bluuebunny/crossref_metadata_2025 huggingface dataset:
Photonic crystal cavity based gas sensor
Authors: Sünner T. , Stichel T. , Kwon S.-H. , Schlereth T. W. , Höfling S. , Kamp M. , Forchel A.
Published: July 2008

We have studied the response of a photonic crystal cavity to changes of the ambient refractive index. Transmission measurements of the cavity under different gaseous environments and pressures showed a linear dependence of the resonance wavelength on the refractive index of the ambient gas. A change of the refractive index by 10−4 leads to a shift of the resonance by 8pm, which is readily detectable due to the high quality factor of the cavity. The observed wavelength shifts agree well with finite-difference time domain simulations of the cavity.
Effect of CdSe quantum dots on hole transport in poly(3-hexylthiophene) thin films
Authors: Kumari Kusum , Chand Suresh , Kumar Pankaj , Sharma Shailesh N. , Vankar V. D. , Kumar Vikram
Published: July 2008

This letter demonstrates the effect of cadmium selenide (CdSe) quantum dots on hole transport in poly(3-hexylthiophene) (P3HT) thin films. Current-voltage characteristics of P3HT and P3HT:CdSe thin films have been studied in the temperature range of 288–85K, in hole only device configurations, i.e., indium tin oxide (ITO)/poly(ethylene-dioxthiophene):polystyrenesulphonate (PEDOT:PSS)/P3HT/Au and ITO/PEDOT:PSS/P3HT:CdSe∕Au. The incorporation of CdSe quantum dots in P3HT results in the enhancement in hole current and switches the transport from dual conduction mechanism, viz., trap and mobility models to only trap model. This is attributed to the reduction in characteristic trap energy from 60to32meV and trap density from 2.5×1018to1.7×1018cm−3.
Effect of gas pressure on ion flux in 2MHz capacitive discharge
Authors: Schweigert I. V.
Published: July 2008

We have studied the ion energy and angular distribution functions in a 2MHz capacitive discharge using combined particle in cell Monte Carlo collision simulations. We found that secondary electrons produced by ion bombardment from the electrodes make important contribution to the ionization at higher gas pressure. Calculations showed that the ion flux on the electrode is very sensitive to the plasma parameters. However, the ion angular distribution function weakly responds to a change of the gas pressure.
Multistability in nonlinear left-handed transmission lines
Authors: Powell David A. , Shadrivov Ilya V. , Kivshar Yuri S.
Published: July 2008

Employing a nonlinear left-handed transmission line as a model system, we demonstrate experimentally the multistability phenomena predicted theoretically for microstructured left-handed metamaterials with a nonlinear response. We show that the bistability is associated with the period doubling, which at higher power may result in chaotic dynamics of the transmission line.
Large electrostrain near the phase transition temperature of (Bi0.5Na0.5)TiO3–SrTiO3 ferroelectric ceramics
Authors: Hiruma Yuji , Imai Yoshitaka , Watanabe Yoshinori , Nagata Hajime , Takenaka Tadashi
Published: July 2008

( 1 - x ) ( Bi 0.5 Na 0.5 ) Ti O 3 – x Sr Ti O 3 (abbreviated as BNST100x) was prepared by a conventional ceramic fabrication process. The depolarization temperature Td, rhombohedral-tetragonal phase transition temperature TR-T, and the temperature Tm of the maximum dielectric constant were determined from the temperature dependence of the dielectric and piezoelectric properties. It is revealed that BNST100x forms a morphotropic phase boundary of rhombohedral ferroelectric and pseudocubic (tetragonal) paraelectric at x=0.26–0.28 for BNST100x, and a very large strain and normalized strain d33* of 0.29% and 488pm∕V, respectively, were obtained at x=0.28. In addition, it was clarified that the intermediate phase between TR-T (⩾Td) and Tm shows relaxor behavior.
A hierarchical construction scheme for accurate potential energy surface generation: An application to the F+H2 reaction
Authors: Fu Bina , Xu Xin , Zhang Dong H.
Published: July 2008

We present a hierarchical construction scheme for accurate ab initio potential energy surface generation. The scheme is based on the observation that when molecular configuration changes, the variation in the potential energy difference between different ab initio methods is much smaller than the variation for potential energy itself. This means that it is easier to numerically represent energy difference to achieve a desired accuracy. Because the computational cost for ab initio calculations increases very rapidly with the accuracy, one can gain substantial saving in computational time by constructing a high accurate potential energy surface as a sum of a low accurate surface based on extensive ab initio data points and an energy difference surface for high and low accuracy ab initio methods based on much fewer data points. The new scheme was applied to construct an accurate ground potential energy surface for the FH2 system using the coupled-cluster method and a very large basis set. The constructed potential energy surface is found to be more accurate on describing the resonance states in the FH2 and FHD systems than the existing surfaces.
Optical property and electronic band structure of a piezoelectric compound Ga3PO7 studied by the first-principles calculation
Authors: Cheng Z. X. , Wang X. L.
Published: July 2008

The structure, electronic, and optical properties of a piezoelectric material, Ga3PO7, were studied by first-principles calculations in the framework of density functional theory. The calculated structure is in agreement with the experimental data. Band structure reveals that Ga3PO7 has a band gap of 3.69eV. Analysis of partial density of states and Mulliken charge population indicates existence of GaO5 and PO4 anion groups in Ga3PO7. Furthermore, its optical properties, including dielectric constant, absorption, reflectivity, refractive index, and electron loss were calculated and analyzed, which show that Ga3PO7 has potential applications based on combination of its piezoelectric and optical properties.
Grating-coupled surface emitting quantum cascade ring lasers
Authors: Mujagić E. , Schartner S. , Hoffmann L. K. , Schrenk W. , Semtsiv M. P. , Wienold M. , Masselink W. T. , Strasser G.
Published: July 2008

We report on the fabrication and operation of quantum cascade ring lasers providing grating-coupled surface emission. The devices exhibit tunable far fields, ranging from spot- to ring-shaped symmetric beam cross sections, depending on the grating period. This—along with threshold current densities as low as for comparable Fabry–Pérot lasers—demonstrates the compatibility of reduced beam divergence and two-dimensional integrability, resulting in an attractive light source for applications in midinfrared spectroscopy and imaging.
Electron-scattering experiments resolve short-range correlations among nucleons
Authors: Wilson Mark
Published: July 2008

Researchers at Jefferson Lab confirm that high-momentum neutron–proton pairs in a carbon nucleus are 20 times more prevalent than proton–proton pairs.
Budding engineers compete to build more efficient, greener cars
Authors: Kramer David
Published: July 2008

University teams take varied technological approaches in vying for the Challenge X prize.
Home photovoltaic systems for physicists
Authors: Murphy Thomas W.
Published: July 2008

Installing a modest photovoltaic system and using it to run a suite of appliances can be educational and immensely satisfying. This brief how-to guide will help get you started.
How do auroras form?
Authors: Strangeway Robert J.
Published: July 2008

A key element is a current, aligned along Earth’s magnetic field, that results from the coupling of plasmas in and above our planet’s atmosphere
Energy efficiency in the built environment
Authors: Glicksman Leon R.
Published: July 2008

Residential and commercial buildings constitute the largest energy-consuming sector in the US. Implementing efficiency measures can be an economically viable solution for reducing greenhouse gas emissions
Bioresistive identification of heat shock protein 90
Authors: Chandrasekaran Arvind , Pakkiriswami Shanmugasundaram , You Jian Liang , Acharya Ashwin , Packirisamy Muthukumaran , Maxwell Denis
Published: July 2008

90 kDa heat shock protein (HSP90) is a ubiquitous molecular chaperone and is one of the abundant proteins present in a cell under normal and stressed conditions. The adenosine triphosphate (ATP) binding region of HSP90 is currently under a great degree of study because of the interest of its role in cancer and protein maintenance; the binding of ATP to HSP90 induces a large conformational change in the protein as a result of the activity of different types of stressors within the cells. In the present paper, a simple microfluidic biosensor is proposed for the characterization of ATP-HSP90 interactions through the principle of bioresistive variation. The experimental results prove that the present biosensor system is highly suitable for the detection of heat shock proteins present in a real-time biological sample, which is very useful for in-situ biomedical applications and rapid pathogenic detections.
Identification and characterisation of barley (Hordeum vulgare) respiratory burst oxidase homologue family members
Authors: J. Lightfoot Damien , Boettcher Annette , Little Alan , Shirley Neil , Able Amanda J.
Published: July 2008

Respiratory burst oxidase homologues (RBOHs) of the human phagocyte gp91phox gene have been isolated from several plant species and the proteins that they encode have been shown to play important roles in the cellular response to biotic stress via the production of superoxide. In this study we have identified and preliminarily characterised six RBOHs from barley (Hordeum vulgare L.). Conservation of the genomic structure and conceptual protein sequence was observed between all six barley RBOH genes when compared with Arabidopsis and rice RBOH gene family members. Four of the six barley RBOH transcripts had wide-spread constitutive spatial expression patterns. The inducible expression profiles of HvRBOHF1 and HvRBOHF2 in response to infection by the necrotrophic fungal pathogens Pyrenophora teres f. teres Drechsler and Rhynchosporium secalis (Oudem) J. Davis were further characterised by quantitative real-time PCR (qPCR). Increased expression of both transcripts was observed in leaf epidermal tissue in response to infection, which is in keeping with a suggested role for both transcripts in the early oxidative burst during the plant response to pathogen invasion. This research provides a basis for further analysis and establishment of the roles of this RBOH family in various reactive oxygen species dependent processes in barley.
An ecosystem services framework to support both practical conservation and economic development
Authors: Tallis Heather , Kareiva Peter , Marvier Michelle , Chang Amy
Published: July 2008

The core idea of the Millennium Ecosystem Assessment is that the human condition is tightly linked to environmental condition. This assertion suggests that conservation and development projects should be able to achieve both ecological and social progress without detracting from their primary objectives. Whereas “win–win” projects that achieve both conservation and economic gains are a commendable goal, they are not easy to attain. An analysis of World Bank projects with objectives of alleviating poverty and protecting biodiversity revealed that only 16% made major progress on both objectives. Here, we provide a framework for anticipating win–win, lose–lose, and win–lose outcomes as a result of how people manage their ecosystem services. This framework emerges from detailed explorations of several case studies in which biodiversity conservation and economic development coincide and cases in which there is joint failure. We emphasize that scientific advances around ecosystem service production functions, tradeoffs among multiple ecosystem services, and the design of appropriate monitoring programs are necessary for the implementation of conservation and development projects that will successfully advance both environmental and social goals. The potentially bright future of jointly advancing ecosystem services, conservation, and human well-being will be jeopardized unless a global monitoring effort is launched that uses the many ongoing projects as a grand experiment.
An operational model for mainstreaming ecosystem services for implementation
Authors: Cowling Richard M. , Egoh Benis , Knight Andrew T. , O'Farrell Patrick J. , Reyers Belinda , Rouget Mathieu , Roux Dirk J. , Welz Adam , Wilhelm-Rechman Angelika
Published: July 2008

Research on ecosystem services has grown markedly in recent years. However, few studies are embedded in a social process designed to ensure effective management of ecosystem services. Most research has focused only on biophysical and valuation assessments of putative services. As a mission-oriented discipline, ecosystem service research should be user-inspired and user-useful, which will require that researchers respond to stakeholder needs from the outset and collaborate with them in strategy development and implementation. Here we provide a pragmatic operational model for achieving the safeguarding of ecosystem services. The model comprises three phases: assessment, planning, and management. Outcomes of social, biophysical, and valuation assessments are used to identify opportunities and constraints for implementation. The latter then are transformed into user-friendly products to identify, with stakeholders, strategic objectives for implementation (the planning phase). The management phase undertakes and coordinates actions that achieve the protection of ecosystem services and ensure the flow of these services to beneficiaries. This outcome is achieved via mainstreaming, or incorporating the safeguarding of ecosystem services into the policies and practices of sectors that deal with land- and water-use planning. Management needs to be adaptive and should be institutionalized in a suite of learning organizations that are representative of the sectors that are concerned with decision-making and planning. By following the phases of our operational model, projects for safeguarding ecosystem services are likely to empower stakeholders to implement effective on-the-ground management that will achieve resilience of the corresponding social-ecological systems.
Navigating the transition to ecosystem-based management of the Great Barrier Reef, Australia
Authors: Olsson Per , Folke Carl , Hughes Terry P.
Published: July 2008

We analyze the strategies and actions that enable transitions toward ecosystem-based management using the recent governance changes of the Great Barrier Reef Marine Park as a case study. The interplay among individual actors, organizations, and institutions at multiple levels is central in such transitions. A flexible organization, the Great Barrier Reef Marine Park Authority, was crucial in initiating the transition to ecosystem-based management. This agency was also instrumental in the subsequent transformation of the governance regime and provided leadership throughout the process. Strategies involved internal reorganization and management innovation, leading to an ability to coordinate the scientific community, to increase public awareness of environmental issues and problems, to involve a broader set of stakeholders, and to maneuver the political system for support at critical times. The transformation process was induced by increased pressure on the Great Barrier Reef (from terrestrial runoff, overharvesting, and global warming) that triggered a new sense of urgency to address these challenges. The focus of governance shifted from protection of selected individual reefs to stewardship of the larger-scale seascape. The study emphasizes the significance of stewardship that can change patterns of interactions among key actors and allow for new forms of management and governance to emerge in response to environmental change. This example illustrates that enabling legislations or other social bounds are essential, but not sufficient for shifting governance toward adaptive comanagement of complex marine ecosystems.
Global mapping of ecosystem services and conservation priorities
Authors: Naidoo R. , Balmford A. , Costanza R. , Fisher B. , Green R. E. , Lehner B. , Malcolm T. R. , Ricketts T. H.
Published: July 2008

Global efforts to conserve biodiversity have the potential to deliver economic benefits to people (i.e., “ecosystem services”). However, regions for which conservation benefits both biodiversity and ecosystem services cannot be identified unless ecosystem services can be quantified and valued and their areas of production mapped. Here we review the theory, data, and analyses needed to produce such maps and find that data availability allows us to quantify imperfect global proxies for only four ecosystem services. Using this incomplete set as an illustration, we compare ecosystem service maps with the global distributions of conventional targets for biodiversity conservation. Our preliminary results show that regions selected to maximize biodiversity provide no more ecosystem services than regions chosen randomly. Furthermore, spatial concordance among different services, and between ecosystem services and established conservation priorities, varies widely. Despite this lack of general concordance, “win–win” areas—regions important for both ecosystem services and biodiversity—can be usefully identified, both among ecoregions and at finer scales within them. An ambitious interdisciplinary research effort is needed to move beyond these preliminary and illustrative analyses to fully assess synergies and trade-offs in conserving biodiversity and ecosystem services.
Accounting for ecosystem services as a way to understand the requirements for sustainable development
Authors: Mäler Karl-Göran , Aniyar Sara , Jansson Åsa
Published: July 2008

Millennium Ecosystem Assessment documented the importance of ecosystem services. It is therefore important that these services are included in our economic accounts (Standard National Accounts), as long as we believe that these accounts should tell us something about our wellbeing. This requires measures of the ecosystem assets and their accounting prices. This article discusses how the concept of inclusive wealth can be exploited for creating such accounts.
Consistency and functional specialization in the default mode brain network
Authors: Harrison Ben J. , Pujol Jesus , López-Solà Marina , Hernández-Ribas Rosa , Deus Joan , Ortiz Hector , Soriano-Mas Carles , Yücel Murat , Pantelis Christos , Cardoner Narcís
Published: July 2008

The notion of a “default mode of brain function” has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during (
i
) eyes-closed spontaneous rest, (
ii
) activation by moral dilemma, and (
iii
) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.
α-Helix folding in the presence of structural constraints
Authors: Ihalainen Janne A. , Paoli Beatrice , Muff Stefanie , Backus Ellen H. G. , Bredenbeck Jens , Woolley G. Andrew , Caflisch Amedeo , Hamm Peter
Published: July 2008

We have investigated the site-specific folding kinetics of a photoswitchable cross-linked α-helical peptide by using single
13
C =
18
O isotope labeling together with time-resolved IR spectroscopy. We observe that the folding times differ from site to site by a factor of eight at low temperatures (6°C), whereas at high temperatures (45°C), the spread is considerably smaller. The trivial sum of the site signals coincides with the overall folding signal of the unlabeled peptide, and different sites fold in a noncooperative manner. Moreover, one of the sites exhibits a decrease of hydrogen bonding upon folding, implying that the unfolded state at low temperature is not unstructured. Molecular dynamics simulations at low temperature reveal a stretched-exponential behavior which originates from parallel folding routes that start from a kinetically partitioned unfolded ensemble. Different metastable structures (i.e., traps) in the unfolded ensemble have a different ratio of loop and helical content. Control simulations of the peptide at high temperature, as well as without the cross-linker at low temperature, show faster and simpler (i.e., single-exponential) folding kinetics. The experimental and simulation results together provide strong evidence that the rate-limiting step in formation of a structurally constrained α-helix is the escape from heterogeneous traps rather than the nucleation rate. This conclusion has important implications for an α-helical segment within a protein, rather than an isolated α-helix, because the cross-linker is a structural constraint similar to those present during the folding of a globular protein.
A synthetic mammalian gene circuit reveals antituberculosis compounds
Authors: Weber Wilfried , Schoenmakers Ronald , Keller Bettina , Gitzinger Marc , Grau Thomas , Daoud-El Baba Marie , Sander Peter , Fussenegger Martin
Published: July 2008

Synthetic biology provides insight into natural gene-network dynamics and enables assembly of engineered transcription circuitries for production of difficult-to-access therapeutic molecules. In
Mycobacterium tuberculosis
EthR binds to a specific operator (O
ethR
) thereby repressing
ethA
and preventing EthA-catalyzed conversion of the prodrug ethionamide, which increases the resistance of the pathogen to this last-line-of-defense treatment. We have designed a synthetic mammalian gene circuit that senses the EthR–O
ethR
interaction in human cells and produces a quantitative reporter gene expression readout. Challenging of the synthetic network with compounds of a rationally designed chemical library revealed 2-phenylethyl-butyrate as a nontoxic substance that abolished EthR's repressor function inside human cells, in mice, and within
M. tuberculosis
where it triggered derepression of
ethA
and increased the sensitivity of this pathogen to ethionamide. The discovery of antituberculosis compounds by using synthetic mammalian gene circuits may establish a new line of defense against multidrug-resistant
M. tuberculosis
.
Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain
Authors: Mast Natalia , White Mark Andrew , Bjorkhem Ingemar , Johnson Eric F. , Stout C. David , Pikuleva Irina A.
Published: July 2008

By converting cholesterol to 24S-hydroxycholesterol, cytochrome P450 46A1 (CYP46A1) initiates the major pathway for cholesterol removal from the brain. Two crystal structures of CYP46A1 were determined. First is the 1.9-Å structure of CYP46A1 complexed with a high-affinity substrate cholesterol 3-sulfate (CH-3S). The second structure is that of the substrate-free CYP46A1 at 2.4-Å resolution. CH-3S is bound in the productive orientation and occupies the entire length of the banana-shaped hydrophobic active-site cavity. A unique helix B′–C loop insertion (residues 116–120) contributes to positioning cholesterol for oxygenation catalyzed by CYP46A1. A comparison with the substrate-free structure reveals substantial substrate-induced conformational changes in CYP46A1 and suggests that structurally distinct compounds could bind in the enzyme active site.
In vitro
assays were performed to characterize the effect of different therapeutic agents on cholesterol hydroxylase activity of purified full-length recombinant CYP46A1, and several strong inhibitors and modest coactivators of CYP46A1 were identified. Structural and biochemical data provide evidence that CYP46A1 activity could be altered by exposure to some therapeutic drugs and potentially other xenobiotics.
The tumor suppressor genes
dachsous
and
fat
modulate different signalling pathways by regulating
dally
and
dally-like
Authors: Baena-Lopez Luis Alberto , Rodríguez Isabel , Baonza Antonio
Published: July 2008

The activity of different signaling pathways must be precisely regulated during development to define the final size and pattern of an organ. The
Drosophila
tumor suppressor genes
dachsous
(
ds
) and
fat
(
ft
) modulate organ size and pattern formation during imaginal disc development. Recent studies have proposed that Fat acts through the conserved Hippo signaling pathway to repress the expression of
cycE
,
bantam
, and
diap-1.
However, the combined ectopic expression of all of these target genes does not account for the hyperplasic phenotypes and patterning defects displayed by Hippo pathway mutants. Here, we identify the glypicans
dally
and
dally-like
as two target genes for both
ft
and
ds
acting via the Hippo pathway. Dally and Dally-like modulate organ growth and patterning by regulating the diffusion and efficiency of signaling of several morphogens such as Decapentaplegic, Hedgehog, and Wingless. Our findings therefore provide significant insights into the mechanisms by which mutations in the Hippo pathway genes can simultaneously alter the activity of several signaling pathways, compromising the control of growth and pattern formation.
Fluoroscopy-guided percutaneous lung biopsy: a valuable alternative to computed tomography
Authors: Kurban L. A. , Gomersall L. , Weir J. , Wade P.
Published: July 2008

Background: Computed tomography (CT) fluoroscopy nowadays is the most preferred method of guidance to perform percutaneous lung biopsy of pulmonary masses. Conventional fluoroscopy is an increasingly forgotten technique that still can be used to perform lung biopsies, with many advantages.

Purpose: To compare the accuracy, safety, and effective dose (ED) of conventional fluoroscopy-guided needle lung biopsy (FNLB) with CT-guided needle lung biopsy procedures (CTNLB) reported in the literature.

Material and Methods: 100 consecutive patients who underwent FNLB were reviewed retrospectively. Using the final histological diagnoses and the clinical and radiological course of the disease as references, the accuracy and sensitivity of FNLB were calculated. The complication rates of FNLB were assessed. Using computer software (XDOSE), the ED was calculated. The accuracy, complication rates, and the ED of FNLB were compared with CTNLB reported in the literature.

Results: The overall accuracy rate and sensitivity of FNLB were both 87%, which are comparable to the range of accuracies reported in the literature for CTNLB (74–97%). The complication rates of FNLB were also comparable to the complication rates reported for CTNLB. The commonest complication was pneumothorax, at a rate of 25%. The ED of FNLB was small, significantly lower than reported in the literature for CT-guided procedures. The mean ED of FNLB was 0.029 mSv, which is approximately equivalent to one chest X-ray.

Conclusion: Conventional fluoroscopy is an accurate, safe, and low-dose alternative modality to CT to obtain an image-guided histological diagnosis of pulmonary lesions.
Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of t1 shortening
Authors: Morell A. , Ahlstrom H. , Schoenberg S. O. , Abildgaard A. , Bock M. , Bjørnerud A.
Published: July 2008

Background: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage.

Purpose: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response.

Material and Methods: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data.

Results: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339±60 ml/min/100 g, 41±8 ml/100 g, and 7.3±1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254±47 ml/min/100 g, 27±3 ml/100 g, and 6±1.2 s, respectively.

Conclusion: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.
Differential diagnosis between osteomyelitis and bone tumors
Authors: Shimose S. , Sugita T. , Kubo T. , Matsuo T. , Nobuto H. , Ochi M.
Published: July 2008

Background: Hematogenous osteomyelitis is often difficult to distinguish from a bone tumor because clinical findings are noncontributory and radiological features can mimic a bone tumor. Recently, the penumbra sign, a higher signal intensity feature of the thin layer of granulation tissue which lines the abscess cavity on T1-weighted magnetic resonance (MR) images, has been reported to be helpful for discriminating subacute osteomyelitis.

Purpose: To determine helpful findings for distinguishing osteomyelitis from bone tumors.

Material and Methods: The laboratory and imaging findings of a consecutive series of 244 patients referred to our institution with a suspected bone tumor were reviewed. There were 15 cases of osteomyelitis, 160 bone tumors, and 69 tumor-like lesions.

Results: In osteomyelitis, the C-reactive protein (CRP) level increased in nine patients and the penumbra sign was seen in 11 patients. In bone tumors and tumor-like lesions, a high CRP level was observed in 21 patients and the penumbra sign was seen in two patients. The sensitivity of the penumbra sign for osteomyelitis was 73.3%, with a specificity of 99.1%.

Conclusion: The penumbra sign and a high CRP level support the diagnosis of osteomyelitis and may help to exclude the presence of a tumor.
Rapid Antibacterial Activity of 2 Novel Hand Soaps: Evaluation of the Risk of Development of Bacterial Resistance to the Antibacterial Agents
Authors: Geraldo Ingrid M. , Gilman Allan , Shintre Milind S. , Modak Shanta M.
Published: July 2008

Objective.

To evaluate the antimicrobial efficacy of and risk of organisms developing resistance to 2 novel hand soaps: (1) a soap containing triclosan, polyhexamethylene biguanide, and benzethonium chloride added to a soap base (TPB soap); and (2) a soap containing farnesol, polyhexamethylene biguanide, and benzethonium chloride added to a soap base (FPB soap). Tests also included soaps containing only triclosan.

Design.

The risk of emergence of resistant bacterial mutants was investigated by determining the susceptibility changes after repeated exposure of bacteria to the drugs and soaps in vitro. The effectiveness of the soaps was evaluated using an in vitro tube dilution method, a volunteer method (the ASTM standard), and 2 pig skin methods.

Results.

The minimum inhibitory concentration and minimum bactericidal concentration of triclosan against Staphylococcus, aureus increased 8- to 62.5-fold, whereas those of TPB and FPB (both alone and in soap) were unchanged. In vitro, TPB and FPB soaps produced higher log10 reductions in colony-forming units of all tested organisms (4.95-8.58) than did soaps containing triclosan alone (0.29-4.86). In the test using the pig skin and volunteer methods, TPB soap produced a higher log10 reduction in colony-forming units (3.1-3.3) than did the soap containing triclosan alone (2.6-2.8).

Conclusion.

The results indicate that TPB and FPB soaps may provide superior rapid and broad-spectrum efficacy with a lower risk of organisms developing resistance than do soaps containing triclosan alone. Pig skin methods may be used to predict the efficacy of antibacterial soaps in the rapid disinfection of contaminated hands. Hand washing with TPB and FPB soaps by healthcare workers and the general population may reduce the transmission of pathogens, with a lower risk of promoting the emergence of resistant organisms.
Myosin IIC: A Third Molecular Motor Driving Neuronal Dynamics
Authors: Wylie Steven R. , Chantler Peter D.
Published: July 2008

Neuronal dynamics result from the integration of forces developed by molecular motors, especially conventional myosins. Myosin IIC is a recently discovered nonsarcomeric conventional myosin motor, the function of which is poorly understood, particularly in relation to the separate but coupled activities of its close homologues, myosins IIA and IIB, which participate in neuronal adhesion, outgrowth and retraction. To determine myosin IIC function, we have applied a comparative functional knockdown approach by using isoform-specific antisense oligodeoxyribonucleotides to deplete expression within neuronally derived cells. Myosin IIC was found to be critical for driving neuronal process outgrowth, a function that it shares with myosin IIB. Additionally, myosin IIC modulates neuronal cell adhesion, a function that it shares with myosin IIA but not myosin IIB. Consistent with this role, myosin IIC knockdown caused a concomitant decrease in paxillin-phospho-Tyr118 immunofluorescence, similar to knockdown of myosin IIA but not myosin IIB. Myosin IIC depletion also created a distinctive phenotype with increased cell body diameter, increased vacuolization, and impaired responsiveness to triggered neurite collapse by lysophosphatidic acid. This novel combination of properties suggests that myosin IIC must participate in distinctive cellular roles and reinforces our view that closely related motor isoforms drive diverse functions within neuronal cells.
Effect of 27nt Small RNA on Endothelial Nitric-Oxide Synthase Expression
Authors: Zhang Ming-Xiang , Zhang Cheng , Shen Ying H. , Wang Jian , Li Xiao-Nan , Chen Liang , Zhang Yun , Coselli Joseph S. , Wang Xing Li
Published: July 2008

We have reported previously that the 27nt repeat polymorphism in endothelial nitric-oxide synthase (eNOS) intron 4—a source of 27nt small RNA—inhibits eNOS expression. In the current study, we have investigated how 27nt small RNA suppresses eNOS expression. Using a chromatin immunoprecipitation assay, we examined histone acetylation in the 27nt repeat element of eNOS intron 4, the promoter region up to −1486 bp, and the 5′ enhancer region (−4583/−4223bp) in human aortic endothelial cells (HAECs) treated with 27nt RNA duplex. 27nt RNA duplex induced hyperacetylation in H3 (lysine8, 12, and 23) and H4 (lysine 9 and 12) at the 27nt repeat element, which then interacted with nuclear actin, histone deacetylase 3 (HDAC3), and NonO proteins. In contrast, the histone H3 and H4 became hypoacetylated at the eNOS core promoter. HAECs treated with 27nt RNA duplex had reduced eNOS expression, but treatment with either HDAC3 small interfering RNA or NonO siRNA significantly attenuated the 27nt small RNA-induced suppression. We further found that 27nt small RNA induced DNA methylation in a region approximately 750nt upstream of the intron 4 repeats, and a methyltransferase inhibitor reversed the effect on methylation and eNOS expression. Our study demonstrates that 27nt small RNA may suppress eNOS expression by altering histone acetylation and DNA methylation in regions adjacent to the 27nt repeat element and core promoter.
Casein Kinase 2 Binds to the C Terminus of Na+/H+exchanger 3 (NHE3) and Stimulates NHE3 Basal Activity by Phosphorylating a Separate Site in NHE3
Authors: Sarker Rafiquel , Grønborg Mads , Cha Boyoung , Mohan Sachin , Chen Yueping , Pandey Akhilesh , Litchfield David , Donowitz Mark , Li Xuhang
Published: July 2008

Na+/H+exchanger 3 (NHE3) is the epithelial-brush border isoform responsible for most intestinal and renal Na+absorption. Its activity is both up- and down-regulated under normal physiological conditions, and it is inhibited in most diarrheal diseases. NHE3 is phosphorylated under basal conditions and Ser/Thr phosphatase inhibitors stimulate basal exchange activity; however, the kinases involved are unknown. To identify kinases that regulate NHE3 under basal conditions, NHE3 was immunoprecipitated; LC-MS/MS of trypsinized NHE3 identified a novel phosphorylation site at S719of the C terminus, which was predicted to be a casein kinase 2 (CK2) phosphorylation site. This was confirmed by an in vitro kinase assay. The NHE3-S719A mutant but not NHE3-S719D had reduced NHE3 activity due to less plasma membrane NHE3. This was due to reduced exocytosis plus decreased plasma membrane delivery of newly synthesized NHE3. Also, NHE3 activity was inhibited by the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole DMAT when wild-type NHE3 was expressed in fibroblasts and Caco-2 cells, but the NHE3-S719mutant was fully resistant to DMAT. CK2 bound to the NHE3 C-terminal domain, between amino acids 590 and 667, a site different from the site it phosphorylates. CK2 binds to the NHE3 C terminus and stimulates basal NHE3 activity by phosphorylating a separate single site on the NHE3 C terminus (S719), which affects NHE3 trafficking.
Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport
Authors: Peretti Diego , Dahan Nili , Shimoni Eyal , Hirschberg Koret , Lev Sima
Published: July 2008

Lipid transport between intracellular organelles is mediated by vesicular and nonvesicular transport mechanisms and is critical for maintaining the identities of different cellular membranes. Nonvesicular lipid transport between the endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the lipid composition of the Golgi membranes. Here, we show that the integral ER–membrane proteins VAP-A and VAP-B affect the structural and functional integrity of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the Golgi membranes, and it leads to substantial inhibition of Golgi-mediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterol-binding protein (OSBP), and ceramide-transfer protein (CERT), which interact with VAPs via their FFAT motif. The effect of VAPs on PI4P levels is mediated by the phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required for Golgi targeting of OSBP and CERT and the subsequent production of diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function coordinately at the ER–Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities.
Synchronous versus asynchronous modeling of gene regulatory networks
Authors: Garg Abhishek , Di Cara Alessandro , Xenarios Ioannis , Mendoza Luis , De Micheli Giovanni
Published: July 2008

Motivation:  In silico modeling of gene regulatory networks has gained some momentum recently due to increased interest in analyzing the dynamics of biological systems. This has been further facilitated by the increasing availability of experimental data on gene–gene, protein–protein and gene–protein interactions. The two dynamical properties that are often experimentally testable are perturbations and stable steady states. Although a lot of work has been done on the identification of steady states, not much work has been reported on in silico modeling of cellular differentiation processes.

Results: In this manuscript, we provide algorithms based on reduced ordered binary decision diagrams (ROBDDs) for Boolean modeling of gene regulatory networks. Algorithms for synchronous and asynchronous transition models have been proposed and their corresponding computational properties have been analyzed. These algorithms allow users to compute cyclic attractors of large networks that are currently not feasible using existing software.

Hereby we provide a framework to analyze the effect of multiple gene perturbation protocols, and their effect on cell differentiation processes. These algorithms were validated on the T-helper model showing the correct steady state identification and Th1–Th2 cellular differentiation process.

Availability: The software binaries for Windows and Linux platforms can be downloaded from http://si2.epfl.ch/~garg/genysis.html.

Contact:  abhishek.garg@epfl.ch
Yale Image Finder (YIF): a new search engine for retrieving biomedical images
Authors: Xu Songhua , McCusker Jamie , Krauthammer Michael
Published: July 2008

Summary: Yale Image Finder (YIF) is a publicly accessible search engine featuring a new way of retrieving biomedical images and associated papers based on the text carried inside the images. Image queries can also be issued against the image caption, as well as words in the associated paper abstract and title. A typical search scenario using YIF is as follows: a user provides few search keywords and the most relevant images are returned and presented in the form of thumbnails. Users can click on the image of interest to retrieve the high resolution image. In addition, the search engine will provide two types of related images: those that appear in the same paper, and those from other papers with similar image content. Retrieved images link back to their source papers, allowing users to find related papers starting with an image of interest. Currently, YIF has indexed over 140 000 images from over 34 000 open access biomedical journal papers.

Availability: http://krauthammerlab.med.yale.edu/imagefinder/

Contact: michael.krauthammer@yale.edu
Dynamical modeling and multi-experiment fitting with PottersWheel
Authors: Maiwald Thomas , Timmer Jens
Published: July 2008

Motivation: Modelers in Systems Biology need a flexible framework that allows them to easily create new dynamic models, investigate their properties and fit several experimental datasets simultaneously. Multi-experiment-fitting is a powerful approach to estimate parameter values, to check the validity of a given model, and to discriminate competing model hypotheses. It requires high-performance integration of ordinary differential equations and robust optimization.

Results: We here present the comprehensive modeling framework Potters-Wheel (PW) including novel functionalities to satisfy these requirements with strong emphasis on the inverse problem, i.e. data-based modeling of partially observed and noisy systems like signal transduction pathways and metabolic networks. PW is designed as a MATLAB toolbox and includes numerous user interfaces. Deterministic and stochastic optimization routines are combined by fitting in logarithmic parameter space allowing for robust parameter calibration. Model investigation includes statistical tests for model-data-compliance, model discrimination, identifiability analysis and calculation of Hessian- and Monte-Carlo-based parameter confidence limits. A rich application programming interface is available for customization within own MATLAB code. Within an extensive performance analysis, we identified and significantly improved an integrator–optimizer pair which decreases the fitting duration for a realistic benchmark model by a factor over 3000 compared to MATLAB with optimization toolbox.

Availability: PottersWheel is freely available for academic usage at http://www.PottersWheel.de/. The website contains a detailed documentation and introductory videos. The program has been intensively used since 2005 on Windows, Linux and Macintosh computers and does not require special MATLAB toolboxes.

Contact:  maiwald@fdm.uni-freiburg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
GP Participation and Recruitment of Patients to RCTs: Lessons from Trials of Acupuncture and Exercise for Low Back Pain in Primary Care
Authors: Bell-Syer Sally E. M. , Thorpe Lucy N. , Thomas Kate , MacPherson Hugh
Published: July 2008

The objective of this study was to identify factors associated with general practitioner (GP) participation and the recruitment of people to trials in primary care, based on data from two trials of interventions for treating chronic low back pain. The study was based on data from two randomized controlled trials (RCTs), one involving exercise, the other acupuncture, and subsequent reporting by GPs in a postal questionnaire. The exercise trial achieved 62% recruitment whereas the acupuncture trial achieved 100% recruitment. In both trials GPs most efficient at referring patients were those with a special interest in the subject area, and those known personally to the research team. A follow‐up GP questionnaire found that both trials had maintained a high profile with over 80% of GPs, and successful recruitment strategies included project reminder letters, updates and personal contacts. Achieving target recruitment of patients in the acupuncture trial was aided by the deliberate application of lessons learned in the exercise trial, in particular the need to keep initial study entry criteria broad, with subsequent filtering undertaken by the study researcher. In addition the use of effective methods of maintaining the trial profile, the involvement of a GP advisor, the decision to maximize the recruitment of GPs early in the trial and the direct recruitment of interested individual GPs. The successful recruitment of patients to trials in primary care requires careful planning and continuous monitoring from the outset. Prior to starting recruitment, it is useful to identify previous trials in a similar environment in order to learn from their experience and optimize patient recruitment.
DsbB Is Required for the Pathogenesis Process of Xanthomonas campestris pv. campestris
Authors: Jiang Bo-Le , Liu Jiao , Chen Li-Feng , Ge Ying-Ying , Hang Xiao-Hong , He Yong-Qiang , Tang Dong-Jie , Lu Guang-Tao , Tang Ji-Liang
Published: July 2008

The DsbA/DsbB oxidation pathway is one of the two pathways that catalyze disulfide bond formation of proteins in the periplasm of gram-negative bacteria. It has been demonstrated that DsbA is essential for multiple virulence factors of several animal bacterial pathogens. In this article, we present genetic evidence to show that the open reading frame XC_3314 encodes a DsbB protein that is involved in disulfide bond formation in periplasm of Xanthomonas campestris pv. campestris, the causative agent of crucifer black rot disease. The dsbB mutant of X. campestris pv. campestris exhibited attenuation in virulence, hypersensitive response, cell motility, and bacterial growth in planta. Furthermore, mutation in the dsbB gene resulted in ineffective type II and type III secretion systems as well as flagellar assembly. These findings reveal that DsbB is required for the pathogenesis process of X. campestris pv. campestris.