bluuebunny/crossref_metadata_2025 huggingface dataset:
Following the excited state relaxation dynamics of indole and 5-hydroxyindole using time-resolved photoelectron spectroscopy
Authors: Livingstone Ruth , Schalk Oliver , Boguslavskiy Andrey E. , Wu Guorong , Therese Bergendahl L. , Stolow Albert , Paterson Martin J. , Townsend Dave
Published: November 2011

Time-resolved photoelectron spectroscopy was used to obtain new information about the dynamics of electronic relaxation in gas-phase indole and 5-hydroxyindole following UV excitation with femtosecond laser pulses centred at 249 nm and 273 nm. Our analysis of the data was supported by ab initio calculations at the coupled cluster and complete-active-space self-consistent-field levels. The optically bright 1La and 1Lb electronic states of 1ππ* character and spectroscopically dark and dissociative 1πσ* states were all found to play a role in the overall relaxation process. In both molecules we conclude that the initially excited 1La state decays non-adiabatically on a sub 100 fs timescale via two competing pathways, populating either the subsequently long-lived 1Lb state or the 1πσ* state localised along the N-H coordinate, which exhibits a lifetime on the order of 1 ps. In the case of 5-hydroxyindole, we conclude that the 1πσ* state localised along the O-H coordinate plays little or no role in the relaxation dynamics at the two excitation wavelengths studied.
Monte Carlo simulation studies of ring polymers at athermal and theta conditions
Authors: Fuereder Ingo , Zifferer Gerhard
Published: November 2011

By use of an intramolecular criterion, i.e., the direct proportionality between mean square dimension and chain length, theta conditions for linear chains and ring shaped polymers are evaluated for several types of cubic lattice chains (simple cubic, body centered cubic, and face centered cubic). The properties of the rings are evaluated for the same thermodynamic conditions under which they are prepared thus allowing for a natural amount of knots which have been identified by use of Alexander polynomials. For the limit of infinite chain lengths the same theta parameter is found for linear chains and rings. On the contrary, a significant theta point depression occurs due to an additional excluded volume effect if unknots are exclusively regarded. Parameters characteristic of the shape of rings and chains under theta conditions extrapolated to infinite chain length fairly well coincide with respective data for random walks. Mean square dimensions (characteristic of the size) of theta systems are slightly in excess as compared to nonreversal random walks due to the necessity of avoiding overlaps on a local scale. Furthermore athermal systems are studied as well for comparison; mean square dimensions are described by use of scaling relations with proper short chain corrections, shape parameters are given in the limit of infinite chain length.
Counting spanning trees in self-similar networks by evaluating determinants
Authors: Lin Yuan , Wu Bin , Zhang Zhongzhi , Chen Guanrong
Published: November 2011

Spanning trees are relevant to various aspects of networks. Generally, the number of spanning trees in a network can be obtained by computing a related determinant of the Laplacian matrix of the network. However, for a large generic network, evaluating the relevant determinant is computationally intractable. In this paper, we develop a fairly generic technique for computing determinants corresponding to self-similar networks, thereby providing a method to determine the numbers of spanning trees in networks exhibiting self-similarity. We describe the computation process with a family of networks, called (x, y)-flowers, which display rich behavior as observed in a large variety of real systems. The enumeration of spanning trees is based on the relationship between the determinants of submatrices of the Laplacian matrix corresponding to the (x, y)-flowers at different generations and is devoid of the direct laborious computation of determinants. Using the proposed method, we derive analytically the exact number of spanning trees in the (x, y)-flowers, on the basis of which we also obtain the entropies of the spanning trees in these networks. Moreover, to illustrate the universality of our technique, we apply it to some other self-similar networks with distinct degree distributions, and obtain explicit solutions to the numbers of spanning trees and their entropies. Finally, we compare our results for networks with the same average degree but different structural properties, such as degree distribution and fractal dimension, and uncover the effect of these topological features on the number of spanning trees.
Multipolar polarizabilities and two-body dispersion coefficients for Na by a variationally stable procedure
Authors: Sun Qiu-Feng , Huang Shi-Zhong
Published: November 2011

Based on the weakest bound electron potential model theory, the ground-state wave function of Na is investigated. The variationally stable procedure of Gao and Starace is then employed to evaluate the static multipolar polarizabilities of Na, and the two-body dispersion coefficients for the Na–Na system. Calculated values show that our results are in general agreement with those previously reported in the literature.
Orientational order in concentrated suspensions of spherical microswimmers
Authors: Evans Arthur A. , Ishikawa Takuji , Yamaguchi Takami , Lauga Eric
Published: November 2011

We use numerical simulations to probe the dynamics of concentrated suspensions of spherical microswimmers interacting hydrodynamically. Previous work in the dilute limit predicted orientational instabilities of aligned suspensions for both pusher and puller swimmers, which we confirm computationally. Unlike previous work, we show that isotropic suspensions of spherical swimmers are also always unstable. Both types of initial conditions develop long-time polar order of a nature which depends on the hydrodynamic signature of the swimmer but very weakly on the volume fraction up to very high volume fractions.
Thermal conductivity of carbon nanotube—polyamide-6,6 nanocomposites: Reverse non-equilibrium molecular dynamics simulations
Authors: Alaghemandi Mohammad , Müller-Plathe Florian , Böhm Michael C.
Published: November 2011

The thermal conductivity of composites of carbon nanotubes and polyamide-6,6 has been investigated using reverse non-equilibrium molecular dynamics simulations in a full atomistic resolution. It is found, in line with experiments, that the composites have thermal conductivities, which are only moderately larger than that of pure polyamide. The composite conductivities are orders of magnitude less than what would be expected from naïve additivity arguments. This means that the intrinsic thermal conductivities of isolated nanotubes, which exceed the best-conducting metals, cannot be harnessed for heat transport, when the nanotubes are embedded in a polymer matrix. The main reason is the high interfacial thermal resistance between the nanotubes and the polymer, which was calculated in addition to the total composite thermal conductivity as well as that of the subsystem. It hinders heat to be transferred from the slow-conducting polymer into the fast-conducting nanotubes and back into the polymer. This interpretation is in line with the majority of recent simulation works. An alternative explanation, namely, the damping of the long-wavelength phonons in nanotubes by the polymer matrix is not supported by the present calculations. These modes provide most of the polymers heat conduction. An additional minor effect is caused by the anisotropic structure of the polymer phase induced by the nearby nanotube surfaces. The thermal conductivity of the polymer matrix increases slightly in the direction parallel to the nanotubes, whereas it decreases perpendicular to it.
Focused excimer laser initiated, radio frequency sustained high pressure air plasmas
Authors: Giar Ryan , Scharer John
Published: November 2011

Measurements and analysis of air breakdown processes and plasma production by focusing 193 nm, 300 mJ, 15 MW high power laser radiation inside a 6 cm diameter helical radio frequency (RF) coil are presented. Quantum resonant multi-photon ionization (REMPI) and collisional cascade laser ionization processes are exploited that have been shown to produce high-density (ne ∼ 7 × 1016/cm3) cylindrical seed plasmas at 760 Torr. Air breakdown in lower pressures (from 7–22 Torr), where REMPI is the dominant laser ionization process, is investigated using an UV 18 cm focal length lens, resulting in a laser flux of 5.5 GW/cm2 at the focal spot. The focused laser power absorption and associated shock wave produce seed plasmas for sustainment by the RF (5 kW incident power, 1.5 s) pulse. Measurements of the helical RF antenna load impedance in the inductive and capacitive coupling regimes are obtained by measuring the loaded antenna reflection coefficient. A 105 GHz interferometer is used to measure the plasma electron density and collision frequency. Spectroscopic measurements of the plasma and comparison with the SPECAIR code are made to determine translational, rotational, and vibrational neutral temperatures and the associated neutral gas temperature. From this and the associated measurement of the gas pressure the electron temperature is obtained. Experiments show that the laser-formed seed plasma allows RF sustainment at higher initial air pressures (up to 22 Torr) than that obtained via RF-only initiation (<18 Torr) by means of a 0.3 J UV laser pulse.
Redox processes in silicon dioxide thin films using copper microelectrodes
Authors: Tappertzhofen S. , Menzel S. , Valov I. , Waser R.
Published: November 2011

Although SiO2 is a typical insulator, we demonstrate an electrochemical characteristic of the Cu/Cu+ oxidation at the interface with 30 nm thick silicon dioxide thin films studied by cyclic voltammetry. This study reveals the process of anodic oxidation and subsequent reduction of oxidized Cu ions injected in the SiO2 layer with special attention to the kinetics of the redox process. We estimated the diffusion coefficient and the mobility of Cu ions in SiO2. The results gain deeper insight in the processes involved during resistive switching of Cu/SiO2 based nonvolatile memory devices.
Irradiation-induced molecular dipole reorientation in inverted polymer solar cell using small molecular electron collection layer
Authors: Xu Zai-Quan , Sun Fu-Zhou , Li Jian , Lee Shuit-Tong , Li Yan-Qing , Tang Jian-Xin
Published: November 2011

Inverted polymer solar cell is developed using small molecular tris(8-hydroxyquinolinato) aluminum (Alq3) as an electron collection layer between the active layer and indium-tin-oxide bottom cathode. Upon post-processing light irradiation by simulated solar illumination, the open-circuit voltage of the inverted device increases from 0.52 V to 0.60 V, resulting in the enhancement of the power conversion efficiency from 2.54% to 3.33% with negligible change in the short-circuit current. The performance improvement is attributed to the removal of surface potential due to irradiation-induced molecular dipole reorientation in the Alq3 layer, which reduces the charge transport barrier and improves the charge collection efficiency.
In-well pumping of InGaN/GaN vertical-external-cavity surface-emitting lasers
Authors: Wunderer Thomas , Northrup John E. , Yang Zhihong , Teepe Mark , Strittmatter André , Johnson Noble M. , Rotella Paul , Wraback Michael
Published: November 2011

In-well-pumped blue InGaN/GaN vertical-external-cavity surface-emitting lasers are demonstrated. The laser structures were grown on bulk GaN substrates by using metal-organic vapor phase epitaxy near atmospheric pressure. The active zone consisted of up to 20 InGaN quantum wells distributed in a resonant periodic gain configuration. High-reflectivity dielectric distributed Bragg-reflectors were used as mirrors. Laser emission with a single longitudinal mode at 440 nm was achieved by exclusively pumping the quantum wells with the 384 nm emission line of a dye-/N2-laser.
Nutritive value of corn silage in mixture with vine peas
Authors: Zhu Y. , Bai C. S. , Guo X. S. , Xue Y. L. , Ataku Kazuo
Published: November 2011

Combining corn with legumes for silage is a feasible strategy to improve crude protein concentration in corn silage. This study was conducted to determine the fermentation characteristics and overall nutritive value of ensiled corn (Zea mays L.), vine peas (Pisum sativum L.), and mixtures of the two crops at three different ratios. The two crops were ensiled in corn/pea mixtures containing 0, 33, 50, 67, and 100% corn in vacuumed plastic bags for 60 days at room temperature. The addition of peas to corn crude protein and dry matter concentrations in the ensiled forages had a negligible influence on neutral detergent fibre concentration compared with corn silage. Corn silage had a greater (P < 0.05) lactic acid concentration than vine peas silage and the mixtures. There were no differences (P > 0.05) in in vitro dry matter and neutral detergent fibre digestibility among the silages made from the vine peas, corn, and mixtures. Improved fermentation characteristics were obtained in vine peas and corn mixture silage at a ratio of 33 : 67 compared with the other mixtures and vine peas silage. Results generated from this study suggest that combining vine peas with corn for silage could provide livestock with not only a high energy concentration feed, but a high concentration of crude protein as well.
Comparative Study of the Adsorption of Aromatic Pollutants onto TiO2 (100) Surface via Molecular Simulation
Authors: Wahab Hilal S. , Koutselos Andreas D.
Published: November 2011

The adsorption mode of benzoic acid onto the anatase TiO2 (100) surface has been studied through the semi-empirical self-consistent field molecular orbital method MSINDO and is compared with previously determined modes of four aromatic compounds: chlorobenzene, aniline, p-chlorophenol and nitrobenzene. The simulation results reveal that aniline and p-chlorophenol molecules are adsorbed with their aromatic ring positioned parallel to the surface although they are linked to a surface lattice titanium atom via the amino nitrogen and phenolic oxygen respectively. In contrast, chlorobenzene, nitrobenzene and benzoic acid are found in perpendicular configurations and they are attached to the surface via the chlorine and oxygen atoms of the NO2 and COOH groups respectively. The calculated substrate–surface interaction energy is influenced by the degree of basicity of the lone pair of the donating atoms, the number of linkages between the substrate and the surface and, further, the hydrogen bonding between the acidic hydrogen and lattice oxygen atom. The computed vibrational density of states for these adsorbed organic pollutants is in reasonably good agreement with available experimental data and previous theoretical results.
Packing Effect on the Transfer Integrals and Mobility in α,α′-bis(dithieno[3,2-b:2′,3′-d]thiophene) (BDT) and its Heteroatom-Substituted Analogues
Authors: Irfan Ahmad , Al-Sehemi Abdullah G. , Muhammad Shabbir , Zhang Jingping
Published: November 2011

Theoretically calculated mobility has revealed that BDT is a hole transfer material, which is in good agreement with experimental investigations. The BDT, NHBDT, and OBDT are predicted to be hole transfer materials in the C2/c space group. Comparatively, hole mobility of BHBDT is 7 times while electron mobility is 20 times higher than the BDT. The packing effect for BDT and designed crystals was investigated by various space groups. Generally, mobility increases in BDT and its analogues by changing the packing from space group C2/c to space groups P1 or . In the designed ambipolar material, BHBDT hole mobility has been predicted 0.774 and 3.460 cm2 Vs–1 in space groups P1 and , which is 10 times and 48 times higher than BDT (0.075 and 0.072 cm2 Vs–1 in space groups P1 and ), respectively. Moreover, the BDT behaves as an electron transfer material by changing the packing from the C2/c space group to P1 and .
Reaching those with the greatest need: how Australian primary health care service managers, practitioners and funders understand and respond to health inequity
Authors: Freeman Toby , Baum Fran , Lawless Angela , Jolley Gwyn , Labonte Ronald , Bentley Michael , Boffa John
Published: November 2011

Equity of access to services and in health outcomes are key goals of primary health care. This study considers understandings of equity and perceptions of current performance in relation to equity among primary health care service staff, health service executives and funders. Semi-structured interviews were conducted with managers, practitioners and administration staff at five primary health care services in Adelaide and one in Alice Springs, as well as with South Australian funders and regional health service executives (n = 68). Services were responding to health inequity by taking actions to improve equitable access to their service, facilitating equitable access to health care more generally, and advocating and taking action on the social determinants of health inequities. As well as availability, affordability and acceptability, our analysis indicated a fourth dimension of equity of access we named ‘engagement’. Our respondents were less able to point to examples of advocacy or action on the social determinants of health inequities than they were to examples of actions to improve equity of access. These findings indicate current strengths and also scope to encourage a broader and more comprehensive role for primary health care in addressing health inequities.
An equity - effectiveness framework linking health programs and healthy life expectancy
Authors: Banham David , Lynch John , Karnon Jon
Published: November 2011

South Australia’s Strategic Plan includes a target to improve the population’s healthy life expectancy. A common question among health policy and service planners is: ‘How do health programs and services in the community relate to healthy life expectancy?’ In response, this paper outlines an effectiveness and equity framework (EEF) for evaluating health interventions in applied settings. Using the example of coronary heart disease (CHD) management in general practice in South Australia, the EEF: (1) applies an internally consistent approach to accounting for population healthy life expectancy at state and smaller geographic levels; (2) estimates average population health gains from health programs, and gains across different socioeconomic subgroups within the community; (3) conducts economic evaluation by equating health gains against health system costs in population subgroups; (4) summarises relevant information about candidate intervention programs within a multi-criteria performance matrix for presentation to decision makers; (5) reassesses outcomes (and processes) following the implementation of a program and iteratively adds to the relevant knowledge and evidence base. The EEF offers a practical approach to selecting and evaluating intervention programs. The challenge is to develop system culture and data capture methods clearly focussed on linking health system activities to population health outcomes.
General practitioners' patterns of treatment of febrile travellers in north Queensland: an exploratory study
Authors: Engström Kajsa L. , Mills Jane , McBride William J. H. , Johansson Caroline M.
Published: November 2011

In north Queensland, recurring epidemics of dengue fever are a public health concern. Each epidemic is initiated by an index case: an infected person arriving from an endemic country or region with dengue activity who then transmits the disease to local mosquitoes. A timely diagnosis of dengue in an index case and notification to public health services is essential to prevent epidemics. This qualitative study explores north Queensland general practitioners’ experiences and patterns of treatment of febrile travellers. Individual, semi-structured interviews with 50 general practitioners working in north Queensland were conducted. Analysis of the data resulted in four themes for discussion: characteristics of febrile travellers presenting to local general practitioners, the cost of pathology tests as a barrier to diagnosis, appropriate pathology testing, and notifying tropical public health services. Recommendations from this study point to a need for ongoing education and training for general practitioners in best practice with regards pathology testing for suspected dengue fever cases. As well, there is a need to provide clearer guidelines to general practitioners on when to notify tropical public health services of suspicious diagnoses of dengue.
GP and community nurse co-location in a disadvantaged community
Authors: Rose Vanessa K. , Harris Elizabeth , Comino Elizabeth , Anderson Teresa , Harris Mark F.
Published: November 2011

People living in socioeconomically disadvantaged communities have a high burden of disease but often receive ‘inverse care’. We explored a model of general practitioner and community nurse co-location in a disadvantaged community in south-west Sydney, Australia. Co-location resulted in increased referrals from doctors to the community nurse, including an increase in referrals related to psychosocial issues. This small study suggests integrated primary health care might have an impact on specialised state-based psychosocial health services.
Runoff losses from irrigated dairy pastures treated with phosphorus fertilisers of differing solubility in south-eastern Australia
Authors: Weatherley A. J. , Quin B. F. , Dassanayake K. B. , Rowarth J. S.
Published: November 2011

In response to increasing concern about environmental quality, water authorities in many countries are imposing legislation limiting phosphorus (P) concentrations in water, which is having an impact on farming practice. This experiment investigated the agronomic effects and runoff losses associated with different forms of P fertiliser applied to an irrigated dairy pasture (soils were Vertic Calcic Red Chromosols; average Olsen P, 50 mg P/kg) in north-central Victoria, Australia. Single superphosphate (SSP), a sulfurised diammonium phosphate, or partially acidulated phosphate rock was surface-applied at 50 kg P/ha in March 2005 to a border-check, flood-irrigated dairy pasture (ryegrass–white clover) ten days before a scheduled irrigation. Dissolved reactive P (DRP) and total P (TP) were measured in runoff from whole bays on one replicate and from microplots on all three replicates for a period of 9 weeks. In all runoff events and all treatments, concentrations of DRP and TP in runoff greatly exceeded water quality guidelines for acceptable limits (0.045 mg P/L). The SSP resulted in significantly higher concentrations of P in runoff than the less water-soluble fertilisers. Even after the fifth irrigation, runoff from all fertilisers still exceeded the control. These results suggest that: (i) P fertilisers should not be applied in high-risk situations as insurance against yield loss; (ii) the current recommendation of withholding irrigation for 3 days after fertiliser application is insufficient to prevent potentially significant losses occurring; and (iii) runoff losses were dependent on the type of fertiliser applied, with a smaller proportion of P applied as sulfurised DAP lost in runoff.
Eucalypt plantation effects on organic carbon and aggregation of three different-textured soils in Brazil
Authors: Zinn Yuri L. , Lal Rattan , Resck Dimas V. S.
Published: November 2011

Short-cycle (~7 years) tropical eucalypt plantations can sequester much carbon (C) in biomass, but their impact on soil organic C (SOC) varies considerably according to soil properties. Three Oxisols (sandy, loamy, and clayey) under 14-year-old eucalypt (Eucalytus camaldulensis Dehnh.) coppice stands and native cerrado vegetation were sampled to a depth of 1 m, in order to assess whether soil texture controls SOC response to afforestation in central Brazil. Both SOC concentration and stocks were proportional to contents of clay+silt to 1 m depth, with no effect of eucalypt plantation. However, there was a 40% decrease in water-stable aggregates of 2–8 mm size in all soils under eucalypt stands in the 0–0.05 m depth, which probably helped to release occluded particulate organic matter (POM) into free POM. In the 0–0.05 m depth, SOC partition throughout particle-size fractions (sand, silt, and clay) was unaltered in the loamy and clayey Oxisols, whereas in the sandy Oxisol, clay-bound SOC strongly decreased simultaneously with a strong increase in free POM. As free POM is often more susceptible to decay than clay-bound SOC, this change suggests a higher susceptibility to SOC change in sandy soils. Soil respiration in the 0–0.05 m depth was more strongly correlated with the mean weight diameter and clay+silt contents than with SOC and nitrogen concentrations, with no effect of eucalypt plantation. In conclusion, soil texture affects total SOC retention and soil respiration, with little or no effect of eucalypt plantation. However, decreased aggregation and lower POM occlusion occurred in all soils planted with eucalyptus, suggesting that SOC levels in eucalypt plantations can be better conserved with less intensive soil preparation practices, especially in coarse-textured soils.
Organ aging and susceptibility to cancer may be related to the geometry of the stem cell niche
Authors: Blagoev Krastan B.
Published: November 2011

Telomere loss at each cell replication limits the proliferative capacity of normal cells, including adult stem cells. Entering replicative senescence protects dividing cells from neoplastic transformation, but also contributes to aging of the tissue. Recent experiments have shown that intestinal mouse stem cells divide symmetrically, at random make decisions to remain stem cells or to differentiate, and gradually lose telomeric DNA. A cell’s decision whether to differentiate or to remain a stem cell depends on the local cellular and chemical environment and thus tissue architecture is expected to play role in cell proliferation dynamics. To take into account the structure of the stem cell niche in determining its proliferative potential and susceptibility to cancer, a theoretical model is introduced and the niche proliferative potential is quantified for different architectures. The niche proliferative potential is quantitatively related to the proliferative potential of the individual stem cells for different structural classes of the stem cell niche. Stem cells at the periphery of a niche are under pressure to divide and to differentiate, as well as to maintain the stem cell niche boundary, and thus the geometry of the stem cell niche is expected to play a role in determining the stem cell division sequence and differentiation. Smaller surface-to-volume ratio is associated with higher susceptibility to cancer, higher tissue renewal capacity, and decreased aging rate. Several testable experimental predictions are discussed, as well the presence of stochastic effects.
Friction mechanism of individual multilayered nanoparticles
Authors: Tevet Ofer , Von-Huth Palle , Popovitz-Biro Ronit , Rosentsveig Rita , Wagner H. Daniel , Tenne Reshef
Published: November 2011

Inorganic nanoparticles of layered [two-dimensional (2D)] compounds with hollow polyhedral structure, known as fullerene-like nanoparticles (IF), were found to have excellent lubricating properties. This behavior can be explained by superposition of three main mechanisms: rolling, sliding, and exfoliation-material transfer (third body). In order to elucidate the tribological mechanism of individual nanoparticles in different regimes, in situ axial nanocompression and shearing forces were applied to individual nanoparticles using a high resolution scanning electron microscope. Gold nanoparticles deposited onto the IF nanoparticles surface served as markers, delineating the motion of individual IF nanoparticle. It can be concluded from these experiments that rolling is an important lubrication mechanism for IF-WS
2
in the relatively low range of normal stress (0.96±0.38 GPa). Sliding is shown to be relevant under slightly higher normal stress, where the spacing between the two mating surfaces does not permit free rolling of the nanoparticles. Exfoliation of the IF nanoparticles becomes the dominant mechanism at the high end of normal stress; above 1.2 GPa and (slow) shear; i.e., boundary lubrication conditions. It is argued that the
modus operandi
of the nanoparticles depends on their degree of crystallinity (defects); sizes; shape, and their mechanical characteristics. This study suggests that the rolling mechanism, which leads to low friction and wear, could be attained by improving the sphericity of the IF nanoparticle, the dispersion (deagglomeration) of the nanoparticles, and the smoothness of the mating surfaces.
An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondria
Authors: Means Christopher K. , Lygren Birgitte , Langeberg Lorene K. , Jain Ankur , Dixon Rose E. , Vega Amanda L. , Gold Matthew G. , Petrosyan Susanna , Taylor Susan S. , Murphy Anne N. , Ha Taekjip , Santana Luis F. , Tasken Kjetil , Scott John D.
Published: November 2011

A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) to intracellular sites where they preferentially phosphorylate target substrates. Most AKAPs exhibit nanomolar affinity for the regulatory (RII) subunit of the type II PKA holoenzyme, whereas dual-specificity anchoring proteins also bind the type I (RI) regulatory subunit of PKA with 10–100-fold lower affinity. A range of cellular, biochemical, biophysical, and genetic approaches comprehensively establish that sphingosine kinase interacting protein (SKIP) is a truly type I-specific AKAP. Mapping studies located anchoring sites between residues 925–949 and 1,140–1,175 of SKIP that bind RI with dissociation constants of 73 and 774 nM, respectively. Molecular modeling and site-directed mutagenesis approaches identify Phe 929 and Tyr 1,151 as RI-selective binding determinants in each anchoring site. SKIP complexes exist in different states of RI-occupancy as single-molecule pull-down photobleaching experiments show that 41 ± 10% of SKIP sequesters two YFP-RI dimers, whereas 59 ± 10% of the anchoring protein binds a single YFP-RI dimer. Imaging, proteomic analysis, and subcellular fractionation experiments reveal that SKIP is enriched at the inner mitochondrial membrane where it associates with a prominent PKA substrate, the coiled-coil helix protein ChChd3.
Social network models predict movement and connectivity in ecological landscapes
Authors: Fletcher Robert J. , Acevedo Miguel A. , Reichert Brian E. , Pias Kyle E. , Kitchens Wiley M.
Published: November 2011

Network analysis is on the rise across scientific disciplines because of its ability to reveal complex, and often emergent, patterns and dynamics. Nonetheless, a growing concern in network analysis is the use of limited data for constructing networks. This concern is strikingly relevant to ecology and conservation biology, where network analysis is used to infer connectivity across landscapes. In this context, movement among patches is the crucial parameter for interpreting connectivity but because of the difficulty of collecting reliable movement data, most network analysis proceeds with only indirect information on movement across landscapes rather than using observed movement to construct networks. Statistical models developed for social networks provide promising alternatives for landscape network construction because they can leverage limited movement information to predict linkages. Using two mark-recapture datasets on individual movement and connectivity across landscapes, we test whether commonly used network constructions for interpreting connectivity can predict actual linkages and network structure, and we contrast these approaches to social network models. We find that currently applied network constructions for assessing connectivity consistently, and substantially, overpredict actual connectivity, resulting in considerable overestimation of metapopulation lifetime. Furthermore, social network models provide accurate predictions of network structure, and can do so with remarkably limited data on movement. Social network models offer a flexible and powerful way for not only understanding the factors influencing connectivity but also for providing more reliable estimates of connectivity and metapopulation persistence in the face of limited data.
Evolutionary dynamics of feedback escape and the development of stem-cell–driven cancers
Authors: Rodriguez-Brenes Ignacio A. , Komarova Natalia L. , Wodarz Dominik
Published: November 2011

Cancers are thought to arise in tissue stem cells, and similar to healthy tissue, are thought to be maintained by a small population of tumor stem or initiating cells, whereas the majority of tumor cells are more differentiated with limited replicative potential. Healthy tissue homeostasis is achieved by feedback loops, and particular importance has been attached to signals secreted from differentiated cells that inhibit stem-cell division and stem-cell self-renewal, as documented in the olfactory epithelium and other tissues. Therefore, a key event in carcinogenesis must be escape from these feedback loops, which is studied here using evolutionary computational models. We find that out of all potential evolutionary pathways, only one unique sequence of phenotypic transitions can lead to complete escape in stem-cell–driven tumors, even though the required mutations for these transitions are certainly tissue specific. This insight, supported by data, facilitates the search for driver mutations and for therapeutic targets. Different growth patterns can result from feedback escape, which we call “inhibited,” “uninhibited,” and “sigmoidal,” and which are found in published data. The finding of inhibited growth patterns in data indicates that besides architecture, the regulatory mechanisms of healthy tissue continue to operate to a degree in tumors.
Crystal structure of the Lassa virus nucleoprotein–RNA complex reveals a gating mechanism for RNA binding
Authors: Hastie Kathryn M. , Liu Tong , Li Sheng , King Liam B. , Ngo Nhi , Zandonatti Michelle A. , Woods Virgil L. , de la Torre Juan Carlos , Saphire Erica Ollmann
Published: November 2011

Arenaviruses cause disease in industrialized and developing nations alike. Among them, the hemorrhagic fever virus Lassa is responsible for ∼300,000–500,000 infections/y in Western Africa. The arenavirus nucleoprotein (NP) forms the protein scaffold of the genomic ribonucleoprotein complexes and is critical for transcription and replication of the viral genome. Here, we present crystal structures of the RNA-binding domain of Lassa virus NP in complex with ssRNA. This structure shows, in contrast to the predicted model, that RNA binds in a deep, basic crevice located entirely within the N-terminal domain. Furthermore, the NP-ssRNA structures presented here, combined with hydrogen-deuterium exchange/MS and functional studies, suggest a gating mechanism by which NP opens to accept RNA. Directed mutagenesis and functional studies provide a unique look into how the arenavirus NPs bind to and protect the viral genome and also suggest the likely assembly by which viral ribonucleoprotein complexes are organized.
Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis
Authors: Nagai Hirotaka , Okazaki Yasumasa , Chew Shan Hwu , Misawa Nobuaki , Yamashita Yoriko , Akatsuka Shinya , Ishihara Toshikazu , Yamashita Kyoko , Yoshikawa Yutaka , Yasui Hiroyuki , Jiang Li , Ohara Hiroki , Takahashi Takashi , Ichihara Gaku , Kostarelos Kostas , Miyata Yasumitsu , Shinohara Hisanori , Toyokuni Shinya
Published: November 2011

Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2–20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of
Cdkn2a/2b
tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health.
Parasitoid-specific induction of plant responses to parasitized herbivores affects colonization by subsequent herbivores
Authors: Poelman Erik H. , Zheng Si-Jun , Zhang Zhao , Heemskerk Nanda M. , Cortesero Anne-Marie , Dicke Marcel
Published: November 2011

Plants are exposed to a suite of herbivorous attackers that often arrive sequentially. Herbivory affects interactions between the host plants and subsequently attacking herbivores. Moreover, plants may respond to herbivory by emitting volatile organic compounds (VOCs) that attract carnivorous natural enemies of the herbivores. However, information borne by VOCs is ubiquitous and may attract carnivores, such as parasitoids, that differ in their effectiveness at releasing the plant from its herbivorous attackers. Furthermore, the development of parasitoids within their herbivorous hosts, attacking a given host plant, may influence the elicitation of defensive reactions in the host plant. This may, in turn, affect the behavior of subsequent herbivores attacking the host plant. Here, we show that the species identity of a parasitoid had a more significant effect on defense responses ofBrassica oleraceaplants than the species identity of the herbivorous hosts of the parasitoids. Consequently,B. oleraceaplants that were damaged by caterpillars (Pierisspp.) parasitized by different parasitoid species varied in the degree to which diamondback moths (Plutella xylostella) selected the plants for oviposition. Attracting parasitoids in general benefitted the plants by reducing diamondback moth colonization. However, the species of parasitoid that parasitized the herbivore significantly affected the magnitude of this benefit by its species-specific effect on herbivore–plant interactions mediated by caterpillar regurgitant. Our findings show that information-mediated indirect defense may lead to unpredictable consequences for plants when considering trait-mediated effects of parasitized caterpillars on the host plant and their consequences because of community-wide responses to induced plants.
LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel
Authors: Yang Chengtao , Zeng Xu-Hui , Zhou Yu , Xia Xiao-Ming , Lingle Christopher J.
Published: November 2011

KSper, a pH-dependent K
+
current in mouse spermatozoa that is critical for fertility, is activated by alkalization in the range of pH 6.4–7.2 at membrane potentials between −50 and 0 mV. Although the KSper pore-forming subunit is encoded by the
Slo3
gene, heterologously expressed Slo3 channels are largely closed at potentials negative to 0 mV at physiological pH. Here we identify a Slo3-associating protein, LRRC52 (leucine-rich repeat-containing 52), that shifts Slo3 gating into a range of voltages and pH values similar to that producing KSper current activation. Message for LRRC52, a homolog of the Slo1-modifying LRRC26 protein, is enriched in testis relative to other homologous LRRC subunits and is developmentally regulated in concert with that for Slo3. LRRC52 protein is detected only in testis. It is markedly diminished from

Slo3
−/−

testis and completely absent from

Slo3
−/−

sperm, indicating that LRRC52 expression is critically dependent on the presence of Slo3. We also examined the ability of other LRRC subunits homologous to LRRC26 and LRRC52 to modify Slo3 currents. Although both LRRC26 and LRRC52 are able to modify Slo3 function, LRRC52 is the stronger modifier of Slo3 function. Effects of other related subunits were weaker or absent. We propose that LRRC52 is a testis-enriched Slo3 auxiliary subunit that helps define the specific alkalization dependence of KSper activation. Together, LRRC52 and LRRC26 define a new family of auxiliary subunits capable of critically modifying the gating behavior of Slo family channels.
Construction of regulatory networks using expression time-series data of a genotyped population
Authors: Yeung Ka Yee , Dombek Kenneth M. , Lo Kenneth , Mittler John E. , Zhu Jun , Schadt Eric E. , Bumgarner Roger E. , Raftery Adrian E.
Published: November 2011

The inference of regulatory and biochemical networks from large-scale genomics data is a basic problem in molecular biology. The goal is to generate testable hypotheses of gene-to-gene influences and subsequently to design bench experiments to confirm these network predictions. Coexpression of genes in large-scale gene-expression data implies coregulation and potential gene–gene interactions, but provide little information about the direction of influences. Here, we use both time-series data and genetics data to infer directionality of edges in regulatory networks: time-series data contain information about the chronological order of regulatory events and genetics data allow us to map DNA variations to variations at the RNA level. We generate microarray data measuring time-dependent gene-expression levels in 95 genotyped yeast segregants subjected to a drug perturbation. We develop a Bayesian model averaging regression algorithm that incorporates external information from diverse data types to infer regulatory networks from the time-series and genetics data. Our algorithm is capable of generating feedback loops. We show that our inferred network recovers existing and novel regulatory relationships. Following network construction, we generate independent microarray data on selected deletion mutants to prospectively test network predictions. We demonstrate the potential of our network to discover de novo transcription-factor binding sites. Applying our construction method to previously published data demonstrates that our method is competitive with leading network construction algorithms in the literature.
Prophylactic effect of hot pack on symptoms of eccentric exercise‐induced muscle damage of the wrist extensors
Authors: Khamwong Peanchai , Nosaka Kazunori , Pirunsan Ubon , Paungmali Aatit
Published: November 2011

This study investigated whether hot pack treatment could provide prophylactic effects on muscle damage induced by eccentric exercise of the wrist extensors. Twenty‐eight healthy men (age 21±1 years, weight 65±16 kg, height 171±6 cm) were randomly placed into hot pack (n = 14) and control (n = 14) groups. All participants performed an exercise consisting of 300 maximal eccentric contractions of the wrist extensors of the non‐dominant arm using an isokinetic dynamometer. A hot pack was applied for 20 min to the wrist extensors of the exercised arm before the exercise for the hot pack group. The control group received no treatment before the exercise. Measured variables included pain intensity assessed by a visual analogue scale and a modified Likert's scale, cold thermal pain threshold, pressure pain threshold (PPT), range of motion in active wrist flexion (ROM‐AF) and extension (ROM‐AE), range of motion in passive wrist flexion (ROM‐PF) and extension (ROM‐PE), grip strength, and wrist extension strength. Changes in these variables before, immediately after, and 1 to 8 days following the exercise were compared between groups by a two‐way repeated measures ANOVA. All outcome measures from both groups (except for the cold thermal pain threshold of the hot pack group) demonstrated a significant change within the first 2–3 days following exercise. Significant differences between groups were only found at a single point in time for PPT, ROM‐PF, ROM‐PE and ROM‐AE, and the changes were smaller for the hot pack group in comparison to the control group. These results suggest that the prophylactic effects of hot pack treatment on eccentric exercise‐induced muscle damage of the wrist extensors are limited.
Feature-based classifiers for somatic mutation detection in tumour–normal paired sequencing data
Authors: Ding Jiarui , Bashashati Ali , Roth Andrew , Oloumi Arusha , Tse Kane , Zeng Thomas , Haffari Gholamreza , Hirst Martin , Marra Marco A. , Condon Anne , Aparicio Samuel , Shah Sohrab P.
Published: November 2011

Motivation: The study of cancer genomes now routinely involves using next-generation sequencing technology (NGS) to profile tumours for single nucleotide variant (SNV) somatic mutations. However, surprisingly few published bioinformatics methods exist for the specific purpose of identifying somatic mutations from NGS data and existing tools are often inaccurate, yielding intolerably high false prediction rates. As such, the computational problem of accurately inferring somatic mutations from paired tumour/normal NGS data remains an unsolved challenge.

Results: We present the comparison of four standard supervised machine learning algorithms for the purpose of somatic SNV prediction in tumour/normal NGS experiments. To evaluate these approaches (random forest, Bayesian additive regression tree, support vector machine and logistic regression), we constructed 106 features representing 3369 candidate somatic SNVs from 48 breast cancer genomes, originally predicted with naive methods and subsequently revalidated to establish ground truth labels. We trained the classifiers on this data (consisting of 1015 true somatic mutations and 2354 non-somatic mutation positions) and conducted a rigorous evaluation of these methods using a cross-validation framework and hold-out test NGS data from both exome capture and whole genome shotgun platforms. All learning algorithms employing predictive discriminative approaches with feature selection improved the predictive accuracy over standard approaches by statistically significant margins. In addition, using unsupervised clustering of the ground truth ‘false positive’ predictions, we noted several distinct classes and present evidence suggesting non-overlapping sources of technical artefacts illuminating important directions for future study.

Availability: Software called MutationSeq and datasets are available from http://compbio.bccrc.ca.

Contact:  saparicio@bccrc.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Gene set analysis in the cloud
Authors: Zhang Lu , Gu Shengchang , Liu Yuan , Wang Bingqiang , Azuaje Francisco
Published: November 2011

Summary: Cloud computing offers low cost and highly flexible opportunities in bioinformatics. Its potential has already been demonstrated in high-throughput sequence data analysis. Pathway-based or gene set analysis of expression data has received relatively less attention. We developed a gene set analysis algorithm for biomarker identification in the cloud. The resulting tool, YunBe, is ready to use on Amazon Web Services. Moreover, here we compare its performance to those obtained with desktop and computing cluster solutions.

Availability and implementation:  YunBe is open-source and freely accessible within the Amazon Elastic MapReduce service at s3n://lrcv-crp-sante/app/yunbe.jar. Source code and user's guidelines can be downloaded from http://tinyurl.com/yunbedownload.

Contact:  francisco.azuaje@crp-sante.lu