bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface contact toxicity and synergism of several insecticides against different stages of the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae)
Authors: How Yee‐Fatt , Lee Chow‐Yang
Published: March 2011

BACKGROUND: Five formulated insecticides (lambda‐cyhalothrin at 10 mg m−2, bifenthrin at 50 mg m−2, fipronil at 10 mg m−2, fenitrothion at 50 mg m−2, imidacloprid at 5 mg m−2) and one active ingredient (DDT at 500 mg m−2) were evaluated using a surface contact method against early and late instars and adults of two strains of the tropical bed bug, Cimex hemipterus (F.). Synergism of lambda‐cyhalothrin and fipronil using piperonyl butoxide (PBO) was also assessed.

RESULTS: The order of susceptibility of different stages of bed bugs was as follows: early stage − lambda‐cyhalothrin > bifenthrin = imidacloprid > fipronil > fenitrothion > DDT; late stage—lambda‐cyhalothrin > bifenthrin > fenitrothion > imidacloprid > fipronil > DDT; adult—lambda‐cyhalothrin > imidacloprid > bifenthrin > fenitrothion > fipronil > DDT. The late instars exhibited significantly higher LT50 among the life stages. The addition of PBO to fipronil increased the susceptibility of the insects.

CONCLUSIONS: Lambda‐cyhalothrin, bifenthrin, fenitrothion and fipronil at the recommended application rates were effective against C. hemipterus. Although imidacloprid demonstrated good initial response against C. hemipterus, the insects showed substantial recovery 72 h post‐treatment. The late instars (fourth and fifth instars) should be used as the model for toxicological evaluation. Copyright © 2011 Society of Chemical Industry
Antifeedant effect of commercial chemicals and plant extracts againstSchistocerca americana(Orthoptera: Acrididae) andDiaprepes abbreviatus(Coleoptera: Curculionidae)
Authors: Sandoval‐Mojica Andres F , Capinera John L
Published: March 2011

BACKGROUND:The deterrent effect of seven commercial compounds againstSchistocerca americana(Drury) nymphs andDiaprepes abbreviatusL. adults, two important citrus pests, was investigated. Extracts of three Florida local plants were also tested as deterrents. Antifeedant activity was assayed using a leaf‐disk bioassay in choice and no‐choice tests. The residual activity of the commercial compounds that significantly deterred the insects was assayed by applying them to foliage of citrus plants exposed to three time intervals of sunlight.

RESULTS:Sabadilla, azadirachtin and ryanodine effectively deterredS. americana, whereas rotenone, sabadilla and ryanodine reduced the feeding activity ofD. abbreviatus. Methanol and methylene chloride extracts ofCeratiola ericoidesMichaux deterredD. abbreviatus, but only methylene chloride extract dissuadedS. americana. Methanol extract ofArdisia crenataSims functioned as a feeding deterrent against bothS. americanaandD. abbreviatus, but only the latter species was deterred by methylene chloride extract ofA. crenata. Extracts ofIllicium parviflorumMichaux ex Ventetat only dissuaded the insects in choice bioassays. Rapid loss of effectiveness was observed under field conditions. Sabadilla was the only compound that maintained its antifeedant properties in the field, but only againstS. americana.

CONCLUSION:Based on their deterrency, some of the commercial products and plant extracts have potential for use as substitute crop protectants against the pest species tested. Copyright © 2011 Society of Chemical Industry
Magnetization of Fe‐oxide based nanocomposite tuned by surface charging
Authors: Traußnig Thomas , Topolovec Stefan , Nadeem Kashif , Vinga Szabó Dorothée , Krenn Heinz , Würschum Roland
Published: March 2011

Aiming at a voltage‐control of magnetism, the magnetization of a porous γ‐Fe2O3–Pt nanocomposite is studied under the influence of charging the surfaces of the porous structure in an electrolyte. Reversible variations of the magnetization of up to 10.4% could be achieved upon charging in the regime where electrochemical adsorption and desorption occurs. The observed variation of the magnetization with electrochemical charging is assigned to the γ‐Fe2O3 nanoparticles whereas the conductive network of Pt nanoparticles is necessary for charging. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Distributed state estimation for uncertain Markov‐type sensor networks with mode‐dependent distributed delays
Authors: Liang Jinling , Wang Zidong , Liu Xiaohui
Published: March 2011

In this paper, the distributed state estimation problem is investigated for a class of sensor networks described by uncertain discrete‐time dynamical systems with Markovian jumping parameters and distributed time‐delays. The sensor network consists of sensor nodes characterized by a directed graph with a nonnegative adjacency matrix that specifies the interconnection topology (or the distribution in the space) of the network. Both the parameters of the target plant and the sensor measurements are subject to the switches from one mode to another at different times according to a Markov chain. The parameter uncertainties are norm‐bounded that enter into both the plant system as well as the network outputs. Furthermore, the distributed time‐delays are considered, which are also dependent on the Markovian jumping mode. Through the measurements from a small fraction of the sensors, this paper aims to design state estimators that allow the nodes of the sensor network to track the states of the plant in a distributed way. It is verified that such state estimators do exist if a set of matrix inequalities is solvable. A numerical example is provided to demonstrate the effectiveness of the designed distributed state estimators. Copyright © 2011 John Wiley & Sons, Ltd.
Image noise cross‐correlation for signal‐to‐noise ratio estimation in scanning electron microscope images
Authors: Sim K. S. , Nia M. E. , Tso C. P.
Published: March 2011

A new and robust parameter estimation technique, named image noise cross‐correlation, is proposed to predict the signal‐to‐noise ratio (SNR) of scanning electron microscope images. The results of SNR and variance estimation values are tested and compared with nearest neighborhood and first‐order interpolation. Overall, the proposed method is best as its estimations for the noise‐free peak and SNR are most consistent and accurate to within a certain acceptable degree, compared with the others. SCANNING 33: 82–93, 2011. © 2011 Wiley
Periodicals, Inc.
Investigation of Tibetian Plateau varnish: new findings at the nanoscale using focused ion beam and transmission electron microscopy techniques
Authors: Langworthy Kurt A. , Krinsley David H. , Dorn Ronald I.
Published: March 2011

Dual‐beam focused ion beam microscopy (FIB/SEM) preparation of rock varnish for high‐resolution transmission electron microscopy (HR‐TEM) has enabled us to characterize unreported nanostructures. Fossils, unreported textures, and compositional variability were observed at the nanoscale. These techniques could provide a method for studying ancient terrestrial and extra‐terrestrial environments to better understand geological processes at the nanoscale. SCANNING 33: 78–81, 2011. © 2011 Wiley Periodicals, Inc.
Effect of Magnetic Field Intensity on Microstructure and Orientation of Proeutectoid Ferrite in Fe‐0.76%C Alloy
Authors: Wu Y. , Gong M. L. , Wang S. Y. , Zhao X. , Zuo L.
Published: March 2011

Effect of high magnetic field annealing on microstructure and orientation of proeutectoid ferrite in Fe–0.76%C alloy was investigated. It was found that the high magnetic field increases the number of proeutectoid ferrite grains considerably, and the elongation tendency of proeutectoid ferrite grains along the magnetic field direction is increased by the applied magnetic field, too. These effects increased with the enhancement of magnetic filed intensity. Crystallographic orientation analysis by EBSD showed that no preferential orientations exist in the proeutectoid ferrite when applied a magnetic field with different intensity. Possible reasons of the above phenomena were discussed in the paper.
Transductive confidence machines
Authors: Rogers James
Published: March 2011

The field of statistical learning theory has developed alternatives to induction. Instead of using all the available points to induce a model, the data, or usually a small subset of the data, can be used to estimate unknown properties of points to be tested (e.g., membership to a class). This idea leads to algorithms that use standard statistical tests to compute the confidence on the estimation. Using transduction, researchers have built transductive confidence machines which are able to estimate the unknown class of a point and attach confidence to the estimate, and also to determine outliers in a data set. WIREs Comp Stat 2011 3 216–220 DOI: 10.1002/wics.154

This article is categorized under:

Statistical Learning and Exploratory Methods of the Data Sciences > Pattern Recognition

Statistical Learning and Exploratory Methods of the Data Sciences > Knowledge Discovery
Global navigation satellite systems
Authors: Grewal Mohinder S.
Published: March 2011

Global Navigation Satellite Systems (GNSS) are satellite constellations that generate signals that can be received virtually anywhere, anytime, and in any weather anywhere in the world. The article discusses the systems that are fully active and those that are still being developed. The systems are intended to be independent, complementary, and interoperable. Most future aviation users are likely to rely on multi‐constellation receivers, i.e., receive and process the GNSS signals to complement and enhance each other. The general description of how the systems work concludes with some of the remaining challenges. WIREs Comp Stat 2011 3 383–384 DOI: 10.1002/wics.158

This article is categorized under:

Applications of Computational Statistics > Signal and Image Processing and Coding
Mesopotamia in British Strategy, 1903–1914
Authors: Cohen Stuart
Published: March 2011

Britain's strategic interest in Mesopotamia in the nineteenth and early twentieth centuries was a consequence of her control over India. The valleys of the Tigris and the Euphrates constitute a natural highway from Syria to the Persian Gulf, and thence to the Indian Ocean. Not until a relatively late stage in Imperial history, however, did Britain extend her formal protection to this region. In the nineteenth century successive British governments had refused to finance the establishment of either a Mesopotamian steamer service or railway line. Subsequently, they had first (1903) rejected participation in an international Baghdad railway scheme, and then (1914) sanctioned complete German control over the project as far as Basra. A small Indian force was despatched to the head of the Persian Gulf in October 1914, but the subsequent Mesopotamian campaign was ‘a haphazard affair from start to finish’ lacking political or military direction. Thus, the De Bunsen committee, which reported on Britain's desiderata in Asiatic Turkey in June 1915, had concluded that Ottoman “devolutionary control” over Mesopotamia was preferable to Indian annexation of any part of the region other than the Basra vilayet; that October, the War Cabinet experienced difficulty in deciding whether to sanction an advance on Baghdad. No proclamation of political interest in Mesopotamia was in fact made by a British government until the capture of the city in 1917. The immediate and local arguments impelling that operation have been fully investigated. By contrast, the strategic tradition that deprecated it has been relatively neglected. This paper proposes to survey the latter and to indicate the degree to which the extension of the Mesopotamian campaign contradicted previous British strategy toward the region.
Influence of age at first lambing on reproductive and productive performance of Lacaune dairy sheep under an intensive management system
Authors: Hernandez Fernando , Elvira Laura , Gonzalez-Martin Juan-Vicente , Gonzalez-Bulnes Antonio , Astiz Susana
Published: March 2011

The present study investigated the effect of age at first lambing (AFL) on the performance of Lacaune sheep under intensive management conditions. Records from 3088 maiden sheep from one farm, for the period 2005–2010, were classified into four experimental groups: group E (early) ewes with AFL ⩽390 d; group M (middle) with AFL of 391–450 d; group L (late) with AFL of 451–510 d; and group A (aged) with AFL ⩾511 d. The higher the number of lactations, the lower were the yield/lactation and yield/Day in Milk. Ewes from group M up to 450 days old lambed 0·2 times more often and had 0·25 more lactations than the ewes from group L; in addition, the former group lambed 0·5 times more often and had 0·49 more lactations than ewes from group A. Group A had the lowest yield per lifetime; the yield followed the sequence: group E (1032 l) >group M (1051 l) >group L (989 l) > group A (859 l) (P<0·0001). Yield/lactation was affected by AFL during the first three lactations (P<0·05). Group E produced significantly less milk in the first lactation than ewes from groups M, L and A. AFL correlated negatively with the number of lactations in life (r= −0·26; P<0·0001) and with total milk yield (r= −209; P<0·0001). The productive performance between the ewes that reached puberty early (n=404) or late (n=2684) in life were different (P<0·0001) with the early sheep having a lower total milk yield (591 v. 1073 l, P<0·0001). In conclusion, the current study indicates that the optimal AFL for the Lacaune breed under an intensive dairy system is between 390 and 450 d. Ewes with AFL earlier than 390 d or later than 450 d are likely to have a shorter productive life and a lower lifetime milk production.
Milk fatty acid characterization and genetic parameter estimates for milk conjugated linoleic acid in buffaloes
Authors: Tonhati Humberto , Lima André LF , Lanna Dante PD , de Camargo Gregório MF , Baldi Fernando , de Albuquerque Lucia G , Montrezor Jeanne MCD
Published: March 2011

The objectives of this study were to analyse buffalo milk fat composition, to verify the activity of Delta(9)-desaturase enzyme in the mammary gland, as well as to estimate additive genetic variances for milk, fat and protein yield, and milk cis-9,trans-11 conjugated linoleic acid percentage (cis-9,trans-11 CLA%). A total of 3929 lactation milk yields (MY) records from 2130 buffaloes and 1598 lactation fat (FY) and protein (PY) yield records from 914 buffaloes were analysed. For cis-9,trans-11 CLA%percentage, a total of 661 milk samples from 225 buffaloes, daughters of 8 sires, belonging to 4 herds and calving in 2003 and 2004, were used. The genetic parameters and variance components were estimated by Restricted Maximum Likelihood applying an animal model. The fixed effects considered in the model were: contemporary group (herd, year, calving season) and age at calving (linear and quadratic effects) and lactation length (linear and quadratic effects) as covariables. Additive genetic and permanent environment effects were considered as random. The MY, FY, PY and CLA% means were 1482±355 kg, 90·1±24·6 kg, 56·9±15·2 kg and 0·69±0·16%, respectively. Heritability estimates for MY, FY, PY and CLA% were 0·28±0·05, 0·26±0·11, 0·25±0·11 and 0·35±0·14, respectively. There is enough additive genetic variation for buffalo milk, protein and fat yield to improve these traits through selection. The cis-9,trans-11 CLA% can be enhanced by selection in buffaloes and will contribute to improving human health. The activity and efficiency of Delta(9)-desaturase in the mammary was measured and confirmed.
Steady longitudinal vortices in supersonic turbulent separated flows
Authors: SCHÜLEIN ERICH , TROFIMOV VICTOR M.
Published: March 2011

Large-scale longitudinal vortices in high-speed turbulent separated flows caused by relatively small irregularities at the model leading edges or at the model surfaces are investigated in this paper. Oil-flow visualization and infrared thermography techniques were applied in the wind tunnel tests at Mach numbers 3 and 5 to investigate the nominally 2-D ramp flow at deflection angles of 20°, 25° and 30°. The surface contour anomalies have been artificially simulated by very thin strips (vortex generators) of different shapes and thicknesses attached to the model surface. It is shown that the introduced streamwise vortical disturbances survive over very large downstream distances of the order of 104 vortex-generator heights in turbulent supersonic flows without pressure gradients. It is demonstrated that each vortex pair induced in the reattachment region of the ramp is definitely a child of a vortex pair, which was generated originally, for instance, by the small roughness element near the leading edge. The dependence of the spacing and intensity of the observed longitudinal vortices on the introduced disturbances (thickness and spanwise size of vortex generators) and on the flow parameters (Reynolds numbers, boundary-layer thickness, compression corner angles, etc.) has been shown experimentally.
Evoked response audiometry in scrub typhus: prospective, randomised, case–control study
Authors: Thakur J S , Mohindroo N K , Sharma D R , Soni K , Kaushal S S
Published: March 2011

Objective:

To investigate the hypothesis of cochlear and retrocochlear damage in scrub typhus, using evoked response audiometry.

Study design:

Prospective, randomised, case–control study.

Methods:

The study included 25 patients with scrub typhus and 25 controls with other febrile illnesses not known to cause hearing loss. Controls were age- and sex-matched. All subjects underwent pure tone audiometry and evoked response audiometry before commencing treatment.

Results:

Six patients presented with hearing loss, although a total of 23 patients had evidence of symmetrical high frequency loss on pure tone audiometry. Evoked response audiometry found significant prolongation of absolute latencies of wave I, III, V, and wave I–III interpeak latency. Two cases with normal hearing had increased interpeak latencies. These findings constitute level 3b evidence.

Conclusion:

Findings were suggestive of retrocochlear pathology in two cases with normal hearing. In other patients, high frequency hearing loss may have led to altered evoked response results. Although scrub typhus appears to cause middle ear cochlear and retrocochlear damage, the presence of such damage could not be fully confirmed by evoked response audiometry.
Tuning information packaging: intonational realization of topic and focus in child Dutch
Authors: CHEN AOJU
Published: March 2011

This study examined how four- to five-year-olds and seven- to eight-year-olds used intonation (accent placement and accent type) to encode topic and focus in Dutch. Naturally spoken declarative sentences with either sentence-initial topic and sentence-final focus or sentence-initial focus and sentence-final topic were elicited via a picture-matching game. Results showed that the four- to five-year-olds were adult-like in topic-marking, but were not yet fully adult-like in focus-marking, in particular, in the use of accent type in sentence-final focus (i.e. showing no preference for H*L). Between age five and seven, the use of accent type was further developed. In contrast to the four- to five-year-olds, the seven- to eight-year-olds showed a preference for H*L in sentence-final focus. Furthermore, they used accent type to distinguish sentence-initial focus from sentence-initial topic in addition to phonetic cues.
Video observation of hand hygiene practices at a petting zoo and the impact of hand hygiene interventions
Authors: ANDERSON M. E. C. , WEESE J. S.
Published: March 2011

Petting zoos are popular attractions, but can also be associated with zoonotic disease outbreaks. Hand hygiene is critical to reducing disease risks; however, compliance can be poor. Video observation of petting zoo visitors was used to assess animal and environmental contact and hand hygiene compliance. Compliance was also compared over five hand hygiene intervention periods. Descriptive statistics and multivariable logistic regression were used for analysis. Overall hand hygiene compliance was 58% (340/583). Two interventions had a significant positive association with hand hygiene compliance [improved signage with offering hand sanitizer, odds ratio (OR) 3·38, P<0·001; verbal hand hygiene reminders, OR 1·73, P=0·037]. There is clearly a need to improve hand hygiene compliance at this and other animal exhibits. This preliminary study was the first to demonstrate a positive impact of a hand hygiene intervention at a petting zoo. The findings suggest that active, rather than passive, interventions are more effective for increasing compliance.
Is there a relation between onset age of bilingualism and enhancement of cognitive control?
Authors: LUK GIGI , DE SA ERIC , BIALYSTOK ELLEN
Published: March 2011

Young English-speaking monolingual and bilingual adults were examined for English proficiency, language use history, and performance on a flanker task. The bilinguals, who were about twenty years old, were divided into two groups (early bilinguals and late bilinguals) according to whether they became actively bilingual before or after the age of ten years. Early bilinguals and monolinguals demonstrated similar levels of English proficiency, and both groups were more proficient in English than late bilinguals. In contrast, early bilinguals produced the smallest response time cost for incongruent trials (flanker effect) with no difference between monolinguals and late bilinguals. Moreover, across the whole sample of bilinguals, onset age of active bilingualism was negatively correlated with English proficiency and positively correlated with the flanker effect. These results suggest a gradient in which more experience in being actively bilingual is associated with greater advantages in cognitive control and higher language proficiency.
Analytical modeling of degradation product partitioning kinetics in source zones containing entrapped DNAPL
Authors: Ramsburg C. Andrew , Christ John A. , Douglas Scott R. , Boroumand Ali
Published: March 2011

Liquid‐liquid equilibrium experiments indicate that there is a strong thermodynamic driving force for the reversible sequestration of cis‐dichloroethene (DCE) within microbially active dense nonaqueous phase liquid (DNAPL) source zones containing chlorinated ethene solvents. Assessment of the importance of degradation product sequestration, however, requires accurate description of the mass transfer kinetics. Partitioning kinetics of cis‐DCE were assessed in a series of transport experiments conducted in sandy columns containing uniformly entrapped tetrachloroethene (PCE)‐nonaqueous phase liquids (NAPL). Effluent data from these experiments were simulated using an analytical solution adapted from the sorption literature. The solution permits interrogation of the relative importance of mass transfer resistance in the aqueous phase and NAPL. Column data and simulations suggest that the kinetic exchange of cis‐DCE may be described with mass transfer correlations developed for the dissolution of pure component NAPLs. Diffusive transport within the entrapped ganglia was relatively fast, offering limited resistance to mass exchange. These results (1) establish the applicability of dissolution‐based mass transfer correlations for modeling both absorption and dissolution of degradation products, (2) quantify the thermodynamic driving force for the partitioning of cis‐DCE in PCE‐NAPL by assessing the ternary phase behavior, and (3) guide incorporation and deployment of partitioning kinetics into multiphase compositional simulators when assessing or designing metabolic reductive dechlorination within DNAPL source zones. While focus is placed on examining degradation product partitioning in DNAPL source zones, results may also be useful when considering rate limitations in other liquid‐liquid partitioning processes, such as partitioning tracer tests.
Jobs for the boys
Authors: Jacobs Howy
Published: March 2011

The gender gap at the top‐end of academia remains wide, despite all attempts to overcome it. To redress gender imbalances in bioscence, Howy argues that we need to build a proper career track with fair evaluation criteria at each step.
Any questions?
Authors: Streeter Jennifer , Miller Francis J
Published: March 2011

Talks and presentations are an integral part of a scientist's life; conducting an engaging and mutually beneficial Q&A session after a talk is as important as the talk itself.
To protect and save
Authors: Hunter Philip
Published: March 2011

A more complete catalogue of the Earth's fauna and flora and a more holistic view of man‐made environmental problems could help to slow the rate of biodiversity loss.
Real-Time Ultrasound Brain Perfusion Imaging with Analysis of Microbubble Replenishment in Acute MCA Stroke
Authors: Kern Rolf , Diels Anna , Pettenpohl Johanna , Kablau Micha , Brade Joachim , Hennerici Michael G , Meairs Stephen
Published: March 2011

Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2 ± 13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau ( A) of acoustic intensity, and A×β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β = 0.58 ± 0.40 versus 1.25 ± 0.83; P = 0.001; A = 1.44 ± 1.75 versus 2.63 ± 2.31; P = 0.05; A×β = 1.14 ± 2.25 versus 2.98 ± 2.70; P = 0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; P < 0.001). From the analysis of receiver operating characteristic curves, β and A×β had the largest areas under the curve with optimal cutoff values of β < 0.76 and A×β < 1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.
Upregulation of Lipid Synthesis in Small Rat Adipocytes by Microvesicle‐Associated CD73 From Large Adipocytes
Authors: Müller Günter , Schneider Marion , Biemer‐Daub Gabriele , Wied Susanne
Published: March 2011

Filling‐up lipid stores is critical for size increase of mammalian adipocytes. The glycosylphosphatidylinositol (GPI)‐anchored protein, CD73, is released from adipocytes into microvesicles in response to the lipogenic stimuli, palmitate, the antidiabetic sulfonylurea drug glimepiride, phosphoinositolglycans (PIG), and H2O2. Upon incubation of microvesicles with adipocytes, CD73 is translocated to cytoplasmic lipid droplets (LD) and esterification is upregulated. The role of CD73‐harboring microvesicles in coordinating esterification between differently sized adipocytes was studied here. Populations consisting of either small or large or of both small and large isolated rat adipocytes as well as native adipose tissue pieces from young and old rats were incubated with or depleted of endogenous microvesicles and analyzed for translocation of CD73 and esterification in response to the lipogenic stimuli. Large adipocytes exhibited higher and lower efficacy in releasing CD73 into microvesicles and in translocating CD73 to LD, respectively, compared to small adipocytes. Populations consisting of both small and large adipocytes were more active in esterification in response to the lipogenic stimuli than either small or large adipocytes. With both adipocytes and adipose tissue pieces from young rats esterification stimulation by the lipogenic stimuli was abrogated by depletion of CD73‐harboring microvesicles from the incubation medium and interstitial spaces, respectively. In conclusion, stimulus‐induced lipid synthesis between differently sized adipocytes is controlled by the release of microvesicle‐associated CD73 from large cells and its subsequent translocation to LD of small cells. This information transfer via microvesicles harboring GPI‐anchored proteins may shift the burden of triacylglycerol storage from large to small adipocytes.
Impact of Intra‐ and Extra‐Osseous Soft Tissue Composition on Changes in Bone Mineral Density With Weight Loss and Regain
Authors: Bosy‐Westphal Anja , Later Wiebke , Schautz Britta , Lagerpusch Merit , Goele Kristin , Heller Martin , Glüer Claus‐C. , Müller Manfred J.
Published: March 2011

Recent studies report a significant gain in bone mineral density (BMD) after diet‐induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra‐ and extra‐osseous soft tissue composition on bone measurements by dual X‐ray absorptiometry (DXA) in a longitudinal study of diet‐induced weight loss and regain in 55 women and 17 men (19–46 years, BMI 28.2–46.8 kg/m2). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet‐induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3‐compartment model. Skeletal muscle (SM) mass, extra‐osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was −9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra‐osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMDpelvis correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMDlegs were reversed after weight regain and inversely correlated with BMDlegs decreases. No other associations between changes in BMD and intra‐ or extra‐osseous soft tissue composition were found. In conclusion, changes in extra‐osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.
Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: involvement of the cAMP/PKA signalling pathway
Authors: Valenti Daniela , Manente Gabriella Arcangela , Moro Laura , Marra Ersilia , Vacca Rosa Anna
Published: March 2011

DS (Down's syndrome) is the most common human aneuploidy associated with mental retardation and early neurodegeneration. Mitochondrial dysfunction has emerged as a crucial factor in the pathogenesis of numerous neurological disorders including DS, but the cause of mitochondrial damage remains elusive. In the present study, we identified new molecular events involved in mitochondrial dysfunction which could play a role in DS pathogenesis. We analysed mitochondrial respiratory chain function in DS-HSFs (Down's syndrome human foetal skin fibroblasts; human foetal skin fibroblasts with chromosome 21 trisomy) and found a selective deficit in the catalytic efficiency of mitochondrial complex I. The complex I deficit was associated with a decrease in cAMP-dependent phosphorylation of the 18 kDa subunit of the complex, due to a decrease in PKA (protein kinase A) activity related to reduced basal levels of cAMP. Consistently, exposure of DS-HSFs to db-cAMP (dibutyryl-cAMP), a membrane-permeable cAMP analogue, stimulated PKA activity and consequently rescued the deficit of both the cAMP-dependent phosphorylation and the catalytic activity of complex I; conversely H89, a specific PKA inhibitor, suppressed these cAMP-dependent activations. Furthermore, in the present paper we report a 3-fold increase in cellular levels of ROS (reactive oxygen species), in particular superoxide anion, mainly produced by DS-HSF mitochondria. ROS accumulation was prevented by db-cAMP-dependent activation of complex I, suggesting its involvement in ROS production. Taken together, the results of the present study suggest that the drastic decrease in basal cAMP levels observed in DS-HSFs participates in the complex I deficit and overproduction of ROS by DS-HSF mitochondria.
Assembly states of the nucleosome assembly protein 1 (NAP-1) revealed by sedimentation velocity and non-denaturing MS
Authors: Noda Masanori , Uchiyama Susumu , McKay Adam R. , Morimoto Akihiro , Misawa Shigeki , Yoshida Akihiro , Shimahara Hideto , Takinowaki Hiroto , Nakamura Shota , Kobayashi Yuji , Matsunaga Sachihiro , Ohkubo Tadayasu , Robinson Carol V. , Fukui Kiichi
Published: March 2011

Proteins often exist as ensembles of interconverting states in solution which are often difficult to quantify. In the present manuscript we show that the combination of MS under nondenaturing conditions and AUC-SV (analytical ultracentrifugation sedimentation velocity) unambiguously clarifies a distribution of states and hydrodynamic shapes of assembled oligomers for the NAP-1 (nucleosome assembly protein 1). MS established the number of associated units, which was utilized as input for the numerical analysis of AUC-SV profiles. The AUC-SV analysis revealed that less than 1% of NAP-1 monomer exists at the micromolar concentration range and that the basic assembly unit consists of dimers of yeast or human NAP-1. These dimers interact non-covalently to form even-numbered higher-assembly states, such as tetramers, hexamers, octamers and decamers. MS and AUC-SV consistently showed that the formation of the higher oligomers was suppressed with increasing ionic strength, implicating electrostatic interactions in the formation of higher oligomers. The hydrodynamic shapes of the NAP-1 tetramer estimated from AUC-SV agreed with the previously proposed assembly models built using the known three-dimensional structure of yeast NAP-1. Those of the hexamer and octamer could be represented by new models shown in the present study. Additionally, MS was used to measure the stoichiometry of the interaction between the human NAP-1 dimer and the histone H2A–H2B dimer or H3–H4 tetramer. The present study illustrates a rigorous procedure for the analysis of protein assembly and protein–protein interactions in solution.
Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide
Authors: Akif Mohd , Schwager Sylva L. , Anthony Colin S. , Czarny Bertrand , Beau Fabrice , Dive Vincent , Sturrock Edward D. , Acharya K. Ravi
Published: March 2011

Human ACE (angiotensin-I-converting enzyme) has long been regarded as an excellent target for the treatment of hypertension and related cardiovascular diseases. Highly potent inhibitors have been developed and are extensively used in the clinic. To develop inhibitors with higher therapeutic efficacy and reduced side effects, recent efforts have been directed towards the discovery of compounds able to simultaneously block more than one zinc metallopeptidase (apart from ACE) involved in blood pressure regulation in humans, such as neprilysin and ECE-1 (endothelin-converting enzyme-1). In the present paper, we show the first structures of testis ACE [C-ACE, which is identical with the C-domain of somatic ACE and the dominant domain responsible for blood pressure regulation, at 1.97Å (1 Å=0.1 nm)] and the N-domain of somatic ACE (N-ACE, at 2.15Å) in complex with a highly potent and selective dual ACE/ECE-1 inhibitor. The structural determinants revealed unique features of the binding of two molecules of the dual inhibitor in the active site of C-ACE. In both structures, the first molecule is positioned in the obligatory binding site and has a bulky bicyclic P1′ residue with the unusual R configuration which, surprisingly, is accommodated by the large S2′ pocket. In the C-ACE complex, the isoxazole phenyl group of the second molecule makes strong pi–pi stacking interactions with the amino benzoyl group of the first molecule locking them in a ‘hand-shake’ conformation. These features, for the first time, highlight the unusual architecture and flexibility of the active site of C-ACE, which could be further utilized for structure-based design of new C-ACE or vasopeptidase inhibitors.
Mitochondrial protection by the thioredoxin-2 and glutathione systems in an in vitro endothelial model of sepsis
Authors: Lowes Damon A. , Galley Helen F.
Published: March 2011

Oxidative stress and mitochondrial dysfunction are common features in patients with sepsis and organ failure. Within mitochondria, superoxide is converted into hydrogen peroxide by MnSOD (manganese-containing superoxide dismutase), which is then detoxified by either the mGSH (mitochondrial glutathione) system, using the enzymes mGPx-1 (mitochondrial glutathione peroxidase-1), GRD (glutathione reductase) and mGSH, or the TRX-2 (thioredoxin-2) system, which uses the enzymes PRX-3 (peroxiredoxin-3) and TRX-2R (thioredoxin reductase-2) and TRX-2. In the present paper we investigated the relative contribution of these two systems, using selective inhibitors, in relation to mitochondrial dysfunction in endothelial cells cultured with LPS (lipopolysaccharide) and PepG (peptidoglycan). Specific inhibition of both the TRX-2 and mGSH systems increased the intracellular total radical production (P<0.05) and reduced mitochondrial membrane potentials (P<0.05). Inhibition of the TRX-2 system, but not mGSH, resulted in lower ATP production (P<0.001) with high metabolic activity (P<0.001), low oxygen consumption (P<0.001) and increased lactate production (P<0.001) and caspase 3/7 activation (P<0.05). Collectively these results show that the TRX-2 system appears to have a more important role in preventing mitochondrial dysfunction than the mGSH system in endothelial cells under conditions that mimic a septic insult.
Next-generation Akt inhibitors provide greater specificity: effects on glucose metabolism in adipocytes
Authors: Tan Shixiong , Ng Yvonne , James David E.
Published: March 2011

Many human tumours exhibit activation of the PI3K (phosphoinositide 3-kinase)/Akt pathway, and inhibition of this pathway slows tumour growth. This led to the development of specific Akt inhibitors for in vivo use. However, activation of Akt is also necessary for processes including glucose metabolism. Therefore a potential complication of such anticancer drugs is insulin resistance and/or diabetes. In the process of characterizing the metabolic effects of early-phase Akt inhibitors, we discovered an off-target inhibitory effect on mammalian facilitative glucose transporters. In view of the crucial role of glucose transport for all mammalian cells, such an off-target effect would have major implications for further development of this family of compounds. In the present study, we have characterized a next-generation Akt inhibitor, MK-2206. MK-2206 is an orally active allosteric Akt inhibitor under development for treating solid tumours. We report that MK-2206 potently inhibits Thr308Akt and Ser473Akt phosphorylation in 3T3-L1 adipocytes (IC50 0.11 and 0.18 μM respectively) as well as downstream effects of insulin on GLUT4 (glucose transporter 4) translocation (IC50 0.47 μM) and glucose transport (IC50 0.14 μM). Notably, the potency of MK-2206 is approximately 1 log higher than previous inhibitors and its specificity is significantly improved with modest inhibitory effects on glucose transport in GLUT4-expressing adipocytes and GLUT1-rich human erythrocytes, independently of Akt. Nevertheless, MK-2206 clearly has potent effects on Akt2, the principal isoform involved in peripheral insulin action, in which case insulin resistance will probably be a major complication following in vivo administration. We conclude that MK-2206 provides an optimal tool for studying the effects of Akt in vitro.
The interplay of DNA binding, ATP hydrolysis and helicase activities of the archaeal MCM helicase
Authors: Liew Li Phing , Bell Stephen D.
Published: March 2011

The MCM (minichromosome maintenance) proteins of archaea are widely believed to be the replicative DNA helicase of these organisms. Most archaea possess a single MCM orthologue that forms homo-multimeric assemblies with a single hexamer believed to be the active form. In the present study we characterize the roles of highly conserved residues in the ATPase domain of the MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results identify a potential conduit for communicating DNA-binding information to the ATPase active site.
Anti-MDR and antitumoral action of acetylsalicylic acid on leukaemic cells
Authors: Carrett-Dias Michele , Votto Ana Paula de Souza , Filgueira Daza de Moraes Vaz Batista , Almeida Daniela Volcan , Vallochi Adriana Lima , D'Oca Marcelo Gonçalves Montes , Marins Luis Fernando , Trindade Gilma Santos
Published: March 2011

ASA (acetylsalicylic acid) is an NSAID (non-steroidal anti-inflammatory drug). ASA has gained attention as a potential chemopreventive and chemotherapeutic agent for several neoplasms. The aim of this study was to analyse the possible antitumoural effects of ASA in two erythroleukaemic cell lines, with or without the MDR (multidrug resistance) phenotype. The mechanism of action of different concentrations of ASA were compared in K562 (non-MDR) and Lucena (MDR) cells by analysing cell viability, apoptosis and necrosis, intracellular ROS (reactive oxygen species) formation and bcl-2, p53 and cox-2 gene expression. ASA inhibited the cellular proliferation or induced toxicity in K562 and Lucena cell lines, irrespective of the MDR phenotype. The ASA treatment provoked death by apoptosis and necrosis in K562 cells and only by necrosis in Lucena cells. ASA also showed antioxidant activity in both cell lines. The bcl-2, p53 and cox-2 genes in both cell lines treated with ASA seem to exhibit different patterns of expression. However, normal lymphocytes treated with the same ASA concentrations were more resistant than tumoral cells. The results of this work show that both cell lines responded to treatment with ASA, demonstrating a possible antitumoral and anti-MDR role for this drug.
Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity
Authors: Lockhart Christopher J. , Agnew Christina E. , McCann Aaron , Hamilton Paul K. , Quinn Cathy E. , McCall Damien O. , Plumb Rick D. , McClenaghan Vivienne C. N. , McGivern R. Canice , Harbinson Mark T. , McVeigh Gary E.
Published: March 2011

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.
Time-resolved imaging of laser-induced refractive index changes in transparent media
Authors: Mermillod-Blondin Alexandre , Mauclair Cyril , Bonse Jörn , Stoian Razvan , Audouard Eric , Rosenfeld Arkadi , Hertel Ingolf V.
Published: March 2011

We describe a method to visualize ultrafast laser-induced refractive index changes in transparent materials with a 310 fs impulse response and a submicrometer spatial resolution. The temporal profile of the laser excitation sequence can be arbitrarily set on the subpicosecond and picosecond time scales with a pulse shaping unit, allowing for complex laser excitation. Time-resolved phase contrast microscopy reveals the real part of the refractive index change and complementary time-resolved optical transmission microscopy measurements give access to the imaginary part of the refractive index in the irradiated region. A femtosecond laser source probes the complex refractive index changes from the excitation time up to 1 ns, and a frequency-doubled Nd:YAG laser emitting 1 ns duration pulses is employed for collecting data at longer time delays, when the evolution is slow. We demonstrate the performance of our setup by studying the energy relaxation in a fused silica sample after irradiation with a double pulse sequence. The excitation pulses are separated by 3 ps. Our results show two dimensional refractive index maps at different times from 200 fs to 100 μs after the laser excitation. On the subpicosecond time scale we have access to the spatial characteristics of the energy deposition into the sample. At longer times (800 ps), time-resolved phase contrast microscopy shows the appearance of a strong compression wave emitted from the excited region. On the microsecond time scale, we observe energy transfer outside the irradiated region.
Design of mechanical components for vibration reduction in an atomic force microscope
Authors: Kim Chulsoo , Jung Jongkyu , Youm Woosub , Park Kyihwan
Published: March 2011

Vibration is a key factor to be considered when designing the mechanical components of a high precision and high speed atomic force microscope (AFM). It is required to design the mechanical components so that they have resonant frequencies higher than the external and internal vibration frequencies. In this work, the mechanical vibration in a conventional AFM system is analyzed by considering its mechanical components, and a vibration reduction is then achieved by reconfiguring the mechanical components. To analyze the mechanical vibration, a schematic of the lumped model of the AFM system is derived and the vibrational influences of the AFM components are experimentally examined. Based on this vibration analysis, a reconfigured AFM system is proposed and its effects are compared to a conventional system through a series of simulations and experiments.
Optimizing a low-energy electron diffraction spin-polarization analyzer for imaging of magnetic surface structures
Authors: Frömter Robert , Hankemeier Sebastian , Oepen Hans Peter , Kirschner Jürgen
Published: March 2011

A newly designed scanning electron microscope with polarization analysis (SEMPA or spin-SEM) for the acquisition of magnetic images is presented. Core component is the spin detector, based on the scattering of low-energy electrons at a W(100) surface in ultrahigh vacuum. The instrument has been optimized with respect to ease of handling and efficiency. The operation and performance of a general low-energy electron diffraction (LEED) detector for SEMPA have been modeled in order to find the optimum operating parameters and to predict the obtainable image asymmetry. Based on the energy dependence of the secondary electron polarization and intensity, the detector output is simulated. For our instrument with optimized performance we demonstrate experimentally 8.6% polarization asymmetry in the domain structure of an iron whisker. This corresponds to 17.2% image contrast, in excellent agreement with the predicted simulated value. A contrast to noise ratio of 27 is achieved at 5 ms acquisition time per pixel.