A radial basis function network classifier to maximise leave-one-out mutual information

tWe develop an orthogonal forward selection (OFS) approach to construct radial basis function (RBF)network classifiers for two-class problems. Our approach integrates several concepts in probabilisticmodelling, including cross validation, mutual information and Bayesian hyperparameter fitting. At eachstage of the OFS procedure, one model term is selected by maximising the leave-one-out mutual infor-mation (LOOMI) between the classifier’s predicted class labels and the true class labels. We derive theformula of LOOMI within the OFS framework so that the LOOMI can be evaluated efficiently for modelterm selection. Furthermore, a Bayesian procedure of hyperparameter fitting is also integrated into theeach stage of the OFS to infer the l2-norm based local regularisation parameter from the data. Since eachforward stage is effectively fitting of a one-variable model, this task is very fast. The classifier construc-tion procedure is automatically terminated without the need of using additional stopping criterion toyield very sparse RBF classifiers with excellent classification generalisation performance, which is par-ticular useful for the noisy data sets with highly overlapping class distribution. A number of benchmarkexamples are employed to demonstrate the effectiveness of our proposed approach.

Transreal arithmetic as a consistent basis for paraconsistent logics

Paraconsistent logics are non-classical logics which allow non-trivial and consistent reasoning about inconsistent axioms. They have been pro- posed as a formal basis for handling inconsistent data, as commonly arise in human enterprises, and as methods for fuzzy reasoning, with applica- tions in Artificial Intelligence and the control of complex systems. Formalisations of paraconsistent logics usually require heroic mathe- matical efforts to provide a consistent axiomatisation of an inconsistent system. Here we use transreal arithmetic, which is known to be consis- tent, to arithmetise a paraconsistent logic. This is theoretically simple and should lead to efficient computer implementations. We introduce the metalogical principle of monotonicity which is a very simple way of making logics paraconsistent. Our logic has dialetheaic truth values which are both False and True. It allows contradictory propositions, allows variable contradictions, but blocks literal contradictions. Thus literal reasoning, in this logic, forms an on-the- y, syntactic partition of the propositions into internally consistent sets. We show how the set of all paraconsistent, possible worlds can be represented in a transreal space. During the development of our logic we discuss how other paraconsistent logics could be arithmetised in transreal arithmetic.

The statistical downscaling model-decision centric (SDSM-DC): conceptual basis and applications

Regional climate downscaling has arrived at an important juncture. Some in the research community favour continued refinement and evaluation of downscaling techniques within a broader framework of uncertainty characterisation and reduction. Others are calling for smarter use of downscaling tools, accepting that conventional, scenario-led strategies for adaptation planning have limited utility in practice. This paper sets out the rationale and new functionality of the Decision Centric (DC) version of the Statistical DownScaling Model (SDSM-DC). This tool enables synthesis of plausible daily weather series, exotic variables (such as tidal surge), and climate change scenarios guided, not determined, by climate model output. Two worked examples are presented. The first shows how SDSM-DC can be used to reconstruct and in-fill missing records based on calibrated predictor-predictand relationships. Daily temperature and precipitation series from sites in Africa, Asia and North America are deliberately degraded to show that SDSM-DC can reconstitute lost data. The second demonstrates the application of the new scenario generator for stress testing a specific adaptation decision. SDSM-DC is used to generate daily precipitation scenarios to simulate winter flooding in the Boyne catchment, Ireland. This sensitivity analysis reveals the conditions under which existing precautionary allowances for climate change might be insufficient. We conclude by discussing the wider implications of the proposed approach and research opportunities presented by the new tool.

Climatic impacts of land-use change due to crop yield increases and a universal carbon tax from a scenario model*

Future land cover will have a significant impact on climate and is strongly influenced by the extent of agricultural land use. Differing assumptions of crop yield increase and carbon pricing mitigation strategies affect projected expansion of agricultural land in future scenarios. In the representative concentration pathway 4.5 (RCP4.5) from phase 5 of the Coupled Model Intercomparison Project (CMIP5), the carbon effects of these land cover changes are included, although the biogeophysical effects are not. The afforestation in RCP4.5 has important biogeophysical impacts on climate, in addition to the land carbon changes, which are directly related to the assumption of crop yield increase and the universal carbon tax. To investigate the biogeophysical climatic impact of combinations of agricultural crop yield increases and carbon pricing mitigation, five scenarios of land-use change based on RCP4.5 are used as inputs to an earth system model [Hadley Centre Global Environment Model, version 2-Earth System (HadGEM2-ES)]. In the scenario with the greatest increase in agricultural land (as a result of no increase in crop yield and no climate mitigation) there is a significant -0.49 K worldwide cooling by 2100 compared to a control scenario with no land-use change. Regional cooling is up to -2.2 K annually in northeastern Asia. Including carbon feedbacks from the land-use change gives a small global cooling of -0.067 K. This work shows that there are significant impacts from biogeophysical land-use changes caused by assumptions of crop yield and carbon mitigation, which mean that land carbon is not the whole story. It also elucidates the potential conflict between cooling from biogeophysical climate effects of land-use change and wider environmental aims.

GRID and docking analyses reveal a molecular basis for flavonoid inhibition of src-family kinase activity

Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase (PI3K), Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK, and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src-family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts, and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src-family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates.

Synapses in digital medium: computational investigations of neural basis of anticipation

Anticipation is an emerging concept that can provide a bridge between the deepest philosophical theories about the nature of life and cognition on one hand and the empirical biological sciences steeped in reductionist and Newtonian conception of causality. Three conceptions of anticipation have been emerging from the literature that may be operationalised in a way leading to a viable empirical programme. The discussion of the research into a novel dynamical concept of anticipating synchronisation lends credence to such a possibility and suggests further links between the three anticipation paradigms. A careful progress mindful to the deep philosophical concerns but also respecting empirical evidence will ultimately lead towards unifying theoretical and empirical biological sciences and may offer progress where reductionist science have been so far faltering.

Influence of individual ethical orientation on tax compliance: evidence among Ghanaian taxpayers

Even though Africa has constantly emphasized the need to reduce deficit financing through mobilization of more internal revenues, this has not been achieved. Perhaps encouraging voluntary tax compliance can improve internal revenue mobilization. This study explores the relationship between ethical orientation and tax compliance and finds that ethical persons are generally more tax compliant than unethical persons but are more influenced by considerations of tax rate and withholding positions compared to unethical persons. The findings of this study differ from Reckers et al. in a number of ways and contribute to the literature by providing a possible explanation of the cause(s) of tax non- compliance.

Transmathematical basis of infinitely scalable pipeline machines

We describe infinitely scalable pipeline machines with perfect parallelism, in the sense that every instruction of an inline program is executed, on successive data, on every clock tick. Programs with shared data effectively execute in less than a clock tick. We show that pipeline machines are faster than single or multi-core, von Neumann machines for sufficiently many program runs of a sufficiently time consuming program. Our pipeline machines exploit the totality of transreal arithmetic and the known waiting time of statically compiled programs to deliver the interesting property that they need no hardware or software exception handling.

Molecular basis of platelet activation by an alphaIIbbeta3-CHAMPS peptide.

The present study demonstrates that the alphaIIb-CHAMPS peptide induces platelet activation through integrin alphaIIbbeta3-dependent and independent pathways with the former mediating tyrosine phosphorylation of FcR gamma-chain and Syk. The use of the alphaIIb-CHAMPS peptide to study integrin alphaIIbbeta3 function is compromised by non-integrin-mediated effects.

Syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance

Background Arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. Therefore, arbovirus infections are often neglected by travel diagnostics. Here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. Method To map the patients high at risk of missed clinical arboviral infections we compared the quantity of all arboviral diagnostic requests by physicians in the Netherlands, from 2009 through 2013, with a literature-based assessment of the travelers’ likely exposure to an arbovirus. Results 2153 patients, with travel and clinical history were evaluated. The diagnostic assay for dengue virus (DENV) was the most commonly requested (86%). Of travelers returning from Southeast Asia with symptoms compatible with chikungunya virus (CHIKV), only 55% were tested. For travelers in Europe, arbovirus diagnostics were rarely requested. Over all, diagnostics for most arboviruses were requested only on severe clinical presentation. Conclusion Travel destination and syndrome were used inconsistently for triage of diagnostics, likely resulting in vast under-diagnosis of arboviral infections of public health significance. This study shows the need for more awareness among physicians and standardization of syndromic diagnostic algorithms

Consent and the use of force: an examination of ‘intervention by invitation’ as a basis for US drone strikes in Pakistan, Somalia and Yemen

Drone strikes are becoming a key feature of the United States’ global military response to nonstate actors, and it has been widely adduced that these strikes have been carried out with the consent of the host states in which such non-state actors reside. This article examines the degree to which assertions of consent (or ‘intervention by invitation’), provided as a justification for drone strikes by the United States in Pakistan, Yemen and Somalia, can be said to accord with international law. First the article provides a broad sketch of the presence of consent in international law. It then analyses in detail the individual elements of consent as provided by Article 20 of the International Law Commission Draft Articles of State Responsibility. These require that consent should be ‘valid’, given by the legitimate government and expressed by an official empowered to do so. These elements will be dealt with individually, and each in turn will be applied to the cases of Pakistan, Yemen and Somalia. Finally, the article will examine the breadth of the exculpatory power of consent, and the extent to which it can preclude the wrongfulness of acts carried out in contravention of international law other than the prohibition of the use of force under Article 2(4) of the Charter of the United Nations.

Do investors care about corporate tax?

This paper conducts a comprehensive examination of the link between corporation tax payment and financial performance in the UK. We find no discernible link between tax rates and stock returns for the UK, no matter how tax payment is measured. This is true throughout the sample period and for both customer-facing and non-customer-facing companies. However, allowing for industry norms and a host of firm characteristics, companies with lower effective tax rates have significantly higher levels of stock market risk. Firms that are reported in the newspapers in a negative way in relation to their level of corporation tax payment experience small negative stock returns, which are partially reversed within a month. However, the initial negative effects and subsequent rebound are both more pronounced for smaller companies. News announcements of the potential involvement of a firm in a corporate inversion (expatriation) result in steeper and much longer-lasting falls in share prices, whereas news stories of a more general nature relating to a firm's tax avoidance or tax payments have little noticeable effect.

Simulating the impact on health of internalising the cost of carbon in food prices combined with a tax on sugar-sweetened beverages

Rising greenhouse gas emissions (GHGEs) have implications for health and up to 30 % of emissions globally are thought to arise from agriculture. Synergies exist between diets low in GHGEs and health however some foods have the opposite relationship, such as sugar production being a relatively low source of GHGEs. In order to address this and to further characterise a healthy sustainable diet, we model the effect on UK non-communicable disease mortality and GHGEs of internalising the social cost of carbon into the price of food alongside a 20 % tax on sugar sweetened beverages (SSBs). Developing previously published work, we simulate four tax scenarios: (A) a GHGEs tax of £2.86/tonne of CO2 equivalents (tCO2e)/100 g product on all products with emissions greater than the mean across all food groups (0.36 kgCO2e/100 g); (B) scenario A but with subsidies on foods with emissions lower than 0.36 kgCO2e/100 g such that the effect is revenue neutral; (C) scenario A but with a 20 % sales tax on SSBs; (D) scenario B but with a 20 % sales tax on SSBs. An almost ideal demand system is used to estimate price elasticities and a comparative risk assessment model is used to estimate changes to non-communicable disease mortality. We estimate that scenario A would lead to 300 deaths delayed or averted, 18,900 ktCO2e fewer GHGEs, and £3.0 billion tax revenue; scenario B, 90 deaths delayed or averted and 17,100 ktCO2e fewer GHGEs; scenario C, 1,200 deaths delayed or averted, 18,500 ktCO2e fewer GHGEs, and £3.4 billion revenue; and scenario D, 2,000 deaths delayed or averted and 16,500 ktCO2e fewer GHGEs. Deaths averted are mainly due to increased fibre and reduced fat consumption; a SSB tax reduces SSB and sugar consumption. Incorporating the social cost of carbon into the price of food has the potential to improve health, reduce GHGEs, and raise revenue. The simple addition of a tax on SSBs can mitigate negative health consequences arising from sugar being low in GHGEs. Further conflicts remain, including increased consumption of unhealthy foods such as cakes and nutrients such as salt.

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies