bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel ETFDH mutation and imaging findings in an adult with glutaric aciduria type II
Authors: Rosenbohm Angela , Süssmuth Sigurd D. , Kassubek Jan , Müller Hans‐Peter , Pontes Christina , Abicht Angela , Bulst Stefanie , Ludolph Albert C. , Pinkhardt Elmar
Published: July 2013

Introduction: Glutaric aciduria type II (GAII) is a rare autosomal recessive disorder with variable clinical course. The disorder is caused by a defect in the mitochondrial electron transfer flavoprotein or the electron transfer flavoprotein dehydrogenase (ETFDH). Methods: We performed clinical characterization, brain and whole body MRI, muscle histopathology, and genetic analysis of the ETFDH gene in a young woman. Results: She presented with rhabdomyolysis and severe quadriparesis. We identified a novel homozygous missense mutation in ETFDH (c.1544G>T, p.Ser515Ile). Body fat MRI revealed a large amount of subcutaneous fat but no increase in visceral fat despite steatosis of liver and muscle. Diffusion tensor imaging (DTI) of cerebral MRI revealed reduced directionality of the white matter tracts. Histopathological findings showed lipid storage myopathy. Conclusions: In this study, we highlight diagnostic clues and body fat MRI in this rare metabolic disorder. Muscle Nerve 49:446–450, 2013
Blowing‐out effect and temperature profile in condensed phase in flame retarding epoxy resins by phosphorus‐containing oligomeric silsesquioxane
Authors: Zhang Wenchao , Li Xiangmei , Yang Rongjie
Published: July 2013

A series of flame retardant epoxy resins (EPs) containing phosphorus‐containing oligomeric silsesquioxane are prepared, and an interesting blowing‐out effect is detected in flame retardant EPs. The temperature profiles show that blowing‐out effect slows the heat transfer from the fire to the unburned matrix; furthermore, this blowing‐out effect can even take away some heat from the surface zone by the spurting gases. The thermo gravimetric analyzer and Fourier transform infrared spectrometer result shows that the spurting gases during the blowing‐out effect have a high content of CO2, which could reduce the combustion capability of the jetting gases. The flame retardancy of these EPs is tested by limit oxygen index and UL‐94. The incorporation of 2.5 wt% phosphorus‐containing oligomeric silsesquioxane into EP gives a remarkable blowing‐out effect, which results in a significant enhancement of limit oxygen index value and UL‐94 rating. The flame retardancy mechanism of blowing‐out effect is quite different from the traditional mechanisms. The char strength and morphology of EP composites are also investigated to explain the mechanism of the blowing‐out effect. Copyright © 2013 John Wiley & Sons, Ltd.
Validation of a yeast functional assay for p53 mutations using clonal sequencing
Authors: Iggo Richard , Rudewicz Justine , Monceau Elodie , Sevenet Nicolas , Bergh Jonas , Sjoblom Tobias , Bonnefoi Hervé
Published: July 2013

We have previously tested biopsies from 1469 breast tumours with a p53 functional assay in the context of a prospective clinical trial (EORTC 10994/BIG 1–00). The goal of the trial was to determine whether p53 status could be used to select patients who would benefit from inclusion of taxanes in anthracycline‐based chemotherapy. The results of the trial were negative. To test whether this was because the functional assay misclassified the tumours, we have reanalysed two groups of biopsies by Sanger sequencing and Roche 454 next generation sequencing (NGS). Comparison of yeast data with pooled cDNA sequencing data in an initial cohort of 69 biopsies showed that conventional sequencing is insensitive when the mutant p53 content is low. A second cohort of 48 biopsies was used to compare directly the yeast assay with Sanger and NGS technology. The mutant sequence was difficult to detect in sequence chromatograms of pooled cDNA, whereas NGS unequivocally identified mutations in every case classified as mutant by the functional assay. The NGS data showed that small deletions, probably caused by PCR splicing, account for most of the unexplained background in the yeast assay. We conclude that mutation detection techniques that test multiple clones, such as the p53 functional assay and NGS, are more reliable than Sanger sequencing of pooled DNA; that the high p53 mutation rate (44%) seen with the yeast assay in the EORTC 10994/BIG 1–00 trial reflects this high sensitivity; and that NGS with Roche 454 technology could be used to identify the p53 mutations in the remaining tumours previously tested in yeast in the EORTC10994/BIG 1–00 trial. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk
Authors: Thorpe Phoebe G. , Gilboa Suzanne M. , Hernandez‐Diaz Sonia , Lind Jennifer , Cragan Janet D. , Briggs Gerald , Kweder Sandra , Friedman Jan M. , Mitchell Allen A. , Honein Margaret A. ,   The National Birth Defects Prevention Study
Published: July 2013

Purpose

To determine which medications are most commonly used by women in the first trimester of pregnancy and identify the critical gaps in information about fetal risk for those medications.

Methods

Self‐reported first‐trimester medication use was assessed among women delivering liveborn infants without birth defects and serving as control mothers in two large case–control studies of major birth defects. The Teratology Information System (TERIS) expert Advisory Board ratings of quality and quantity of data available to assess fetal risk were reviewed to identify information gaps.

Results

Responses from 5381 mothers identified 54 different medication components used in the first trimester by at least 0.5% of pregnant women, including 31 prescription and 23 over‐the‐counter medications. The most commonly used prescription medication components reported were progestins from oral contraceptives, amoxicillin, progesterone, albuterol, promethazine, and estrogenic compounds. The most commonly used over‐the‐counter medication components reported were acetaminophen, ibuprofen, docusate, pseudoephedrine, aspirin, and naproxen. Among the 54 most commonly used medications, only two had “Good to Excellent” data available to assess teratogenic risk in humans, based on the TERIS review.

Conclusions

For most medications commonly used in pregnancy, there are insufficient data available to characterize the fetal risk fully, limiting the opportunity for informed clinical decisions about the best management of acute and chronic disorders during pregnancy. Future research efforts should be directed at these critical knowledge gaps. Copyright © 2013 John Wiley & Sons, Ltd.
EPR study of impurity defects in diamonds grown in carbonate medium
Authors: Komarovskikh Andrey , Nadolinny Vladimir , Palyanov Yuri , Kupriyanov Igor
Published: July 2013

Three previously unobserved paramagnetic centers: OX1, OX2, and OX3, have been revealed by the EPR studies of synthetic diamonds grown in Na2CO3–CO2–C system. All of these centers have electron spin S = 1/2 and have not got hyperfine structure. High g‐factor anisotropy of the studied OX1, OX2, and OX3 centers in the absence of transition metal ions in diamond structure may be indicative that there is an oxygen atom in the structure of these defects. IR spectra of the studied diamonds contain intensive line at 1332 cm−1, which confirms high content of positive charge state of substitutional nitrogen (N+) in studied diamonds. It was supposed that all of these three centers have negative charge states. In the paper structures of OX1, OX2, and OX3 centers are discussed according to the obtained experimental data.
Self‐induced growth of GaN nanowires by molecular beam epitaxy: A critical review of the formation mechanisms
Authors: Consonni V.
Published: July 2013

GaN nanowires, also called nanocolumns, have emerged over the last decade as promising nanosized building blocks for a wide variety of optoelectronic devices. In contrast to other III–V semiconductors, GaN nanowires have the ability to grow catalyst‐free within the self‐induced approach by plasma‐assisted molecular beam epitaxy, which does not require the use of any foreign materials or patterned substrate. The self‐induced growth has accordingly been considered as a valuable growth mode to form GaN nanowires on a wide number of substrates such as Si, Al2O3, diamond or SiC. The formation mechanisms have extensively been investigated and are specifically reviewed here from the very onset of the nucleation phase through the elongation phase to the coalescence process. A general approach of the self‐induced growth of GaN nanowires is gained. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simultaneous characterization of methane and carbon dioxide produced by cultured methanogens using gas chromatography/isotope ratio mass spectrometry and gas chromatography/mass spectrometry
Authors: Ai Guomin , Zhu Jinxing , Dong Xiuzhu , Sun Tong
Published: July 2013

RATIONALE

The stable carbon isotope ratios of methanogen‐produced CH4 and CO2 are useful information for identifying and quantifying methanogenic pathways. Isotope ratio mass spectrometry combined with gas chromatography (GC/IRMS) is a very attractive tool for performing high‐precision compound‐specific isotope analysis. However, no GC/IRMS techniques have yet been available or been validated that give baseline separation of methanogen‐produced CH4 and CO2 from N2/N‐oxides and H2O vapor at ambient temperature and compatibility with analysis by mass spectrometry.

METHODS

Microbe‐produced CH4 and CO2 in headspace gases were separated from N2/N‐oxides and H2O vapor in a single run on a GS‐CarbonPLOT column at 35°C and with a maximum operating temperature of 120–140°C. The simultaneous characterization of CH4 and CO2 was then performed by GC/IRMS using an optimized backflush time to eliminate the interference from N2/N‐oxides and H2O vapor, and by GC/MS due to there being no interference from O2 gas in the culture.

RESULTS

GC/MS and GC/IRMS were used to calculate the ionization efficiency of CO2 as 8.22–8.84 times that of CH4 in GC/MS analysis, and it was deduced that the N‐oxides, which can potentially interfere with δ13C analysis, were probably produced mainly in the source of the isotope ratio mass spectrometer. We also determined the aceticlastic methanogenic pathway.

CONCLUSIONS

The established GC/MS and GC/IRMS techniques are suitable for characterizing the gaseous carbon‐containing compounds produced by microbial cultures. Through high‐precision carbon isotope analysis by GC/IRMS combined with low concentrations of 13C‐labelled substrates, the technique has great potential for identifying and quantifying methanogen‐mediated carbon metabolic processes and pathways. Copyright © 2013 John Wiley & Sons, Ltd.
IL-4 receptor blockade abrogates satellite cell: Rhabdomyosarcoma fusion and prevents tumor establishment
Authors: Li Guangheng , Kikuchi Ken , Radka Megan , Abraham Jinu , Rubin Brian P. , Keller Charles
Published: July 2013

Tumor cells of the muscle-related cancer alveolar rhabdomyosarcoma (aRMS) have dysregulated terminal myogenic differentiation that is characterized by continuous proliferation, decreased capacity to express markers of terminal differentiation, and inability of tumor cells to fuse to one another in the manner seen for normal myoblasts. Whether aRMS tumor cells can fuse with normal myogenic progenitors such as skeletal muscle stem cells (satellite cells) or myoblasts is unknown, as is the biological effect of fusion events if the phenomenon occurs. To study this possibility, we isolated primary satellite cells harboring a lacZ Cre-LoxP reporter gene for coculture with murine aRMS primary tumor cells expressing Cre. Results of in vitro and in vivo experiments demonstrated tumor cell—muscle cell progenitor fusion events as well as accelerated rates of tumor establishment and progression when satellite cells and derived muscle progenitors were coinjected with tumor cells in an orthotopic allograft model. Interleukin 4 receptor (IL-4R) blocking antibody treatment reversed fusion events in vitro and blocked tumor initiation and progression in vivo. Taken together, this study supports a potential role of tumor cell—host cell fusion and the strong therapeutic potential of IL-4R blockade to prevent the establishment of RMS tumors at new anatomical sites.
Fault current calculation in distribution systems with inverter‐based distributed generations
Authors: Van Tu Dao , Chaitusaney Surachai , Yokoyama Akihiko
Published: July 2013

Fault current calculation in distribution systems faces the problem with participation of inverter‐based distributed generation (IBDG). This paper analyzes the fault response of IBDG in order to model it under fault condition. An adaptive algorithm based on an iterative technique is then proposed to calculate the fault current in a system with the installation of IBDG. This algorithm is first validated by the conventional fault calculation technique in case of a system without IBDG. Then, a time‐variant simulation is performed to validate the proposed algorithm for the system with IBDG. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
The neural correlates of temporal reward discounting
Authors: Scheres Anouk , de Water Erik , Mies Gabry W.
Published: July 2013

Temporal reward discounting (TD) refers to the decrease in subjective value of a reward when the delay to that reward increases. In recent years, a growing number of studies on the neural correlates of temporal reward discounting have been conducted. This article focuses on functional magnetic resonance imaging (fMRI) studies on TD in humans. First, we describe the different types of tasks (also from behavioral studies) and the dependent variables. Subsequently, we discuss the evidence for three neurobiological models of TD: the dual‐systems model, the single‐system model and the self‐control model. Further, studies in which nontraditional tasks (e.g., with nonmonetary rewards) were used to study TD are reviewed. Finally, we discuss the neural correlates of individual differences in discounting, and its development across the lifespan. We conclude that the evidence for each of the three neurobiological models of TD is mixed, in that all models receive (partial) support, and several studies provide support for multiple models. Because of large differences between studies in task design and analytical approach, it is difficult to draw a firm conclusion regarding which model provides the best explanation of the neural correlates of temporal discounting. We propose that some components of these models can complement each other, and future studies should test the predictions offered by different models against each other. Several future research directions are suggested, including studying the connectivity between brain regions in relation to discounting, and directly comparing the neural mechanisms involved in discounting of monetary and primary rewards. WIREs Cogn Sci 2013, 4:523–545. doi: 10.1002/wcs.1246

This article is categorized under:

Psychology > Brain Function and Dysfunction

Neuroscience > Cognition
A contact problem for electro‐elastic materials
Authors: Hüeber S. , Matei A. , Wohlmuth B.
Published: July 2013

We analyze the frictionless unilateral contact between an electro‐elastic body and a rigid electrically conductive foundation. On the potential contact zone, we use the Signorini condition with non‐zero gap and an electric contact condition with a conductivity depending on the Cauchy vector. We provide a weak variationally consistent formulation and show existence, uniqueness and stability of the solution. Our analysis is based on fixed point techniques for weakly sequentially continuous maps. We conclude by a numerical example that illustrates the applicability of the model.
Engineering of the glycerol decomposition pathway and cofactor regulation in an industrial yeast improves ethanol production
Authors: Zhang Liang , Tang Yan , Guo Zhongpeng , Shi Guiyang
Published: July 2013

Glycerol is a major by-product of industrial ethanol production and its formation consumes up to 4 % of the sugar substrate. This study modified the glycerol decomposition pathway of an industrial strain of Saccharomyces cerevisiae to optimize the consumption of substrate and yield of ethanol. This study is the first to couple glycerol degradation with ethanol formation, to the best of our knowledge. The recombinant strain overexpressing GCY1 and DAK1, encoding glycerol dehydrogenase and dihydroxyacetone kinase, respectively, in glycerol degradation pathway, exhibited a moderate increase in ethanol yield (2.9 %) and decrease in glycerol yield (24.9 %) compared to the wild type with the initial glucose concentration of 15 % under anaerobic conditions. However, when the mhpF gene, encoding acetylating NAD+-dependent acetaldehyde dehydrogenase from Escherichia coli, was co-expressed in the aforementioned recombinant strain, a further increase in ethanol yield by 5.5 % and decrease in glycerol yield by 48 % were observed for the resultant recombinant strain GDMS1 when acetic acid was added into the medium prior to inoculation compared to the wild type. The process outlined in this study which enhances glycerol consumption and cofactor regulation in an industrial yeast is a promising metabolic engineering strategy to increase ethanol production by reducing the formation of glycerol.
Randomized controlled trial of ‘teens and toddlers’: A teenage pregnancy prevention intervention combining youth development and voluntary service in a nursery
Authors: Bonell Chris , Maisey Ruth , Speight Svetlana , Purdon Susan , Keogh Peter , Wollny Ivonne , Sorhaindo Annik , Wellings Kaye
Published: July 2013

We conducted an independent evaluation of the “Teens and Toddlers” intervention. Our randomized trial examined effects on self‐reported last sex without contraception, >1 episode of sex without contraception in previous 3 months, expectation of teenage parenthood and youth development score, plus secondary outcomes among 449 at‐risk girls age 13/14 in England. The intervention involves 18–20 weekly sessions in pre‐school nurseries. Response rates were 95% post‐intervention and 91% one year later. At follow‐up two, there was no evidence of intervention benefits for primary outcomes and a positive impact for our secondary outcome, low self‐esteem. At follow‐up one, there was no evidence of benefits for our primary outcomes but evidence of benefits for our secondary outcomes: low self‐esteem; low sexual health knowledge; and difficulty discussing the contraceptive pill. The intervention should be refined, with a clearer logic model and more emphasis on sex education, and re‐evaluated.
II. Descriptions of some New Palæozoic Crustacea
Authors: Woodward Henry
Published: July 2013

We are indebted to Mr. David Page for having first pointed out two very well marked genera of Palæozoic Crustacea of the family Eurypteridœ, namely, Slimonia and Stylonurus. I gave a description of Silmonia in the ‘Intellectual Observer’ for November, 1863; and I now propose to point out the characters of Stylonurus.
Ruminal dry matter and nitrogen degradation in relation to condensed tannin and protein molecular structures in sainfoin (Onobrychis viciifolia) and lucerne (Medicago sativa)
Authors: AUFRÈRE J. , THEODORIDOU K. , MUELLER-HARVEY I. , YU P. , ANDUEZA D.
Published: July 2013

Sainfoin is a temperate legume that contains condensed tannins (CT), i.e. polyphenols that are able to bind proteins and thus reduce protein degradation in the rumen. A reduction in protein degradation in the rumen can lead to a subsequent increase in amino acid flow to the small intestine. The effects of CT in the rumen and the intestine differ according to the amount and structure of CT and the nature of the protein molecular structure. The objective of the present study was to investigate the degradability in the rumen of three CT-containing sainfoin varieties and CT-free lucerne in relation to CT content and structure (mean degree of polymerization, proportion of prodelphinidins andcis-flavanol units) and protein structure (amide I and II bands, ratio of amide I-to-amide II,α-helix,β-sheet, ratio ofα-helix-to-β-sheet). Protein molecular structures were identified using Fourier transform/infrared-attenuated total reflectance (FT/IR-ATR) spectroscopy. Thein situdegradability of three sainfoin varieties (Ambra, Esparcette and Villahoz) was studied in 2008, during the first growth cycle at two harvest dates (P1 and P2, i.e. 5 May and 2 June, respectively) and at one date (P3) during the second growth cycle (2 June) and these were compared with a tannin-free legume, lucerne (Aubigny). Loss of dry matter (DMDeg) and nitrogen (NDeg) in polyester bags suspended in the rumen was measured using rumen-fistulated cows. The NDeg of lucerne compared with sainfoin was 0·80v.0·77 at P1, 0·78v.0·65 at P2 and 0·79v.0·70 at P3, respectively. NDeg was related to the rapidly disappearing fraction (‘a’) fraction (r=0·76), the rate of degradation (‘c’) (r=0·92), to the content (r=−0·81) and structure of CT. However, the relationship between NDeg and the slowly disappearing fraction (‘b’) was weak. There was a significant effect of date and species×date, for NDeg and ‘a’ fraction. The secondary protein structure varied with harvest date (species×date) and was correlated with the fraction ‘b’. Both tannin and protein structures influenced the NDeg degradation. CT content and structure were correlated to the ‘a’ fraction and to the ‘c’. Features of the protein molecular secondary structure were correlated to the ‘b’ fraction.
To Perform Nascent Knowledge: Perceptual Constructs and Meanings in Sankai Juku's Shijima
Authors: Yellin Liora Malka
Published: July 2013

The focal point of this article is sensory perception in terms of action and experience. Perceptual constructs are both physical and cognitive acts that carry meaning in themselves, thus being a vital element of expression in performance making. Liora Malka Yellin's theoretical discussion here draws on J. J. Gibson's information-based model of perception and Maurice Merleau-Ponty's phenomenology of perception, relating aspects of their thought to that of theatre practitioners and their practice. At the centre of these reflections are references to the shifts undergone by Butoh since its beginnings in the 1960s, and an analysis of Shijima, a dance-theatre work by the Japanese group Sankai Juku, based in Paris. This analysis of the perceptual constructs embedded in the configuration of bodily movement directs attention to what can be called corporeal narrative. Liora Malka Yellin is a Lecturer in Theatre and Dance Studies in the Department of Theatre Arts and the Interdisciplinary Program in the Arts at Tel Aviv University.
X-ray powder diffraction data for peiminine
Authors: Xiao Dan , Zhang Li Li , Wu Xiao Qing , Yan Jin , Luo Wei , Li Hui
Published: July 2013

X-ray powder diffraction data, unit-cell parameters and space group for peiminine, C27H43NO3, are reported (a = 30.2026 Å,b = 5.8468 Å,c = 14.4344 Å,β = 96.9456°, unit-cell volumeV = 2530.23 Å3,Z = 2 and space groupP21). All measured lines were indexed and are consistent with theP21space group. No detectable impurity was observed.
The Problem of Paternal Motives
Authors: MILLS CHRIS
Published: July 2013

In this article I assess the ability of motivational accounts of paternalism to respond to a particular challenge: can its proponents adequately explain the source of the distinctive form of disrespect that animates this view? In particular I examine the recent argument put forward by Jonathan Quong that we can explain the presumptive wrong of paternalism by relying on a Rawlsian account of moral status. I challenge the plausibility of Quong's argument, claiming that although this approach can provide a clear response to the explanatory challenge, it is only successful in doing so when it relies on the strength of its rival: the argument from personal autonomy. In doing so I illustrate that such responses are conceptually dependent on an account of respect for persons, and thus much of the relevant controversy is actually disagreement over how we respect other individuals.
Genesis of a red-light district: prostitution in Nantes between 1750 and 1810
Authors: PLUSKOTA MARION
Published: July 2013

This article examines the origins of a red-light district in a French provincial city before the implementation of official regulation. It aims at redefining the role of prostitutes, police and society in the development of ‘reserved districts’. Based on the study of judicial archives over a 60-year period, the mapping of the spatial distribution of prostitutes in Nantes reveals the spread of prostitution in most of the city's districts. However, the migrations and movement of prostitutes within the city show a gradual clustering over two districts: this was motivated by economic rationales and was initiated by the prostitutes and, only later in the century, encouraged by the police and community.
Early Stuart Chester as a centre for regional portraiture
Authors: TITTLER ROBERT
Published: July 2013

Scholarship on provincial towns and cities has thus far overlooked their role as centres of painting in the early modern era, leaving the false impression that painting, and art itself, remained the preserve of London. Chester proves a vibrant centre for such activities in the era 1590–1640. This article shows how and why the distinctive characteristics of Chester and its wider hinterland encouraged and shaped its production of portraiture. It also places Chester in the wider context of painting activity in other such provincial centres.
Die Rolle sozialer Unterstützung, Religiosität und Achtsamkeit im Rahmen der Krankheitsverarbeitung bei Brustkrebspatientinnen
Authors: Hofner Marion , Michalak Johannes
Published: July 2013

Hintergrund: Eine Krebsdiagnose und die nachfolgende Behandlung bedeuten für die meisten Betroffenen eine hohe psychische Belastung. Fragestellung: Ziel der vorliegenden Studie war es, die prädiktive Bedeutung von Achtsamkeit und Körperachtsamkeit für die Entwicklung von depressiven Symptomen nach einer Krebsdiagnose zu untersuchen. Methode: Die Studienteilnehmerinnen waren 51 Frauen mit erstdiagnostiziertem Mamma-Karzinom. Mittels hierarchischer Regressionsanalysen wurde untersucht, inwieweit das Ausmaß von selbstzugeschriebener Achtsamkeit und Körperachtsamkeit kurz nach der Diagnose den psychischen Zustand der Patientinnen im Krankheitsverlauf über acht Wochen vorhersagen kann. Die Variablen soziale Unterstützung und Religiosität wurden hierbei statistisch kontrolliert. Ergebnisse: Die soziale Unterstützung ermöglichte eine Prognose der selbstbeurteilten Depressivität im Krankheitsverlauf. Darüber hinaus hatte weder Achtsamkeit noch Körperachtsamkeit oder Religiosität einen Vorhersagewert. Schlussfolgerung: In der vorliegenden Studie konnte kein Hinweis darauf gefunden werden, dass Achtsamkeit oder Körperachtsamkeit bei der Krankheitsverarbeitung von relevanter Bedeutung sind. Mögliche methodische Gründe für diese Ergebnis werden diskutiert.
Quantitative Systems Pharmacology Model of NO Metabolome and Methemoglobin Following Long‐Term Infusion of Sodium Nitrite in Humans
Authors: Vega‐Villa K , Pluta R , Lonser R , Woo S
Published: July 2013

A long‐term sodium nitrite infusion is intended for the treatment of vascular disorders. Phase I data demonstrated a significant nonlinear dose‐exposure‐toxicity relationship within the therapeutic dosage range. This study aims to develop a quantitative systems pharmacology model characterizing nitric oxide (NO) metabolome and methemoglobin after sodium nitrite infusion. Nitrite, nitrate, and methemoglobin concentration–time profiles in plasma and RBC were used for model development. Following intravenous sodium nitrite administration, nitrite undergoes conversion in RBC and tissue. Nitrite sequestered by RBC interacts more extensively with deoxyhemoglobin, which contributes greatly to methemoglobin formation. Methemoglobin is formed less‐than‐proportionally at higher nitrite doses as characterized with facilitated methemoglobin removal. Nitrate‐to‐nitrite reduction occurs in tissue and via entero‐salivary recirculation. The less‐than‐proportional increase in nitrite and nitrate exposure at higher nitrite doses is modeled with a dose‐dependent increase in clearance. The model provides direct insight into NO metabolome disposition and is valuable for nitrite dosing selection in clinical trials.

CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e60; doi:10.1038/psp.2013.35; published online 31 July 2013
SOcK, MiSTs, MASK and STicKs: the GCKIII (germinal centre kinase III) kinases and their heterologous protein–protein interactions
Authors: Sugden Peter H. , McGuffin Liam J. , Clerk Angela
Published: July 2013

The GCKIII (germinal centre kinase III) subfamily of the mammalian Ste20 (sterile 20)-like group of serine/threonine protein kinases comprises SOK1 (Ste20-like/oxidant-stress-response kinase 1), MST3 (mammalian Ste20-like kinase 3) and MST4. Initially, GCKIIIs were considered in the contexts of the regulation of mitogen-activated protein kinase cascades and apoptosis. More recently, their participation in multiprotein heterocomplexes has become apparent. In the present review, we discuss the structure and phosphorylation of GCKIIIs and then focus on their interactions with other proteins. GCKIIIs possess a highly-conserved, structured catalytic domain at the N-terminus and a less-well conserved C-terminal regulatory domain. GCKIIIs are activated by tonic autophosphorylation of a T-loop threonine residue and their phosphorylation is regulated primarily through protein serine/threonine phosphatases [especially PP2A (protein phosphatase 2A)]. The GCKIII regulatory domains are highly disorganized, but can interact with more structured proteins, particularly the CCM3 (cerebral cavernous malformation 3)/PDCD10 (programmed cell death 10) protein. We explore the role(s) of GCKIIIs (and CCM3/PDCD10) in STRIPAK (striatin-interacting phosphatase and kinase) complexes and their association with the cis-Golgi protein GOLGA2 (golgin A2; GM130). Recently, an interaction of GCKIIIs with MO25 has been identified. This exhibits similarities to the STRADα (STE20-related kinase adaptor α)–MO25 interaction (as in the LKB1–STRADα–MO25 heterotrimer) and, at least for MST3, the interaction may be enhanced by cis-autophosphorylation of its regulatory domain. In these various heterocomplexes, GCKIIIs associate with the Golgi apparatus, the centrosome and the nucleus, as well as with focal adhesions and cell junctions, and are probably involved in cell migration, polarity and proliferation. Finally, we consider the association of GCKIIIs with a number of human diseases, particularly cerebral cavernous malformations.
Vesicular uptake of N-acetylaspartylglutamate is catalysed by sialin (SLC17A5)
Authors: Lodder-Gadaczek Julia , Gieselmann Volkmar , Eckhardt Matthias
Published: July 2013

NAAG (N-acetylaspartylglutamate) is an abundant neuropeptide in the vertebrate nervous system. It is released from synaptic terminals in a calcium-dependent manner and has been shown to act as an agonist at the type II metabotropic glutamate receptor mGluR3. It has been proposed that NAAG may also be released from axons. So far, however, it has remained unclear how NAAG is transported into synaptic or other vesicles before it is secreted. In the present study, we demonstrate that uptake of NAAG and the related peptide NAAG2 (N-acetylaspartylglutamylglutamate) into vesicles depends on the sialic acid transporter sialin (SLC17A5). This was demonstrated using cell lines expressing a cell surface variant of sialin and by functional reconstitution of sialin in liposomes. NAAG uptake into sialin-containing proteoliposomes was detectable in the presence of an active H+-ATPase or valinomycin, indicating that transport is driven by membrane potential rather than H+ gradient. We also show that sialin is most probably the major and possibly only vesicular transporter for NAAG and NAAG2, because ATP-dependent transport of both peptides was not detectable in vesicles isolated from sialin-deficient mice.
AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex
Authors: Shen Jia X. , Cooper Dermot M. F.
Published: July 2013

AC2 (adenylate cyclase 2) is stimulated by activation of Gq-coupled muscarinic receptors through PKC (protein kinase C) to generate localized cAMP in HEK (human embryonic kidney)-293 cells. In the present study, we utilized a sensitive live-cell imaging technique to unravel the proteins that play essential roles in a Gq-coupled muscarinic receptor-mediated cAMP signalling complex. We reveal that, upon agonist binding to the Gq-coupled muscarinic receptor, AKAP79 (A-kinase-anchoring protein 79) recruits PKC to activate AC2 to produce cAMP. The cAMP formed is degraded by PDE4 (phosphodiesterase 4) activated by an AKAP-anchored PKA (protein kinase A). Calcineurin, a phosphatase bound to AKAP79, is not involved in this regulation. Overall, a transient cAMP increase is generated from AC2 by Gq-coupled muscarinic receptor activation, subject to sophisticated regulation through AKAP79, PKC, PDE4 and PKA, which significantly enhances acetylcholine-mediated signalling.
Validating Dynamic Assessment of Triadic Gaze for Young Children With Severe Disabilities
Authors: Olswang Lesley B. , Feuerstein Julie L. , Pinder Gay Lloyd , Dowden Patricia
Published: July 2013

Purpose

This research investigated the use of a dynamic assessment (DA) to identify differences among young children with severe disabilities, which would predict progress in learning behaviors indicating coordinated joint attention (CJA).

Method

Six children 10–24 months of age were enrolled in a 16-week treatment for behaviors indicating CJA, specifically triadic gaze (TG), which is a 3-point gaze shift between object and adult. An initial static assessment documented the children's eligibility for the study and their baseline performance of TG. DA procedures were then implemented to determine each child's performance with examiner support in producing behaviors suggesting joint attention (i.e., tracking, gaze toward an object or an adult, scanning between objects, scanning an object and adult, and TG).

Results

Results demonstrated differences among children during the DA via a DA score and a behavioral profile. These results were predictive of differences among children in subsequent learning of TG.

Conclusion

These data support the validity of DA for describing heterogeneity among young children with severe disabilities who look similar on static assessment but appear differentially ready to learn behaviors associated with joint attention. This knowledge will assist clinicians in planning more efficacious services for young children who struggle to communicate and are at risk for extended therapeutic needs.
A nano-patterned photonic crystal laser with a dye-doped liquid crystal
Authors: Ko Doo-Hyun , Morris Stephen M. , Lorenz Alexander , Castles Flynn , Butt Haider , Gardiner Damian J. , Qasim Malik M. , Wallikewitz Bodo , Hands Philip J. W. , Wilkinson Timothy D. , Amaratunga Gehan A. J. , Coles Harry J. , Friend Richard H.
Published: July 2013

Covering a nano-patterned titanium dioxide photonic crystal (PC) within a well-oriented film of dye-doped liquid crystal (LC), a distributed feedback laser is constructed whereby the emission characteristics can be manipulated in-situ using an electric field. This hybrid organic-inorganic structure permits simultaneous selectivity of both the beam pattern and laser wavelength by electrical addressing of the LC director. In addition, laser emission is obtained both in the plane and normal to the PC. Along with experimental data, a theoretical model is presented that is based upon an approximate calculation of the band structure of this birefringent, tuneable laser device.
How a solute-pump/solvent-probe spectroscopy can reveal structural dynamics: Polarizability response spectra as a two-dimensional solvation spectroscopy
Authors: Sun Xiang , Stratt Richard M.
Published: July 2013

The workhorse spectroscopy for studying liquid-state solvation dynamics, time-dependent fluorescence, provides a powerful, but strictly limited, perspective on the solvation process. It forces the evolution of the solute-solvent interaction energy to act as a proxy for what may be fairly involved changes in solvent structure. We suggest that an alternative, a recently demonstrated solute-pump/solvent-probe experiment, can serve as a kind of two-dimensional solvation spectroscopy capable of separating out the structural and energetic aspects of solvation. We begin by showing that one can carry out practical, molecular-level, calculations of these spectra by means of a hybrid theory combining instantaneous-normal-mode ideas with molecular dynamics. Applying the resulting formalism to a model system displaying preferential solvation reveals that the solvent composition changes near the solute do indeed display slow dynamics similar to, but measurably different from, that of the solute-solvent interaction – and that this two-dimensional spectroscopy can effectively single out those local structural changes.
Optomechanical effects of two-level systems in a back-action evading measurement of micro-mechanical motion
Authors: Suh J. , Weinstein A. J. , Schwab K. C.
Published: July 2013

We show that the two-level systems (TLS) in lithographic superconducting circuits act as a power-dependent dielectric leading to non-linear responses in a parametrically coupled electromechanical system. Driven TLS shift the microwave resonance frequency and modulate the mechanical resonance through the optical spring effect. By pumping with two tones in a back-action evading measurement, these effects produce a mechanical parametric instability which limits single quadrature imprecision to 1.4 xzp. The microwave resonator noise is also consistent to a TLS-noise model. These observations suggest design strategies for minimizing TLS effects to improve ground-state cooling and quantum non-demolition measurements of motion.
The free rigid body dynamics: Generalized versus classic
Authors: Tudoran Răzvan M.
Published: July 2013

In this paper we analyze some normal forms of a general quadratic Hamiltonian system defined on the dual of the Lie algebra \documentclass[12pt]{minimal}\begin{document}$\mathfrak {o}(K)$\end{document}o(K) of real K-skew-symmetric matrices, where K is an arbitrary 3×3 real symmetric matrix. A consequence of the main results is that any first-order autonomous three-dimensional differential equation possessing two independent quadratic constants of motion, which admit a positive/negative definite linear combination, is affinely equivalent to the classical “relaxed” free rigid body dynamics with linear control parameters.
Theory of the circular closed loop antenna in the terahertz, infrared, and optical regions
Authors: McKinley A. F. , White T. P. , Catchpole K. R.
Published: July 2013

Modern antenna theory forms the bulwark of our knowledge of how radiation and metallic structures interact in the radio frequency (RF) and microwave (MW) regions. The theory has not yet penetrated the terahertz, infrared, and optical regions to the same degree. In this paper, we provide a rigorous analysis of closed circular loop antennas from first principles. Using antenna theory, we tie together their long wavelength behavior with their behavior at short wavelengths through the visible region. We provide analytic forms for the input impedance, current, quality factor, radiation resistance, ohmic loss, and radiation efficiency. We provide an exact circuit model for the closed loop in the RF and MW regions, and extend it through the optical region. We also provide an implicit analytic form for the determination of all modal resonances, allowing prediction of the resonance saturation wavelength for loops. Through simulations, we find that this behavior extends to hexagonal and square loops. All results are applicable to loop circumferences as short as 350 nm. Finally, we provide a precise analytic model of the index of refraction, as a tool in these computations, which works equally well for metals and semi-conductors.
Two-dimensional simulations of thermonuclear burn in ignition-scale inertial confinement fusion targets under compressed axial magnetic fields
Authors: Perkins L. J. , Logan B. G. , Zimmerman G. B. , Werner C. J.
Published: July 2013

We report for the first time on full 2-D radiation-hydrodynamic implosion simulations that explore the impact of highly compressed imposed magnetic fields on the ignition and burn of perturbed spherical implosions of ignition-scale cryogenic capsules. Using perturbations that highly convolute the cold fuel boundary of the hotspot and prevent ignition without applied fields, we impose initial axial seed fields of 20–100 T (potentially attainable using present experimental methods) that compress to greater than 4 × 104 T (400 MG) under implosion, thereby relaxing hotspot areal densities and pressures required for ignition and propagating burn by ∼50%. The compressed field is high enough to suppress transverse electron heat conduction, and to allow alphas to couple energy into the hotspot even when highly deformed by large low-mode amplitudes. This might permit the recovery of ignition, or at least significant alpha particle heating, in submarginal capsules that would otherwise fail because of adverse hydrodynamic instabilities.
Optical bandgap and phase transition in relaxor ferroelectric Pb(Mg1∕3Nb2∕3)O3-xPbTiO3 single crystals: An inherent relationship
Authors: Zhang X. L. , Hu Z. G. , Xu G. S. , Zhu J. J. , Li Y. W. , Zhu Z. Q. , Chu J. H.
Published: July 2013

We report band to band transition behaviors of relaxor ferroelectric Pb(Mg1∕3Nb2∕3)O3-xPbTiO3 (PMN-xPT) single crystals derived from temperature-dependent spectral transmittance. A typical bandgap formula with the temperature and composition (8 K≤Texp≤453 K, 0.1≤x≤0.4) has been presented. Moreover, the phase diagram of PMN-xPT crystals can be well proposed, which is based on the bandgap variations and can be explained by electronic structure evolution. It reveals an intrinsic relationship between fundamental bandgap and phase transition of PMN-xPT single crystals, which pioneers an effective methodology to explore the phase transition of ferroelectric oxides.
Non-volatile memory with self-assembled ferrocene charge trapping layer
Authors: Zhu Hao , Hacker Christina A. , Pookpanratana Sujitra J. , Richter Curt A. , Yuan Hui , Li Haitao , Kirillov Oleg , Ioannou Dimitris E. , Li Qiliang
Published: July 2013

A metal/oxide/molecule/oxide/Si capacitor structure containing redox-active ferrocene molecules has been fabricated for non-volatile memory application. Cyclic voltammetry and X-ray photoelectron spectroscopy were used to measure the molecules in the structure, showing that the molecules attach on SiO2/Si and the molecules are functional after device fabrication. These solid-state molecular memory devices have fast charge-storage speed and can endure more than 109 program/erase cycles. This excellent performance is derived from the intrinsic properties of the redox-active molecules and the hybrid Si-molecular device structure. These molecular devices are very attractive for future high-level non-volatile memory applications.
Spawning-habitat selection of an Indo-Pacific amphidromous gobiid fish, Sicyopterus lagocephalus (Pallas)
Authors: Teichert Nils , Valade Pierre , Bosc Pierre , Richarson Marine , Gaudin Philippe
Published: July 2013

Freshwater-fish populations of the Indo-pacific region are characterised by a large proportion of amphidromous species. We analysed the spawning-habitat selection of Sicyopterus lagocephalus (Gobiidae: Sicydiinae) within two rivers of the Reunion Island. Reproduction traces are rare events, so a presence-only sampling procedure was performed to collect egg clutches and a random description of available habitat was conducted to generate pseudo-absence data. Logistic models showed a strong selection for microhabitat variables and mesohabitat units. S. lagocephalus selected areas where availability of potential nests was high (small cobble to small boulder) and where interstitial substratum allowed intragravel flow. Our results suggest that the availability of favourable substratum may be a limiting factor, which could result in occupancy of suboptimal areas. Water depth and velocity had less of an effect on the selection of a spawning area. Higher selection for shallow (<60 cm) and lotic (>30 cm s–1) geomorphic units, with an optimum for riffle and cascade, suggested that mesohabitat could be a satisfactory approach to quickly assess the availability of spawning areas within a watercourse for expertise studies.
Homing of Sockeye Salmon within Hidden Lake, Alaska, Can Be Used to Achieve Hatchery Management Goals
Authors: Habicht Christopher , Tobias Terri M. , Fandrei Gary , Webber Nathan , Lewis Bert , Grant W. Stewart
Published: July 2013

The supplementation of natural populations of Pacific salmon Oncorhynchus spp. with hatchery fish poses unique management challenges. Two such challenges addressed in this study are limiting the number of hatchery fish spawning with natural-origin fish and maximizing the number of natural-origin fish in the supplementation broodstock. In this study, we focus on stock enhancement of Sockeye Salmon O. nerka in Hidden Lake, Alaska, where the Trail Lakes Hatchery supplements the natural population with hatchery-raised fry. Production in Hidden Lake is limited by the availability of spawning habitat and not by juvenile rearing capacity. The hatchery collects broodstock from the lake and releases fry with thermally marked otoliths at one of two primary natural spawning sites in Hidden Lake each year. During this study, an average of 58% of the fish returning to the lake through a weir on the outlet stream were of hatchery origin. However, an average of 88% of the fish at the release site were hatchery-origin fish, indicating a nonrandom distribution of hatchery-origin spawners. This pattern is consistent with homing to specific sites within the lake of either or both hatchery- and wild-origin fish. However, this distribution results in a larger-than-desirable proportion of hatchery-origin fish spawning with natural-origin fish at the release site. The proportion of hatchery-origin fish used for brood is also larger than desirable because the site is also the broodstock collection site. We propose that releasing hatchery fish at a new location removed from the primary spawning areas and the hatchery broodstock collection site will reduce the proportion of hatchery-origin fish spawning with wild-origin fish and increase the proportion of wild-origin fish in the broodstock, if our results are due, at least in part, to homing of hatchery fish.

Received May 12, 2012; accepted May 20, 2013