism of F‐driven viral fusion during paramyxoviral infection and 101F epitope conservation revealed from the recent crystal structure of RSV‐F in the post‐fusion state. Copyright © 2012 John Wiley & Sons, Ltd.
Equilibrium and kinetic analysis of human interleukin‐13 and IL‐13 receptor alpha‐2 complex formation
Authors: Lacy Eilyn R.
Published: March 2012

Interleukin 13 (IL‐13) is a pleiotropic cytokine secreted by activated T cells. Both IL‐13 and its polymorphic variant (IL‐13‐R110Q) have been shown to be associated with multiple diseases such as asthma and allergy. Two IL‐13 receptors have been identified, IL‐13R alpha‐1 receptor (IL‐13Rα1) and IL‐13R alpha‐2 receptor (IL‐13Rα2). It has been well established that IL‐13 binds to IL‐13Rα1 alone with low nM affinity while binding to the IL‐13Rα1/IL‐4R receptor complex is significantly tighter (pM). The affinity between IL‐13 and IL‐13Rα2, however, remains elusive. Several values have been reported in the literature varying from 20 pM to 2.5 nM. The affinities previously reported were obtained using surface plasmon resonance (SPR) or Scatchard analysis of 125I‐IL‐13 binding data. This report presents the results for the kinetics and equilibrium binding analysis studies performed using label‐free kinetic exclusion assay (KEA) for the interaction of human IL‐13 and IL‐13Rα2. KEA equilibrium analysis showed that the affinities of IL‐13Rα2 are 107 and 56 pM for IL‐13 and its variant (IL‐13‐R110Q), respectively. KEA kinetic analysis showed that a tight and very stable complex is formed between IL‐13Rα2 and IL‐13, as shown by calculated dissociation rate constants slower than 5 × 10−5 per second. Kinetic analysis also showed significant differences in the kinetic behavior of wild type (wt) versus IL‐13‐R110Q. IL‐13‐R110Q not only associates to IL‐13Rα2 slower than wt human IL‐13 (wt‐IL‐13), as previously reported, but IL‐13‐R110Q also dissociates slower than wt‐IL‐13. These results show that IL‐13Rα2 is a high affinity receptor and provide a new perspective on kinetic behavior that could have significant implications in the understanding of the role of IL‐13‐R110Q in the disease state. Copyright © 2012 John Wiley & Sons, Ltd.
Enhancing the efficiency of removing support material from rapid prototype parts
Authors: Kuo C.‐C. , Tsou Y.‐C. , Chen B.‐C.
Published: March 2012

The optimal process parameters for removing support material from rapid prototype (RP) part using the Taguchi method are investigated. Four parameters of pH value, solvent temperature, depth of the RP, and distance of the RP part are considered as control factors. The experimental trials based on L9 (34) orthogonal array are carried out. Based on the results of analysis of variance, the most significant factor is the solvent temperature having a percentage contribution of 83.32%. Through the confirmation experiment, the savings in the removing time can exceed 70% using the optimal parameters. The mechanism of removing support material from RP part is presented in this work.
Effects of various parameters on ultrasonic separation of inclusions from magnesium alloy melt
Authors: Shao Z.‐W. , Le Q.‐C. , Zhang Z.‐Q. , Cui J.‐Z.
Published: March 2012

The acoustic radiation force generated by ultrasonic standing wave in the flow media can make solid particles suspending in the liquid agglomerate at the nodal planes of the waves and then realize their separation, which is also known as ultrasonic agglomeration in chemical industry. In this paper, ultrasonic waves were employed to promote and accelerate the separation of inclusions from magnesium alloy melt, and the effect of acoustic radiation forces on oxide inclusions removal from magnesium alloy melts were studied by numerical calculation. The agglomeration behavior of the inclusions was also obtained by solving the equations of motion for inclusions. Finally, parametric studies, usually very helpful for continued optimization and design efforts, were carried out to evaluate the effects of various parameters such as ultrasonic power, ultrasonic treating time, particle size and density difference between particle and melt on the inclusions distribution. The results indicate that when a moderate ultrasonic power was applied, most of inclusions could agglomerate at wave nodes in a short time which finally enhanced and accelerated the separation of inclusions from magnesium alloy melt.
Features of austenitic steels' microstructure following plastic deformation
Authors: Gershteyn G. , Shevchenko N. , Diekamp M. , Brosius A. , Schaper M. , Bach Fr.‐W.
Published: March 2012

The carried out transmission electron microscopic (TEM) analysis of steels 316L and TWIP, has shown that important mechanisms of plastic deformation are mechanical twinning, shear band formation and deformation martensitic transformations. Mechanical twinning is a characteristic feature of a plastic deformation at ε ≈ (20–50) % deformation degrees. At ε = (20–70) % the basic contribution in plastic deformation of a material brings shear band formation. The contribution deformation martensitic transformations into plastic deformation is defined by level of phase instability of steels.
Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS
Authors: Mirbahai Ladan , Wilson Martin , Shaw Christopher S. , McConville Carmel , Malcomson Roger D. G. , Kauppinen Risto A. , Peet Andrew C.
Published: March 2012

Biomarkers of early response to treatment have the potential to improve cancer therapy by allowing treatment to be tailored to the individual. Alterations in lipids detected by in vivo MRS have been suggested as noninvasive biomarkers of cell stress and early indicators of cell death. An improved understanding of the relationship between MRS lipids and cell stress in vitro would aid in the translation of this technique into clinical use. Rat BT4C glioma cells were treated with 50 µ m cis‐dichlorodiammineplatinum II (cisplatin), a commonly used chemotherapeutic agent, and harvested at several time points up to 72 h. High‐resolution magic angle spinning 1H MRS of cells was then performed on a 600‐MHz NMR spectrometer. The metabolites were quantified using a time domain fitting method, TARQUIN. Increases were detected in saturated and polyunsaturated fatty acid resonances early during the exposure to cisplatin. The fatty acid CH2/CH3 ratio was unaltered by treatment after allowing for contributions of macromolecules. Polyunsaturated fatty acids increased on treatment, with the group –CH = CH–CH2–CH = CH– accounting for all the unsaturated fatty acid signals. Transmission electron microscopy, in addition to Nile red and 4',6‐diamino‐2‐phenylindole co‐staining, revealed that the lipid increase was associated with cytoplasmic neutral lipid droplets. Small numbers of apoptotic and necrotic cells were detected by trypan blue, annexin V–fluorescein isothiocyanate‐labelled flow cytometry and DNA laddering after up to 48 h of cisplatin exposure. Propidium iodide flow cytometry revealed that cells accumulated in the G1 stage of the cell growth cycle. In conclusion, an increase in the size of the lipid droplets is detected in morphologically viable cells during cisplatin exposure. 1H MRS can detect lipid alterations during cell cycle arrest and progression of cell death, and has the potential to provide a noninvasive biomarker of treatment efficacy in vivo. Copyright © 2012 John Wiley & Sons, Ltd.
Lactate and glycine—potential MR biomarkers of prognosis in estrogen receptor‐positive breast cancers
Authors: Giskeødegård Guro F. , Lundgren Steinar , Sitter Beathe , Fjøsne Hans E. , Postma Geert , Buydens Lutgarde M. C. , Gribbestad Ingrid S. , Bathen Tone F.
Published: March 2012

Breast cancer is a heterogeneous disease with a variable prognosis. Clinical factors provide some information about the prognosis of patients with breast cancer; however, there is a need for additional information to stratify patients for improved and more individualized treatment. The aim of this study was to examine the relationship between the metabolite profiles of breast cancer tissue and 5‐year survival. Biopsies from breast cancer patients (n = 98) were excised during surgery and analyzed by high‐resolution magic angle spinning MRS. The data were analyzed by multivariate principal component analysis and partial least‐squares discriminant analysis, and the findings of important metabolites were confirmed by spectral integration of the metabolite peaks. Predictions of 5‐year survival using metabolite profiles were compared with predictions using clinical parameters. Based on the metabolite profiles, patients with estrogen receptor (ER)‐positive breast cancer (n = 71) were separated into two groups with significantly different survival rates (p = 0.024). Higher levels of glycine and lactate were found to be associated with lower survival rates by both multivariate analyses and spectral integration, and are suggested as biomarkers for breast cancer prognosis. Similar metabolic differences were not observed for ER‐negative patients, where survivors could not be separated from nonsurvivors. Predictions of 5‐year survival of ER‐positive patients using metabolite profiles gave better and more robust results than those using traditional clinical parameters. The results imply that the metabolic state of a tumor may provide additional information concerning breast cancer prognosis. Further studies should be conducted in order to evaluate the role of MR metabolomics as an additional clinical tool for determining the prognosis of patients with breast cancer. Copyright © 2012 John Wiley & Sons, Ltd.
Occipitalization of the Atlas in Archaeological Material from the 16th–19th Century
Authors: Bašić Z. , Anterić I. , Škorić E. , Vilović K. , Anđelinović š.
Published: March 2012

During the anthropological analysis of skeletal material dated in the 16th–19th century from St Katarina monastery in Split, a female skull with occipitalization of atlas has been found. Anterior part of atlas and foramen magnum were fused, with numerous perforations on auricular surface of atlas. As the age at death was estimated at more than 70 years, it is most likely that this woman had progressive course of illness. Copyright © 2012 John Wiley & Sons, Ltd.
Critical issues for safer dryer operations
Authors: Kwasny R.
Published: March 2012

Drying is an especially hazardous operation. To make this operation safer, it is critical to understand the hazards associated with decomposition, fire, and explosion including worst‐case scenarios resulting from operational and control failures.

This article describes the tests and standards required to prevent accidents when handling bulk powders and dusts. The outcome of these tests and standards is to quantify the risks for normal and upset conditions and to implement adequate safeguards to prevent accidents. © 2012 American Institute of Chemical Engineers Process Saf Prog, 2012
Japanese encephalitis and Japanese encephalitis virus in mainland China
Authors: Zheng Yayun , Li Minghua , Wang Huanyu , Liang Guodong
Published: March 2012

Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV) infection, is the most important viral encephalitis in the world. Approximately 35,000–50,000 people suffer from JE every year, with a mortality rate of 10,000–15,000 people per year. Although the safety and efficacy of JE vaccines (inactivated and attenuated) have been demonstrated, China still accounts for 50% of the reported JE cases worldwide. In this review, we provide information about the burden of JE in mainland China and the corresponding epidemiology from 1949 to 2010, including the morbidity and mortality of JE; the age, gender, and vocational distribution of JE cases; its regional and seasonal distribution; and JE immunization. In addition, we discuss the relationships among vectors, hosts, and JEV isolates from mainland China; the dominant vector species for JEV transmission; the variety of JEV genotypes and the different biological characteristics of the different JEV genotypes; and the molecular evolution of JEV. Copyright © 2012 John Wiley & Sons, Ltd.
Microstructure and surface roughness of graphite‐like carbon films deposited on silicon substrate by molecular dynamic simulation
Authors: Huang Deming , Pu Jibin , Lu Zhibin , Xue Qunji
Published: March 2012

Molecular dynamics simulations are performed on the atomic origin of the growth process of graphite‐like carbon film on silicon substrate. The microstructure, mass density, and internal stress of as‐deposited films are investigated systematically. A strong energy dependence of microstructure and stress is revealed by varying the impact energy of the incident atoms (in the range 1–120 eV). As the impact energy is increased, the film internal stress converts from tensile stress to compressive stress, which is in agreement with the experimental results, and the bonding of C‐Si in the film is also increased for more substrate atoms are sputtered into the grown film. At the incident energy 40 eV, a densification of the deposited material is observed and the properties such as density, sp3 fraction, and compressive stress all reach their maximums. In addition, the effect of impact energy on the surface roughness is also studied. The surface morphology of the film exhibits different characteristics with different incident energy. When the energy is low (<40 eV), the surface roughness is reduced with the increasing of incident energy, and it reaches the minimum at 50 eV. Copyright © 2012 John Wiley & Sons, Ltd.
Polyaniline/carbon nanotube composite films electrosynthesis through diazonium salts electroreduction and electrochemical polymerization
Authors: Pilan Luisa , Raicopol Matei , Pruna Alina , Branzoi Viorel
Published: March 2012

In this work, we combine two widely used techniques to produce modified electrodes, that is, the electroreduction of diazonium salts and the electropolymerization of conductive polymers in order to obtain polyaniline (PANI)/carbon nanotube (CNTs) composites. Thus, in a first step, a CNTs electrode was functionalized with 4‐nitrophenyl group by electrochemical reduction of 4‐nitrobenzenediazonium salt in nonaqueous media. Then, the nitro group was reduced electrochemically to amine functionality. Cyclic voltammetry and electrochemical impedance spectroscopy were used to trace the reactions in each step. The PANI film can easily be grafted onto the surface of such obtained aminophenyl‐modified CNTs electrodes. The PANI/CNTs films generated by this strategy show electrochemical behavior similar to that of PANI simply electrodeposited on CNTs electrodes, but exhibit significantly improved stability and higher capacitance values. Copyright © 2012 John Wiley & Sons, Ltd.
X‐ray photoelectron spectroscopy: surface and depth profiling studies of glasses doped with Nd and Yb ions
Authors: Rivera‐López F. , Pérez Mariano
Published: March 2012

In this work, a chemical characterization of phosphate glasses doped with Nd and Yb ions by means of high‐resolution X‐ray photoelectron spectroscopy (XPS) is presented. The results obtained are correlated with both the infrared absorption and luminescence spectra after laser excitation. One of the important goals of this work is to obtain information about the rare‐earth dopant distribution in the glass. In this sense, valuable information is obtained by high‐resolution XPS depth profiling, in order to study the uniform/non‐uniform distribution of precursor element concentrations from the surface to deeper zones. When this Nd‐Yb co‐doped glass system is considered as a potential laser device, the distribution of precursor elements can affect the rare‐earth optical output luminescence properties depending on the focused pumping point. In addition, the XPS technique also permitted a chemical characterization of the glasses both in surface and volume, giving information about the valence state of the rare‐earth ions in these glasses and the vibrational properties. Copyright © 2012 John Wiley & Sons, Ltd.
A Modern Dilemma for Chemistry and Civic Responsibility: The Tragic Life of Clara Immerwahr
Authors: Meschel Susan V.
Published: March 2012

Clara Immerwahr was a talented chemist born at the end of the 19th century. In 1900, she received the first doctorate in chemistry awarded to a woman candidate at Breslau University, Germany. She married Nobel Laureate Fritz Haber and vehemently opposed his well‐known work on chemical warfare during WWI. Popular works, including theater and documentary film, dramatize her dilemma in a way that can catalyze meaningful discussion in college‐level chemistry courses on scientists' ethical and civic responsibilities. This paper surveys her life, accomplishments in chemistry, and her legacy.
A Series of [Mn6] Complexes with Terminal Functional Groups
Authors: Hołyńska Małgorzata , Dehnen Stefanie
Published: March 2012

A series of [Mn6O2(R1OH)4(sao)6(R2COO)2] complexes with terminal functional groups (1: R1 = CH3, R2 = HO‐C6H4, 2: R1 = C2H5, R2 = H2N‐C6H4, 3: R1 = CH3, R2 = Cl‐C6H4, 4: R1 = CH3, R2 = CH3S‐C6H4, 5: R1 = CH3, R2 = I‐C6H4, 6: R1 = CH3, R2 = pymSCH2, 7: R1 = CH3, R2 = ortho‐pyr‐SCH3, 8: R1 = C2H5, R2 = (CH3)3OOCNHCH2C6H4; sao = doubly deprotonated salicylaldoxime ligand, pym = pyrimidyl, pyr = pyridyl) have been obtained in a reaction of a ligand R2C6H4COOH, salicylaldoxime, manganese(II) perchlorate and [NEt4](OH) in methanol or a 1:1 mixture of ethanol and dichloromethane. In this report, structural aspects as well as preliminary studies of magnetic and thermal properties are presented. Compounds 1, 3, 6, 8 exhibit an antiferromagnetic coupling of the Mn2+ ions, whereas 4 and 7 show ferromagnetic interactions. The title compounds may act as starting materials for further derivatization addressing the functional groups.
{nBuMg(OR)}2 und {Mg(OR)2}2 (R = 2, 4, 6‐tBu3C6H2) – sterisch überfrachtete Magnesiumalkoholate
Authors: Flörke Ulrich , Henkel Gerald , Kuhn Annette , Kuhn Norbert , Laufer Stefan , Maichle‐Mößmer Cäcilia
Published: March 2012

Reaction of 2, 4, 6‐tri‐tert‐butylphenol (1) with di‐n‐butylmagnesium in the molar ratio 1:1 allows the synthesis of {(nBu)Mg(μ‐OR)2Mg(nBu)} (2) (R = 2, 4, 6‐tBu3C6H2), which reacts with excess 1 to give the homoleptic alcoholate complex {(RO)Mg(μ‐OR)2Mg(OR)} (3) (R = 2, 4, 6‐tBu3C6H2). The structures of 2 and 3 were determined by X‐ray crystallography.
The clinical implementation of whole genome sequencing: a conversation with seven scientific experts
Authors: Lerner‐Ellis Jordan P.
Published: March 2012

This commentary is based on the key note address given by Jordan Lerner‐Ellis at the annual symposium of the Society for the Study of Inborn Errors of Metabolism, held in Geneva, Switzerland in August 2011. The content of the address was developed from a series of discussions with seven clinicians and medical geneticists, all having a long‐time interest in genetic testing and genomic medicine (the interviews were not intended to be a forum for the introduction of new data). All participants were asked to offer their views on five questions: the benefits of using whole genome sequencing (WGS) in the clinic; the corresponding risks; the limitations on its wider use; the interviewees’ particular interests in using WGS in their practice; and projected timelines for successful adoption in clinical medicine.
Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation
Authors: de Laat Paul , Koene Saskia , den van Heuvel Lambert P. W. J. , Rodenburg Richard J. T. , Janssen Mirian C. H. , Smeitink Jan A. M.
Published: March 2012

The m.3243A > G mutation has become known as the MELAS mutation. However, many other clinical phenotypes associated with this mutation have been described, most frequently being maternally inherited diabetes and deafness (MIDD). The m.3243A > G mutation, can be detected in virtually all tissues, however heteroplasmy differs between samples. Recent reports indicate, a preference to perform mutation analysis in urinary epithelial cells (UEC). To test this, and to study a correlation between the mutational load in different tissues with two mitochondrial scoring systems (NMDAS and NPMDS) we investigated 34 families carrying the m.3243A > G mutation. Heteroplasmy was determined in three non‐invasively collected samples, namely leucocytes, UEC and buccal mucosa. We included 127 patients, of which 82 carried the m.3243A > G mutation. None of the children (n = 11) had specific complaints. In adults (n = 71), a median NMDAS score of 15 (IQR 10‐24) was found. The most prevalent symptoms were hearing loss(48%), gastro‐intestinal problems(42%), exercise intolerance(38%) and glucose intolerance(37%). Ten patients had neurologic involvement. Buccal mucosa had the best correlation with the NMDAS in all adults (r = 0.437,p < 0.001), whereas UEC had the strongest correlation with the NMDAS in severely affected patients (r = 0.593,p = 0.002). Heteroplasmy declined significantly with increasing age in all three samples (leucocytes r = ‐0.705 (p < 0.001), UEC r = ‐0.374(p = 0.001), buccal mucosa r = ‐0.460(p < 0.001). In our cohort of 82 patients, the m.3243A > G mutation causes a wide variety of signs and symptoms, MIDD being far more prevalent than MELAS. Looking at the characteristics of the three non‐invasively available tissues for testing heteroplasmy we confirm that UEC are the preferred sample to test.
Gene therapy for metabolic disorders: an overview with a focus on urea cycle disorders
Authors: Alexander Ian E. , Kok Cindy , Dane Allison P. , Cunningham Sharon C.
Published: March 2012

Many metabolic diseases are compelling candidates for gene therapy, and are the subject of vigorous pre‐clinical research. Successful phenotype correction in mouse models is now commonplace and research effort is increasingly being directed towards addressing the translational challenges inherent in human clinical trials. This paper places current efforts to develop gene therapy approaches to metabolic disease in historical context and describes contemporary research in the authors’ laboratory on urea cycle defects, particularly ornithine transcarbamylase deficiency, in a manner that is illustrative of the general state of the field.
Lysine triggers apoptosis through a NADPH oxidase‐dependent mechanism in human renal tubular cells
Authors: Verzola Daniela , Famà Annamaria , Villaggio Barbara , Di Rocco Maia , Simonato Alchiede , D'Amato Elena , Gianiorio Fabio , Garibotto Giacomo
Published: March 2012

Progressive chronic kidney disease (CKD) is common in lysinuric protein intolerance (LPI), a primary inherited aminoaciduria characterized by massive Lysine excretion in urine. However, by which mechanisms Lysine may cause kidney damage to tubule cells is still not understood. This study determined whether Lysine overloading of human proximal tubular cells (HK‐2) in culture enhances apoptotic cell loss and its associated mechanisms. Overloading HK‐2 with Lysine levels reproducing those observed in urine of patients affected by LPI (10 mM) increased apoptosis (+30%; p < 0.01 vs.C), as well as Bax and Apaf‐1 expressions (+30‐50% p < 0.05), while downregulated Bcl‐2 (‐40% p < 0.05). Apoptosis induced by high Lysine was no longer observed after addition of caspase‐9 and caspase‐3 inhibitors while caspase‐8 inhibitor had no protective effect. High Lysine induced elevations in ROS generation and NADPH oxidase subunits mRNAs (p22 phox +106±23%, p67 phox +108±22% and gp91 phox +75±4% p < 0.05‐0.01). In addition, the NADPH oxidase inhibitor DPI prevented both ROS production and apoptosis. Treating HK‐2 with antioxidants, such as Cysteine and its analog, N‐acetyl‐l‐cysteine (NAC), rescued the HK‐2 from apoptosis induced by Lysine. In summary, our data show that high Lysine in vitro increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signaling. This event may represent a key cellular effect in the increasing the susceptibility of human tubular cells to apoptosis when the tubules cope with a high Lysine load. This effect is instrumental to renal damage and disease progression in patients with LPI.
Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease
Authors: Yau Thomas , Wong Hilda , Chan Pierre , Yao T. J. , Pang R. , Cheung T. T. , Fan S. T. , Poon Ronnie T.
Published: March 2012

Background The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment. Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed. Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28–61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08–1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08–11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities. Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.
Parsimonious Structural Equation Models for Repeated Measures Data, with Application to the Study of Consumer Preferences
Authors: Elrod Terry , Häubl Gerald , Tipps Steven W.
Published: March 2012

Recent research reflects a growing awareness of the value of using structural equation models to analyze repeated measures data. However, such data, particularly in the presence of covariates, often lead to models that either fit the data poorly, are exceedingly general and hard to interpret, or are specified in a manner that is highly data dependent. This article introduces methods for developing parsimonious models for such data. The underlying technology uses reduced-rank representations of the variances, covariances and means of observed and latent variables. The value of this approach, which may be implemented using standard structural equation modeling software, is illustrated in an application study aimed at understanding heterogeneous consumer preferences. In this application, the parsimonious representations characterize systematic relationships among consumer demographics, attitudes and preferences that would otherwise be undetected. The result is a model that is parsimonious, illuminating, and fits the data well, while keeping data dependence to a minimum.
Posterior spinal fusion in patients with Ehlers–Danlos syndrome: A report of six cases
Authors: Rabenhorst Brien Michael , Garg Sumeet , Herring J. Anthony
Published: March 2012

Purpose

There is a paucity of literature describing posterior spinal fusion (PSF) in the Ehlers–Danlos syndrome (EDS) patient. The vast majority of these studies diagnosed EDS clinically. The purpose of this study is to discuss the management and complications of EDS patients with scoliosis treated with PSF at a single institution.

Methods

Clinical and radiographic data are presented describing six patients who had PSF for EDS. The diagnoses were confirmed by a geneticist.

Results

All of the patients in the current cohort underwent posterior fusion only, with no anterior approach. Neuromonitoring was also used in the majority. Half of our patients experienced complications. One patient had a hemoperitoneum that was initially treated nonoperatively but, unfortunately, they expired 1 month after discharge from abdominal bleeding. Another patient suffered neuropathic pain attributed to the type of implant used. A third underwent a total of seven procedures beginning at the age of 3 years in a different era of spinal surgery. The mean major curve, percentage correction, and estimated blood loss of the current cohort are similar to previous studies.

Conclusion

The fragility of the EDS patient population cannot be overlooked. Despite a conservative surgical approach, half of our patients experienced complications. The surgeon choosing to operate on EDS patients must do so with extreme caution.
Asymmetric states of vitamin B12 transporter BtuCD are not discriminated by its cognate substrate binding protein BtuF
Authors: Korkhov Vladimir M. , Mireku Samantha A. , Hvorup Rikki N. , Locher Kaspar P.
Published: March 2012

BtuF, BtuD and BtuC physically interact by X‐ray crystallography (View interaction)
Promiscuity and specificity in BMP receptor activation
Authors: Mueller Thomas D. , Nickel Joachim
Published: March 2012

Bone Morphogenetic Proteins (BMPs), together with Transforming Growth Factor (TGF)‐β and Activins/Inhibins constitute the TGF‐β superfamily of ligands. This superfamily is formed by more than 30 structurally related secreted proteins. Since TGF‐β members act as morphogens, either a strict relation between a particular ligand to a distinct cellular receptor and/or temporospatial expression patterns of ligands and receptors is expected. Instead, only a limited number of receptors exist implicating promiscuous interactions of ligands and receptors. Furthermore, in complex tissues a multitude of different ligands can be found, which signal via overlapping subsets of receptors. This raises the intriguing question how concerted interactions of different ligands and receptors generate highly specific cellular signals, which are required during development and tissue homeostasis.
Mdm2 and MdmX partner to regulate p53
Authors: Wang Xinjiang , Jiang Xuejun
Published: March 2012

Mdm2 regulates the stability, translation, subcellular localization and transcriptional activity of p53 protein. Mdm2‐dependent p53 inhibition is essential in regulating p53 activity during embryonic development and in adult tissues. MdmX, an Mdm2 homolog, is also essential for p53 inhibition in vivo. Recent advances in the field from biochemical and genetic studies have revealed an essential role for the MdmX RING domain in Mdm2‐dependent p53 polyubiquitination and degradation. Mdm2 on its own is a monoubiquitin E3 ligase for p53, but is converted to a p53 polyubiquitin E3 ligase by MdmX through their RING–RING domain interactions. MdmX acts as an activator as well as a substrate of Mdm2/MdmX E3 complex. The insufficiency of Mdm2 for p53 polyubiquitination also demands other p53 E3 ligases or E4 factors be incorporated into the p53 degradation arena. Deubiquitinases nullify the effects of E3 actions and reverse the ubiquitination process, which permits a diverse and dynamic pattern of p53 stability control. Unsurprisingly, stress signals target MdmX to disengage the p53/Mdm2 feedback loop for timely and appropriate p53 responses to these stresses.