461 research outputs found

    Maximum Likelihood Estimator for Hidden Markov Models in continuous time

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    The paper studies large sample asymptotic properties of the Maximum Likelihood Estimator (MLE) for the parameter of a continuous time Markov chain, observed in white noise. Using the method of weak convergence of likelihoods due to I.Ibragimov and R.Khasminskii, consistency, asymptotic normality and convergence of moments are established for MLE under certain strong ergodicity conditions of the chain.Comment: Warning: due to a flaw in the publishing process, some of the references in the published version of the article are confuse

    When Does Reward Maximization Lead to Matching Law?

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    What kind of strategies subjects follow in various behavioral circumstances has been a central issue in decision making. In particular, which behavioral strategy, maximizing or matching, is more fundamental to animal's decision behavior has been a matter of debate. Here, we prove that any algorithm to achieve the stationary condition for maximizing the average reward should lead to matching when it ignores the dependence of the expected outcome on subject's past choices. We may term this strategy of partial reward maximization “matching strategy”. Then, this strategy is applied to the case where the subject's decision system updates the information for making a decision. Such information includes subject's past actions or sensory stimuli, and the internal storage of this information is often called “state variables”. We demonstrate that the matching strategy provides an easy way to maximize reward when combined with the exploration of the state variables that correctly represent the crucial information for reward maximization. Our results reveal for the first time how a strategy to achieve matching behavior is beneficial to reward maximization, achieving a novel insight into the relationship between maximizing and matching

    Persistence of contrasting traditions in cultural evolution: Unpredictable payoffs generate slower rates of cultural change

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    We report an experimental test of the hypothesis that contrasting traditions will persist for longer, maintaining cultural differences between otherwise similar groups, under conditions of uncertainty about payoffs from individual learning. We studied the persistence of two alternative, experimentally-introduced, task solutions in chains of human participants. In some chains, participants were led to believe that final payoffs would be difficult to predict for an innovative solution, and in others, participants were aware that their final payoff would be directly linked to their immediate solution. Although the difference between the conditions was illusory (only participants' impressions were manipulated, not actual payoffs) clear differences were found between the conditions. Consistent with predictions, in the chains that were less certain about final payoffs, the distinctive variants endured over several replacement "generations" of participants. In contrast, in the other chains, the influence of the experimentally-introduced solutions was rapidly diluted by participants' exploration of alternative approaches. The finding provides support for the notion that rates of cultural change are likely to be slower for behaviors for which the relationship between performance and payoff may be hard to predict

    Behavioural Correlate of Choice Confidence in a Discrete Trial Paradigm

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    How animals make choices in a changing and often uncertain environment is a central theme in the behavioural sciences. There is a substantial literature on how animals make choices in various experimental paradigms but less is known about the way they assess a choice after it has been made in terms of the expected outcome. Here, we used a discrete trial paradigm to characterise how the reward history shaped the behaviour on a trial by trial basis. Rats initiated each trial which consisted of a choice between two drinking spouts that differed in their probability of delivering a sucrose solution. Critically, sucrose was delivered after a delay from the first lick at the spouts – this allowed us to characterise the behavioural profile during the window between the time of choice and its outcome. Rats' behaviour converged to optimum choice, both during the acquisition phase and after the reversal of contingencies. We monitored the post-choice behaviour at a temporal precision of 1 millisecond; lick-response profiles revealed that rats spent more time at the spout with the higher reward probability and exhibited a sparser lick pattern. This was the case when we exclusively examined the unrewarded trials, where the outcome was identical. The differential licking profiles preceded the differential choice ratios and could thus predict the changes in choice behaviour

    Expression of RECK and matrix metalloproteinase-2 in ameloblastoma

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    <p>Abstract</p> <p>Background</p> <p>Ameloblastoma is a frequent odontogenic benign tumor characterized by local invasiveness, high risk of recurrence and occasional metastasis and malignant transformation. Matrix metalloproteinase-2 (MMP-2) promotes tumor invasion and progression by destroying the extracellular matrix (ECM) and basement membrane. For this proteolytic activity, the endogenous inhibitor is reversion-inducing cysteine rich protein with Kazal motifs (RECK). The aim of this study was to characterize the relationship between RECK and MMP-2 expression and the clinical manifestation of ameloblastoma.</p> <p>Methods</p> <p>Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were employed to detect the protein and mRNA expression of RECK and MMP-2 in keratocystic odontogenic tumor (KCOT), ameloblastoma and ameloblastic carcinoma.</p> <p>Results</p> <p>RECK protein expression was significantly reduced in KCOT (87.5%), ameloblastoma (56.5%) and ameloblastic carcinoma (0%) (P < 0.01), and was significantly lower in recurrent ameloblastoma compared with primary ameloblastoma (P < 0.01), but did not differ by histological type of ameloblastoma. MMP-2 protein expression was significantly higher in ameloblastoma and ameloblastic carcinoma compared with KCOT (P < 0.01). RECK mRNA expression was significantly lower in ameloblastoma than in KCOT (P < 0.01), lower in recurrent ameloblastoma than in primary ameloblastoma, and was negative in ameloblastic carcinoma. MMP-2 mRNA expression was significantly higher in ameloblastoma compared with KCOT (P < 0.01), but was no different in recurrent ameloblastoma versus primary ameloblastoma. RECK protein expression was negatively associated with MMP-2 protein expression in ameloblastoma (r = -0.431, P < 0.01).</p> <p>Conclusion</p> <p>Low or no RECK expression and increased MMP-2 expression may be associated with negative clinical findings in ameloblastoma. RECK may participate in the invasion, recurrence and malignant transformation of ameloblastoma by regulating MMP-2 at the post-transcriptional level.</p

    Response of Coastal Fishes to the Gulf of Mexico Oil Disaster

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    The ecosystem-level impacts of the Deepwater Horizon disaster have been largely unpredictable due to the unique setting and magnitude of this spill. We used a five-year (2006–2010) data set within the oil-affected region to explore acute consequences for early-stage survival of fish species inhabiting seagrass nursery habitat. Although many of these species spawned during spring-summer, and produced larvae vulnerable to oil-polluted water, overall and species-by-species catch rates were high in 2010 after the spill (1,989±220 fishes km-towed−1 [μ ± 1SE]) relative to the previous four years (1,080±43 fishes km-towed−1). Also, several exploited species were characterized by notably higher juvenile catch rates during 2010 following large-scale fisheries closures in the northern Gulf, although overall statistical results for the effects of fishery closures on assemblage-wide CPUE data were ambiguous. We conclude that immediate, catastrophic losses of 2010 cohorts were largely avoided, and that no shifts in species composition occurred following the spill. The potential long-term impacts facing fishes as a result of chronic exposure and delayed, indirect effects now require attention

    Emerging roles and competencies of district and sub-district pharmacists: a case study from Cape Town

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    District and sub-district pharmacist positions were created during health sector reform in South Africa. High prevalence of HIV/AIDS, tuberculosis and increasing chronic non-communicable diseases have drawn attention to their pivotal roles in improving accessibility and appropriate use of medicines at the primary level. This research describes new roles and related competencies of district and sub-district pharmacists in Cape Town. Between 2008 and 2011, the author (HB) conducted participatory action research in Cape Town Metro District, an urban district in the Western Cape Province of South Africa, partnering with pharmacists and managers of the two government primary health care (PHC) providers. The two providers function independently delivering complementary PHC services across the entire geographic area, with one provider employing district pharmacists and the other sub-district pharmacists. After an initiation phase, the research evolved into a series of iterative cycles of action and reflection, each providing increasing understanding of district and sub-district pharmacists’ roles and competencies. Data was generated through workshops, semi-structured interviews and focus groups with pharmacists and managers which were recorded and transcribed. Thematic analysis was carried out iteratively during the 4-year engagement and triangulated with document reviews and published literature. Five main roles for district and sub-district pharmacists were identified: district/sub-district management; planning, co-ordination and monitoring of pharmaceuticals; information and advice; quality assurance and clinical governance; and research (district pharmacists)/dispensing at clinics (sub-district pharmacists). Although the roles looked similar, there were important differences, reflecting the differing governance and leadership models and services of each provider. Five competency clusters were identified: professional pharmacy practice; health system and public health; management; leadership; and personal, interpersonal and cognitive competencies. Whilst professional pharmacy competencies were important, generic management and leadership competencies were considered critical for pharmacists working in these positions. Similar roles and competencies for district and sub-district pharmacists were identified in the two PHC providers in Cape Town, although contextual factors influenced precise specifications. These insights are important for pharmacists and managers from other districts and sub-districts in South Africa and inform health workforce planning and capacity development initiatives in countries with similar health systems.Web of Scienc

    The Actin-Binding Protein Capulet Genetically Interacts with the Microtubule Motor Kinesin to Maintain Neuronal Dendrite Homeostasis

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    BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease

    RNA Interference of Four Genes in Adult Bactrocera dorsalis by Feeding Their dsRNAs

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    BACKGROUND: RNA interference (RNAi) is a powerful method to inhibit gene expression in a sequence specific manner. Recently silencing the target gene through feeding has been successfully carried out in many insect species. METHODOLOGY/PRINCIPAL FINDINGS: Escherichia coli strain HT115 was genetically engineered to express dsRNA targeting genes that encode ribosomal protein Rpl19, V type ATPase D subunit, the fatty acid elongase Noa and a small GTPase Rab11. qRT-PCR showed that mRNA level of four target genes was reduced compared to ds-egfp control by feeding either engineered bacteria or dsRNAs. The maximum down-regulation of each gene varied from 35% to 100%. Tissue specific examination indicated that RNAi could be observed not only in midgut but also in other tissues like the ovary, nervous system and fat body. Silencing of rab11 through ingestion of dsRNA killed 20% of adult flies. Egg production was affected through feeding ds-noa and ds-rab11 compared to ds-egfp group. Adult flies were continuously fed with dsRNA and bacteria expressing dsRNA for 14 days and up-regulations of target genes were observed during this process. The transcripts of noa showed up-regulation compared to ds-egfp control group in four tissues on day 7 after continuous feeding either dsRNA or engineered bacteria. The maximum over-expression is 21 times compared to ds-egfp control group. Up-regulation of rab11 mRNA level could be observed in testes on day 7 after continuous bacteria treatment and in midgut on day 2 after ds-rab11 treatment. This phenomenon could also be observed in rpl19 groups. CONCLUSIONS: Our results suggested that it is feasible to silence genes by feeding dsRNA and bacteria expressing dsRNA in Bactrocera dorsalis. Additionally the over-expression of the target gene after continuously feeding dsRNA or bacteria was observed
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