bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma and urine proteomic profiles in childhood idiopathic nephrotic syndrome
Authors: Andersen René Frydensbjerg , Palmfeldt Johan , Jespersen Bente , Gregersen Niels , Rittig Søren
Published: August 2012

Purpose

Idiopathic nephrotic syndrome (NS) is characterized by proteinuria, edema, and hypoalbuminemia. The aim of the study was to identify differentially expressed proteins in urine and plasma during NS compared with remission.

Experimental design

Plasma and urine samples were collected during NS and at remission. Proteomic profiling was performed by iTRAQ labeling followed by nano‐LC‐MS/MS to yield data on relative protein amounts. Protein validation was performed by ELISA.

Results

A total of 388 and 425 proteins were detected in plasma and urine, respectively. In total, 18 plasma and 38 urinary proteins were significantly altered (p <0.05). E‐cadherin was one of the proteins with reduced urinary concentration during NS, a finding validated by ELISA. The slit diaphragm protein P‐cadherin was identified by nano‐LC‐MS/MS and shown to be reduced in urine during NS by ELISA.

Conclusions and clinical relevance

The present study identified more than 50 differentially altered proteins comparing NS with remission. Several proteins were found to be linked to the major clinical symptoms of NS, and further studies must elucidate if P‐cadherin is involved in proteinuria during NS, and if low urinary E‐cadherin level is linked to altered epithelial cell to cell contact in the distal part of the nephron.
Potential biomarkers for early detection of acute graft‐versus‐host disease
Authors: Lochmanová Gabriela , Jedličková Lenka , Potěšil David , Tomancová Alexandra , Verner Jan , Pospíšilová Šárka , Doubek Michael , Mayer Jiří , Zdráhal Zbyněk
Published: August 2012

Acute graft‐versus‐host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HCT), resulting in considerable morbidity and mortality. Currently, the diagnosis of aGVHDis largely made based on clinical parameters and invasive biopsies. For the past 20 years, researchers have been trying to find reliable biomarkers to enable early and accurate diagnosis of aGVHD. Although a number of potential aGVHDbiomarkers have been published, as yet, no validated diagnostic test is available. Proteomics encompasses a broad range of rapidly developing technologies, which have shown tremendous promise for early detection of aGVHD. In this article, we review the current state of aGVHDbiomarker discovery, provide a summary of the key proteins of interest and the most common analytical procedures for the clinic, as well as outlining the significant challenges faced in their use.
Using lectins in biomarker research: Addressing the limitations of sensitivity and availability
Authors: Haab Brian B.
Published: August 2012

Carbohydrates have fundamental roles throughout biology, yet they have not been as well studied as proteins and nucleic acids, in part due to limitations in the experimental tools. Improved methods for studying glycans could spur significant advances in the understanding and application of glycobiology. The use of affinity reagents, such as lectins and glycan‐binding antibodies, is a valuable complement to methods involving mass spectrometry and chromatography. This article addresses two limitations that have prevented the broader experimental use of glycan‐binding proteins: sensitivity and availability. The sensitivity limitation stems from the poor affinity that many glycan‐binding proteins have as isolated analytical reagents. To address this problem, I propose making use of multivalent interactions between lectins and glycans, mimicking those frequently found in the biological setting. Recent experiments show that a practical technique for producing lectin multimers can significantly improve detection sensitivity. The second limitation, availability, is the difficulty of finding and obtaining glycan‐binding proteins that recognize less common or arbitrarily defined glycan structures. To address this problem, I propose translating the wealth of existing glycan array data into a quantitative, searchable database of the specificities of glycan‐binding proteins. Such a resource would allow us to more easily identify proteins with defined specificities and perform detailed comparisons between reagents. Solutions to these two limitations could lead to the more effective use of, and a broader range of, glycan‐binding reagents.
Serum proteome profiling of pancreatitis using recombinant antibody microarrays reveals disease‐associated biomarker signatures
Authors: Sandström Anna , Andersson Roland , Segersvärd Ralf , Löhr Mattias , Borrebaeck Carl A. K. , Wingren Christer
Published: August 2012

Purpose

Pancreatitis is an inflammatory state of the pancreas, for which high‐performing serological biomarkers are lacking. The aim of the present study was to evaluate the use of affinity proteomics for identifying potential markers of disease and stratifying pancreatitis subtypes.

Experimental design

High‐content, recombinant antibody microarrays were applied for serum protein expression profiling of 113 serum samples from patients with chronic, acute, and autoimmune pancreatitis, as well as healthy controls. The sample groups were compared using supervised classification based on support vector machine analysis.

Results

This discovery study showed that pancreatitis subtypes could be discriminated with high accuracy. Using unfiltered data, the individual subtypes, as well as the combined pancreatitis cohort, were distinguished from healthy controls with high AUC values (0.96–1.00). Moreover, characteristic protein patterns and AUC values in the range of 0.69–0.95 were observed for the individual pancreatitis entities when compared to each other, and to all other samples combined.

Conclusions and clinical relevance

This study demonstrated the potential of the antibody microarray approach for stratification of pancreatitis. Distinct candidate multiplex serum biomarker signatures for chronic, acute, and autoimmune pancreatitis were defined, which could enhance our fundamental knowledge of the underlying molecular mechanisms, and potentially lead to improved diagnosis.
Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis
Authors: Varshavsky Alexander
Published: August 2012

Despite extensive understanding of sleep regulation, the molecular‐level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca2+ fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca2+‐activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca2+ transients) while fragment‐destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness‐increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol‐induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca2+ alone or Ca2+ and its ionophore (Erickson et al., Science 1978;199:1219–1221; Harris, Pharmacol Biochem Behav 1979;10:527–534; Erickson et al., Pharmacol Biochem Behav 1980;12:651–656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.
Comparison of the structures and stabilities of coiled‐coil proteins containing hexafluoroleucine and t‐butylalanine provides insight into the stabilizing effects of highly fluorinated amino acid side‐chains
Authors: Buer Benjamin C. , Meagher Jennifer L. , Stuckey Jeanne A. , Marsh E. Neil G.
Published: August 2012

Highly fluorinated analogs of hydrophobic amino acids are well known to increase the stability of proteins toward thermal unfolding and chemical denaturation, but there is very little data on the structural consequences of fluorination. We have determined the structures and folding energies of three variants of a de novo designed 4‐helix bundle protein whose hydrophobic cores contain either hexafluoroleucine (hFLeu) or t‐butylalanine (tBAla). Although the buried hydrophobic surface area is the same for all three proteins, the incorporation of tBAla causes a rearrangement of the core packing, resulting in the formation of a destabilizing hydrophobic cavity at the center of the protein. In contrast, incorporation of hFLeu, causes no changes in core packing with respect to the structure of the nonfluorinated parent protein which contains only leucine in the core. These results support the idea that fluorinated residues are especially effective at stabilizing proteins because they closely mimic the shape of the natural residues they replace while increasing buried hydrophobic surface area.
The story of a new insecticidal chemistry class: the diamides
Authors: Jeanguenat André
Published: August 2012

This paper describes the story of the invention of the diamides, a novel chemical class of insecticides. It starts with the pioneering work by Nihon Nohyaku researchers, who developed a herbicide lead with weak insecticidal activity to flubendiamide, a highly potent lepidoptericide. The journey continues with Nissan's isoxazolines and the invention of the anthranilamides by DuPont, culminating in the discovery of the blockbuster chlorantraniliprole and its analogue cyantraniliprole. The next steps are Syngenta's sulfoximines and bicyclic anthranilamides, Ishihara Sangyo Kaisha's cyclopropylamides, Sumitomo's hydrazides, Bayer's pyrazoles and tetrazoles, BASF's sulfoximines and more recent contributions from Chinese agrochemical companies and academic institutions. The diamides affect calcium homeostasis by binding to ryanodine receptors and releasing calcium from the intracellular stores. Investigations at Nihon Nohyaku, DuPont and Bayer on the action of the diamides on ryanodine receptors will be briefly reported.
Design, synthesis and structure–activity relationship of novel insecticidal dichloro‐allyloxy‐phenol derivatives containing substituted pyrazol‐3‐ols
Authors: Li Miao , Liu Chang‐Ling , Zhang Jing , Wu Qiao , Hao Shu‐Lin , Song Yu‐quan
Published: August 2012

BACKGROUND

Pyridalyl, consisting of dicholoro‐allyoxy‐phenol moiety, is a novel class of insecticide showing extraordinary activities against various lepidopterous and thysanopterous pests on cotton and vegetables. To discover further novel insecticides, a series of new dichloro‐allyloxy‐phenol derivatives containing substituted pyrazol‐3‐ol moieties were designed and synthesised via the intermediate derivatisation method.

RESULTS

The target compounds were characterised by 1H NMR, IR, MS and elemental analysis. Bioassays indicated that some of these compounds exhibited good insecticidal activities against diamondback moth (Plutella xylostella) at 6.25 mg L−1. The structure–activity relationship is discussed.

CONCLUSION

The present work demonstrates that dichloro‐allyloxy‐phenol derivatives with substituted phenylpyrazole moieties can be used as lead compounds to develop further novel insecticides.© 2012 Society of Chemical Industry
A positively charged surface patch is important for hainantoxin‐IV binding to voltage‐gated sodium channels
Authors: Liu Yu , Li Dan , Wu Zhe , Li Jing , Nie Dongsong , Xiang Yang , Liu Zhonghua
Published: August 2012

Hainantoxin‐IV (HNTX‐IV), isolated from the venom of the spider Ornithoctonus hainana, is a specific antagonist of tetrodotoxin‐sensitive (TTX‐S) voltage‐gated sodium channels in rat dorsal root ganglion (DRG) cells. It adopts an inhibitor cystine knot motif, and structural analysis revealed a positively charged patch consisting of Arg26, Lys27, His28, Arg29 and Lys32 distributed on its molecular surface. Our previous study demonstrated that Lys27 and Arg29 but not Arg26 were critical residues for HNTX‐IV binding to TTX‐S sodium channels. In the present study, we examined the roles of His28 and Lys32 in the interaction of HNTX‐IV with its target. Two mutants, HNTX‐IV‐H28D and HNTX‐IV‐K32A, were generated by solid‐phase chemical synthesis and purified by reverse‐phase HPLC after refolding and oxidation, yielding two compounds of high purity with monoisotopic masses of 3962.66 and 3927.70 Da, respectively, as determined by MALDI‐TOF mass spectrometry. This indicated the presence of six cysteine residues forming three disulfide bonds. Moreover, circular dichroism spectroscopy analysis demonstrated that the substitution of His28 or Lys32 did not affect the overall structure of HNTX‐IV. The inhibitory activity of HNTX‐IV‐H28D and HNTX‐IV‐K32A against TTX‐S sodium channels in rat DRG cells was analyzed by whole‐cell patch‐clamp technique. The IC50 values for the mutants were 0.57 and 5.80 μM (17‐fold and 170‐fold lower than the activity of the native toxin), indicating that His28 and Lys32 may be important for the inhibitory activity of HNTX‐IV. Taken together, our results suggest that the positively charged patch might be the binding site for the interaction of HNTX‐IV with TTX‐S sodium channels. These findings might contribute to the elucidation of the structure and function relationship of HNTX‐IV. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Broadband non‐selective excitation of plutonium isotopes for isotope ratio measurements in resonance ionization mass spectrometry: a theoretical study
Authors: Sankari M.
Published: August 2012

RATIONALE

Making isotope ratio measurements with minimum isotope bias has always been a challenging task to mass spectrometrists, especially for the specific case of plutonium, owing to the strategic importance of the element. In order to use resonance ionization mass spectrometry (RIMS) as a tool for isotope ratio measurements, optimization of the various laser parameters and other atomic and system parameters is critical to minimize isotopic biases.

METHODS

Broadband simultaneous non‐selective excitation of the isotopes of plutonium in the triple resonance excitation scheme with λ1 = 420.77 nm, λ2 = 847.28 nm, and λ3 = 767.53 nm based on density matrix formalism has been theoretically computed for the determination of isotope ratios. The effects of the various laser parameters and other factors such as the atomization temperature and the dimensions of the atomic beam on the estimation of isotope ratios were studied. The effects of Doppler broadening, and time‐dependent excitation parameters such as Rabi frequencies, ionization rate and the effect of non‐Lorenztian lineshape have all been incorporated.

RESULTS

The average laser powers and bandwidths for the three‐excitation steps were evaluated for non‐selective excitation. The laser intensity required to saturate the three‐excitation steps were studied. The two‐dimensional lineshape contour and its features were investigated, while the reversal of peak asymmetry of two‐step and two‐photon excitation peaks under these conditions is discussed. Optimized powers for the non‐selective ionization of the three transitions were calculated as 545 mW, 150 mW and 545 mW and the laser bandwidth for all the three steps was ~20 GHz.

CONCLUSIONS

The isotopic bias between the resonant and off‐resonant isotope under the optimized conditions was no more than 9%, which is better than an earlier reported value. These optimized laser power and bandwidth conditions are better than in the earlier experimental work since these comprehensive calculations yield simultaneous and much more accurate isotope ratios than those in the sequential and less accurate determination reported earlier. Application of these theoretical calculations to minimize the isotopic biases under these conditions for the rapid, efficient and accurate isotope ratio measurements using RIMS has been outlined. Copyright © 2012 John Wiley & Sons, Ltd.
Comparing Solar Water Heater Popularization Policies in China, Israel and Australia: The Roles of Governments in Adopting Green Innovations
Authors: Li Wei , Rubin Tzameret H. , Onyina Paul A.
Published: August 2012

Studying the roles of governments in adopting green innovations is significant for analysing the transition to a more sustainable energy system. This article presents a comparative study of policies for popularizing domestic solar water heaters in three countries: China, Israel and Australia. Expanding the analysis beyond the economics of innovation, it demonstrates the institutional dimension of green technology deployment in these three countries. By examining the diverging roles of governments in facilitating green technology adoption in existing social routines and practices, it finds that governments' motivations, support and implementation mechanisms are remarkably different in these three countries. In particular, the paper argues that solar water heater popularization has been distinguished as a business opportunity in China, energy security in Israel and environmental responsibility in Australia. In addition, the institutional settings have a real impact on governments' roles in adopting green innovations, in terms of the policy instruments chosen and implementation mechanisms. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment.
A practical model‐based statistical approach for generating functional test cases: application in the automotive industry
Authors: Awedikian Roy , Yannou Bernard
Published: August 2012

With the growing complexity of industrial software applications, industrials are looking for efficient and practical methods to validate the software. This paper develops a model‐based statistical testing approach that automatically generates online and offline test cases for embedded software. It discusses an integrated framework that combines solutions for three major software testing research questions: (i) how to select test inputs; (ii) how to predict the expected results of a test; and (iii) when to stop testing software. The automatic selection of test inputs is based on a stochastic test model that accounts for the main particularity of embedded software: time sensitivity. Software test practitioners may design one or more test models when they generate random, user‐oriented, or fault‐oriented test inputs. A formal framework integrating existing and appropriate specification techniques was developed for the design of automated test oracles (executable software specifications) and the formal measurement of functional coverage. The decision to stop testing software is based on both test coverage objectives and cost constraints. This approach was tested on two representative case studies from the automotive industry. The experiment was performed at unit testing level in a simulated environment on a host personal computer (automatic test execution). The two software functionalities tested had previously been unit tested and validated using the test design approach conventionally used in the industry. Applying the proposed model‐based statistical testing approach to these two case studies, we obtained significant improvements in performing functional unit testing in a real and complex industrial context: more bugs were detected earlier and in a shorter time. Copyright © 2012 John Wiley & Sons, Ltd.
Wolves and lynx: Plausible ideas make for testable hypotheses
Authors: Wirsing Aaron J. , Buskirk Steven W. , Ripple William J. , Beschta Robert L.
Published: August 2012

We recently wrote an opinion piece (Ripple et al. 2011) hypothesizing that the presence of wolves (Canis lupus) could indirectly benefit Canada lynx (Lynx canadensis) by suppressing competition with coyotes (Canis latrans). Subsequent comments by Hodges (2012) and Squires et al. (2012) raise several issues regarding our essay. In our reply, we 1) emphasize that many valid hypotheses precede rather than follow data collection, 2) provide additional evidence showing negative effects of wolves on coyotes and an inverse relationship between wolf and coyote abundance, 3) indicate that wolves could increase the availability of hares to lynx by reducing not only hare predation by coyotes but also potential impacts on hare habitat by ungulates, and 4) reject the notion that our expressed views conflict in any way with existing conservation and recovery goals for lynx in the continental United States. We conclude by reaffirming our support for opinion pieces in professional journals, whether or not they are buttressed by large amounts of data, as vehicles for new ideas and catalysts for scientific debate and discussion. © 2012 The Wildlife Society.
Role of fibroblast growth factor signaling in vascular formation and maintenance: orchestrating signaling networks as an integrated system
Authors: Murakami Masahiro , Sakurai Takashi
Published: August 2012

The vascular system has begun to be perceived as a dynamic organ actively controlling a wide variety of physiological processes. The structural and functional integrity of blood vessels, regulated by signaling activities finely modulating cell–cell and cell–matrix interactions, is crucial for vessel physiology, as well as basic functionality of the tissue. Throughout the process of new vessel formation, while blood vessels are actively reorganized and remodeled with migration and proliferation of vascular cells, maintenance of vascular barrier function is essentially important. These conflicting properties, i.e., dynamic cellular mobilization and maintenance of barrier integrity, are simultaneously achieved through the interaction of highly organized signaling networks governing coordinated cell–cell interplay. Recent evidence suggests that the fibroblast growth factor (FGF) system plays a regulatory role in several physiological conditions in the vascular system. In this article, we will attempt to summarize current knowledge in order to understand the mechanism of this coordination and evaluate the pivotal role of FGF signaling in integrating a diverse range of signaling events in vascular growth and maintenance. WIREs Syst Biol Med 2012, 4:615–629. DOI: 10.1002/wsbm.1190

This article is categorized under:

Biological Mechanisms > Cell Signaling

Physiology > Mammalian Physiology in Health and Disease

Biological Mechanisms > Regulatory Biology
Microbial transformation of 2-amino-4-methyl-3-nitropyridine
Authors: Tully Thomas , Liu Mark , Huang Yande , Ye Qingmei , Patel Ramesh N , Goswami Animesh
Published: August 2012

Biotransformation of the highly substituted pyridine derivative 2-amino-4-methyl-3-nitropyridine by Cunninghamella elegans ATCC 26269 yielded three products each with a molecular weight of 169 Da which were identified as 2-amino-5-hydroxy-4-methyl-3-nitropyridine, 2-amino-4-hydroxymethyl-3-nitropyridine, and 2-amino-4-methyl-3-nitropyridine-1-oxide. Biotransformation by Streptomyces antibioticus ATCC 14890 gave two different products each with a molecular weight of 169 Da; one was acid labile and converted to the other stable product under acidic conditions. The structure of the stable product was established as 2-amino-4-methyl-3-nitro-6(1H)-pyridinone, and that of the less stable product was assigned as its tautomer 2-amino-6-hydroxy-4-methyl-3-nitropyridine. Four of the five biotransformation products are new compounds. Several strains of Aspergillus also converted the same substrate to the lactam 2-amino-4-methyl-3-nitro-6(1H)-pyridinone. Microbial hydroxylation by C. elegans was found to be inhibited by sulfate ion. In order to improve the yield and productivity of the 5-hydroxylation reaction by C. elegans, critical process parameters were determined and Design of Experiments (DOE) analyses were performed. Biotransformation by C. elegans was scaled up to 15-l fermentors providing 2-amino-5-hydroxy-4-methyl-3-nitropyridine at ca. 13 % yield in multi-gram levels. A simple isolation process not requiring chromatography was developed to provide purified 2-amino-5-hydroxy-4-methyl-3-nitropyridine of excellent quality.
Improving Quality in Outpatient Services
Authors: Mariotti Nadine
Published: August 2012

Improving Quality in Outpatient Services Carole Guinane, Noreen Davis 2011, CRC Press 279 pages, hardcover
Suppression of metastases of small cell lung cancer cells in mice by a peptidic CXCR4 inhibitor TF14016
Authors: Otani Yasushi , Kijima Takashi , Kohmo Satoshi , Oishi Shinya , Minami Toshiyuki , Nagatomo Izumi , Takahashi Ryo , Hirata Haruhiko , Suzuki Mayumi , Inoue Koji , Takeda Yoshito , Kida Hiroshi , Tachibana Isao , Fujii Nobutaka , Kumanogoh Atsushi
Published: August 2012

CXCL12 is a chemokine essential for the organ‐specific spread of a variety of cancers including small cell lung cancer (SCLC). Here, we examined the anti‐metastatic efficacy of TF14016, a small peptidic inhibitor of CXCL12 receptor CXCR4, in SCLC. Treatment of mice with TF14016 significantly suppressed pulmonary metastases of CXCR4‐expressing SCLC in size and number. Furthermore, histological examination revealed that the expression of vascular endothelial cell growth factor and the density of CD31‐positive microvessels in metastatic foci were both significantly reduced in TF14016‐treated mice. Collectively, CXCR4 could be an attractive target for anti‐metastatic and anti‐angiogenic therapy in SCLC.
Correlation between the ossification of nuchal ligament and clinical cervical disorders
Authors: Tsai Yu‐Lin , Weng Ming‐Cheng , Chen Tien‐Wen , Hsieh Yi‐Lun , Chen Chia‐Shin , Huang Mao‐Hsiung
Published: August 2012

This is a correlation analysis between severity of the ossification of the nuchal ligament (ONL) and clinical cervical disorders including neck dysfunction, cervical malalignment, and morphologic changes of the cervical neural foramen (CNF). The clinical effects of ONL on active range of motion (AROM) of neck, cervical radiculopathy, abnormal cervical curvature, and the degree of CNF stenosis in patients with painful neck stiffness are investigated. Studies have investigated the predisposing factors to cervical dysfunction and degenerative disorders; however, few studies have examined the influence of the ONL on neck function and cervical spine. A total of 31 participants with painful neck stiffness were recruited. They accepted measurement of cervical AROM and serial cervical radiographs at anterior–posterior view, lateral view, and bilateral oblique views. Parameters of radiographs measurement included cervical lordotic curve, and cross‐sectional areas (CSA) of the ONL and CNF (C2–C3, C4–C5, C5–C6, and C6–C7 levels). The ratio of CSA of the lower CNF (C4–C5, C5–C6, C6–C7) to CSA of the upper CNF (C2–C3) was used as a CNF stenosis ratio. The correlations of ONL size, neck symptoms, cervical AROM, lordotic curve, and CNF stenosis ratio were analyzed. More than half of all patients were positive in cervical root signs and prone to have larger ONL. Neck AROM of all participants was significantly below normal average in all directions, and a moderate negative association was found between the ONL CSA and AROM in flexion–extension. Most patients had moderate loss of cervical lordotic curve despite there being no significant correlation between ONL CSA and cervical curvature. Moreover, CNF stenosis ratio significantly negatively correlated with ONL CSA. Patients with larger ONL had more severe cervical radiculopathy, more stiffness in flexion–extension direction, more complex degenerative change of spine, and worse CNF stenosis.
Laser plasma accelerator driven by a super-Gaussian pulse
Authors: OSTERMAYR TOBIAS , PETROVICS STEFAN , IQBAL KHALID , KLIER CONSTANTIN , RUHL HARTMUT , NAKAJIMA KAZUHISA , DENG AIHUA , ZHANG XIAOMEI , SHEN BAIFEI , LIU JIANSHENG , LI RUXIN , XU ZHIZHAN , TAJIMA TOSHIKI
Published: August 2012

A laser wakefield accelerator (LWFA) with a weak focusing force is considered to seek improved beam quality in LWFA. We employ super-Gaussian laser pulses to generate the wakefield and study the behavior of the electron beam dynamics and synchrotron radiation arising from the transverse betatron oscillations through analysis and computation. We note that the super-Gaussian wakefields radically reduce the betatron oscillations and make the electron orbits mainly ballistic over a single stage. This feature permits to obtain small emittance and thus high luminosity, while still benefitting from the low-density operation of LWFA (Nakajima et al. 2011 Phys. Rev. ST Accel. Beams14, 091301), such as the reduced radiation loss, less number of stages, less beam instabilities, and less required wall plug power than in higher density regimes.
Optimum angle for side injection of electrons into linear plasma wakefields
Authors: LOTOV K. V.
Published: August 2012

A unified model of electron penetration into linear plasma wakefields is formulated and studied. The optimum angle for side injection of electrons is found. At smaller angles, all electrons are reflected radially. At larger angles, electrons enter the wakefield with superfluous transverse momentum that is unfavorable for trapping. Separation of incident electrons into penetrated and reflected fractions occurs in the outer region of the wakefield at some ‘reflection’ radius that depends on electron energy.
DANCING SOCIAL
Authors: Browning Barbara , Osterweis Ariel
Published: August 2012

Editor's Note: For this issue of Critical Stages, Ari Osterweis and Barbara Browning consider the multiple publics at play in the work of artist-performer Narcissister.
Core functions for the public health nutrition workforce in Europe: a consensus study
Authors: Jonsdottir Svandis , Thorsdottir Inga , Kugelberg Susanna , Yngve Agneta , Kennedy Nicholas P , Hughes Roger
Published: August 2012

Objective

To assess and develop a consensus among a European panel of public health nutrition workforce stakeholders (academics and employers) regarding core functions required for effective public health nutrition practice.

Design

A modified Delphi study involving data from two rounds of questionnaires administered among a panel of public health nutrition workforce stakeholders.

Setting

Europe.

Subjects

A panel of fifty-three public health nutrition development stakeholders, including thirty-three academics and twenty employers, sampled from eighteen European countries.

Results

Panellists rated 50 % (19/38) of the initially listed functions as core (i.e. without which public health capacity is limited), using a majority cut-off (>50 %). Out of the nineteen core functions seven were categorised under the headingIntervention management, emphasising high agreement on the importance of managing interventions in public health nutrition work. Only one of the identified core public health nutrition functions was rated differently between academics and employers, suggesting consistent identification of core functions between stakeholder groups.

Conclusions

This consensus on core functions of the public health nutrition workforce in Europe can be used to promote a consistent understanding of the role and value of public health nutritionists as a discrete disciplinary sub-specialty of the public health workforce. The convergence of opinions of academics and employers, as well as comparison with previous international studies, indicates that there is a set of core public health nutrition functions transferable between countries that can be used as a benchmark to guide further development of the public health nutrition workforce in Europe.
The Amsterdam–St. Paul Plateau: A complex hot spot/DUPAL‐flavored MORB interaction
Authors: Janin M. , Hémond C. , Maia M. , Nonnotte P. , Ponzevera E. , Johnson K. T. M.
Published: August 2012

The Amsterdam–St Paul (ASP) oceanic plateau results from the interaction between the ASP hot spot and the Southeast Indian ridge. A volcanic chain, named the Chain of the Dead Poets (CDP), lies to its northward tip and is related to the hot spot intraplate activity. The ASP plateau and CDP study reveals that ASP plume composition is inherited from oceanic crust and pelagic sediments recycled in the mantle through a 1.5 Ga subduction process. The ASP plateau lavas have a composition (major and trace elements and Sr‐Nd‐Pb‐Hf isotopes) reflecting the interaction between ASP plume and the Indian MORB mantle, including some clear DUPAL input. The Indian upper mantle below ASP plateau is heterogeneous and made of a depleted mantle with lower continental crust (LCC) fragments probably delaminated during the Gondwana break‐up. The lower continental crust is one of the possible reservoirs for the DUPAL anomaly origin that our data support. The range of magnitude of each end‐member required in ASP plateau samples is (1) 45% to 75% of ASP plume and (2) 25% to 55% of Indian DM within 0% to a maximum of 6% of LCC layers included within. The three end‐members involved (plume, upper mantle and lower continental crust) and their mixing in different proportions enhances the geochemical variability in the plateau lavas. Consequently, the apparent composition homogeneity of Amsterdam Island, an aerial summit of the plateau, may result from the presence of intermediate magmatic chambers into the plateau structure.
Longitudinal variability of thermospheric temperatures from WINDII O(1S) dayglow
Authors: Shepherd Marianna G. , Shepherd Gordon G. , Cho Young‐Min
Published: August 2012

A topic of great current interest in atmospheric dynamics is the developing recognition of the influence of the diurnal eastward‐propagating non‐migrating tide of wave number 3 (DE3) on the thermosphere. Longitudinal variations of the equatorialFregion ionospheric electron density show a zonal wave number 4 (wave‐4, WN4) pattern, expected for satellite observations at a fixed local time with respect to a rotating Earth. WINDII observations of airglow O(1S) volume emission rate (VER), excited by photoelectron impact on atomic oxygen at 250 km have previously been interpreted as neutral density observations; they have shown the wave 4 to be a common density perturbation in the equatorial thermosphere. The analysis has been extended further by examining thermospheric neutral temperatures from September 1992 to April 1993 at 245 km height derived from the vertical gradient of the observed daytime O(1S) VERs at 235–255 km yielding the atomic oxygen density scale heights centered at this altitude. The thermospheric temperatures show a distinct and persistent wave‐4 signature at 20°S–40°S with a pronounced increase during March equinox.
Asian dust height and infrared optical depth retrievals over land from hyperspectral longwave infrared radiances
Authors: Yao Zhigang , Li Jun , Han Hyo‐Jin , Huang Allen , Sohn B. J. , Zhang Peng
Published: August 2012

The dust top height and infrared optical depth over land are retrieved from the Atmospheric Infrared Sounder (AIRS) longwave infrared measurements by using a one‐dimensional‐variation retrieval algorithm for different Asian dust storms. By combining particle size measurements from a 10‐year ground observation data set from the Dunhuang Skynet station located to the east of the Taklimakan Desert in China and the Optical Properties of Aerosols and Clouds data set of optical properties, the mineral dust scattering and absorption coefficients are obtained and then used to compute brightness temperatures with RTTOV 9.3. The retrieved dust thermal infrared optical depths are compared with the Ozone Monitoring Instrument and Moderate Resolution Imaging Spectroradiometer (MODIS) products. The retrieved dust top heights are compared against the extinction backscatter profiles obtained from the Cloud‐Aerosol Lidar with Orthogonal Polarization lidar. Infrared optical depths from AIRS correlate favorably with visible optical depths from MODIS, and dust top heights agree reasonably with lidar observations for the single‐layered dust storms over the Taklimakan Desert.
Atmospheric waves and their interactions in the thermospheric neutral wind as observed by the Arecibo incoherent scatter radar
Authors: Huang Chunming , Zhang Shaodong , Zhou Qihou , Yi Fan , Huang Kaiming
Published: August 2012

Atmospheric waves and their interactions in the thermospheric neutral wind are studied based on Arecibo incoherent scatter radar observations. Our analysis suggests that the thermospheric atmosphere is usually disturbed by certain types of waves, including tides, gravity waves, and planetary waves, of which the diurnal tide is almost always the dominant disturbance. Strong interactions (defined as the coexistence of strong positive and negative correlations among the interacting waves) between the diurnal tide and gravity waves are frequently observed during the entire observation period. These strong interactions can persist for several days, although they are highly intermittent. Moreover, the sum and difference interactions between the diurnal tide and gravity waves always occur simultaneously and the energy exchange between the interacting waves is sometimes reversible. In addition to tide–gravity wave interactions, tide–planetary wave and tide–tide interactions are also found in our data. In tide–planetary wave interactions, the tidal oscillations are modulated at the interacting planetary wave periods. A combination of bispectral and correlation analyses verifies the occurrence of nonlinear interactions among different tidal components in the middle thermosphere. Moreover, during tide–tide interactions, the energy transfer trend changes very frequently, indicating that tidal energy is frequently redistributed among different tidal components. Generally, our study provides proof of strong tide–gravity wave, tide–planetary wave, and tide–tide interactions in the middle thermosphere, which has rarely been reported to date.
Textural and modal analyses of picritic basalts with ChemCam Laser‐Induced Breakdown Spectroscopy
Authors: Cousin A. , Sautter V. , Fabre C. , Maurice S. , Wiens R. C.
Published: August 2012

The ChemCam instrument suite on the Mars Science Laboratory rover Curiosity provides standoff compositional information using the first Laser‐Induced Breakdown Spectroscopy (LIBS) on a planetary mission and provides visual data on sample texture using a remote microimager. The LIBS technique is normally used to provide both qualitative (PCA, ICA) and quantitative (PLS) measurements. In this study we test its ability to evaluate variations in the proportion of different mineral phases, the distribution of mineral grains and the relative proportions of pyroxene and plagioclase in five basaltic rocks: (1) three picritic samples: Martian shergottite Dar al Gani 476 with olivine phenocrysts in a coarse‐grained pyroxene‐rich matrix; a terrestrial analog of Gusev basalt with a fine‐grained matrix and equal amounts of pyroxene and plagioclase; a synthetic microlitic glass and (2) two basaltic terrestrial rocks. LIBS measurements were acquired at a 3‐m standoff distance using a constant 400 μm beam size. The number of analysis locations per sample was fixed to five regardless of the rock texture. Results show that olivine phenocrysts can be easily distinguished from groundmass. The standard deviation of Ca/Al emission line ratios correlates with the grain size of the analyzed rocks and corresponds to the amount of plagioclase and pyroxene in the sample, even when the grain size is smaller than the laser spot size.
The role of secretory and endocytic pathways in the maintenance of cell polarity
Authors: Ang Su Fen , Fölsch Heike
Published: August 2012

Epithelial cells line virtually every organ cavity in the body and are important for vectorial transport through epithelial monolayers such as nutrient uptake or waste product excretion. Central to these tasks is the establishment of epithelial cell polarity. During organ development, epithelial cells set up two biochemically distinct plasma membrane domains, the apical and the basolateral domain. Targeting of correct constituents to each of these regions is essential for maintaining epithelial cell polarity. Newly synthesized transmembrane proteins destined for the basolateral or apical membrane domain are sorted into separate transport carriers either at the TGN (trans-Golgi network) or in perinuclear REs (recycling endosomes). After initial delivery, transmembrane proteins, such as nutrient receptors, frequently undergo multiple rounds of endocytosis followed by re-sorting in REs. Recent work in epithelial cells highlights the REs as a potent sorting station with different subdomains representing individual targeting zones that facilitate the correct surface delivery of transmembrane proteins.
Cell wars: regulation of cell survival and proliferation by cell competition
Authors: Vivarelli Silvia , Wagstaff Laura , Piddini Eugenia
Published: August 2012

During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels. Many of the pathways implicated in cell competition have been previously linked with cancer, and this has led to the hypothesis that cell competition could play a role in tumour formation. Cell competition could be co-opted by cancer cells to kill surrounding normal cells and boost their own tissue colonization. However, in some cases, cell competition could have a tumour suppressor role, as cells harbouring mutations in a subset of tumour suppressor genes are killed by wild-type cells. Originally described in developing epithelia, competitive interactions have also been observed in some stem cell niches, where they play a role in regulating stem cell selection, maintenance and tissue repopulation. Thus competitive interactions could be relevant to the maintenance of tissue fitness and have a protective role against aging.
The control of gene expression and cell proliferation by the epithelial apical junctional complex
Authors: Spadaro Domenica , Tapia Rocio , Pulimeno Pamela , Citi Sandra
Published: August 2012

The AJC (apical junctional complex) of vertebrate epithelial cells orchestrates cell–cell adhesion and tissue barrier function. In addition, it plays a pivotal role in signalling. Several protein components of the AJC, e.g. the cytoplasmic proteins β-catenin, p120-catenin and ZO (Zonula Occludens)-2, can shuttle to the nucleus, where they interact with transcription factors to regulate gene expression and cell proliferation. Other junctional proteins, e.g. angiomotin, α-catenin and cingulin, are believed to act by sequestering either transcription factors, such as YAP (Yes-associated protein), or regulators of small GTPases, such as GEF (guanine-nucleotide-exchange factor)-H1, at junctions. The signalling activities of AJC proteins are triggered by different extracellular and intracellular cues, including cell density, and physiological or pathological activation of developmentally regulated pathways, such as the Wnt pathway. The interplay between junctional protein complexes, the actin cytoskeleton and signalling pathways is of crucial importance in the regulation of gene expression and cell proliferation.
Apicobasal polarity and cell proliferation during development
Authors: Sabherwal Nitin , Papalopulu Nancy
Published: August 2012

Cell polarization and cell division are two fundamental cellular processes. The mechanisms that establish and maintain cell polarity and the mechanisms by which cells progress through the cell cycle are now fairly well understood following decades of experimental work. There is also increasing evidence that the polarization state of a cell affects its proliferative properties. The challenge now is to understand how these two phenomena are mechanistically connected. The aim of the present chapter is to provide an overview of the evidence of cross-talk between apicobasal polarity and proliferation, and the current state of knowledge of the precise mechanism by which this cross-talk is achieved.
Epithelial cell polarity: what flies can teach us about cancer
Authors: Bergstralh Daniel T. , St Johnston Daniel
Published: August 2012

Epithelial cells are polarized along their apical–basal axis. Much of the cellular machinery that goes into establishing and maintaining epithelial cell polarity is evolutionarily conserved. Model organisms, including the fruit fly, Drosophila melanogaster, are thus particularly useful for the study of cell polarity. Work in Drosophila has identified several important components of the polarity machinery and has also established the surprising existence of a secondary cell polarity pathway required only under conditions of energetic stress. This work has important implications for the understanding of human cancer. Most cancers are epithelial in origin, and the loss of cell polarity is a critical step towards malignancy. Thus a better understanding of how polarity is established and maintained in epithelial cells will help us to understand the process of malignant transformation and may lead to improved therapies. In the present chapter we discuss the current understanding of how epithelial cell polarity is regulated and the known associations between polarity factors and cancer.
The Scribble–Dlg–Lgl polarity module in development and cancer: from flies to man
Authors: Elsum Imogen , Yates Laura , Humbert Patrick O. , Richardson Helena E.
Published: August 2012

The Scribble, Par and Crumbs modules were originally identified in the vinegar (fruit) fly, Drosophila melanogaster, as being critical regulators of apico–basal cell polarity. In the present chapter we focus on the Scribble polarity module, composed of Scribble, discs large and lethal giant larvae. Since the discovery of the role of the Scribble polarity module in apico–basal cell polarity, these proteins have also been recognized as having important roles in other forms of polarity, as well as regulation of the actin cytoskeleton, cell signalling and vesicular trafficking. In addition to these physiological roles, an important role for polarity proteins in cancer progression has also been uncovered, with loss of polarity and tissue architecture being strongly correlated with metastatic disease.
Mesenchymal stem cells overexpressing PEDF decrease the angiogenesis of gliomas
Authors: Wang Qiaoshu , Zhang Zhaoyun , Ding Tianling , Chen Zi , Zhang Tao
Published: August 2012

The present study is an exploration of a novel strategy to target a therapeutic gene to brain tumour tissues. In the present study, we evaluated the feasibility of using hMSCs (human mesenchymal stem cells) to deliver PEDF (pigment epithelium-derived factor), a potent inhibitor of tumour angiogenesis, in a model of intracranial gliomas. To assess its potential of tracking gliomas, MSCs (mesenchymal stem cells) were injected into the cerebral hemisphere and it showed that MSCs infiltrated into the vessel beds and scattered throughout the tumour. In vitro migration assay showed that the VEGF (vascular endothelial growth factor) enhanced MSC migration. In contrast, the migratory activity of MSCs was significantly inhibited with the presence of PEDF. Systematic delivery of AAV (adeno-associated virus)–PEDF to established glioma xenografts resulted in increased apoptosis of gliomas. In addition, MSC–PEDF treatment prolonged the survival of mice bearing U87 gliomas. Taken together, these data validate that MSCs–PEDF can migrate and deliver PEDF to target glioma cells, which may be a novel and promising therapeutic approach for refractory brain tumour.