bluuebunny/crossref_metadata_2025 huggingface dataset:
Superhard B2C2N2 compounds from first-principles calculations
Authors: Xiaoguang Luo , Luyan Li , Weihua Wang , Yongjun Tian
Published: January 2011

The structural, electronic, and mechanical properties as well as phase transitions under hydrostatic pressures have been investigated for six possible B2C2N2 structures, which are deduced from 3C–SiC unit cell. Our calculation results show that B2C2N2-1 with the maximum numbers of C–C and B–N bonds has the lowest total energy. The B2C2N2-1 is a large gap semiconductor with indirect band gap of 4.10 eV. The calculated elastic stiffness constants and phonon spectrum have confirmed its mechanical and dynamical stability. The calculated bulk and shear moduli, and Vickers hardness of B2C2N2-1 indicate that it is one potential superhard material with hardness larger that of cubic boron nitride. The pressure-induced structural transition between its low and high dense phases have shown that B2C2N2-1 could be synthesized using high-temperature and high-pressure method.
Structure and physical properties of GexAsySe1−x−y glasses with the same mean coordination number of 2.5
Authors: Wang R. P. , Bulla D. , Smith Anita , Wang T. , Luther-Davies Barry
Published: January 2011

We have prepared and analyzed five different compositions of GexAsySe1−x−y glasses that have the same mean coordination number (MCN) of 2.5 in order to understand whether MCN or chemical composition has the dominant effect on the physical properties of the glass. Density measurements showed a maximum for the chemically stoichiometric Ge12.5As25Se62.5 sample and suggested that some rearrangement of the atoms was occurring as one atom substituted for another. The measurements of Tg, however, showed that the glasses had almost same glass transition temperature and suggested that the glass network connectivity did not change much with composition. Although Raman scattering and x-ray photoelectron spectra of the glasses indicate that the percentage of the different structural units changes with the composition, there was no evidence of the existence of structural units that could change the overall connectivity of the glass network. Therefore, we concluded that glasses with same MCN but different composition have similar glass network connectivity, and that chemical composition has only a secondary effect on the physical properties of the glasses.
Making a geometrically asymmetric capacitive rf discharge electrically symmetric
Authors: Schulze Julian , Schüngel Edmund , Czarnetzki Uwe , Gebhardt Markus , Brinkmann Ralf Peter , Mussenbrock Thomas
Published: January 2011

The electrical asymmetry effect in a spherical, geometrically asymmetric capacitive argon discharge driven by two consecutive harmonics is investigated using particle in cell simulations and analytical modeling. We find that the discharge asymmetry can be reduced electrically by tuning the phase shift between the driving frequencies, i.e., the absolute value of the dc self-bias voltage can be completely reduced and the mean ion energies at both electrodes can be adapted.
Diagnosis of low-frequency noise sources in contact resistance of staggered organic transistors
Authors: Xu Y. , Gwoziecki R. , Coppard R. , Benwadih M. , Minari T. , Tsukagoshi K. , Chroboczek J. A. , Balestra F. , Ghibaudo G.
Published: January 2011

A diagnostic procedure for the contact low-frequency noise sources of staggered organic transistors is presented. Like the conventional process for channel noise, the two models of carrier number fluctuations and Hooge mobility fluctuations are concerned. Both models apply to bis(triisopropylsilylethynyl) pentacene transistors at lower and higher current densities, where the contact defect density is 1000 times higher than that in the channel and a Hooge parameter around 1 is obtained, respectively. The Hooge mobility fluctuations model well accounts for the contact noise in pentacene transistors with a Hooge parameter in the range of 0.5–3.
High dielectric permittivity and low percolation threshold in polymer composites based on SiC-carbon nanotubes micro/nano hybrid
Authors: Yuan Jin-Kai , Li Wei-Long , Yao Sheng-Hong , Lin You-Qin , Sylvestre Alain , Bai Jinbo
Published: January 2011

Vertically aligned carbon nanotubes (CNTs) were synthesized on SiC microplates. Resultant SiC-CNTs hybrids were further incorporated into poly(vinylidene fluoride) (PVDF) as conductive filler to prepare percolative composites. They exhibited a much low percolation threshold (1.47 vol %), but the dielectric permittivity was enhanced significantly. The largest dielectric permittivity of 8700 was observed in the SiC-CNTs/PVDF composites with 2.3 vol % CNTs at 100 Hz. A microcapacitor model was proposed to explain the obtained results based on the special geometry of the hybrid SiC-CNTs filler.
Two features at the two-dimensional freezing transitions
Authors: Wang Ziren , Qi Weikai , Peng Yi , Alsayed Ahmed M. , Chen Yong , Tong Penger , Han Yilong
Published: January 2011

We studied the two-dimensional freezing transitions in monolayers of microgel colloidal spheres with short-ranged repulsions in video-microscopy experiments, and monolayers of hard disks, and Yukawa particles in simulations. These systems share two common features at the freezing points: (1) the bimodal distribution profile of the local orientational order parameter; (2) the two-body excess entropy, \documentclass[12pt]{minimal}\begin{document}$s_2$\end{document}s2, reaches \documentclass[12pt]{minimal}\begin{document}$-4.5\pm 0.5\,k_B$\end{document}−4.5±0.5kB. Both features are robust and sensitive to the freezing points, so that they can potentially serve as empirical freezing criteria in two dimensions. Compared with the conventional freezing criteria, the first feature has no finite-size ambiguities and can be resolved adequately with much less statistics; and the second feature can be directly measured in macroscopic experiments without the need for microscopic information.
Vulnerability of the fetal primate brain to moderate reduction in maternal global nutrient availability
Authors: Antonow-Schlorke Iwa , Schwab Matthias , Cox Laura A. , Li Cun , Stuchlik Kristina , Witte Otto W. , Nathanielsz Peter W. , McDonald Thomas J.
Published: January 2011

Moderate maternal nutrient restriction during pregnancy occurs in both developing and developed countries. In addition to poverty, maternal dieting, teenage pregnancy, and uterine vascular problems in older mothers are causes of decreased fetal nutrition. We evaluated the impact of global 30% maternal nutrient reduction (MNR) on early fetal baboon brain maturation. MNR induced major cerebral developmental disturbances without fetal growth restriction or marked maternal weight reduction. Mechanisms evaluated included neurotrophic factor suppression, cell proliferation and cell death imbalance, impaired glial maturation and neuronal process formation, down-regulation of gene ontological pathways and related gene products, and up-regulated transcription of cerebral catabolism. Contrary to the known benefits from this degree of dietary reduction on life span, MNR in pregnancy compromises structural fetal cerebral development, potentially having an impact on brain function throughout life.
Policy Considerations for Mandating Agriculture in a Greenhouse Gas Emissions Trading Scheme
Authors: Ancev Tiho
Published: January 2011

The question of whether or not the agricultural sector should be covered in a GHG ETS is prominent in policy debates surrounding the design and implementation of such proposed schemes in many developed nations. This paper identifies two key economic elements that determine both the costs and the benefits of mandating agriculture in an ETS. These are: the costs of reducing GHG emissions in agriculture, and the transactions costs pertinent to covering agriculture in an ETS. Published data on these elements is used to derive a likely range of the overall social costs of mandating the agricultural sector in a GHG ETS. Current indicators of those costs for agriculture, and for the other sectors of the economy, do not offer evidence that mandating agriculture in an ETS would be socially beneficial. Alternative approaches to engaging the agricultural sector in GHG emission reduction, e.g. through voluntary opt‐in or through offsetting credits, are likely to be more beneficial.
Can maintaining cognitive function at 65 years old predict successful ageing 6 years later? The PROOF study
Authors: Castro-Lionard Karine , Thomas-Antérion Catherine , Crawford-Achour Emilie , Rouch Isabelle , Trombert-Paviot Béatrice , Barthélémy Jean-Claude , Laurent Bernard , Roche Frédéric , Gonthier Régis
Published: January 2011

Background: preservation of cognitive abilities is required to have a good quality of life. The predictive value of cognitive functioning at 65 years old on successful ageing 6 years later is not established.

Methods: nine hundred and seventy-six questionnaires were sent by mail to a sample of healthy and voluntary French pensioners. Successful ageing was defined through health status and well-being. Cognitive abilities had been assessed 6 years earlier according to an objective method (Free and Cued Selective Recall Reminding Test (FCSRT), the Benton visual retention test and the similarities subtest of the Wechsler Adult Intelligence Scale-Revised) and a subjective one (Goldberg's anxiety scale, Mac Nair's scale and a Visual Analogue Scale to evaluate memory abilities change in the last 5 years).

Results: six hundred and eighty-six questionnaires could be analysed. The mean age was 72.9 ± 1.2 years old with 59% of women and 99% lived at home. Well-being was negatively correlated with the FCSRT (r = −0.08, P = 0.0318) but positively related with the Benton (r = 0.09, P = 0.0125) and the similarities tests (r = 0.09, P = 0.0118). There is a negative correlation between anxious and cognitive complaints measured at baseline, and successful ageing indicators 6 years later.

Conclusion: preservation of cognitive abilities at the age of retirement can predict a successful ageing 6 years later.

ClinicalTrials.gov Identifier: NCT00759304.
N-Octanoylhomoserine lactone signalling mediated by the BpsI–BpsR quorum sensing system plays a major role in biofilm formation of Burkholderia pseudomallei
Authors: Gamage Akshamal Mihiranga , Shui Guanghou , Wenk Markus R. , Chua Kim Lee
Published: January 2011

The genome ofBurkholderia pseudomalleiencodes three acylhomoserine lactone (AHL) quorum sensing systems, each comprising an AHL synthase and a signal receptor/regulator. The BpsI–BpsR system producesN-octanoylhomoserine lactone (C8HL) and is positively auto-regulated by its AHL product. The products of the remaining two systems have not been identified. In this study, tandem MS was used to identify and quantify the AHL species produced by three clinicalB. pseudomalleiisolates – KHW, K96243 and H11 – three isogenic KHW mutants that each contain a null mutation in an AHL synthase gene, and recombinantEscherichia coliheterologously expressing each of the threeB. pseudomalleiAHL synthase genes. BpsI synthesized predominantly C8HL, which accounted for more than 95 % of the extracellular AHLs produced in stationary-phase KHW cultures. The major products of BpsI2and BpsI3wereN-(3-hydroxy-octanoyl)homoserine lactone (OHC8HL) andN-(3-hydroxy-decanoyl)homoserine lactone, respectively, and their corresponding transcriptional regulators, BpsR2and BpsR3, were capable of driving reporter gene expression in the presence of these cognate lactones. Formation of biofilm byB. pseudomalleiKHW was severely impaired in mutants lacking either BpsI or BpsR but could be restored to near wild-type levels by exogenous C8HL. BpsI2was not required, and BpsI3was partially required for biofilm formation. Unlike thebpsImutant, biofilm formation in thebpsI3mutant could not be restored to wild-type levels in the presence of OHC8HL, the product of BpsI3. C8HL and OHC8HL had opposite effects on biofilm formation; exogenous C8HL enhanced biofilm formation in both thebpsI3mutant and wild-type KHW while exogenous OHC8HL suppressed the formation of biofilm in the same strains. We propose that exogenous OHC8HL antagonizes biofilm formation inB. pseudomallei, possibly by competing with endogenous C8HL for binding to BpsR.
UafB is a serine-rich repeat adhesin of Staphylococcus saprophyticus that mediates binding to fibronectin, fibrinogen and human uroepithelial cells
Authors: King Nathan P. , Beatson Scott A. , Totsika Makrina , Ulett Glen C. , Alm Richard A. , Manning Paul A. , Schembri Mark A.
Published: January 2011

Staphylococcus saprophyticus is an important cause of urinary tract infection (UTI), particularly among young women, and is second only to uropathogenic Escherichia coli as the most frequent cause of UTI. The molecular mechanisms of urinary tract colonization by S. saprophyticus remain poorly understood. We have identified a novel 6.84 kb plasmid-located adhesin-encoding gene in S. saprophyticus strain MS1146 which we have termed uro-adherence factor B (uafB). UafB is a glycosylated serine-rich repeat protein that is expressed on the surface of S. saprophyticus MS1146. UafB also functions as a major cell surface hydrophobicity factor. To characterize the role of UafB we generated an isogenic uafB mutant in S. saprophyticus MS1146 by interruption with a group II intron. The uafB mutant had a significantly reduced ability to bind to fibronectin and fibrinogen. Furthermore, we show that a recombinant protein containing the putative binding domain of UafB binds specifically to fibronectin and fibrinogen. UafB was not involved in adhesion in a mouse model of UTI; however, we observed a striking UafB-mediated adhesion phenotype to human uroepithelial cells. We have also identified genes homologous to uafB in other staphylococci which, like uafB, appear to be located on transposable elements. Thus, our data indicate that UafB is a novel adhesin of S. saprophyticus that contributes to cell surface hydrophobicity, mediates adhesion to fibronectin and fibrinogen, and exhibits tropism for human uroepithelial cells.
Large duplications at reciprocal translocation breakpoints that might be the counterpart of large deletions and could arise from stalled replication bubbles
Authors: Howarth Karen D. , Pole Jessica C.M. , Beavis Juliet C. , Batty Elizabeth M. , Newman Scott , Bignell Graham R. , Edwards Paul A.W.
Published: January 2011

Reciprocal chromosome translocations are often not exactly reciprocal. Most familiar are deletions at the breakpoints, up to megabases in extent. We describe here the opposite phenomenon—duplication of tens or hundreds of kilobases at the breakpoint junction, so that the same sequence is present on both products of a translocation. When the products of the translocation are mapped on the genome, they overlap. We report several of these “overlapping-breakpoint” duplications in breast cancer cell lines HCC1187, HCC1806, and DU4475. These lines also had deletions and essentially balanced translocations. In HCC1187 and HCC1806, we identified five cases of duplication ranging between 46 kb and 200 kb, with the partner chromosome showing deletions between 29 bp and 31 Mb. DU4475 had a duplication of at least 200 kb. Breakpoints were mapped using array painting, i.e., hybridization of chromosomes isolated by flow cytometry to custom oligonucleotide microarrays. Duplications were verified by fluorescent in situ hybridization (FISH), PCR on isolated chromosomes, and cloning of breakpoints. We propose that these duplications are the counterpart of deletions and that they are produced at a replication bubble, comprising two replication forks with the duplicated sequence in between. Both copies of the duplicated sequence would go to one daughter cell, on different products of the translocation, while the other daughter cell would show deletion. These duplications may have been overlooked because they may be missed by FISH and array-CGH and may be interpreted as insertions by paired-end sequencing. Such duplications may therefore be quite frequent.
Design and Testing of ITER TF Coil Insulations
Authors: Hooker Matthew W. , Walsh Jennifer K. , Haynes Mark W. , Munshi Naseem A.
Published: January 2011

The design of the ITER Toroidal Field (TF) coils requires an insulation system that is amenable to the very large scale vacuum impregnation processes planned for the construction of these devices, and that will provide reliable electro-mechanical performance after radiation exposure. To address this need, CTD has developed an epoxy/cyanate ester resin system designated CTD-425. This material meets the processing requirements for use in the TF coils, and cyclic mechanical testing of conductor assemblies has demonstrated its electro-mechanical strength after 60,000 mechanical cycles. In addition, this product recently passed radiation exposure tests coordinated by the ITER International Organization and is now qualified for use in constructing the TF coils. This paper summarizes the performance characterization and qualification test results for this insulation.
Hypoglycemic/hypoxic condition in vitro mimicking the tumor microenvironment markedly reduced the efficacy of anticancer drugs
Authors: Onozuka Hiroko , Tsuchihara Katsuya , Esumi Hiroyasu
Published: January 2011

Tumor tissues are often hypoxic because of defective vasculature. We previously showed that tumor tissues are also often deprived of glucose. The efficacy of anticancer drugs is affected by the tumor microenvironment, partly because of the drug delivery and cellular drug resistance; however, the precise mechanisms remain to be clarified. In the present study, we attempted to clarify whether hypoglycemic/hypoxic condition, which mimics the tumor microenvironment, might induce drug resistance, and if it did, to elucidate the underlying mechanisms. Pancreatic cancer‐derived PANC‐1 cells were treated with serial dilutions of anticancer drugs and incubated in either normoglycemic (1.0 g/L glucose) or hypoglycemic (0 g/L glucose) and normoxic (21% O2) or hypoxic (1% O2) conditions. The 50% inhibitory concentration of gemcitabine was 1000 times higher for PANC‐1 cells incubated under the hypoglycemic/hypoxic condition than for those incubated under the normoglycemic/normoxic condition. Conventional anticancer drugs target rapidly growing cells, so that non‐proliferating or slowly proliferating cells usually show resistance to drugs. Though the cell cycle was delayed, sufficient cellular uptake and DNA incorporation of gemcitabine occurred under the hypoglycemic/hypoxic condition to cause DNA lesions and S‐phase arrest. To overcome hypoglycemic/hypoxia‐induced drug resistance, we examined kinase inhibitors targeting Chk1 or cell‐survival signaling pathways. Among the compounds examined, the combination of UCN‐01 and LY294002 partially sensitized the cells to gemcitabine under the hypoglycemic/hypoxic condition. These findings suggested that the adoption of suitable strategies may enhance the cytotoxicities of clinically used anticancer drugs against cancer cells. (Cancer Sci 2011; 102: 975–982)
A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non‐Hodgkin lymphoma risk
Authors: Hosgood H. Dean , Purdue Mark P. , Wang Sophia S. , Zheng Tongzhang , Morton Lindsay M. , Lan Qing , Menashe Idan , Zhang Yawei , Cerhan James R. , Grulich Andrew , Cozen Wendy , Yeager Meredith , Holford Theodore R. , Vajdic Claire M. , Davis Scott , Leaderer Brian , Kricker Anne , Schenk Maryjean , Zahm Shelia H. , Chatterjee Nilanjan , Chanock Stephen J. , Rothman Nathaniel , Hartge Patricia , Armstrong Bruce
Published: January 2011

Genetic variation in immune‐related genes may play a role in the development of non‐Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population‐based case‐control studies (1946 cases and 1808 controls). Gene‐based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per‐allele odds ratio = 1·15, 95% confidence interval = 1·05–1·27; Ptrend = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.
Revaccination of children after completion of standard chemotherapy for acute lymphoblastic leukaemia: a pilot study comparing different schedules
Authors: Lehrnbecher Thomas , Schubert Ralf , Allwinn Regina , Dogan Kader , Koehl Ulrike , Grüttner Hans‐Peter
Published: January 2011

Given that a significant proportion of children with acute lymphoblastic leukaemia (ALL) lose immune protection to tetanus, diphtheria, and poliomyelitis, revaccination is indicated after chemotherapy. Our randomized pilot study comparing different revaccination schedules suggests that children with ALL might be revaccinated with non‐live vaccines as early as 3 months after chemotherapy.
Effects on fibrin network porosity of anticoagulants with different modes of action and reversal by activated coagulation factor concentrate*
Authors: Blombäck Margareta , He Shu , Bark Niklas , Wallen Håkan N. , Elg Margareta
Published: January 2011

Orally available direct thrombin inhibitors (DTI) and direct activated factor X inhibitors (DFXaI) may replace vitamin K antagonists in patients needing long‐term anticoagulant treatment. We investigated the influence on the fibrin network of anticoagulants with different modes of action: AR‐H067637 (DTI), the active metabolite of AZD0837, apixaban (DFXaI), fondaparinux (indirect FXaI) and warfarin. Counteraction of the anticoagulant effect by FEIBA® (Factor Eight Inhibitor Bypass Activity) was also investigated. Tissue factor, phospholipids and calcium were used to initiate coagulation in human platelet poor plasma. The permeability constant (Ks), reflecting the amount of buffer passing through the coagulum, was calculated and the fibrin network was visualized by 3D confocal microscopy. Warfarin (International Normalized Ratio 2‐3) increased Ks in plasma by 28–50% compared with control. ‘Therapeutic’ plasma concentrations of AR‐H067637 (0·3–0·6 μmol/l), apixaban (0·2–0·4 μmol/l) and fondaparinux (0·1–0·3 μmol/l) increased Ks by 72–91%, 58–76% and 36–53% respectively. Addition of FEIBA® totally reversed the warfarin effect but only partially reversed effects of the other anticoagulants at concentrations that increased Ks by 50% or more. Fibrin network observed with 3D confocal microscopy agreed well with the permeability results. In conclusion, all examined anticoagulants rendered the fibrin network more porous. FEIBA® reversed the increased permeability in warfarin plasma but had only partial effects on the other anticoagulants.
High plasma retinol binding protein 4 (RBP4) is associated with systemic inflammation independently of low RBP4 adipose expression and is normalized by transplantation in nonobese, nondiabetic patients with chronic kidney disease
Authors: Barazzoni Rocco , Zanetti Michela , Semolic Annamaria , Pirulli Alessia , Cattin Maria Rosa , Biolo Gianni , Bosutti Alessandra , Panzetta Giovanni , Bernardi Annamaria , Guarnieri Gianfranco
Published: January 2011

Objective  Adipose‐secreted retinol binding protein 4 (RBP4) circulates in free (active) and transthyretin (TTR)‐bound forms and may be associated with obesity‐related inflammation. Potential involvement of plasma and adipose RBP4 in systemic inflammation in the absence of obesity and diabetes is unknown. Inflammation reduces survival in chronic kidney disease (CKD) [particularly in maintenance haemodialysis (MHD)], and plasma RBP4 may increase with renal dysfunction. We investigated (i) potential associations between RBP4 and inflammation in CKD and (ii) the role of adipose tissue in this putative interaction.

Design  Cross‐sectional.

Patients  Nonobese, nondiabetic patients with CKD undergoing conservative (CT: n = 10) or MHD treatment (n = 25) and healthy control subjects (C: n = 11). Renal transplant recipients (n = 5) were studied to further assess the impact of restored near‐normal renal function.

Measurements  Plasma RBP4, TTR and C‐reactive protein (CRP), adipose RBP4 expression.

Results  Plasma RBP4, TTR and CRP were highest in MHD (P < 0·05). Adipose RBP4 mRNA was, however, comparably low in CT and MHD (P < 0·05 vs C), and all parameters were normalized in transplant recipients (P < 0·05 vs MHD). In all subjects (n = 51), creatinine and TTR (P < 0·05) but not adipose RBP4 mRNA were associated with plasma RBP4. Plasma RBP4 but not its adipose expression was in turn associated positively (P < 0·05) with CRP independently of creatinine‐TTR.

Conclusions  High plasma RBP4 and inflammation are clustered in CKD in the absence of obesity and diabetes and are normalized by transplantation. Adipose RBP4 expression is not involved in plasma RBP4 elevation, which appears to be mainly because of passive accumulation, or in CKD‐associated inflammation.
Significant genetic boundaries and spatial dynamics of giant pandas occupying fragmented habitat across southwest China
Authors: ZHU LIFENG , ZHANG SHANNING , GU XIAODONG , WEI FUWEN
Published: January 2011

Understanding population history and genetic structure are key drivers of ecological research. Here, we studied two highly fragmented and isolated populations (Xiaoxiangling and Daxiangling) of giant pandas (Ailuropoda melanoleuca) at the extreme southwestern edge of their distribution. This area also contains the Dadu River, national road 108 and various human infrastructure and development, providing an ideal region in which we can identify the effects of different barriers on animal movements. We used partial mitochondrial control region (mtDNA) and nine microsatellite loci (nuclear DNA) data derived from 192 faecal and one blood sample collected from the wild. We found 136 genotypes corresponding to 53 unique multilocus genotypes and eight unique control region haplotypes (653 bp). Significant genetic boundaries correlated spatially with the Dadu River (K = 2). We estimate that a major divergence took place between these populations 26 000 years bp, at around the similar time the rock surface of valley bottom formed in Dadu River. The national road has resulted in further recent population differentiation (Pairwise FS on mtDNA and nuclear DNA) so that in effect, four smaller sub‐populations now exist. Promisingly, we identified two possible first‐generation migrants and their migration paths, and recommended the immediate construction of a number of corridors. Fortunately, the Chinese government has accepted our advice and is now planning corridor construction.
Using tunable diode laser spectroscopy to measure carbon isotope discrimination and mesophyll conductance to CO2 diffusion dynamically at different CO2 concentrations
Authors: TAZOE YOUSHI , VON CAEMMERER SUSANNE , ESTAVILLO GONZALO M. , EVANS JOHN R.
Published: January 2011

In C3 leaves, the mesophyll conductance to CO2 diffusion, gm, determines the drawdown in CO2 concentration from intercellular airspace to the chloroplast stroma. Both gm and stomatal conductance limit photosynthetic rate and vary in response to the environment. We investigated the response of gm to changes in CO2 in two Arabidopsis genotypes (including a mutant with open stomata, ost1), tobacco and wheat. We combined measurements of gas exchange with carbon isotope discrimination using tunable diode laser absorption spectroscopy with a CO2 calibration system specially designed for a range of CO2 and O2 concentrations. CO2 was initially increased from 200 to 1000 ppm and then decreased stepwise to 200 ppm and increased stepwise back to 1000 ppm, or the sequence was reversed. In 2% O2 a step increase from 200 to 1000 ppm significantly decreased gm by 26–40% in all three species, whereas following a step decrease from 1000 to 200 ppm, the 26–38% increase in gm was not statistically significant. The response of gm to CO2 was less in 21% O2. Comparing wild type against the ost1 revealed that mesophyll and stomatal conductance varied independently in response to CO2. We discuss the effects of isotope fractionation factors on estimating gm.
Comparative ionomics and metabolomics in extremophile and glycophytic Lotus species under salt stress challenge the metabolic pre‐adaptation hypothesis
Authors: SANCHEZ DIEGO H. , PIECKENSTAIN FERNANDO L. , ESCARAY FRANCISCO , ERBAN ALEXANDER , KRAEMER UTE , UDVARDI MICHAEL K. , KOPKA JOACHIM
Published: January 2011

The legume genus Lotus includes glycophytic forage crops and other species adapted to extreme environments, such as saline soils. Understanding salt tolerance mechanisms will contribute to the discovery of new traits which may enhance the breeding efforts towards improved performance of legumes in marginal agricultural environments. Here, we used a combination of ionomic and gas chromatography‐mass spectrometry (GC‐MS)‐based metabolite profilings of complete shoots (pooling leaves, petioles and stems) to compare the extremophile Lotus creticus, adapted to highly saline coastal regions, and two cultivated glycophytic grassland forage species, Lotus corniculatus and Lotus tenuis. L. creticus exhibited better survival after exposure to long‐term lethal salinity and was more efficient at excluding Cl‐ from the shoots than the glycophytes. In contrast, Na+ levels were higher in the extremophile under both control and salt stress, a trait often observed in halophytes. Ionomics demonstrated a differential rearrangement of shoot nutrient levels in the extremophile upon salt exposure. Metabolite profiling showed that responses to NaCl in L. creticus shoots were globally similar to those of the glycophytes, providing little evidence for metabolic pre‐adaptation to salinity. This study is the first comparing salt acclimation responses between extremophile and non‐extremophile legumes, and challenges the generalization of the metabolic salt pre‐adaptation hypothesis.
A recurrent 1.71 Mb genomic imbalance at 2q13 increases the risk of developmental delay and dysmorphism
Authors: Yu HE , Hawash K , Picker J , Stoler J , Urion D , Wu B‐L , Shen Y
Published: January 2011

Yu HE, Hawash K, Picker J, Stoler J, Urion D, Wu B‐L, Shen Y. A recurrent 1.71 Mb genomic imbalance at 2q13 increases the risk of developmental delay and dysmorphism.

Whole genome profiling such as array comparative genomic hybridization has identified novel genomic imbalances. Many of these genomic imbalances have since been shown to associate with developmental delay, intellectual disability and congenital malformation. Here we identified five unrelated individuals who have a recurrent 1.71 Mb deletion/duplication at 2q13 (Human Genome Build 19: 111,392,197‐113,102,594). Four of these individuals have developmental issues, four have cranial dysmorphism. Literature review revealed 14 more cases that had similar genomic imbalances at 2q13. Many of them had developmental delay and dysmorphism. Taken together, 93% and 63% of individuals with this genomic imbalance displayed impaired developmental skills and/or abnormal facial features respectively. This copy number variant (CNV) has not been reported in normal control databases. We, therefore, propose that CNV in this region is a risk factor for developmental delay and dysmorphism.
Pharmacological actions of oximino‐propofol analogues at GABABautoreceptors
Authors: Parker David AS , Marino Victor , Sullivan Thomas , Ong Jennifer , Khalafy Jabbar , Badali Mohammad , Rimaz Mehdi , Prager Rolf H
Published: January 2011

1. GABABautoreceptors are a subclass of GABABreceptors that inhibit the release of [3H]GABA from GABAergic nerve terminals. Baclofen is an agonist that reduces [3H]GABA, whilst the antagonist (+)‐(S)‐5,5‐dimethylmorpholinyl‐2‐acetic acid (Sch 50911) enhances [3H]GABA release in electrically‐stimulated rat neocortical brain slices preloaded with [3H]GABA. Here, the pharmacological actions of a series of compounds derived from the positive allosteric modulator, 2,6‐di‐tert‐butyl‐4‐(3‐hydroxy‐2,2‐dimethyl‐propyl)‐phenol (CGP7930), were examined on GABABautoreceptors.

2. The compound, 3‐(3,5‐ditbutyl‐4‐hydroxyphenyl)‐2,2‐dimethyl‐1‐oximinopropane (compound 2), at 10 μmol/L had little effect on the stimulation‐induced overflow of [3H]GABA when superfused alone, but when superfused in the presence of baclofen (2 μmol/L) inhibited the overflow of [3H]GABA. These effects were reversed by Sch 50911 (10 μmol/L). Although compounds 1‐(4‐chlorophenyl)‐3‐(4‐hydroxy‐3,5‐diisopropylphenyl)‐2‐methyl‐1‐oximinopropane (compound 1), 1‐[(3,5‐ditbutyl‐4‐hydroxyphenyl)methyl]‐1‐oximinomethylcyclohexane (compound 3), 3‐(3,5‐ditbutyl‐4‐hydroxyphenyl)‐1,2‐diphenyl‐1‐oximinopropane (compound 4) and 4‐(3,5‐ditbutyl‐4‐hydroxyphenyl)‐3‐methyl‐2‐oximinobutane (compound 5) (each at 10 μmol/L) tended to reduce the stimulation‐induced overflow in the presence of baclofen, an effect reversed by Sch 50911, their status as modulators is not confirmed in the present study.

3. Another derivative, 3‐(3,5‐ditbutyl‐4‐hydroxyphenyl)‐1‐(4‐chlorophenyl)‐2‐methyl‐1‐oximinopropane (compound 6) (10 μmol/L), acted as an agonist as it inhibited the release of [3H]GABA by 32% (EC50of 3.3 μmol/L), an effect reversed by Sch 50911 (10 μmol/L). The other compounds, 1‐[(3,5‐ditbutyl‐4‐hydroxyphenyl)methyl]‐1‐methyl‐2‐oximinocyclohexane (compound 7), 4‐(3,5‐ditbutyl‐4‐hydroxyphenyl)‐3,3‐dimethyl‐2‐oximinobutane (compound 8) and 4‐(4‐hydroxy‐3,5‐diisopropylphenyl)‐3,3‐dimethyl‐2‐oximinobutane (compound 9) (each at 10 μmol/L), were inactive.

4. These findings indicate that this series of compounds show different modes of activity at GABABautoreceptors.
Post‐operative partial hypoparathyroidism: an under‐recognized disorder
Authors: Prichard Ruth S. , Edhouse Pamela J. , Sidhu Stanley B. , Sywak Mark S. , Delbridge Leigh
Published: January 2011

Background:  Permanent hypoparathyroidism is a well‐recognized complication of total thyroidectomy, and a commonly reported clinical indicator of that procedure. However, a small number of patients still require ongoing calcium supplementation post‐operatively in order to avoid the symptoms of hypocalcaemia, despite a normal serum parathyroid hormone level. The aim of this study was to characterize this disorder of post‐operative partial hypoparathyroidism and to identify any risk factors.

Methods:  A retrospective study of patients undergoing a total thyroidectomy was performed. Patients with permanent hypoparathyroidism were excluded. Patients completed a telephone interview and had serum calcium and parathyroid hormone (PTH) measured. Patient demographics, operative indications and intervention, the number of parathyroid glands autotransplanted, the presence of ongoing symptoms and calcium requirements were documented.

Results:  One hundred ninety‐six patients participated. The overall rate of permanent hypoparathyroidism over the duration of the study was 0.77%. An additional 10 (5%) patients were identified with a normal PTH level but who were still requiring calcium supplementation to prevent the symptoms associated with hypocalcaemia and to maintain a normal serum calcium level. Nine patients were female with a mean age of 48.5 years. A mean of 1.4 parathyroid glands were autotransplanted and the mean PTH level was 3.95 pmol/L.

Conclusion:  This study demonstrates that in a small group of patients following total thyroidectomy, re‐vascularization of parathyroid cells may be partial, with inadequate parathyroid reserve to avoid symptoms despite measurable PTH levels. This disorder of partial hypoparathyroidism has not been previously described and represents a small but important complication of total thyroidectomy.
Correlations between global clotting function tests, duration of operation, and postoperative chest tube drainage in pediatric cardiac surgery
Authors: Hayashi Tamaki , Sakurai Yoshihiko , Fukuda Kazuyoshi , Yada Koji , Ogiwara Kenichi , Matsumoto Tomoko , Yoshizawa Hiroyuki , Takahashi Yukihiro , Yoshikawa Yoshiro , Hayata Yoshihiro , Taniguchi Shigeki , Shima Midori
Published: January 2011

Background:  Systemic coagulation disorders after cardiac surgery represent serious postoperative complications. There have been few reports, however, identifying preoperative coagulation tests that predict postoperative bleeding. The aim of the present study was to investigate the relationship between postoperative hemorrhage and coagulation parameters determined by global coagulation assays, to define potential predictive markers.

Methods:  Twenty‐one pediatric patients were enrolled. Blood samples were collected before and 24 h after cardiac surgery. Laboratory investigations included platelet count, hematocrit, classical coagulation tests [prothrombin time, activated partial thromboplastin time, thrombin‐antithrombin complex (TAT)], rotation thromboelastometry (ROTEM), and the thrombin generation test (TGT). The duration of the surgical procedure was recorded. Chest tube drainage was monitored for 24 h after operation as an index of postoperative hemorrhage.

Results:  Comparisons between preoperative and postoperative results indicated that TAT increased significantly after operation, whereas ROTEM parameters did not show a hypercoagulable pattern. Preoperative endogenous thrombin potential (ETP) measured in the TGT and clot formation time (CFT) in the ROTEM correlated with chest tube drainage. The classical coagulation tests were not informative. Postoperatively, peak height and ETP in TGT, all ROTEM parameters, and duration of surgery were correlated with chest tube drainage. Duration of surgery was correlated with postoperative ROTEM parameters but not with TGT. Postoperative maximum clot firmness and AUC were correlated with platelet count decrease ratio.

Conclusions:  The preoperative CFT and ETP provide useful indices for predicting postoperative chest tube drainage volume. In addition, the duration of surgery also correlated with chest tube drainage and affected ROTEM parameters.
Iron uptake and toxin synthesis in the bloom‐forming Microcystis aeruginosa under iron limitation
Authors: Alexova Ralitza , Fujii Manabu , Birch Debra , Cheng Jennifer , Waite T. David , Ferrari Belinda C. , Neilan Brett A.
Published: January 2011

Toxin production during cyanobacterial blooms poses a significant public health threat in water bodies globally and requires the development of effective bloom management strategies. Previously, synthesis of the hepatotoxin microcystin has been proposed to be regulated by iron availability, but the contribution of the toxin to the adaptation of cyanobacteria to environmental stresses, such as changing light intensity and nutrient limitation, remains unclear. The aim of this study was to compare the iron stress response in toxic and non‐toxic strains of Microcystis aeruginosa subjected to moderate and severe iron limitation. The transcription of a number of genes involved in iron uptake, oxidative stress response, toxin synthesis and transcriptional control of these processes was accessed by quantitative real‐time PCR (qRT‐PCR). The process of adaptation of M. aeruginosa to iron stress was found to be highly dynamic and strain‐specific. Toxin production in PCC 7806 increased in an iron‐dependent manner and appeared to be regulated by FurA. The inability to produce microcystin, either due to natural mutations in the mcy gene cluster or due to insertional inactivation of mcyH, affected the remodelling of the photosynthetic machinery in iron‐stressed cells, the transport of Fe(II) and transcription of the Fur family of transcriptional regulators. The presence of the toxin appears to give an advantage to microcystin‐producing cyanobacteria in the early stages of exposure to severe iron stress and may protect the cell from reactive oxygen species‐induced damage.
MODELLING COGNITIVELY BOUNDED RATIONALITY: AN EVALUATIVE TAXONOMY
Authors: Mallard Graham
Published: January 2011

Abstract Since its origins in the 1950s, the notion of bounded rationality has been incorporated into economic theory using an array of methodological approaches. This paper presents a taxonomy by which these approaches can be categorized and understood, evaluating each approach against a range of important criteria. At a time when the foundations of economic theory are being re‐examined, this paper should be viewed as a first step towards an assessment of the appropriate role that this more realistic view of cognition should take in different areas of economic theory, and also of the desirable characteristics of models that incorporate it.
The anti‐tumour compound, RH1, causes mitochondria‐mediated apoptosis by activating c‐Jun N‐terminal kinase
Authors: Park Moon‐Taek , Song Min‐Jeong , Oh Eun‐Taex , Lee Hyemi , Choi Bo‐Hwa , Jeong Seong‐Yun , Choi Eun‐Kyung , Park Heon Joo
Published: January 2011

BACKGROUND AND PURPOSE 2,5‐diaziridinyl‐3‐(hydroxymethyl)‐6‐methyl‐1,4‐benzoquinone (RH1) is a bioreductive agent that is activated by the two‐electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although the cytotoxic efficacy of RH1 against tumours has been studied extensively, the molecular mechanisms underlying this anti‐cancer activity have not yet been fully elucidated.

EXPERIMENTAL APPROACH 2,5‐diaziridinyl‐3‐(hydroxymethyl)‐6‐methyl‐1,4‐benzoquinone‐induced apoptosis and related signalling pathways in NQO1‐negative and NQO1‐overexpressing cells were evaluated. The role of p53 in RH1‐induced cell death was investigated using parental and p53‐deficient RKO human colorectal cancer cells by assaying clonogenic cell survival. Specific inhibitors and siRNAs targeting factors involved in RH1‐induced apoptosis were used to clarify the roles played by such factors in RH1‐activated apoptotic signalling pathways.

KEY RESULTS 2,5‐diaziridinyl‐3‐(hydroxymethyl)‐6‐methyl‐1,4‐benzoquinone induced apoptosis and clonogenic death, dependent on NQO1 and p53. Treatment of NQO1‐overexpressing cells with RH1 caused rapid disruption of mitochondrial membrane potential, nuclear translocation of apoptosis‐inducing factor (AIF) and endonuclease G (Endo G) from mitochondria, and subsequent caspase‐independent apoptotic cell death. siRNA targeting AIF and Endo G effectively attenuated RH1‐induced apoptotic cell death. Moreover, RH1 induced cleavage of Bax, which targets mitochondria. RH1 significantly activated the c‐Jun N‐terminal kinase (JNK) pathway, and inhibition of this pathway suppressed RH1‐induced mitochondria‐mediated apoptosis. RH1‐induced generation and mitochondrial translocation of cleaved Bax were blocked by the JNK inhibitor, SP600125. Inhibition of JNK with SP600125 attenuated the mitochondrial translocation of JNK.

CONCLUSIONS AND IMPLICATIONS 2,5‐diaziridinyl‐3‐(hydroxymethyl)‐6‐methyl‐1,4‐benzoquinone activated JNK, resulting in mitochondria‐mediated apoptotic cell death that was NQO1‐dependent.
δ‐Opioid receptors stimulate GLUT1‐mediated glucose uptake through Src‐ and IGF‐1 receptor‐dependent activation of PI3‐kinase signalling in CHO cells
Authors: Olianas Maria C , Dedoni Simona , Onali Pierluigi
Published: January 2011

BACKGROUND AND PURPOSEAlthough opioids have been reported to affect glucose homeostasis, relatively little is known on the role of δ‐opioid receptors. We have investigated the regulation of glucose transport by human δ‐opioid receptors expressed in Chinese hamster ovary cells.

EXPERIMENTAL APPROACHThe uptake of [3H]‐2‐deoxy‐D‐glucose and 3‐O‐[methyl‐[3H]]‐D‐glucose in response to δ‐opioid receptor ligands and the expression of GLUT1, GLUT3 and GLUT4 glucose transporters were examined. Moreover, the effects of intracellular signal transduction inhibitors on δ‐opioid receptor‐regulated [3H]‐2‐deoxy‐D‐glucose uptake and protein phosphorylation were investigated.

KEY RESULTSActivation of δ‐opioid receptors rapidly stimulated [3H]‐2‐deoxy‐D‐glucose and 3‐O‐[methyl‐[3H]]‐D‐glucose uptakes, which were blocked by the GLUT inhibitors cytochalasin B and phloretin. The stimulation of [3H]‐2‐deoxy‐D‐glucose uptake that occurred without a change in plasma membrane GLUT1 – required the coupling to Gi/Goproteins – was independent of cAMP and extracellular signal‐regulated protein kinases, and was suppressed by blockade of Src and insulin‐like growth factor‐1 receptor (IGF‐1R) tyrosine kinases. Inhibition of phosphatidylinositol 3‐kinase (PI3K) by wortmannin or LY294002 and by PI3Kα, but not γ, isoform‐selective inhibitors greatly reduced the δ‐opioid receptor stimulation of glucose uptake. Moreover, the response was attenuated by overexpressing a dominant‐negative kinase‐deficient Akt form and by chemical inhibition of Akt. Stimulation of δ‐opioid receptors increased protein kinase Cζ/λ (PKCζ/λ) phosphorylation and a selective PKCζ/λ inhibitor slightly reduced opioid stimulation of glucose uptake.

CONCLUSIONS AND IMPLICATIONSδ‐Opioid receptors stimulated glucose transport probably by enhancing GLUT1 intrinsic activity through a signalling cascade involving Gi/Go, Src, IGF‐1R, PI3Kα, Akt and, to a minor extent, PKCζ/λ. This effect may contribute to the opioid regulation of glucose homeostasis in physio‐pathological conditions.
Cattle Farmers’ Preferences for Disease‐Free Zones in Kenya: An application of the Choice Experiment Method
Authors: Otieno David Jakinda , Ruto Eric , Hubbard Lionel
Published: January 2011

Management of livestock diseases is important in ensuring food safety to consumers in both domestic and export markets. Various measures are prescribed under the Sanitary and Phytosanitary Standards (SPS) agreement of the World Trade Organization. In order to prevent the spread of trans‐boundary cattle diseases, the SPS agreement recommends the establishment of Disease‐Free Zones (DFZs). These have been implemented successfully in some major beef‐exporting countries, but in Kenya are still at a pilot stage. To understand Kenyan farmers’ preferences on the type of DFZ that would be readily acceptable to them, a choice experiment was conducted using a D‐optimal design. Results show that farmers would be willing to pay to participate in a DFZ where: adequate training is provided on pasture development, record keeping and disease monitoring; market information is provided and sales contract opportunities are guaranteed; cattle are properly labelled for ease of identification; and some monetary compensation is provided in the event that cattle die due to severe disease outbreaks. Preferences for the DFZ attributes are shown to be heterogeneous across three cattle production systems. We also derive farmers’ preferences for various DFZ policy scenarios. The findings have important implications for policy on the design of DFZ programmes in Kenya and other countries that face similar cattle disease challenges.
Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis
Authors: Kitagawa Hiroshi , Yamanaka Keiichi , Kakeda Masato , Inada Hiroyasu , Imai Yasutomo , Gabazza Esteban C , Kurokawa Ichiro , Mizutani Hitoshi
Published: January 2011

Abstract:  Atopic dermatitis (AD) is a chronic disease characterized by a polarized Th2 immune response. Propionibacterium acnes (P. acnes) has been shown to elicit strong Th1 immune responses. We hypothesized that the host immune response to P. acnes will prevent the development of AD. To demonstrate this hypothesis, we investigated the effect of P. acnes vaccination on AD that occurs in keratin 14/driven caspase‐1 transgenic mouse. Vaccination with low dose of P. acnes successfully prevented clinical manifestations in the skin of AD mice associated with systemic and cutaneous increased expression of Th1‐type cytokines but without suppression of Th2 cytokines. Interestingly, the numbers of IFN‐γ+T cells, FoxP3+CD4+CD25+T cells (nTreg) and IL‐10+T cells (Tr1) were significantly increased in the spleen. P. acnes vaccination has effects to alter the cytokine milieu and may be useful for the improvement of atopic symptom.