Differential (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models.

The ability of PET to image functional changes in tumors is increasingly being used to evaluate response and predict clinical benefit to conventional and novel cancer therapies. Although the use of (18)F-FDG PET is well established, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET has potential advantages as a more specific marker of cellular proliferation. c-MET signaling is frequently dysregulated in cancer and is therefore an attractive therapeutic target. Crizotinib (PF-2341066) is a novel adenosine triphosphate-competitive c-MET kinase inhibitor with antitumor activity in a range of tumor models. The aim of this study was to investigate the utility of PET of glucose metabolism and cell proliferation to monitor tumor response to crizotinib in 2 cell lines with aberrant c-MET signaling.

Certificateless ignatures: New schemes and security models

We present a study of security in certificateless signatures. We divide potential adversaries according to their attack power, and for the first time, three new kinds of adversaries are introduced into certificateless signatures. They are Normal Adversary, Strong Adversary and Super Adversary (ordered by their attack power). Combined with the known Type I Adversary and Type II Adversary in certificateless cryptography, we then define the security of certificateless signatures in different attack scenarios. Our new security models, together with others in the literature, provide a clear definition of the security in certificateless signatures. Two concrete schemes with different security levels are also proposed in this paper. The first scheme, which is proven secure (in the random oracle model) against Normal Type I and Super Type II adversaries, has the shortest signature length among all known certificateless signature schemes. The second scheme is secure (in the random oracle model) against Super Type I and Type II adversaries. Compared with another scheme that has a similar security level, our second scheme requires less operational cost but a little longer signature length. Two server-aided verification protocols are also proposed to reduce the verification cost on the verifier.

Does urbanization have the potential to create an ecological trap for powerful owls (Ninox strenua)?

Landscape transformation associated with urbanization is one of the most damaging and pervasive impacts humans have on natural ecosystems. The response of species to increasing urbanization has become a major focus of research globally. Powerful owls ( Ninox strenua) are a top-order predator the have been shown to reside in urban environments, but increasing urbanization has also been demonstrated to significantly reduce available habitat. In this paper we use species distribution models established for key food and nesting resources of powerful owls across an urban-forest gradient to constrain habitat predictions from a previously developed powerful owl species distribution model. This multi-criteria decision analysis (MCDA) approach allowed us to investigate the impacts of urbanization on potential powerful owl habitat when challenged with food and nesting requirements. As powerful owls only use tree cavities for nesting we propose that the cue for settlement in an area is associated with the presence of habitat and food and as such breeding requirements may be disconnected from settlement requirements.Our results demonstrate that incorporation of a general prey resource (at least one group of arboreal marsupials) as a cue for settlement does not reduce the amount of available habitat for powerful owls substantially. Further constraining the model with a tree cavity resource, however, leads to a substantial reduction in powerful owl habitat in the urban and urban fringe environments. If a diverse prey resource (two or more groups of arboreal marsupials) is used as the cue for settlement, this sees a substantial reduction in available habitat in urban environments. Incorporation of tree cavities into this model does not reduce the available habitat for powerful owls substantially.We propose that powerful owls do not need a diverse prey base for survival, and that breeding resources are unlikely to be a cue for settlement. As such, we argue in this paper that increasing urbanization has the potential to create an ecological trap for powerful owls as there is a significant difference between habitat capable of supporting powerful owls, and habitat in which owls can breed.Management of powerful owls in urban environments will be difficult, but this research highlights the potential for the use of nest boxes to enhance the breeding activities in increasingly urbanized environments. Replacement of this critical resource may be able to reverse any potential ecological trap that is occurring. © 2014 Elsevier Ltd.

Estimating cumulative exposure of wildlife to non-lethal disturbance using spatially explicit capture-recapture models

Impact assessments often focus on short-term behavioral responses of animals to human disturbance. However, the cumulative effects caused by repeated behavioral disruptions are of management concern because these effects have the potential to influence individuals' survival and reproduction. We need to estimate individual exposure rates to disturbance to determine cumulative effects. We present a new approach to estimate the spatial exposure of minke whales to whalewatching boats in Faxaflõi Bay, Iceland. We used recent advances in spatially explicit capture-recapture modeling to estimate the probability that whales would encounter a disturbance (i.e., whalewatching boat). We obtained spatially explicit individual encounter histories of individually identifiable animals using photo-identification. We divided the study area into 1-km2 grid cells and considered each cell a spatially distinct sampling unit. We used capture history of individuals to model and estimate spatial encounter probabilities of individual minke whales across the study area, accounting for heterogeneity in sampling effort. We inferred the exposure of individual minke whales to whalewatching vessels throughout the feeding season by estimating individual whale encounters with vessels using the whale encounter probabilities and spatially explicit whalewatching intensity in the same area, obtained from recorded whalewatching vessel tracks. We then estimated the cumulative time whales spent with whalewatching boats to assess the biological significance of whalewatching disturbances. The estimated exposure levels to boats varied considerably between individuals because of both temporal and spatial variations in the activity centers of whales and the whalewatching intensity in the area. However, although some whales were repeatedly exposed to whalewatching boats throughout the feeding season, the estimated cumulative time they spent with boats was very low. Although whalewatching boat interactions caused feeding disruptions for the whales, the estimated low cumulative exposure indicated that the whalewatching industry in its current state likely is not having any long-term negative effects on vital rates.

The potential utility of a staging model as a course specifier: a bipolar disorder perspective.

Staging models are widely used in clinical medicine, and offer an insight into the progressive nature of many disorders. In general, the earlier stages of illness may be associated with a better prognosis and a higher treatment response. Once chronicity is reached, more complex and invasive treatments may be required, and the utility of treatments may decline. There is evidence that treatment response is greatest in the early phases of the disorder. There is also a progressive social and psychological burden of ongoing illness. This is paralleled by the twin notions of neuroprotection, which is supported by increasing evidence that structural changes in the disorder may be progressive and reversible with algorithm appropriate treatment, and that of early intervention, which posits that the optimal window for intervention is early in the illness course. A staging model compliments existing and proposed classifications of bipolar disorder, adding a temporal dimension to a cross sectional view. It may inform treatment choice and prognosis, and could have utility as a course specifier.

Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG/2GSH and the availability of Cu(I)

Glutaredoxins have been characterised as enzymes regulating the redox status of protein thiols via cofactors GSSG/GSH. However, such a function has not been demonstrated with physiologically relevant protein substrates in in vitro experiments. Their active sites frequently feature a Cys-xx-Cys motif that is predicted not to bind metal ions. Such motifs are also present in copper-transporting proteins such as Atox1, a human cytosolic copper metallo-chaperone. In this work, we present the first demonstration that: (i) human glutaredoxin 1 (hGrx1) efficiently catalyses interchange of the dithiol and disulfide forms of the Cys(12)-xx-Cys(15) fragment in Atox1 but does not act upon the isolated single residue Cys(41); (ii) the direction of catalysis is regulated by the GSSG/2GSH ratio and the availability of Cu(I); (iii) the active site Cys(23)-xx-Cys(26) in hGrx1 can bind Cu(I) tightly with femtomolar affinity (K(D) = 10(-15.5) M) and possesses a reduction potential of E(o)' = -118 mV at pH 7.0. In contrast, the Cys(12)-xx-Cys(15) motif in Atox1 has a higher affinity for Cu(I) (K(D) = 10(-17.4) M) and a more negative potential (E(o)' = -188 mV). These differences may be attributed primarily to the very low pKa of Cys23 in hGrx1 and allow rationalisation of conclusion (ii) above: hGrx1 may catalyse the oxidation of Atox1(dithiol) by GSSG, but not the complementary reduction of the oxidised Atox1(disulfide) by GSH unless Cu(aq)(+) is present at a concentration that allows binding of Cu(I) to reduced Atox1 but not to hGrx1. In fact, in the latter case, the catalytic preferences are reversed. Both Cys residues in the active site of hGrx1 are essential for the high affinity Cu(I) binding but the single Cys(23) residue only is required for the redox catalytic function. The molecular properties of both Atox1 and hGrx1 are consistent with a correlation between copper homeostasis and redox sulfur chemistry, as suggested by recent cell experiments. These proteins appear to have evolved the features necessary to fill multiple roles in redox regulation, Cu(I) buffering and Cu(I) transport.

Flight altitude of trans-Sahara migrants in autumn: a comparison of radar observations with predictions from meteorological conditions and water and energy balance models

Radar observations on the altitude of bird migration and altitudinal profiles of meteorological conditions over the Sahara desert are presented for the autumn migratory period. Migratory birds fly at an average altitude of 1016 m (a.s.l.) during the day and 571 m during the night. Weather data served to calculate flight range using two models: an energy model (EM) and an energy-and-water model (EWM). The EM assumes that fuel supply limits flight range whereas the EWM assumes that both fuel and water may limit flight range. Flight ranges estimated with the EM were generally longer than those with the EWM. This indicates that trans-Sahara migrants might have more problems balancing their water than their energy budget. However, if we assume fuel stores to consist of 70% instead of 100% fat (the remainder consisting of 9% protein and 21% water), predicted flight ranges of the EM and EWM largely overlap. Increased oxygen extraction, reduced flight costs, reduced exhaled air temperature, reduced cutaneous water loss and increased tolerance to water loss are potential physiological adaptations that would improve the water budget in migrants. Both the EM and EWM predict optimal flight altitudes in agreement with radar observations in autumn. Optimal flight altitudes are differently predicted by the EM and EWM for nocturnal spring migration. During spring, the EWM predicts moderately higher and the EM substantially higher flight altitudes than during autumn. EWM predictions are therefore in better agreement with radar observations on flight altitude of migrants over the Negev desert in spring than EM predictions.

On the potential for psychological researchers and psychologists to promote the social inclusion of people with disability: A review

© 2015 Australian Psychological Society. Objective: This paper outlines different approaches to understanding disability and describes ways in which psychological researchers and psychologists can promote the social inclusion of people with disability. Method: Narrative review drawing on writings and research from psychology and disability studies. Results: Five prominent models of disability appear in the literature (moral, medical, social, biopsychosocial, and post-modern), all of which have relevance to the lives of people with disability. Conceptualisations commonly used to understand the experience of disability from a psychological perspective include stigma and psycho-emotional disablism. There is evidence that people with disability wish to have greater involvement in research (e.g., as consultants and partners in research about them, and as participants in mainstream research) and to see research findings translated into practice. Evidence is emerging that can be used to underpin psychologists work with (a) communities (to foster social change and social justice, and to reduce stigma); (b) organisations, such as schools, workplaces, and disability service providers (to help develop inclusive and supportive environments); (c) families (to promote optimism, alternative understandings of disability, and a sense of control, as well as developing behaviour support plans and providing referrals to other sources of practical support); and (d) people with disability (to assist them with the issues they bring to therapy while being mindful of the potential for psycho-emotional disablism to colour the material presented). Conclusion: Psychological researchers and psychologists have significant potential to contribute to the social inclusion of people with disability.

Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy

Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting.

Stabilizing l1-norm prediction models by supervised feature grouping

Emerging Electronic Medical Records (EMRs) have reformed the modern healthcare. These records have great potential to be used for building clinical prediction models. However, a problem in using them is their high dimensionality. Since a lot of information may not be relevant for prediction, the underlying complexity of the prediction models may not be high. A popular way to deal with this problem is to employ feature selection. Lasso and l1-norm based feature selection methods have shown promising results. But, in presence of correlated features, these methods select features that change considerably with small changes in data. This prevents clinicians to obtain a stable feature set, which is crucial for clinical decision making. Grouping correlated variables together can improve the stability of feature selection, however, such grouping is usually not known and needs to be estimated for optimal performance. Addressing this problem, we propose a new model that can simultaneously learn the grouping of correlated features and perform stable feature selection. We formulate the model as a constrained optimization problem and provide an efficient solution with guaranteed convergence. Our experiments with both synthetic and real-world datasets show that the proposed model is significantly more stable than Lasso and many existing state-of-the-art shrinkage and classification methods. We further show that in terms of prediction performance, the proposed method consistently outperforms Lasso and other baselines. Our model can be used for selecting stable risk factors for a variety of healthcare problems, so it can assist clinicians toward accurate decision making.

Managing undesirable outputs in the Australian construction industry using Data Envelopment Analysis models

Carbon reduction has become one of the most significant challenges for economic growth. This paper presents the preliminary analysis of undesirable output reduction targets and emission schedules in temporal-spatial comparisons based on Data Envelopment Analysis. The reduction targets of undesirable outputs are investigated, including the maximum, input, technical and ideal reduction targets. Four Data Envelopment Analysis models that are based on a sequential benchmark technology and variable returns to scale are introduced to measure these reduction percentages. In order to formulate the optimal emission schedule of undesirable outputs, an optimal model is provided without inflation. Data from the Australian construction industry from 2000 to 2010 are employed to develop the models. The results of the analysis indicate that the Australian Government could achieve its promised carbon reduction targets in the construction industry. Most Australian regions' construction industries possess carbon mitigation potential and some of them could increase their desirable outputs if carbon were decreased. This paper suggests that policymakers can benefit from formulating various suitable undesirable output reduction objectives and schedules through the models developed. The research method can be replicated for other sectors and regions focussing on undesirable output reduction.

Returns to scale, market power, and the nature of price rigidity in new keynesian models with self-fulfilling expectations

Increasing returns to scale and firms' market power are two potential sources of sunspot expectations in neoclassical models. We show that in New Keynesian models, returns to scale and market power can have fundamentally different implications for broad macroeconomic issues, including self-fulfilling expectations, depending on the nature of price rigidity. Our findings suggest that the design of stabilization monetary policy can depend on precise knowledge about the economy's real and nominal features. Therefore, a clear understanding of the specific economic environment and its relevance to monetary policymaking for ensuring macroeconomic stability can be an integrated part of monetary policy practice.

A pixel-based approach to estimation of solar energy potential on building roofs

Precise estimation of solar energy on building roofs plays a critical role in sustainable development and renewable energy consumption of high-density human habitats. Conventional solar radiation models based on costly Light Detection and Ranging (LiDAR) data are only adequate for existing buildings, not for future construction areas. In this paper, a pixel-based methodology is constructed for estimating solar energy potential over roofs. Buildings with flat roofs in a newly planned construction area are chosen as a case study. The solar radiation at a certain cell is mathematically formulated in the pixel unit, and its yields over a certain time period are calculated by considering multiple instantaneous solar irradiances and are visually presented by image processing. Significant spatial and temporal variations in solar radiation are measured. Within the study area, the maximum and minimum annual radiation yields are estimated at 4717.72 MJ/m2/year and 342.58 MJ/m2/year respectively. Radiation contour lines are then mapped for outlining installation ranges of various solar devices. For each apartment building, around 20% of roof areas can obtain 4500 MJ/m2/year or more solar radiation yields. This study will benefit energy investors and urban planners in accurately predicting solar radiation potential and identifying regions with high radiation over building roofs. The results can be utilised in government policies and urban planning to raise awareness of the use of renewable energy sources.

Drought survival strategies, dispersal potential and persistence of invertebrate species in an intermittent stream landscape

Intermittent stream systems create a mosaic of aquatic habitat that changes through time, potentially challenging freshwater invertebrate dispersal. Invertebrates inhabiting these mosaics may show stronger dispersal capacity than those in perennial stream systems. To relate different combinations of dispersal and drought survival strategies to species persistence, we compared the distribution and dispersal potential of six invertebrate species across all streams in a montane landscape where drying is becoming increasingly frequent and prolonged. Invertebrates were collected from seventeen streams in the Victoria Range, Grampians National Park, Victoria, Australia. The species analysed were as follows: the caddisflies Lectrides varians Moseley (Leptoceridae) and Agapetus sp. (Glossosomatidae); the mayflies Nousia AV1 and Koorrnonga AV3 (Leptophlebiidae); the water penny beetle Sclerocyphon sp. (Psephenidae); and a freshwater crayfish Geocharax sp. nov. 1 (Parastacidae). These species were widespread in the streams and varied in their dispersal and drought survival strategies. The distribution of each species across the Victoria Range, their drought responses and within-stream habitat associations were determined. Hypotheses of the dispersal capacity and population structure for each species were developed and compared to four models of gene flow: Death Valley Model (DVM), Stream Hierarchy Model (SHM), Headwater Model (HM) or panmixia (PAN). Molecular genetic methods were then used to infer population structure and dispersal capacity for each species. The large caddisfly Lectrides resisted drought through aestivation and was panmictic (PAN) indicating strong dispersal capacity. Conversely, the small caddisfly Agapetus relied on perennially flowing reaches and gene flow was limited to short distances among stream headwaters, resembling the HM. Both mayflies depended on perennial surface water during drying and showed evidence of gene flow among streams: Koorrnonga mainly dispersed along stream channels within catchments, resembling the SHM, whereas Nousia appeared to disperse across land by adult flight. Sclerocyphon relied on perennial water to survive drying and showed an unusual pattern of genetic structure that indicated limited dispersal but did not resemble any of the models. Geocharax survived drought through aestivation or residence in perennial pools, and high levels of genetic structure indicated limited dispersal among streams, resembling the DVM. Despite good knowledge of species' drought survival strategies, the population structure of four species differed from predictions. Dispersal capacity varied strongly among species; most species were poor dispersers and only one species showed panmixia. Therefore, intermittent stream species may not necessarily be better dispersers than those in perennial streams. Species showing strong drought resistance strategies differed in dispersal capacity. Knowledge of life-history characteristics, distribution and refuge use does not necessarily enable successful prediction of invertebrate dispersal pathways or population structure. Dispersal among intermittent streams may be restricted to relatively short distances (km) for most invertebrate species. Thus, frequent drought refuges (perennial water) that provide strong connectivity to subpopulations through stream flow (hydrological dispersal), or continuous terrestrial vegetation (flight dispersal), will be critical to maintain genetic diversity, adaptability and population persistence.

Transition, school, friends and obesity risk models (the TranSFORM study)

The TranSFORM study demonstrated the impact that a change of school environment has on physical activity, sedentary and dietary behaviour in late childhood. Results provide strong evidence of the influence of friendship networks, and the potential for changing and reinforcing positive weight related behaviour in early adolescence.