bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the hydrological behaviour of an urbanizing basin
Authors: Furusho C. , Andrieu H. , Chancibault K.
Published: January 2013

Suburban areas undergo rapid land‐use changes due to urban growth. Consequently, the mitigation of hydrological impacts is a major issue in the field of flood and water pollution management. Nevertheless, suburban catchments have seldom been studied. This paper presents a method for analyzing the hydrological behaviour of suburban catchments; the particular method is tested on the Chézine catchment, located in a suburban area of Nantes (western France). Chézine provides a typical example of a suburban catchment, yet features the unique behaviour of a response time ranging from 1 to 6 h. It is proposed herein to classify rainfall‐runoff events in homogeneous groups according to their flow coefficient. A group of events is characterized by its mean flow coefficient and by its transfer function, which are considered as the signatures of the hydrological behaviour of these similar events. The transfer function is identified from the available series of rainfall and outflow data. The identified transfer functions serve to estimate the localization of contributing zones over the basin by estimating the basin transfer function from flowpaths. The consistency of these assumptions is then verified by comparing the estimated transfer function with the identified one. The application of this method to the Chézine catchment demonstrates that it is possible to distinguish various types of hydrological behaviour regimes associated with significantly different transfer functions. The joint analysis of the flow coefficient and transfer function of each group confirms that the Chézine catchment reacts like an urban basin with just the urban zones contributing to runoff under dry conditions. Otherwise, the wetter the initial state, the greater the tendency of this basin to react like a natural basin, as reflected by the different transfer function shapes. These results confirm the validity of the proposed method to analyse the various behaviour regimes of suburban catchments. In addition, this method helps define the specifications of hydrological models suited to suburban catchments. Copyright © 2013 John Wiley & Sons, Ltd.
Comprehensive analysis of PTEN status in breast carcinomas
Authors: Jones Natalie , Bonnet Françoise , Sfar Sana , Lafitte Marie , Lafon Delfine , Sierankowski Ghislaine , Brouste Véronique , Banneau Guillaume , Tunon de Lara Christine , Debled Marc , MacGrogan Gaëtan , Longy Michel , Sevenet Nicolas
Published: January 2013

PTEN plays a well‐established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal‐like phenotype (p<0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumors as assessed by human epidermal growth factor receptor 2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumor subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan‐genomic profile. All of these tumors had relapsed and were associated with a poorer prognosis in the context of node negative disease (p=1.4 × 10−13) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome.
Targeting PI3K and mTORC2 in metastatic renal cell carcinoma: New strategies for overcoming resistance to VEGFR and mTORC1 inhibitors
Authors: Figlin Robert A. , Kaufmann Isabelle , Brechbiel Jillian
Published: January 2013

With the advent of molecularly targeted agents, treatment of metastatic renal cell carcinoma (mRCC) has improved significantly. Agents targeting the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin complex 1 (mTORC1) are more effective and less toxic than previous standards of care involving cytotoxic and cytokine therapies. Unfortunately, many patients relapse following treatment with VEGFR and mTORC1 inhibitors as a result of acquired resistance mechanisms, which are thought to lead to the reestablishment of tumor vasculature. Specifically, the loss of negative feedback loops caused by inhibition of mTORC1 leads to upregulation of downstream effectors of the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR pathway and subsequent activation of hypoxia‐inducible factor, an activator of angiogenesis. De novo resistance involving activated PI3K signaling has also been observed. These observations have led to the development of novel agents targeting PI3K, mTORC1/2 and PI3K/mTORC1/2, which have demonstrated antitumor activity in preclinical models of RCC. Several agents—BKM120, BEZ235 and GDC‐0980—are being investigated in clinical trials in patients with metastatic/advanced RCC, and similar agents are being tested in patients with solid tumors. The future success of mRCC treatment will likely involve a combination of agents targeting the multiple pathways involved in angiogenesis, including VEGFR, PI3K and mTORC1/2.
Anti‐tumor activity of CpG‐ODN aerosol in mouse lung metastases
Authors: Sfondrini Lucia , Sommariva Michele , Tortoreto Monica , Meini Alessandra , Piconese Silvia , Calvaruso Marco , Van Rooijen Nick , Bonecchi Raffaella , Zaffaroni Nadia , Colombo Mario P. , Tagliabue Elda , Balsari Andrea
Published: January 2013

Studies in preclinical models have demonstrated the superior anti‐tumor effect of CpG oligodeoxynucleotides (CpG‐ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG‐ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG‐ODN activated a local immune response, as indicated by production of IL‐12p40, IFN‐γ and IL‐1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG‐ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG‐ODN provided anti‐tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor‐bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG‐ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor‐induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.
Retracted: CDP/Cut is an osteoblastic coactivator of the vitamin D receptor (VDR)
Authors: Ochiai Eiji , Kitagawa Hirochika , Takada Ichiro , Fujiyama Sally , Sawatsubashi Shun , Kim Mi-sun , Mezaki Yoshihiro , Tsushima Yu , Takagi Ken-ichiro , Azuma Yoshiaki , Takeyama Ken-ichi , Yamaoka Kazuyoshi , Kato Shigeaki , Kamimura Takashi
Published: January 2013

Retraction: The following article from the Journal of Bone and Mineral Research, “CDP/Cut Is an Osteoblastic Coactivator of the Vitamin D Receptor (VDR)” by Eiji Ochiai, Hirochika Kitagawa, Ichiro Takada, Sally Fujiyama, Shun Sawatsubashi, Mi-sun Kim,Yoshihiro Mezaki, Yu Tsushima, Ken-ichiro Takagi, Yoshiaki Azuma, Ken-ichi Takeyama, Kazuyoshi Yamaoka, Shigeaki Kato, Takashi Kamimura, published online on December 11, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Thomas Clemens, the American Society for Bone and Mineral Research and Wiley Periodicals, Inc. The authors have requested the retraction based on their acknowledgement that several of the figures did not reflect the observations presented.
Disruption of NF-κB1 prevents bone loss caused by mechanical unloading
Authors: Nakamura Hitomi , Aoki Kazuhiro , Masuda Wataru , Alles Neil , Nagano Kenichi , Fukushima Hidefumi , Osawa Kenji , Yasuda Hisataka , Nakamura Ichiro , Mikuni-Takagaki Yuko , Ohya Keiichi , Maki Kenshi , Jimi Eijiro
Published: January 2013

Mechanical unloading, such as in a microgravity environment in space or during bed rest (for patients who require prolonged bed rest), leads to a decrease in bone mass because of the suppression of bone formation and the stimulation of bone resorption. To address the challenges presented by a prolonged stay in space and the forthcoming era of a super-aged society, it will be important to prevent the bone loss caused by prolonged mechanical unloading. Nuclear factor κB (NF-κB) transcription factors are activated by mechanical loading and inflammatory cytokines. Our objective was to elucidate the role of NF-κB pathways in bone loss that are caused by mechanical unloading. Eight-week-old wild-type (WT) and NF-κB1-deficient mice were randomly assigned to a control or mechanically unloaded with tail suspension group. After 2 weeks, a radiographic analysis indicated a decrease in bone mass in the tibias and femurs of the unloaded WT mice but not in the NF-κB1–deficient mice. An NF-κB1 deficiency suppressed the unloading-induced reduction in bone formation by maintaining the proportion and/or potential of osteoprogenitors or immature osteoblasts, and by suppression of bone resorption through the inhibition of intracellular signaling through the receptor activator of NF-κB ligand (RANKL) in osteoclast precursors. Thus, NF-κB1 is involved in two aspects of rapid reduction in bone mass that are induced by disuse osteoporosis in space or bed rest.
Reptiles: A New Model for Brain Evo‐Devo Research
Authors: Nomura Tadashi , Kawaguchi Masahumi , Ono Katsuhiko , Murakami Yasunori
Published: January 2013

Vertebrate brains exhibit vast amounts of anatomical diversity. In particular, the elaborate and complex nervous system of amniotes is correlated with the size of their behavioral repertoire. However, the evolutionary mechanisms underlying species‐specific brain morphogenesis remain elusive. In this review we introduce reptiles as a new model organism for understanding brain evolution. These animal groups inherited ancestral traits of brain architectures. We will describe several unique aspects of the reptilian nervous system with a special focus on the telencephalon, and discuss the genetic mechanisms underlying reptile‐specific brain morphology. The establishment of experimental evo‐devo approaches to studying reptiles will help to shed light on the origin of the amniote brains. J. Exp. Zool. (Mol. Dev. Evol.) 320B:57–73, 2013. © 2013 Wiley Periodicals, Inc.
Greening organizational behavior: An introduction to the special issue
Authors: Andersson Lynne , Jackson Susan E. , Russell Sally V.
Published: January 2013

Each of the six articles in this Special Issue on “Greening Organizational Behavior” offers a perspective that provides unique insight and enriches our understanding of organizational greening. As a set, the articles span all levels of analysis, from a study of individual differences to an investigation of leadership dynamics to the analysis of firms and their institutional environments. Taken together, these articles illustrate the complex nature of organizational greening and highlight the need for research that adopts a systems perspective. The embedded and nested nature of organizational greening behavior requires additional research that investigates the interrelated influences of greening behavior by individual employees, work groups, and organizations. By recognizing and appreciating these multi‐level dynamics, scholars of organizational behavior are poised to improve our understanding of effective organizational greening initiatives and thereby promote advancement toward environmental sustainability. Copyright © 2013 John Wiley & Sons, Ltd.
Mild electrical stimulation with heat stimulation increase heat shock protein 70 in articular chondrocyte
Authors: Hiraoka Nobuyuki , Arai Yuji , Takahashi Kenji A. , Mazda Osam , Kishida Tsunao , Honjo Kuniaki , Tsuchida Shinji , Inoue Hiroaki , Morino Saori , Suico Mary Ann , Kai Hirofumi , Kubo Toshikazu
Published: January 2013

The objective of this study is to investigate the effects of mild electrical stimulation (MES) and heat stress (HS) on heat shock protein 70 (HSP70), that protects chondrocytes and enhances cartilage matrix metabolism, in chondrocyte and articular cartilage. Rabbit articular chondrocytes were treated with MES and/or HS. The safeness was assessed by LDH assay and morphology. HSP70 protein, ubiquitinated proteins and HSP70 mRNA were examined by Western blotting and real‐time PCR. Rat knee joints were treated with MES and/or HS. HSP70 protein, ubiquitinated proteins, HSP70 mRNA and proteoglycan core protein (PG) mRNA in articular cartilage were investigated. In vitro, HS increased HSP70 mRNA and HSP70 protein. MES augmented ubiquitinated protein and HSP70 protein, but not HSP70 mRNA. MES + HS raised HSP70 mRNA and ubiquitinated protein, and significantly increased HSP70 protein. In vivo, HS and MES + HS treatment augmented HSP70 mRNA. HS modestly augmented HSP70 protein. MES + HS significantly increased HSP70 protein and ubiquitinated proteins. PG mRNA was markedly raised by MES + HS. This study demonstrated that MES, in combination with HS, increases HSP70 protein in chondrocytes and articular cartilage, and promotes cartilage matrix metabolism in articular cartilage. MES in combination with HS can be a novel physical therapy for osteoarthritis by inducing HSP70 in articular cartilage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 894–900, 2013
The role of leptin on the organization and expression of cytoskeleton elements in nucleus pulposus cells
Authors: Li Zheng , Shen Jianxiong , Wu William Ka Kei , Yu Xin , Liang Jinqian , Qiu Guixing , Liu Jiaming
Published: January 2013

Obesity is an important risk factor for intervertebral disc degeneration and leptin is a biomarker of obesity. However, the expression of leptin receptors has not been determined in disc tissue. It is not known whether leptin has a direct effect on the nucleus pulposus (NP) cells. To determine whether the NP tissues and cells express leptin receptors (OBRa and OBRb) and whether leptin affects the organization and the expression of major cytoskeletal elements in NP cells. Messenger RNA (mRNA) and protein levels of OBRa and OBRb were measured by real‐time PCR and Western blot, respectively, in NP tissues and cells. Immunofluorescence and real‐time PCR and Western blot were performed to investigate the effect of leptin on cytoskeleton reorganization and expression. Results show that mRNA and proteins of OBRa and OBRb were expressed in all NP tissues and cells, and that OBRb expression was correlated with patients' body weight. Increased expression of β‐actin and reorganization of F‐actin were evident in leptin‐stimulated NP cells. Leptin also induced vimentin expression but had no effect on β‐tubulin in NP cells. These findings provide novel evidence supporting the possible involvement of leptin in the pathogenesis of intervertebral disc degeneration. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 847–857, 2013
Efficacy of voluntary mitigation in reducing harbor seal disturbance
Authors: Hoover‐Miller Anne , Bishop Amanda , Prewitt Jill , Conlon Suzanne , Jezierski Caroline , Armato Peter
Published: January 2013

Marine and coastal tourism has rapidly expanded worldwide in the past 2 decades, often occurring in once secluded habitats. In Alaska, tourism near tidewater glaciers has attracted millions of visitors and increased the presence of ships, tour vessels, and coastal development. Although sustainable tourism, resulting from balanced effects on wildlife and client satisfaction, is a goal of most tourism operators, it is not always achieved. Voluntary compliance with viewing guidelines and codes of conduct have been encouraged, but few assessments have the longitudinal scope to evaluate long‐term changes in impacts on wildlife and the ability of vessel operators and kayak guides to sustain lower impact operating practices over time. This study assessed vessel and kayak visitation and resulting impacts on harbor seals in the Kenai Fjords National Park, southcentral Alaska. We obtained observations from 2002 to 2011, using remotely controlled video cameras located near Aialik and Pedersen Glaciers in the Kenai Fjords National Park. Overall, disturbance was associated with 5.1% of vessel sightings, 28% of vessel interactions (vessel observed within approx. 300 m of seals), 11.5% of kayak sightings, and 61% of kayak interactions. Results demonstrated that voluntary changes in operations significantly reduced vessel and kayak disturbance of seals by 60–80%. Even with prior establishment of operating guidelines, tour vessel captains were able to further reduce their effect on wildlife with more careful operations. Rapid growth of guided kayak excursions that occurred during this study caused greater disturbance to seals than motorized vessels but guide trainings helped reduce disturbances. Diminished impacts of motor vessels and kayakers persisted across years although effects of kayaks were less consistent than motor vessels, which reflected greater variability in inter‐annual spatial use patterns by kayakers. Long‐term monitoring, including assessments of wildlife responses to vessel and kayak operations, combined with 2‐way communication with vessel operators and guides, enhanced the effectiveness of mitigation and facilitated adaptive adjustments to mitigation protocols over time. © 2013 The Wildlife Society.
Marten space use and habitat selection in managed coniferous boreal forests of eastern Canada
Authors: Cheveau Marianne , Imbeau Louis , Drapeau Pierre , Belanger Louis
Published: January 2013

Effects of habitat loss and fragmentation on the behavior of individual organisms may have direct consequences on population viability in altered forest ecosystems. The American marten (Martes americana) is a forest specialist considered as one of the most sensitive species to human‐induced disturbances. As some studies have shown that martens cannot tolerate >30–40% clear‐cuts within their home range, we investigated marten space use (home range size and overlap) and habitat selection in landscapes fragmented by 2 different patterns of timber harvesting in the black spruce boreal forest: dispersed‐cut landscapes (10–80 ha cut‐blocks) and clustered‐cut landscapes (50–200 ha cut‐blocks). We installed radio‐collars on female martens and determined 20 winter home ranges (100% minimum convex polygons and 60–90% kernels) in dispersed‐cut (n = 8) and clustered‐cut (n = 12) landscapes. Home range size was not related to the proportion of clear‐cuts (i.e., habitat loss), but rather to the proportion of mixedwood stands 70–120 years old. However, female body condition was correlated to habitat condition inside their home ranges (i.e., amount of residual forest and recent clear‐cuts). At the home range scale, we determined that mixedwood forests were also among the most used forest stands and the least used were recent clear‐cuts and forested bogs, using resource selection functions. At the landscape scale, home ranges included more mixedwood forests than random polygons and marten high activity zones were composed of more residual forest and less human‐induced disturbances (clear‐cuts, edges, and roads). These results suggest that mixedwood forests, which occupy approximately 10% of the study area, play a critical role for martens in this conifer‐dominated boreal landscape. We recommend permanent retention or special management considerations for these isolated stands, as harvesting mixedwood often leads to forest composition conversion that would reduce the availability of this highly used habitat. © The Wildlife Society, 2013
Photonic time‐stretch digitizer and its extension to real‐time spectroscopy and imaging
Authors: Fard Ali M. , Gupta Shalabh , Jalali Bahram
Published: January 2013

Real‐time wideband digitizers are the key building block in many systems including oscilloscopes, signal intelligence, electronic warfare, and medical diagnostics systems. Continually extending the bandwidth of digitizers has hence become a central challenge in electronics. Fortunately, it has been shown that photonic pre‐processing of wideband signals can boost the performance of electronic digitizers. In this article, the underlying principle of the time‐stretch analog‐to‐digital converter (TSADC) that addresses the demands on resolution, bandwidth, and spectral efficiency is reviewed. In the TSADC, amplified dispersive Fourier transform is used to slow down the analog signal in time and hence to compress its bandwidth. Simultaneous signal amplification during the time‐stretch process compensates for parasitic losses leading to high signal‐to‐noise ratio. This powerful concept transforms the analog signal's time scale such that it matches the slower time scale of the digitizer. A summary of time‐stretch technology's extension to high‐throughput single‐shot spectroscopy, a technique that led to the discovery of optical rouge waves, is also presented. Moreover, its application in high‐throughput imaging, which has recently led to identification of rogue cancer cells in blood with record sensitivity, is discussed.
Tm:Fiber laser ablation with real‐time temperature monitoring for minimizing collateral thermal damage: ex vivo dosimetry for ovine brain
Authors: Tunc Burcu , Gulsoy Murat
Published: January 2013

Background and Objective

The thermal damage of the surrounding tissue can be an unwanted result of continuous‐wave laser irradiations. In order to propose an effective alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real‐time temperature monitoring can be also an effective way to get rid of these negative effects. The aim of the present study is to investigate the potential of a new laser‐thermoprobe, which consists of a continuous‐wave 1,940‐nm Tm:fiber laser and a thermocouple measurement system for brain surgery in an ex vivo study.

Study Design/Materials and Methods

A laser‐thermoprobe was designed for using the near‐by tissue temperature as a real‐time reference for the applicator. Fresh lamb brain tissues were used for experiments. 320 laser shots were performed on both cortical and subcortical tissue.

Results

The relationship between laser parameters, temperature changes, and ablation (removal of tissue) efficiency was determined. The correlation between rate of temperature change and ablation efficiency was calculated.

Conclusion

Laser‐thermoprobe leads us to understand the basic laser–tissue interaction mechanism in a very cheap and easy way, without making a change in the experimental design. It was also shown that the ablation and coagulation (thermally irreversible damage) diameters could be predicted, and carbonization can be avoided by temperature monitoring. Lasers Surg. Med. 45: 48–56, 2013. © 2013 Wiley Periodicals, Inc.
Insights in the Architecture of Silicon‐Based Plasma Polymers Using Partial Network Ethanolysis Combined with Electrospray Tandem Mass Spectrometry
Authors: Fouquet Thierry , Petersen Julien , Ziarelli Fabio , Bour Jérôme , Toniazzo Valérie , Ruch David , Charles Laurence
Published: January 2013

Thin films obtained upon plasma polymerization of D4 and HMDSO precursors at atmospheric pressure are submitted to controlled ethanolysis to produce oligomers amenable to electrospray mass spectrometry. When using high resolution mass spectrometry to assess their elemental composition and tandem mass spectrometry to characterize their end‐groups, a whole set of ethanolysis products is identified, from which the network connectivity in the original film can be reconstructed. Ethanolysis products of ppD4 and ppHMDSO exhibit the same structural features composed of linear and cross‐linked PDMS moieties, the extent of cross‐linking reflecting the inorganic character of the film. Oligomers originally embedded in the solid network and released as intact species upon its dissolution are also observed.

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Vivaldi: Visualization and validation of biomacromolecular NMR structures from the PDB
Authors: Hendrickx Pieter M. S. , Gutmanas Aleksandras , Kleywegt Gerard J.
Published: January 2013

We describe Vivaldi (VIsualization and VALidation DIsplay; http://pdbe.org/vivaldi), a web‐based service for the analysis, visualization, and validation of NMR structures in the Protein Data Bank (PDB). Vivaldi provides access to model coordinates and several types of experimental NMR data using interactive visualization tools, augmented with structural annotations and model‐validation information. The service presents information about the modeled NMR ensemble, validation of experimental chemical shifts, residual dipolar couplings, distance and dihedral angle constraints, as well as validation scores based on empirical knowledge and databases. Vivaldi was designed for both expert NMR spectroscopists and casual non‐expert users who wish to obtain a better grasp of the information content and quality of NMR structures in the public archive. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Deriving how far structural information is transmitted through parallel homodimeric coiled‐coils: A correlation analysis of helical staggers
Authors: Brown Jerry H.
Published: January 2013

How local conformation is affected by local sequence is fairly well understood for alpha‐helical coiled‐coils, but less is known about how local conformation is influenced by distant features. Here, I describe an approach to detect such an effect, based on computing correlation coefficients of local out‐of‐register alignments, or so‐called “staggers” between the helices, as a function of the axial distance between the staggers. This approach requires parallel homodimers, in which each stagger can occur with two “signs,” where either one helix or the other is shifted towards the N terminus. The signs of such staggers separated by up to 12 residues are strongly correlated, indicating that the conformations of the ends of coiled‐coils are commonly influenced by attached structures. Thus, the structures of coiled‐coil residues aberrantly attached to alternative proteins, such as those resulting from leukemogenic chromosomal rearrangements, may be distinguishable from those in normal tissues, and in turn serve as targets of selective drug design. The signs of helical staggers separated by between 13 and 30 residues are moderately yet significantly correlated, indicating that some of the coiled‐coils transmit this conformational feature axially for at least 45 Å. A positive, albeit noisy, correlation also exists among tropomyosin coiled‐coils for signed staggers separated by the 40‐residue actin repeat distance, consistent with the semi‐flexible tropomyosin filament binding F‐actin and regulating skeletal muscle contraction in a partially cooperative manner. Communication of the signs of axial staggers is explained in part by minimization of main‐chain hydrogen bond deformations. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Lipid a from lipopolysaccharide recognition: Structure, dynamics and cooperativity by molecular dynamics simulations
Authors: Garate Jose Antonio , Oostenbrink Chris
Published: January 2013

Molecular dynamics simulations of Lipid A and its natural precursor Lipid IVA from E.coli have been carried out free in solution, bound to the myeliod differentiation protein 2 (MD2) and in the complex of MD2 with the toll like receptor 4 (TLR4). In addition, simulations of the ligand free MD2 and MD2‐TLR4 complex were performed. A structural and energetic characterization of the bound and unbound states of Lipid A/IVA was generated. As the crystal structures depict, the main driving force for MD2‐Lipid A/IVA are the hydrophobic interactions between the aliphatic tails and the MD2 cavity. The charged phosphate groups do strongly interact with positively charged residues, located at the surface of MD2. However, they are not essential for keeping the lipids in the cavity, indicating a more prominent role in binding recognition and ionic interactions with TLR4 at the MD2/TLR4 interface. Interestingly, in the absence of any ligand MD2 rapidly closes, blocking the binding cavity. The presence of TLR4, though changing the dynamics, was not able to impede the aforementioned closing event. We hypothesize that fluctuations of the H1 region are essential for this phenomenon, and it is plausible that an equilibrium between the open and closed states exists, although the lengths of our simulations are not sufficient to encompass the reversible process. The MD2/Lipid A‐TLR4 complex simulations show that the presence of the ligand energetically stabilizes the complex relative to the ligand‐free structures, indicating cooperativity in the binding process. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Hydrophobic environment is a key factor for the stability of thermophilic proteins
Authors: Gromiha M. Michael , Pathak Manish C. , Saraboji Kadhirvel , Ortlund Eric A. , Gaucher Eric A.
Published: January 2013

The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter‐residue interactions, ion‐pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic–mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three‐dimensional structures of elongation factor‐Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the importance of hydrophobicity as the dominating characteristic in the stability of thermophilic proteins, and we anticipate this will be useful in our attempts to engineering thermostable proteins. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Using an ultrahigh‐resolution regional climate model to predict local climatology
Authors: Wang Changgui , Jones Richard , Perry Matthew , Johnson Catrina , Clark Peter
Published: January 2013

Many applications of risk assessment and Environmental Impact Assessments (EIA) require information about the local mesoscale climate at a very fine spatial scale. Current regional climate models (RCMs) with grid resolutions that normally range between 10 and 50 km cannot resolve the local physiographic features that influence the small‐scale features of local climate. This article presents a local climate model (LCM) system with an ultrahigh resolution and demonstrates its application to study the local climatology in a coastal zone where details of orography and coastline are important influences on the climate. The LCM has been developed from the Met Office Unified Model (MetUM) based on the concept of very high‐resolution numerical weather prediction. The ultrahigh‐resolution regional climate modelling is achieved through operating multiple nesting from a spatial resolution of 12 km down to ∼500 m. In this pilot study of the LCM, RCMs were run at 12, 4, 1.5 and 0.5 km grid resolutions to simulate the mesoscale climate of Weymouth Bay and Portland Harbour along the south coast of the United Kingdom. The period simulated was July‐August of the years 1993 to 2002, with model results validated against meteorological station time series. The results demonstrated the added value of the 500 m resolution model compared with the 1.5 km resolution model in modelling very fine local mesoscale climate patterns over the inner domain, including diurnal variations of temperature and winds, such as southwesterly flows, and the effect of wind channelling between the Isle of Portland and the mainland. Lower mean wind speeds are also found along the south‐facing coast to the east and in the shelter of Portland in the 500 m resolution model, particularly showing a sheltering zone between Portland and Weymouth Bay.
D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae
Authors: Stewart Benjamin J. , Navid Ali , Kulp Kristen S. , Knaack Jennifer L. S. , Bench Graham
Published: January 2013

Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae, grown in media containing low, moderate and high glucose concentrations, to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log‐phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high‐glucose media resulted in increased generation of the methylglyoxal metabolite d‐lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high‐glucose media maintained higher glucose uptake flux than cells grown in moderate‐glucose or low‐glucose media. Computational modelling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD+:NADH ratio. Copyright © 2013 John Wiley & Sons, Ltd.
Design and performance analysis of deterministic learning of sampled-data nonlinear systems
Authors: Yuan ChengZhi , Wang Cong
Published: January 2013

In this paper, we extend the deterministic learning theory to sampled-data nonlinear systems. Based on the Euler approximate model, the adaptive neural network identifier with a normalized learning algorithm is proposed. It is proven that by properly setting the sampling period, the overall system can be guaranteed to be stable and partial neural network weights can exponentially converge to their optimal values under the satisfaction of the partial persistent excitation (PE) condition. Consequently, locally accurate learning of the nonlinear dynamics can be achieved, and the knowledge can be represented by using constant-weight neural networks. Furthermore, we present a performance analysis for the learning algorithm by developing explicit bounds on the learning rate and accuracy. Several factors that influence learning, including the PE level, the learning gain, and the sampling period, are investigated. Simulation studies are included to demonstrate the effectiveness of the approach.
Incidence of adverse outcomes associated with gestational diabetes mellitus in low‐ and middle‐income countries
Authors: Wang Zheng , Kanguru Lovney , Hussein Julia , Fitzmaurice Ann , Ritchie Katherine
Published: January 2013

Background

The contribution of medical conditions such as diabetes mellitus to maternal and neonatal ill‐health in low‐ and middle‐income countries is not well documented.

Objectives

To ascertain the incidence of adverse outcomes associated with gestational diabetes mellitus (GDM) in these countries.

Search strategy

Electronic databases were searched between 1990 and 2011.

Selection criteria

Observational, experimental, and quasi‐experimental studies reporting adverse outcomes associated with GDM in mothers and their infants in low‐ and middle‐income countries were included.

Data collection and analysis

Titles and abstracts were screened, and full‐text articles were independently assessed by at least 2 reviewers. Characteristics of studies were tabulated and quality assessment performed. Median and interquartile range (IQR) were computed for each adverse outcome.

Main results

25 articles were included from an initial 1282 citations. High median incidences of cesarean (43.8%; IQR, 34.9%–65.9%), neonatal jaundice (17.1%; IQR, 8.5%–22.9%), and macrosomia (17.0%; IQR, 8.3%–32.5%) were reported in women with GDM.

Conclusions

The high incidence of some complications of GDM is a concern and may indicate poorer care for women with GDM in low‐resource settings. The wide IQRs found indicate uncertainty about the burden of GDM in these settings.
Attachment–aversion (AA) model of customer–brand relationships
Authors: Park C. Whan , Eisingerich Andreas B. , Park Jason Whan
Published: January 2013

The present paper proposes a customer–brand relationships model and empirically tests the following: (1) brand–self distance and brand prominence as representing customers' attachment–aversion relationships (AA Relationships) with a brand, (2) key distinguishing differences between the AA Relationships measure and other alternative relationship measures (i.e., brand attachment, emotional valence and brand attitude strength) based on a set of dependent variables, (3) three key determinants of the AA Relationships and the underlying process between the AA Relationships and behavioral intentions and actual brand behaviors, and (4) customer age as moderating the customer–brand relationships specified in the nomological model of the AA Relationships. The results offer strong support for the unique and important contribution of the AA Relationships model as representing consumers' relationship valence with a brand and its salience.
Long-term talus flatirons formation in the hyperarid northeastern Negev, Israel
Authors: Boroda Ronen , Matmon Ari , Amit Rivka , Haviv Itai , Porat Naomi ,   ASTERTeam, Rood Dylan , Eyal Yehuda , Enzel Yehuda
Published: January 2013

Colluvial sediments of talus relicts (“talus flatirons”) around mesas preserve a record that sheds light on slope-forming processes at temporal scales > 103yr. The sedimentology and soil stratigraphy of two groups of talus flatirons in the northeastern hyperarid Negev desert reveal four deposition events in the younger talus and at least two in the older one. Numerical modeling of high-resolution10Be depth profiles suggests that these taluses were deposited during the middle Pleistocene; the younger talus group first depositional event occurred at 551− 142+ 80ka and its abandonment occurred at 270− 38+ 17ka. The abandonment of the older talus group and stabilization of its surface occurred at 497− 114+ 176ka. These ages indicate that the development of the studied talus sequence is not specifically associated with Pleistocene glacial–interglacial cycles. The10Be modeled concentrations indicate significant differences in the average inheritance of talus flatirons of different groups. These differences can be attributed to variability in the transport distance and duration of gravel exposure during transport but could also reflect some temporal variability in cliff retreat. Our results also demonstrate that talus slopes in hyperarid areas, despite their steepness, can store sediment for long periods (~ 500 ka) and thus constitute a valuable archive.
Does Peacekeeping Work? A Disaggregated Analysis of Deployment and Violence Reduction in the Bosnian War
Authors: Costalli Stefano
Published: January 2013

Cross-country empirical studies have reviewed many aspects of peacekeeping missions, but the findings on their effectiveness diverge. This article draws on recent empirical literature on civil wars using a disaggregated approach, addressing the effectiveness of peacekeeping by examining the local variation in UN troop deployment and violence in the Bosnian civil war. The relationship between the intensity of local violence and troop deployment across Bosnian municipalities and peacekeeping effects on the intensity of subsequent violence are examined with a matching approach. The results indicate that although peacekeeping ‘works’, since it is deployed where the most severe violence takes place, peacekeepers have little effect on subsequent violence. This is consistent with research highlighting the obstacles to UN missions in addressing their objectives.
Why nature really chose phosphate
Authors: Kamerlin Shina C. L. , Sharma Pankaz K. , Prasad Ram B. , Warshel Arieh
Published: January 2013

Phosphoryl transfer plays key roles in signaling, energy transduction, protein synthesis, and maintaining the integrity of the genetic material. On the surface, it would appear to be a simple nucleophile displacement reaction. However, this simplicity is deceptive, as, even in aqueous solution, the low-lying d-orbitals on the phosphorus atom allow for eight distinct mechanistic possibilities, before even introducing the complexities of the enzyme catalyzed reactions. To further complicate matters, while powerful, traditional experimental techniques such as the use of linear free-energy relationships (LFER) or measuring isotope effects cannot make unique distinctions between different potential mechanisms. A quarter of a century has passed since Westheimer wrote his seminal review, ‘Why Nature Chose Phosphate’ (Science 235 (1987), 1173), and a lot has changed in the field since then. The present review revisits this biologically crucial issue, exploring both relevant enzymatic systems as well as the corresponding chemistry in aqueous solution, and demonstrating that the only way key questions in this field are likely to be resolved is through careful theoretical studies (which of course should be able to reproduce all relevant experimental data). Finally, we demonstrate that the reason that naturereallychose phosphate is due to interplay between two counteracting effects: on the one hand, phosphates are negatively charged and the resulting charge-charge repulsion with the attacking nucleophile contributes to the very high barrier for hydrolysis, making phosphate esters among the most inert compounds known. However, biology is not only about reducing the barrier to unfavorable chemical reactions. That is, the same charge-charge repulsion that makes phosphate ester hydrolysis so unfavorable also makes it possible to regulate, by exploiting the electrostatics. This means that phosphate ester hydrolysis can not only be turned on, but also be turned off, by fine tuning the electrostatic environment and the present review demonstrates numerous examples where this is the case. Without this capacity for regulation, it would be impossible to have for instance a signaling or metabolic cascade, where the action of each participant is determined by the fine-tuned activity of the previous piece in the production line. This makes phosphate esters the ideal compounds to facilitate life as we know it.
Remaking the past: Tamil sacred landscape and temple renovations
Authors: Branfoot Crispin
Published: January 2013

This article explores the repeated renovation of south Indian temples over the past millennium and the conception of the Tamil temple-city. Though the requirement for renovation is unremarkable, some “renovations” have involved the wholesale replacement of the central shrine, in theory the most sacred part of the temple. Rather than explaining such radical rebuilding as a consequence of fourteenth-century iconoclasm, temple renovation is considered in this article as an ongoing process. Several periods of architectural reconstruction from the tenth to the early twentieth centuries demonstrate the evolving relationship between building, design and sacred geography over one millennium of Tamil temple history. The conclusion explores the widespread temple “renovations” by the devout Nakarattar (Nattukottai Chettiar) community in the early twentieth century, and the consequent dismay of colonial archaeologists at the perceived destruction of South India's monumental heritage, in order to reassess the lives and meanings of Tamil sacred sites.
XX.—The Equilibrium of the Circular-Arc Bow-Girder
Authors: Gibson A. H.
Published: January 2013

A girder built in to supports at one or at both ends and forming an arc of a circle in plan, is subjected, at each section, to both bending and twisting moments. At the supports, fixing moments of both kinds are called into play, and until these are known the resultant moment tending to cause rupture at any section is indeterminate. The following investigation is devoted to a consideration of the general state of elastic equilibrium of such a girder under various systems of loading.
IX.—On the Establishment of the Elementary Principles of Quaternions on an Analytical Basis
Authors: Plarr Gustav
Published: January 2013

The extension which is required to be given to the meaning of algebraic addition and subtraction, for the purpose of representing a vector by a polynomial expression (by the algebraic sum, namely, of components differing in direction from one another), renders it necessary to investigate into the question of what the geometrical signification of the result of the other elementary operations of algebra will become when these operations are performed on those polynomial expressions?
XXIII.—On the Fossil Osmundaceæ
Authors: Kidston R. , Gwynne-Vaughan D. T.
Published: January 2013

We have already referred in the second part of this series to the opinions held by various authors as to the systematic position of the genera Thamnopteris, Bathypteris and Anomorrhœa, and have given in detail the reasons that have induced us to adopt these names for the specimens included in these genera (cf. Part II., p. 213). It is therefore unnecessary for us to deal any further with the historical aspect of the matter in the present communication, and we will at once proceed to the description of the structure of the Fern stems in question.