Evolving text classification rules with genetic programming

We describe a novel method for using genetic programming to create compact classification rules using combinations of N-grams (character strings). Genetic programs acquire fitness by producing rules that are effective classifiers in terms of precision and recall when evaluated against a set of training documents. We describe a set of functions and terminals and provide results from a classification task using the Reuters 21578 dataset. We also suggest that the rules may have a number of other uses beyond classification and provide a basis for text mining applications

An Extension and Further Validation of a Community-based Consumer Well-being Measure

Cataloged from PDF version of article.The goal of this study is to extend the research and further validation of Lee and colleagues' measure of community-based consumer well-being. The measure is based on the notion that consumers experience well-being to the extent that they are satisfied with local marketplace experiences related to (1) shopping for desired consumer goods and services in the local area, (2) preparing locally purchased consumer durables for personal use, (3) consuming locally purchased goods and services, (4) owning consumer durables purchased in the local area, (5) using repair and maintenance services in the local area, and (6) using selling, trading-in, and disposal services in the local area. Data were collected from ten localities in nine countries/states (California, Minnesota, Canada, Australia, Spain, Germany, Switzerland, Turkey, Egypt, and China) using the mall intercept method. The data provided support for the predictive/nomological validity of the measure by providing empirical support for the relationship between the consumer well-being construct and other well-being constructs such as life satisfaction

Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1

<p>Abstract</p> <p>Background</p> <p>A number of prostaglandins (PGs) sensitize dorsal root ganglion (DRG) neurons and contribute to inflammatory hyperalgesia by signaling through specific G protein-coupled receptors (GPCRs). One mechanism whereby PGs sensitize these neurons is through modulation of "thermoTRPs," a subset of ion channels activated by temperature belonging to the Transient Receptor Potential ion channel superfamily. Acrid, electrophilic chemicals including cinnamaldehyde (CA) and allyl isothiocyanate (AITC), derivatives of cinnamon and mustard oil respectively, activate thermoTRP member TRPA1 via direct modification of channel cysteine residues.</p> <p>Results</p> <p>Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD₂metabolite, 15-deoxy-Δ^12,14-prostaglandin J₂(15d-PGJ₂), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ₂specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ₂and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ₂has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ). Our <it>in vivo </it>studies revealed that 15d-PGJ₂induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors.</p> <p>Conclusion</p> <p>In conclusion, we show that 15d-PGJ₂induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.</p

Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior

The central nucleus of the amygdala (CeA) has been identified as a site of nociceptive processing important for sensitization induced by peripheral injury. However, the cellular signaling components underlying this function remain unknown. Here, we identify metabotropic glutamate receptor 5 (mGluR5) as an integral component of nociceptive processing in the CeA. Pharmacological activation of mGluRs with R,S-3,5-dihydroxyphenylglycine (DHPG) in the CeA of mice is sufficient to induce peripheral hypersensitivity in the absence of injury. DHPG-induced peripheral hypersensitivity is reduced via pharmacological blockade of mGluR5 or genetic disruption of mGluR5. Further, pharmacological blockade or conditional deletion of mGluR5 in the CeA abrogates inflammation-induced hypersensitivity, demonstrating the necessity of mGluR5 in CeA-mediated pain modulation. Moreover, we demonstrate that phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) is downstream of mGluR5 activation in the CeA and is necessary for the full expression of peripheral inflammation-induced behavioral sensitization. Finally, we present evidence of right hemispheric lateralization of mGluR5 modulation of amygdalar nociceptive processing. We demonstrate that unilateral pharmacological activation of mGluR5 in the CeA produces distinct behavioral responses depending on whether the right or left amygdala is injected. We also demonstrate significantly higher levels of mGluR5 expression in the right amygdala compared to the left under baseline conditions, suggesting a potential mechanism for right hemispheric lateralization of amygdala function in pain processing. Taken together, these results establish an integral role for mGluR5 and ERK1/2 in nociceptive processing in the CeA

Revealing research preferences in conservation science

AbstractConservation researchers are increasingly drawing on a wide range of philosophies, methods and values to examine conservation problems. Here we adopt methods from social psychology to develop a questionnaire with the dual purpose of illuminating diversity within conservation research communities and providing a tool for use in cross-disciplinary dialogue workshops. The questionnaire probes the preferences that different researchers have with regards to conservation science. It elicits insight into their motivations for carrying out research, the scales at which they tackle problems, the subjects they focus on, their beliefs about the connections between nature and society, their sense of reality as absolute or socially constituted, and their propensity for collaboration. Testing the questionnaire with a group of 204 conservation scientists at a student conference on conservation science, we illustrate the latent and multidimensional diversity in the research preferences held by conservation scientists. We suggest that creating opportunities to further explore these differences and similarities using facilitated dialogue could enrich the mutual understanding of the diverse research community in the conservation field.</jats:p

Mitochondrial exchanger NCLX plays a major role in the intracellular Ca(2+) signaling, gliotransmission, and proliferation of astrocytes

Mitochondria not only provide cells with energy, but are central to Ca(2+) signaling. Powered by the mitochondrial membrane potential, Ca(2+) enters the mitochondria and is released into the cytosol through a mitochondrial Na(+)/Ca(2+) exchanger. We established that NCLX, a newly discovered mitochondrial Na(+)/Ca(2+) exchanger, is expressed in astrocytes isolated from mice of either sex. Immunoblot analysis of organellar fractions showed that the location of NCLX is confined to mitochondria. Using pericam-based mitochondrial Ca(2+) imaging and NCLX inhibition either by siRNA or by the pharmacological blocker CGP37157, we demonstrated that NCLX is responsible for mitochondrial Ca(2+) extrusion. Suppression of NCLX function altered cytosolic Ca(2+) dynamics in astrocytes and this was mediated by a strong effect of NCLX activity on Ca(2+) influx via store-operated entry. Furthermore, Ca(2+) influx through the store-operated Ca(2+) entry triggered strong, whereas ER Ca(2+) release triggered only modest mitochondrial Ca(2+) transients, indicating that the functional cross talk between the plasma membrane and mitochondrial domains is particularly strong in astrocytes. Finally, silencing of NCLX expression significantly reduced Ca(2+)-dependent processes in astrocytes (i.e., exocytotic glutamate release, in vitro wound closure, and proliferation), whereas Ca(2+) wave propagation was not affected. Therefore, NCLX, by meditating astrocytic mitochondrial Na(+)/Ca(2+) exchange, links between mitochondria and plasma membrane Ca(2+) signaling, thereby modulating cytoplasmic Ca(2+) transients required to control a diverse array of astrocyte functions

Why are feasibility studies accessing routinely collected health data? A systematic review

BACKGROUND: Feasibility trials are often undertaken to determine whether a larger randomised controlled trial (RCT) is achievable. In a recent review, 15 feasibility trials accessed routinely collected health data (RCHD) from UK national databases and registries. This paper looks at attributes of these trials and the reasons why they accessed RCHD. METHODS: We extracted data from all publicly available sources for the 15 feasibility studies found in a previous review of trials successfully accessing RCHD in the UK between 2013–2018 for the purpose of informing or supplementing participant data. We extracted trial characteristics, the registry accessed, and the way the RCHD was used. RESULTS: The 15 feasibility RCTs were conducted in a variety of disease areas, and were generally small (median sample size 100, range 41–4061) and individually randomised (60%, 9/15). The primary trial outcome was predominantly administrative (non-clinical) (80%, 12/15) such as feasibility of patient recruitment. They were more likely to recruit from secondary care (67%, 10/15) settings than primary (33%, 5/15). NHS Digital was the most commonly accessed registry (33% (5/15)) with SAIL databank (20% (3/15)), electronic Data Research and Innovation Service (eDRIS) and Paediatric Intensive Care Audit Network (PICANET) (each 13% 2/15) also being accessed. Where the information was clear, the trials used RCHD for data collection during the trial (47%, 7/15), follow-up after the trial (27%, 4/15) and recruitment (13%, 2/15). CONCLUSIONS: Between 2013 and 2018, 15 feasibility trials successfully accessed UK RCHD. Feasibility trials would benefit, as with other trials, from guidance on reporting the use of RCHD in protocols and publications

Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

INTRODUCTION: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm(2) versus 12.5–15.7 cm(2)). STUDY DESIGN AND METHODS: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B). RESULTS: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo. CONCLUSION: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research