Syllables and bigrams: Orthographic redundancy and syllabic units affect visual word recognition at different processing levels.

Over the last decade, there has been increasing evidence for syllabic processing during visual word recognition. If syllabic effects prove to be independent from orthographic redundancy, this would seriously challenge the ability of current computational models to account for the processing of polysyllabic words. Three experiments are presented to disentangle effects of the frequency of syllabic units and orthographic segments in lexical decision. In Experiment 1 the authors obtained an inhibitory syllable frequency effect that was unaffected by the presence or absence of a bigram trough at the syllable boundary. In Experiments 2 and 3 an inhibitory effect of initial syllable frequency but a facilitative effect of initial bigram frequency emerged when manipulating 1 of the 2 measures and controlling for the other in Spanish words starting with consonant-vowel syllables. The authors conclude that effects of syllable frequency and letter-cluster frequency are independent and arise at different processing levels of visual word recognition. Results are discussed within the framework of an interactive activation model of visual word recognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time to abandon small-sample cohort research in health psychology?

Comments on the original article, "Avoidant coping as a predictor of mortality in veterans with end-stage renal disease" by E. J. Wolf and D. L. Mori (see record 2009-06704-009), in which the authors report that among 61 patients with endstage renal disease (ESRD), avoidant coping more than doubled the odds of mortality in multivariable analysis. The authors concluded that evaluating coping style in patients with ESRD would be clinically useful and that interventions targeting avoidant coping should be investigated. In this commentary, the current authors note that Wolf and Mori’s (2009) finding was based on a sample where only 23 patients died over 9 years, and results were evaluated using a Cox regression model with six covariates, a ratio of only 3.8 outcome events per variable—well below recommended thresholds (e.g., Babyak, 2004; Peduzzi et al., 1995). Beyond this, the model did not assess key variables typically included in studies of ESRD outcomes (e.g., transplant status, cardiovascular problems). Wolf and Mori chose to focus on the relationship between avoidant coping and mortality. However, bivariable correlations and confidence intervals reported or generated from data in the article showed that the association between avoidant coping and mortality (r=.28, 95% CI [.03 to .50]) was not significantly stronger than two other correlations that were in the opposite direction of what would have been expected: hypertension with mortality (r=?.39, 95% CI [?.15 to ?.59]) and medication compliance with mortality (r=.16, 95% CI [?.10 to .40]). Oddities of this sort are often encountered in very small datasets and, as a result, stronger evidence must be accrued from larger, more robust samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smart consumer load balancing: state of the art and an empirical evaluation in the Spanish electricity market

The basis of an efficient functioning of a power grid is an accurate balancing of the electricity demand of all the consumers at any instant with supply. Nowadays, this task involves only the grid operator and retail electricity providers. One of the facets of the Smart Grid vision is that consumers may have a more active role in the problem of balancing demand with supply. With the deployment of intelligent information and communication technologies in domestic environments, homes are becoming smarter and able to play a more active role in the management of energy. We use the term Smart Consumer Load Balancing to refer to algorithms that are run by energy management systems of homes in order to optimise the electricity consumption, to minimise costs and/or meet supply constraints. In this work, we analyse different approaches to Smart Consumer Load Balancing based on (distributed) artificial intelligence. We also put forward a new model of Smart Consumer Load Balancing, where consumers actively participate in the balancing of demand with supply by forming groups that agree on a joint demand profile to be contracted in the market with the mediation of an aggregator. We specify the business model as well as the optimisation model for load balancing, showing the economic benefits for the consumers in a realistic scenario based on the Spanish electricity market.     

The impact of tangled code changes on defect prediction models

When interacting with source control management system, developers often commit unrelated or loosely related code changes in a single transaction. When analyzing version histories, such tangled changes will make all changes to all modules appear related, possibly compromising the resulting analyses through noise and bias. In an investigation of five open-source Java projects, we found between 7 % and 20 % of all bug fixes to consist of multiple tangled changes. Using a multi-predictor approach to untangle changes, we show that on average at least 16.6 % of all source files are incorrectly associated with bug reports. These incorrect bug file associations seem to not significantly impact models classifying source files to have at least one bug or no bugs. But our experiments show that untangling tangled code changes can result in more accurate regression bug prediction models when compared to models trained and tested on tangled bug datasets—in our experiments, the statistically significant accuracy improvements lies between 5 % and 200 %. We recommend better change organization to limit the impact of tangled changes.     

Distributed coordination of emergency medical service for angioplasty patients

In this paper we study the coordination of Emergency Medical Service (EMS) for patients with acute myocardial infarction with ST-segment elevation (STEMI). This is a health problem with high associated mortality. A “golden standard” treatment for STEMI is angioplasty, which requires a catheterization lab and a highly qualified cardiology team. It should be performed as soon as possible since the delay to treatment worsens the patient’s prognosis. The decrease of the delay is achieved by coordination of EMS, which is especially important in the case of multiple simultaneous patients. Nowadays, this process is based on the First-Come-First-Served (FCFS) principle and it heavily depends on human control and phone communication with high proneness to human error and delays. The objective is, therefore, to automate the EMS coordination while minimizing the time from symptom onset to reperfusion and thus to lower the mortality and morbidity resulting from this disease. In this paper, we present a multi-agent decision-support system for the distributed coordination of EMS focusing on urgent out-of-hospital STEMI patients awaiting angioplasty. The system is also applicable to emergency patients of any pathology needing pre-hospital acute medical care and urgent hospital treatment. The assignment of patients to ambulances and angioplasty-enabled hospitals with cardiology teams is performed via a three-level optimization model. At each level, we find a globally efficient solution by a modification of the distributed relaxation method for the assignment problem called the auction algorithm. The efficiency of the proposed model is demonstrated by simulation experiments.     

Interconnector capacity allocation in offshore grids with variable wind generation

Different capacity allocation regimes have a strong impact on the economics of offshore wind farms and on interconnectors in offshore grids. Integrating offshore generation in offshore grids is currently a subject of discussion for different regions, e.g. the North Sea. A novel question is how the interconnector capacity should be allocated for wind generation and for international power trading. The main difficulty arises from the stochastic nature of wind generation: in a case with radial connections to the national coast, the wind park owner has the possibility of aggregating the offshore wind park with onshore installations to reduce balancing demand. This is not necessarily the case if the interconnector capacity is sold through implicit or explicit auctions. Different design options are discussed and quantified for a number of examples based on Danish, Dutch, German and Norwegian power markets. It is concluded that treating offshore generation as a single price zone within the interconnector reduces the wind operator's ability to pool it with other generation. Furthermore, a single offshore price zone between two markets will always receive the lower spot market price of the neighbouring zones, although its generation flows only to the high‐price market. Granting the high‐price market income for wind generation as the opposite design option reduces congestion rents. Otherwise, compensation measures through support schemes or different balancing responsibilities may be discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Combining spectroscopic and potentiometric approaches to characterize competitive binding to humic substances

In an area that contains high concentrations of natural organic matter, it is expected that it plays an important role on the behavior of rare earth elements (REE), like europium, and of trivalent actinides. Competitive interactions with H+, inorganic species, major cations, e.g. Ca(II) or Mg(II), could influence these metals transport and bioavailability. Competitive experiments between cations, which can bind differently to humic substances and Eu3+, will bring an improved understanding of the competitive mechanisms. The aim of this study is to acquire data for Eu(III)/Cu(II) and Eu(III)/Ca(II) competitive binding to a sedimentary originated humic acid (Gorleben, Germany). The NICA-Donnan parameters for Ca2+, Cu2+, and Eu3+ obtained from competitive binding experiments using Ca2+ or Cu2+ ion selective electrodes were used to model time-resolved laser fluorescence spectroscopy (TRLFS) measurements. Eu3+ and CU2+ are in direct competition for the same type of sites, whereas Ca2+ has an indirect influence through electrostatic binding.     

More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins

The calcium-release-activated calcium (CRAC) channel, activated by the release of Ca²⁺ from the endoplasmic reticulum (ER), is critical for Ca²⁺ homeostasis and active signal transduction in a plethora of cell types. Spurred by the long-sought decryption of the molecular nature of the CRAC channel, considerable scientific effort has been devoted to gaining insights into functional and structural mechanisms underlying this signalling cascade. Key players in CRAC channel function are the Stromal interaction molecule 1 (STIM1) and Orai1. STIM1 proteins span through the membrane of the ER, are competent in sensing luminal Ca²⁺ concentration, and in turn, are responsible for relaying the signal of Ca²⁺ store-depletion to pore-forming Orai1 proteins in the plasma membrane. A direct interaction of STIM1 and Orai1 allows for the re-entry of Ca²⁺ from the extracellular space. Although much is already known about the structure, function, and interaction of STIM1 and Orai1, there is growing evidence that CRAC under physiological conditions is dependent on additional proteins to function properly. Several auxiliary proteins have been shown to regulate CRAC channel activity by means of direct interactions with STIM1 and/or Orai1, promoting or hindering Ca²⁺ influx in a mechanistically diverse manner. Various proteins have also been identified to exert a modulatory role on the CRAC signalling cascade although inherently lacking an affinity for both STIM1 and Orai1. Apart from ubiquitously expressed representatives, a subset of such regulatory mechanisms seems to allow for a cell-type-specific control of CRAC channel function, considering the rather restricted expression patterns of the specific proteins. Given the high functional and clinical relevance of both generic and cell-type-specific interacting networks, the following review shall provide a comprehensive summary of regulators of the multilayered CRAC channel signalling cascade. It also includes proteins expressed in a narrow spectrum of cells and tissues that are often disregarded in other reviews of similar topics.     

68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System

The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of ⁶⁸Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [⁶⁸Ga]Ga-HBED-hexadiyne-tropane, showed an IC₅₀ value of 66 nM, together with a log D_7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.     

Single-Dose P2 X4R Single-Chain Fragment Variable Antibody Permanently Reverses Chronic Pain in Male Mice

Non-opioid single-chain variable fragment (scFv) small antibodies were generated as pain-reducing block of P2X4R receptor (P2X4R). A panel of scFvs targeting an extracellular peptide sequence of P2X4R was generated followed by cell-free ribosome display for recombinant antibody selection. After three rounds of bio-panning, a panel of recombinant antibodies was isolated and characterized by ELISA, cross-reactivity analysis, and immunoblotting/immunostaining. Generated scFv antibodies feature binding activity similar to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their ~30% smaller size. Two anti-P2X4R scFv clones (95, 12) with high specificity and affinity binding were selected for in vivo testing in male and female mice with trigeminal nerve chronic neuropathic pain (FRICT-ION model) persisting for several months in untreated BALBc mice. A single dose of P2X4R scFv (4 mg/kg, i.p.) successfully, completely, and permanently reversed chronic neuropathic pain-like measures in male mice only, providing retention of baseline behaviors indefinitely. Untreated mice retained hypersensitivity, and developed anxiety- and depression-like behaviors within 5 weeks. In vitro P2X4R scFv 95 treatment significantly increased the rheobase of larger-diameter (>25 µm) trigeminal ganglia (TG) neurons from FRICT-ION mice compared to controls. The data support use of engineered scFv antibodies as non-opioid biotherapeutic interventions for chronic pain.