bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation analysis for wind speed and failure rate of wind turbines using time series approach
Authors: Su Chun , Jin Quan , Fu Yequn
Published: June 2012

The correlation between wind speed and failure rate (FR) of wind turbines is analyzed with time series approach. The time series of power index (PI) and FR of wind turbines are established based on historical data, which are pretreated by singularity processing, stationarity processing, and wavelet de-noising. The trend variations of the time series are analyzed from both time domain and frequency domain by extracting the indicator functions, including auto-correlation function, cross-correlation function, and spectral density function. A case study is given out to verify the validity of the model and the method, which is based on the wind speed and failure data from January 1995 to December of 2002 in Nordjylland, Denmark. Auto-correlation function and spectral density function show that time series of PI and FR have strong seasonal characteristics and quite similar periodicity, while the cross-correlation function shows they keep high consistency and strong correlation. The results indicate that by calculating and monitoring PI, the failure rule of wind turbines can be forecast, which provides theoretical basis for preventive maintenance of wind turbines.
Toward cardiac electrophysiological mapping based on micro-Tesla NMR: a novel modality for localizing the cardiac reentry
Authors: Kim Kiwoong
Published: June 2012

Matching the proton magnetic resonance frequency to the frequency of a periodic electrophysiological excitation of myocardium enables direct localization of the cardiac reentry by magnetic resonance imaging techniques. The feasibility of this new idea has been demonstrated by conducting a numerical simulation based on a realistic heart model and experimental parameters in SQUID-based micro-Tesla NMR.
Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR
Authors: Knight Michael J. , Pell Andrew J. , Bertini Ivano , Felli Isabella C. , Gonnelli Leonardo , Pierattelli Roberta , Herrmann Torsten , Emsley Lyndon , Pintacuda Guido
Published: June 2012

We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with
1
H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of
15
N and
13
C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu
+
(diamagnetic) or Cu
2+
(paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to
1
H-
1
H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a Gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable.
Seed orchard genetics.
Authors: Funda T. , El-Kassaby Y. A.
Published: June 2012

Seed orchards represent the link between tree breeding and silvicultural activities. Their genetic efficiency is of vital importance as it determines the extent of genetic gain and diversity of future forest tree plantations. Given their importance, seed orchard genetics has received increased scientific and managerial scrutiny. Virtually all aspects affecting seed orchard genetic efficiency have been thoroughly investigated, including their biological model, underpinning assumptions and management practices developed and implemented to improve crop genetic quality. In this review, we systematically address these topics starting with the position of seed orchards in the tree improvement cycle, their population genetics model and the biological factors affecting this model; namely, reproductive investment and success, reproductive phenology, inbreeding, gene flow and finally the biology of the seed. Management practices are reviewed including those implemented during the establishment phase (orchard size, design, number of parents and their representation) and those implemented for enhanced crop management (crown management, supplemental mass pollination, bloom delay, selective seed harvesting and the production of designer crops). The genetic consequences of these issues are discussed. The intention of this article is to produce a state-of-art review of this vital component of every tree improvement delivery system and to facilitate and encourage further research and development for present and future seed orchards.
REDD reckoning: a review of research on a rapidly moving target.
Authors: Seymour F.
Published: June 2012

This review characterizes the major themes of articles on reducing emissions from deforestation and forest degradation (REDD) published between January 2007 and December 2010 in various peer-reviewed journals, as well as selected reports in the 'grey literature'. The main themes of the articles and reports are analysed in relation to four topics: the global architecture of REDD; measurement and monitoring; national and subnational policies, institutions and governance; and the relationship of REDD to other objectives such as biodiversity conservation, poverty reduction and rights protection. The review identifies a number of topics for further research, including empirical validation of the predicted benefits and risks of implementing REDD policies and projects, and analysis of the degree to which REDD is shaping, or being shaped by, the political economy of forest governance at national and global levels.
An Age‐Structured Integrated Assessment of Chinook Salmon Population Dynamics in Lake Huron's Main Basin since 1968
Authors: Brenden Travis O. , Bence James R. , Szalai Emily B.
Published: June 2012

We conducted a statistical catch‐at‐age (SCAA) assessment, also known as an integrated assessment, of the Chinook salmonOncorhynchus tshawytschapopulation in Lake Huron's main basin to describe the dynamics and assess population abundance since the species began being stocked in 1968. The purpose of this assessment was to determine whether recent declines in Chinook salmon recreational harvest were indicative of an overall decrease in population abundance, and to estimate the magnitude of that decline. Data sources integrated into the assessment model included recreational harvest and effort, returns to the Swan River weir by year‐class, age composition of recreational harvest (overall and of mature fish), and proportion mature by age. Parameters estimated included time‐varying age‐0 natural mortality rates and recreational fishing catchabilities, age‐specific recreational fishing selectivities, and the parameters of a logistic function relating maturation probability to fish age and weight. The fitted model did a reasonable job of predicting recreational harvest, Swan River weir returns, age composition of recreational harvest, and proportion mature by age. The model predicted that abundance of age‐1 and older Chinook salmon has declined by approximately 98% since the mid‐1980s, with an estimated abundance of age‐1 and older fish of approximately 65,000 in 2009. The primary cause for this decline has been a substantial increase in age‐0 natural mortality rates, which peaked at an instantaneous rate of around 6.3 in the late 2000s, although fishing mortality rates have also been quite high. Initially, declines in survival were associated with increases in overall predator abundance in the lake. The most recent and large declines were associated with a decrease in the abundance of alewivesAlosa pseudoharengus. We suspect that declines in age‐0 survival reflect both direct effects of food limitation and increased predation mortality by larger fish, and are consequences of decreased abundance of other prey fishes.
Experimental and theoretical study of electron-beam-induced spin-reorientation transition reversal in the CO/Co(1 1 0) system
Authors: Reeve Robert M , Chin Shin-Liang , Kopper Klaus-Peter , Ionescu Adrian , Barnes Crispin H W
Published: June 2012

The spin-reorientation transition (SRT) of Co films on Cu(1 1 0) due to adsorption of CO is investigated using in situ Mott polarimetry to measure the secondary electron spin polarization (SESP). The polarization along the [0 0 1] axis is found to decrease in time as the residual gas adsorbs on the surface, while the polarization along the orthogonal axis increases. By subsequently exposing the films to an electron beam for an extended period, the CO on the surface is perturbed and the process is reversed. The SESP is consequently observed to follow the opposite evolution to that seen during the initial SRT, with the SESP reverting to 83.6 ± 1.1% of its initial value after the complete reversal. Density functional theory calculations suggest that this is due to the electron-beam dissociation of the CO, leaving behind C on the cobalt surface. Furthermore, the calculations show that the C adatom results in a reduction in the SESP signal to 81% of the clean Co(1 1 0) surface, which is in good quantitative agreement with our experimental results. The experimental SESP data are also fitted to an analytical model taking into account the interaction of the electron beam with the surface adsorbate to yield an average electronic cross-section for the process of σ = (5.8 ± 1.1) × 10−18 cm2 and a strikingly small CO coverage responsible for the effect of just 0.065 ± 0.012 ML. A series of in situ magneto-optical Kerr effect measurements were also performed across the sample to show that this reversal effect is localized and confirm the ability to pattern the magnetization by locally modifying the magnetic anisotropy of the system via an electron-beam exposure.
Development of robust flexible OLED encapsulations using simulated estimations and experimental validations
Authors: Lee Chang-Chun , Shih Yan-Shin , Wu Chih-Sheng , Tsai Chia-Hao , Yeh Shu-Tang , Peng Yi-Hao , Chen Kuang-Jung
Published: June 2012

This work analyses the overall stress/strain characteristic of flexible encapsulations with organic light-emitting diode (OLED) devices. A robust methodology composed of a mechanical model of multi-thin film under bending loads and related stress simulations based on nonlinear finite element analysis (FEA) is proposed, and validated to be more reliable compared with related experimental data. With various geometrical combinations of cover plate, stacked thin films and plastic substrate, the position of the neutral axis (NA) plate, which is regarded as a key design parameter to minimize stress impact for the concerned OLED devices, is acquired using the present methodology. The results point out that both the thickness and mechanical properties of the cover plate help in determining the NA location. In addition, several concave and convex radii are applied to examine the reliable mechanical tolerance and to provide an insight into the estimated reliability of foldable OLED encapsulations.
Discharge characteristics of mercury-free flat fluorescent lamps with various electrode configurations analysed through a two-dimensional fluid model simulation
Authors: Kwon Ohyung , Oh Byung Joo , Whang Ki-Woong
Published: June 2012

The discharge characteristics and factors related to the luminous efficacy of mercury-free flat fluorescent lamps (MFFLs) with three different types of coplanar, counter and combination electrode configurations were studied via a two-dimensional numerical simulation. The spatiotemporal distributions of the potential, electric field, electron density, Xe** density and current waveforms of the MFFLs were obtained and analysed. The MFFL with the combination electrode configuration shows the highest vacuum ultraviolet (VUV) efficacy value. The vertical electrode in the MFFL with the combination electrode configuration prevents the electric field at the gap space from decreasing rapidly, and extends the discharge path. The effects of the vertical electrode help one to increase the Xe excitation efficacy. In addition, a new auxiliary electrode was proposed in the original MFFL with the combination electrode configuration. The MFFL with the new auxiliary electrode has broader distributions of electrons and Xe** species, and a higher VUV efficacy value than the original MFFL with the combination electrode configuration at the same voltage.
Polyhedral surfaces and determinant of Laplacian
Authors: Kokotov Alexey
Published: June 2012

An explicit formula for the determinant of the Laplacian on a compact polyhedral surface of genus

g
>
1

g>1

is found. This formula generalizes previously known results for flat surfaces with trivial holonomy and compact polyhedral tori.
The Gardner equation and the 𝐿²-stability of the 𝑁-soliton solution of the Korteweg-de Vries equation
Authors: Alejo Miguel , Muñoz Claudio , Vega Luis
Published: June 2012

Multi-soliton solutions of the Korteweg-de Vries equation (KdV) are shown to be globallyL2L^2-stable, and asymptotically stable in the sense of Martel and Merle. The proof is surprisingly simple and combines the Gardner transform, which links the Gardner and KdV equations, together with the Martel-Merle-Tsai and Martel-Merle recent results on stability and asymptotic stability in the energy space, applied this time to the Gardner equation. As a by-product, the results of Maddocks-Sachs, and Merle-Vega are improved in several directions.
On the semiadditivity of the capacities associated with signed vector valued Riesz kernels
Authors: Prat Laura
Published: June 2012

The aim of this paper is to show the semiadditivity of the capacities associated with the signed vector valued Riesz kernels of homogeneity

−
α

-\alpha

in

R

n

{\mathbb R}^n

,

0
>
α
>
n

0>\alpha >n

.
Relations of circulating vitamin D concentrations with left ventricular geometry and function
Authors: Fall Tove , Shiue Ivy , Bergeå af Geijerstam Per , Sundström Johan , Ärnlöv Johan , Larsson Anders , Melhus Håkan , Lind Lars , Ingelsson Erik
Published: June 2012

Aims

Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community‐based study.

Methods and results

In the PIVUS study, we measured serum 25‐dihydroxyvitamin‐D (25‐OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end‐diastolic diameter, end‐systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52% women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25‐OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (β, –0.42 mm, P = 0.03; β, 0.70%, P = 0.03; and β, 0.91% P = 0.01, respectively), per 1 SD increase in 25‐OH D (SD = 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years.

Conclusion

In our community‐based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross‐sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.
Ebenezer Hopkins Frost (1824–1866)
Authors: LeVasseur Ryan , Desai Sukumar P.
Published: June 2012

Although he was not the first to use ether as an anesthetic, it was not until William Thomas Green Morton's demonstration of the efficacy of ether anesthesia that its use spread rapidly throughout the world. Full identities of the first anesthetized patients of William Edward Clarke and Horace Wells are not known, but we are quite certain that Crawford Williamson Long correctly identified James Venable as his first patient to receive anesthesia. Using municipal records, historical accounts, and recent analyses of Morton's unsavory side, we undertook this study to explore three questions. First, we examine how Morton refined the technique of administering anesthesia based on Wells' failed attempt. Second, we describe the circumstances under which Morton encountered his first patient to receive anesthesia. Third, we offer an explanation as to why Morton insisted on bringing along this patient to attend the grand event we celebrate as Ether Day. This is an essay about William Thomas Green Morton and Ebenezer Hopkins Frost.
A Simulation Study of Common Propofol and Propofol-Opioid Dosing Regimens for Upper Endoscopy
Authors: LaPierre Cris D. , Johnson Ken B. , Randall Benjamin R. , Egan Talmage D.
Published: June 2012

Background

Using models of respiratory compromise, loss of response to esophageal instrumentation, and loss of responsiveness, the authors explored through simulation published dosing schemes for endoscopy using propofol alone and in combination with selected opioids. They hypothesized that models would predict adequate conditions for esophageal instrumentation and once drug administration is terminated, rapid return of responsiveness and minimal respiratory compromise.

Methods

Four published dosing regimens of propofol alone or in combination with opioids were used to predict the probability of loss of response to esophageal instrumentation for a 10-min procedure and the probability of respiratory compromise and return of responsiveness once the procedure had ended.

Results

Propofol alone provided a low probability (9-20%) and propofol-opioid techniques provided a moderate probability (15-58%) of loss of response to esophageal instrumentation. Once the procedure ended, all techniques provided a high likelihood of rapid return of responsiveness (less than 3 min). Propofol-opioid techniques required more time than propofol alone to achieve a high probability of no respiratory compromise (7 vs. 4 min).

Conclusions

Propofol alone would likely lead to inadequate conditions for esophageal instrumentation but would provide a rapid return to responsiveness and low probability of respiratory compromise once the procedure ended. The addition of remifentanil or fentanyl improved conditions for esophageal instrumentation and had an equally rapid return to responsiveness. The time required to achieve a low probability of respiratory compromise was briefly prolonged; this is likely inconsequential given that patients are responsive and can be prompted to breathe.
Anesthetic Protection of Neurons Injured by Hypothermia and Rewarming
Authors: Bickler Philip E. , Warren Daniel E. , Clark John P. , Gabatto Pablo , Gregersen Maren , Brosnan Heather
Published: June 2012

Background

Mild hypothermia is neuroprotective after cerebral ischemia but surgery involving profound hypothermia (PH, temperature less than 18°C) is associated with neurologic complications. Rewarming (RW) from PH injures hippocampal neurons by glutamate excitotoxicity, N-methyl-D-aspartate receptors, and intracellular calcium. Because neurons are protected from hypoxia-ischemia by anesthetic agents that inhibit N-methyl-D-aspartic acid receptors, we tested whether anesthetics protect neurons from damage caused by PH/RW.

Methods

Organotypic cultures of rat hippocampus were used to model PH/RW injury, with hypothermia at 4°C followed by RW to 37°C and assessment of cell death 1 or 24 h later. Cell death and intracellular Ca were assessed with fluorescent dye imaging and histology. Anesthetic agents were present in the culture media during PH and RW or only RW.

Results

Injury to hippocampal CA1, CA3, and dentate neurons after PH and RW involved cell swelling, cell rupture, and adenosine triphosphate (ATP) loss; this injury was similar for 4 through 10 h of PH. Isoflurane (1% and 2%), sevoflurane (3%) and xenon (60%) reduced cell loss but propofol (3 μM) and pentobarbital (100 μM) did not. Isoflurane protection involved reduction in N-methyl-D-aspartate receptor-mediated Ca influx during RW but did not involve γ-amino butyric acid receptors or KATP channels. However, cell death increased over the next day.

Conclusion

Anesthetic protection of neurons rewarmed from 4°C involves suppression of N-methyl-D-aspartate receptor-mediated Ca overload in neurons undergoing ATP loss and excitotoxicity. Unlike during hypoxia/ischemia, anesthetic agents acting predominantly on γ-aminobutyric acid receptors do not protect against PH/RW. The durability of anesthetic protection against cold injury may be limited.
Detecting differential usage of exons from RNA-seq data
Authors: Anders Simon , Reyes Alejandro , Huber Wolfgang
Published: June 2012

RNA-seq is a powerful tool for the study of alternative splicing and other forms of alternative isoform expression. Understanding the regulation of these processes requires sensitive and specific detection of differential isoform abundance in comparisons between conditions, cell types, or tissues. We presentDEXSeq, a statistical method to test for differential exon usage in RNA-seq data.DEXSequses generalized linear models and offers reliable control of false discoveries by taking biological variation into account.DEXSeqdetects with high sensitivity genes, and in many cases exons, that are subject to differential exon usage. We demonstrate the versatility ofDEXSeqby applying it to several data sets. The method facilitates the study of regulation and function of alternative exon usage on a genome-wide scale. An implementation ofDEXSeqis available as an R/Bioconductor package.
Drosophila CTCF tandemly aligns with other insulator proteins at the borders of H3K27me3 domains
Authors: Van Bortle Kevin , Ramos Edward , Takenaka Naomi , Yang Jingping , Wahi Jessica E. , Corces Victor G.
Published: June 2012

Several multiprotein DNA complexes capable of insulator activity have been identified in Drosophila melanogaster, yet only CTCF, a highly conserved zinc finger protein, and the transcription factor TFIIIC have been shown to function in mammals. CTCF is involved in diverse nuclear activities, and recent studies suggest that the proteins with which it associates and the DNA sequences that it targets may underlie these various roles. Here we show that the Drosophila homolog of CTCF (dCTCF) aligns in the genome with other Drosophila insulator proteins such as Suppressor of Hairy wing [SU(HW)] and Boundary Element Associated Factor of 32 kDa (BEAF-32) at the borders of H3K27me3 domains, which are also enriched for associated insulator proteins and additional cofactors. RNAi depletion of dCTCF and combinatorial knockdown of gene expression for other Drosophila insulator proteins leads to a reduction in H3K27me3 levels within repressed domains, suggesting that insulators are important for the maintenance of appropriate repressive chromatin structure in Polycomb (Pc) domains. These results shed new insights into the roles of insulators in chromatin domain organization and support recent models suggesting that insulators underlie interactions important for Pc-mediated repression. We reveal an important relationship between dCTCF and other Drosophila insulator proteins and speculate that vertebrate CTCF may also align with other nuclear proteins to accomplish similar functions.
Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
Authors: Irimia Manuel , Tena Juan J. , Alexis Maria S. , Fernandez-Miñan Ana , Maeso Ignacio , Bogdanović Ozren , de la Calle-Mustienes Elisa , Roy Scott W. , Gómez-Skarmeta José L. , Fraser Hunter B.
Published: June 2012

The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture.
Extensive alternative polyadenylation during zebrafish development
Authors: Ulitsky Igor , Shkumatava Alena , Jan Calvin H. , Subtelny Alexander O. , Koppstein David , Bell George W. , Sive Hazel , Bartel David P.
Published: June 2012

The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3′ untranslated regions (3′ UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-seq reads substantially increased and improved existing 3′ UTR annotations, resulting in confidently identified 3′ UTRs for >79% of the annotated protein-coding genes in zebrafish. mRNAs from most zebrafish genes undergo alternative CPA, with those from more than a thousand genes using different dominant 3′ UTRs at different stages. These included one of the poly(A) polymerase genes, for which alternative CPA reinforces its repression in the ovary. 3′ UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3′ UTRs are highly expressed in the ovary, yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3′ UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3′ UTRs provide a resource for studying gene regulation during vertebrate development.
The timing of multiple retrieval events can alter GluR1 phosphorylation and the requirement for protein synthesis in fear memory reconsolidation
Authors: Jarome Timothy J. , Kwapis Janine L. , Werner Craig T. , Parsons Ryan G. , Gafford Georgette M. , Helmstetter Fred J.
Published: June 2012

Numerous studies have indicated that maintaining a fear memory after retrieval requires de novo protein synthesis. However, no study to date has examined how the temporal dynamics of repeated retrieval events affect this protein synthesis requirement. The present study varied the timing of a second retrieval of an established auditory fear memory and followed this second retrieval with infusions of the protein synthesis inhibitor anisomycin (ANI) into the basolateral amygdala. Results indicated that the memory-impairing effects of ANI were not observed when the second retrieval occurred soon after the first (within 1 h), and that the inhibitor gradually regained effectiveness as the retrieval episodes were spaced further apart. Additionally, if the second of the closely timed retrievals was omitted prior to ANI infusions, long-term memory deficits were observed, suggesting that the altered effectiveness of ANI was due specifically to the second retrieval event. Further experiments revealed that the second retrieval was not associated with a change in Zif268 protein expression but did produce a rapid and persistent dephosphorylation of GluR1 receptors at Ser845, an AMPAR trafficking site known to regulate the stability of GluR2 lacking AMPARs, which have been shown to be important in memory updating. This suggests that the precise timing of multiple CS presentations during the reconsolidation window may affect the destabilization state of the memory trace.
Structure of the signal transduction protein TRAP (target of RNAIII-activating protein)
Authors: Henrick Kim , Hirshberg Miriam
Published: June 2012

The crystal structure of the signal transduction protein TRAP is reported at 1.85 Å resolution. The structure of TRAP consists of a central eight-stranded β-barrel flanked asymmetrically by helices and is monomeric both in solution and in the crystal structure. A formate ion was found bound to TRAP identically in all four molecules in the asymmetric unit.
Structure of the RBD-PRDI fragment of the antiterminator protein GlcT
Authors: Himmel Sebastian , Grosse Christian , Wolff Sebastian , Schwiegk Claudia , Becker Stefan
Published: June 2012

GlcT is a transcriptional antiterminator protein that is involved in regulation of glucose metabolism inBacillus subtilis. Antiterminator proteins bind specific RNA sequences, thus preventing the formation of overlapping terminator stem-loops. The structure of a fragment (residues 3–170) comprising the RNA-binding domain (RBD) and the first regulatory domain (PRDI) of GlcT was solved at 2.0 Å resolution with one molecule in the asymmetric unit. The two domains are connected by a helical linker. Their interface is mostly constituted by hydrophobic interactions.
Prevalence of alcohol and other drugs in fatally injured drivers
Authors: Brady Joanne E. , Li Guohua
Published: June 2012

Aim

This study aims to examine the prevalence of alcohol and/or other drugs (AOD) in a large sample of fatally injured drivers.

Design

Using data from the Fatality Analysis Reporting System for 2005–09, the authors examined the prevalence of AOD detected in fatally injured drivers in the United States.

Setting

Fatal motor vehicle crashes occurring on public roads.

Participants

Drivers who died within 1 hour of the crash in 14 states that performed toxicological testing on more than 80% of these drivers.

Measurements

The prevalence of AOD and multivariable‐adjusted prevalence ratios (aPR).

Findings

Of the 20 150 fatally injured drivers studied, 57.3% tested positive for AOD, including 19.9% being positive for two or more substances. Alcohol was the most commonly detected substance, present in 40.2% of the fatally injured drivers, followed by cannabinols (10.5%), stimulants (9.0%), narcotics (5.7%) and depressants (4.0%). Multivariable analysis revealed that AOD was significantly more prevalent among drivers who died in single‐vehicle crashes [aPR 1.69, 95% confidence interval (CI): 1.62–1.76] or night‐time crashes (aPR 1.43, 95% CI: 1.39–1.47), or who had a driving‐while‐intoxicated conviction within the past 3 years (aPR 1.41, 95% CI: 1.35–1.47), and less prevalent among drivers who were 65 years or older (aPR 0.45, 95% CI: 0.42–0.49), Asian (aPR 0.47, 95% CI 0.41–0.53) or female (aPR 0.88, 95% CI: 0.85–0.91) or who were operating a motor carrier (aPR 0.41, 95% CI 0.34–0.48).

Conclusions

More than half of fatally injured drivers in the United States had been using AOD and approximately 20% had been using polydrugs. The prevalence of AOD use varies significantly with driver and crash characteristics.
A pregnancy physiologically based pharmacokinetic (p‐PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4
Authors: Gaohua Lu , Abduljalil Khaled , Jamei Masoud , Johnson Trevor N. , Rostami‐Hodjegan Amin
Published: June 2012

Aims

Pregnant women are usually not part of the traditional drug development programme. Pregnancy is associated with major biological and physiological changes that alter the pharmacokinetics (PK) of drugs. Prediction of the changes to drug exposure in this group of patients may help to prevent under‐ or overtreatment. We have used a pregnancy physiologically based pharmacokinetic (p‐PBPK) model to assess the likely impact of pregnancy on three model compounds, namely caffeine, metoprolol and midazolam, based on the knowledge of their disposition in nonpregnant women and information from in vitro studies.

Methods

A perfusion‐limited form of a 13‐compartment full‐PBPK model (Simcyp® Simulator) was used for the nonpregnant women, and this was extended to the pregnant state by applying known changes to all model components (including the gestational related activity of specific cytochrome P450 enzymes) and through the addition of an extra compartment to represent the fetoplacental unit. The uterus and the mammary glands were grouped into the muscle compartment. The model was implemented in Matlab Simulink and validated using clinical observations.

Results

The p‐PBPK model predicted the PK changes of three model compounds (namely caffeine, metoprolol and midazolam) for CYP1A2, CYP2D6 and CYP3A4 during pregnancy within twofold of observed values. The changes during the third trimester were predicted to be a 100% increase, a 30% decrease and a 35% decrease in the exposure of caffeine, metoprolol and midazolam, respectively, compared with the nonpregnant women.

Conclusions

In the absence of clinical data, the in silico prediction of PK behaviour during pregnancy can provide a valuable aid to dose adjustment in pregnant women. The performance of the model for drugs metabolized by a single enzyme to different degrees (high and low extraction) and for drugs that are eliminated by several different routes warrants further study.
Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality?
Authors: Simoni Y , Diana J , Ghazarian L , Beaudoin L , Lehuen A
Published: June 2012

T cells reactive to lipids and restricted by major histocompatibility complex (MHC) class I-like molecules represent more than 15% of all lymphocytes in human blood. This heterogeneous population of innate cells includes the invariant natural killer T cells (iNK T), type II NK T cells, CD1a,b,c-restricted T cells and mucosal-associated invariant T (MAIT) cells. These populations are implicated in cancer, infection and autoimmunity. In this review, we focus on the role of these cells in autoimmunity. We summarize data obtained in humans and preclinical models of autoimmune diseases such as primary biliary cirrhosis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis and atherosclerosis. We also discuss the promise of NK T cell manipulations: restoration of function, specific activation, depletion and the relevance of these treatments to human autoimmune diseases.
Adenovirus-mediated delivery of soluble ST2 attenuates ovalbumin-induced allergic asthma in mice
Authors: Yin H , Li X Y , Liu T , Yuan B H , Zhang B B , Hu S L , Gu H B , Jin X B , Zhu J Y
Published: June 2012

Allergic asthma is associated with excessive T helper type 2 (Th2) cells activation and airway hyperreactivity (AHR), implicated in the context of significant morbidity and mortality. Soluble ST2, a member of the interleukin (IL)-1 receptor family, has been shown to play a critical role in modulation of inflammatory disorders, yet the function of soluble ST2 in allergic inflammation remains unclear. In this study, we examined the possibility of regulating ovalbumin (OVA)-challenged airway inflammation by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc before allergen challenge in OVA-immunized mice profoundly reduced serum immunoglobulin (Ig)E secretion, eosinophil infiltration and concentrations of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared with administration of a control Ad vector. Histopathological examination of the lungs revealed that sST2-Fc over-expression markedly suppressed allergen-induced peribronchial inflammation and disruption of the alveolar architecture. Moreover, the beneficial effect of sST2-Fc in allergic lung inflammation is related to blocking the IL–33/ST2L signalling. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of OVA-mediated allergic pulmonary diseases.
Impaired function of regulatory T cells in cord blood of children of allergic mothers
Authors: Hrdý J , Kocourková I , Prokešová L
Published: June 2012

Allergy is one of the most common diseases with constantly increasing incidence. The identification of prognostic markers pointing to increased risk of allergy development is of importance. Cord blood represents a suitable source of cells for searching for such prognostic markers. In our previous work, we described the increased reactivity of cord blood cells of newborns of allergic mothers in comparison to newborns of healthy mothers, which raised the question of whether or not this was due to the impaired function of regulatory T cells (Tregs) in high-risk children. Therefore, the proportion and functional properties of Tregs in cord blood of children of healthy and allergic mothers were estimated by flow cytometry. The proportion of Tregs[CD4+CD25highCD127lowforkhead box protein 3 (FoxP3+)] in cord blood of children of allergic mothers tends to be higher while, in contrast, the median of fluorescence intensity of FoxP3 was increased significantly in the healthy group. Intracellular presence of regulatory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-beta was also higher in Tregs of children of healthy mothers. Although we detected an increased proportion of Tregs in cord blood of children of allergic mothers, the functional indicators (intracellular presence of regulatory cytokines IL-10 and TGF-beta, median of fluorescence intensity of FoxP3) of those Tregs were lower in comparison to the healthy group. We can conclude that impaired function of Tregs in cord blood of children of allergic mothers could be compensated partially by their increased number. Insufficient function of Tregs could facilitate allergen sensitization in high-risk individuals after subsequent allergen encounter.
Ovarian volume and gluco‐insulinaemic markers in the diagnosis of PCOS during adolescence
Authors: Villa Paola , Rossodivita Aurora , Sagnella Francesca , Moruzzi Maria Cristina , Mariano Nicoletta , Lassandro Anna Pia , Pontecorvi Alfredo , Scambia Giovanni , Lanzone Antonio
Published: June 2012

Objective

To evaluate the role of mean ovarian volume (MOV) in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence, and its relationship with metabolic and endocrine parameters.

Design

Observational study.

Patients

A total of 134 young girls, including 86 adolescents with PCOS and 48 controls, were studied.

Measurements

During the early follicular phase, a pelvic ultrasound examination was performed to measure the ovarian volume of both ovaries and to calculate the MOV. All subjects underwent hormonal assessment and an ultrasound examination. PCOS subjects were submitted to an oral glucose tolerance test. The homeostasis model assessment for insulin resistance (HOMA‐IR) and several insulin resistance indexes were also determined.

Results

Androgens, free androgen index (FAI), LH and insulin resistance indexes were higher in the PCOS group. MOV was significantly different between the two groups: control group 4·6 ± 1·9 cm3, adolescent PCOS group 9·6 ± 4·4 cm3. The MOV threshold of 5·596 cm3 offered the best compromise between sensitivity and specificity based on the characteristics of the operating receiver curve analysis. Therefore, an ovarian volume higher than 5·6 increased the risk of PCOS by about 15 times (OR 16·25 IC 95% 6·3–41·3). In adolescent PCOS girls, the ovarian volume was significantly associated with circulating testosterone and insulin, and indices of insulin resistance.

Conclusions

During early adolescence MOV evaluation may offer an effective means to screen and follow up young girls with irregular cycles in order to prevent the long‐term metabolic disturbances of the polycystic ovary syndrome.
Thyroid function and the risk of coronary heart disease: 12‐year follow‐up of the HUNT Study in Norway
Authors: Åsvold Bjørn O. , Bjøro Trine , Platou Carl , Vatten Lars J.
Published: June 2012

Objective

In a mortality follow‐up of the HUNT Study, serum TSH within the reference range was positively associated with the risk of coronary death in women. We now aimed to confirm the association of high serum TSH with the risk of coronary heart disease, using hospital‐based diagnoses of myocardial infarction.

Design

Prospective population‐based study with linkage to hospital information on myocardial infarction and to the national Cause of Death Registry.

Participants

A total of 26 707 people without previously known thyroid or cardiovascular disease or diabetes at baseline.

Measurements

Hazard ratios (HR) of coronary death and HRs of hospitalization with a first‐time acute myocardial infarction, by baseline thyroid function.

Results

During 12 years of follow‐up, 960 (3·6%) participants had been hospitalized with first‐time myocardial infarction and 558 (2·1%) had died from coronary heart disease. High TSH within the reference range was associated with increased risk of coronary death in women (Ptrend 0·005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0·50–1·4 mU/l. However, thyroid function was not associated with the risk of being hospitalized with myocardial infarction.

Conclusions

High serum TSH was associated with increased mortality from coronary heart disease in women, but we found no association of thyroid function with the risk of being hospitalized with myocardial infarction. Thus, the morbidity finding does not confirm the suggestion that low thyroid function within the clinically normal range is associated with increased risk of coronary heart disease.
Large‐scale coherence in New England lobster (Homarus americanus), settlement and associations with regional atmospheric conditions
Authors: PERSHING ANDREW J. , WAHLE RICHARD A. , MEYERS PATRICK C. , LAWTON PETER
Published: June 2012

Time series of American lobster (Homarus americanus) postlarval settlement from southern New England to Atlantic Canada exhibit many common features, and a cluster analysis indicates a block of regions extending from Massachusetts to Maine that have coherent interannual variations. The spatial scale of this block suggests that variability in settlement is related to large‐scale, rather than local, processes. We examined the association between settlement at six reference regions and monthly mean atmospheric conditions (temperature, geopotential height, westerly and southerly wind components, and wind curl) from the North American Regional Reanalysis. We first extracted the dominant modes of variability in monthly averaged geopotential height, temperature, and wind curl. The leading mode from September, which represents high geopotential height, warm temperatures, and negative wind curl throughout the study area, was strongly correlated with settlement at most of the regions. The third mode from August, which represents enhanced southwesterly winds, was correlated with settlement in Rhode Island. Correlations between local atmospheric conditions and lobster settlement confirm the principal component results. Settlement was correlated to varying degrees with geopotential height (positive), temperature (positive) and wind curl (negative) with lobster settlement at the northern sites, with temperature being a stronger indicator in the north and curl a stronger indicator in the south. Rhode Island settlement was strongly correlated with August westerly winds. The correlation between settlement and atmospheric conditions could improve our understanding of stock‐recruit relationships for lobster populations and provides one mechanism for how climate change could impact lobsters.
Does the decline of gastropods in deep water herald ecosystem change in Lakes Malawi and Tanganyika?
Authors: VAN BOCXLAER BERT , SCHULTHEIß ROLAND , PLISNIER PIERRE‐DENIS , ALBRECHT CHRISTIAN
Published: June 2012

1. Ancient, deep lakes have traditionally been considered as stable, ecological islands, well buffered from environmental change because of their great depth. However, they are not immune to anthropogenic and climatic stress. Ecosystems of the permanently stratified warm Lakes Malawi and Tanganyika in the Great East African Rift are particularly delicate. Their stratification regime has historically limited the distribution of benthic biota to a ‘bathtub ring of biodiversity’, namely substrata in the upper, oxygenated water layer.

2. We use historical data on the endemic deep‐water molluscs of these lakes to assess present‐day stress on their benthic ecosystems. During the 20th century, these molluscs have probably decreased in abundance and migrated to shallower water.

3. These apparent trends have a significance beyond species‐based conservation, foremost because deep‐water organisms heavily rely on the position and temporal stability of the oxycline and therefore provide an early warning of large‐scale changes in the distribution of dissolved oxygen. Oxygen demands have increased in the East African Great Lakes over the last century whereas ventilation of deep water has remained the same or declined.

4. The combination of these factors is resulting in a narrowing of the ring of biodiversity and a changed nutrient flux through this ring. Reduction in the habitat available inevitably puts biota at risk, whereas changes in nutrient flux may cause shifts in the entire ecosystem or the collapse of parts of it.

5. Considering the socioeconomic value of these lakes and the potentially grave implications for their faunal biodiversity and entire ecosystems, existing evidence of faunal decline, especially in taxa that depend strongly on the stratification regime, is of great concern. Moreover, because the factors responsible are widespread and include surface‐water warming, increased run‐off and eutrophication, respiration stress may also develop in other tropical and subtropical lakes.