Winner-take-all selection in a neural system with delayed feedback

We consider the effects of temporal delay in a neural feedback system with excitation and inhibition. The topology of our model system reflects the anatomy of the avian isthmic circuitry, a feedback structure found in all classes of vertebrates. We show that the system is capable of performing a `winner-take-all' selection rule for certain combinations of excitatory and inhibitory feedback. In particular, we show that when the time delays are sufficiently large a system with local inhibition and global excitation can function as a `winner-take-all' network and exhibit oscillatory dynamics. We demonstrate how the origin of the oscillations can be attributed to the finite delays through a linear stability analysis.Comment: 8 pages, 6 figure

Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study

Background and Objectives: The Pompe Disease Symptom Scale (PDSS) and Impact Scale (PDIS) were created to measure the severity of symptoms and functional limitations experienced by patients with late-onset Pompe disease (LOPD). The objectives of this analysis were to establish a scoring algorithm and to examine the reliability, validity, and responsiveness of the measures using data from the COMET clinical trial. Methods: The COMET trial was a randomized, double-blind study comparing the efficacy and safety of avalglucosidase alfa and alglucosidase alfa in patients with LOPD aged 16-78 years at baseline. Adult participants (18 years or older) completed the PDSS and PDIS daily for 14 days at baseline and for 2 weeks before quarterly clinic visits for 1 year after randomization using an electronic diary. Data were pooled across treatment groups for the current analyses. Factor analysis and inter-item correlations were used to derive a scoring algorithm. Test-retest and internal consistency analyses examined the reliability of the measures. Correlations with criterion measures were used to evaluate validity and sensitivity to change. Anchor and distribution-based analyses were conducted to estimate thresholds for meaningful change. Results: Five multi-item domain scores were derived from the PDSS (Shortness of Breath, Overall Fatigue, Fatigue/Pain, Upper Extremity Weakness, Pain) and 2 from the PDIS (Mood, Difficulty Performing Activities). Internal consistency (Cronbach α &gt; 0.90) and test-retest reliability (intraclass correlation &gt;0.60) of the scores were supported. Cross-sectional and longitudinal correlations with the criterion measures generally supported the validity of the scores (r &gt; 0.40). Within-patient meaningful change estimates ranging from 1.0 to 1.5 points were generated for the PDSS and PDIS domain scores. Discussion The PDSS and PDIS are reliable and valid measures of LOPD symptoms and functional impacts. The measures can be used to evaluate burden of LOPD and effects of treatments in clinical trials, observational research, and clinical practice.</p

Distribution of Endogenous Farnesyl Pyrophosphate and Four Species of Lysophosphatidic Acid in Rodent Brain

Lysophosphatidic acid (LPA) is the umbrella term for lipid signaling molecules that share structural homology and activate the family of LPA receptors. Farnesyl Pyrophosphate (FPP) is commonly known as an intermediate in the synthesis of steroid hormones; however, its function as a signaling lipid is beginning to be explored. FPP was recently shown to an activator of the G-protein coupled receptor 92 (also known as LPA5) of the calcium channel TRPV3. The LPA receptors (including GPR92) are associated with the signal transduction of noxious stimuli, however, very little is known about the distribution of their signaling ligands (LPAs and FPP) in the brain. Here, using HPLC/MS/MS, we developed extraction and analytical methods for measuring levels of FPP and 4 species of LPA (palmitoyl, stearoyl, oleoyl and arachidonoyl-sn-glycerol-3 phosphate) in rodent brain. Relative distributions of each of the five compounds was significantly different across the brain suggesting divergent functionality for each as signaling molecules based on where and how much of each is being produced. Brainstem, midbrain, and thalamus contained the highest levels measured for each compound, though none in the same ratios while relatively small amounts were produced in cortex and cerebellum. These data provide a framework for investigations into functional relationships of these lipid ligands in specific brain areas, many of which are associated with the perception of pain

Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm

Over the past five decades, k-means has become the clustering algorithm of choice in many application domains primarily due to its simplicity, time/space efficiency, and invariance to the ordering of the data points. Unfortunately, the algorithm's sensitivity to the initial selection of the cluster centers remains to be its most serious drawback. Numerous initialization methods have been proposed to address this drawback. Many of these methods, however, have time complexity superlinear in the number of data points, which makes them impractical for large data sets. On the other hand, linear methods are often random and/or sensitive to the ordering of the data points. These methods are generally unreliable in that the quality of their results is unpredictable. Therefore, it is common practice to perform multiple runs of such methods and take the output of the run that produces the best results. Such a practice, however, greatly increases the computational requirements of the otherwise highly efficient k-means algorithm. In this chapter, we investigate the empirical performance of six linear, deterministic (non-random), and order-invariant k-means initialization methods on a large and diverse collection of data sets from the UCI Machine Learning Repository. The results demonstrate that two relatively unknown hierarchical initialization methods due to Su and Dy outperform the remaining four methods with respect to two objective effectiveness criteria. In addition, a recent method due to Erisoglu et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms (Springer, 2014). arXiv admin note: substantial text overlap with arXiv:1304.7465, arXiv:1209.196

Life satisfaction and mortality in elderly people: The Kangwha Cohort Study

<p>Abstract</p> <p>Background</p> <p>As well as biomedical risk factors, psychological factors have been reported to be related to mortality rate. The purpose of this study was to examine the relationship between life satisfaction and mortality in elderly people through an 11.8-year follow-up study of a prospective cohort.</p> <p>Methods</p> <p>Among 3,600 participants of the Kangwha Cohort Study who survived in 1994, 1,939 respondents of the Life Satisfaction Index (LSI)-A questionnaire were included (men, 821; women, 1118). The mortality risk for the period up to December 2005 was measured using the Cox Proportional Hazard Model.</p> <p>Results</p> <p>When the relationship between LSI and mortality was evaluated in men, the unsatisfied group with lower LSI scores showed a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.83) than the satisfied group with higher LSI scores. In women, the unsatisfied group showed a significantly higher risk of all-cause mortality (HR, 1.51; 95% CI, 1.18-1.92) and cardiovascular mortality (HR, 2.23; 95% CI, 1.30-3.85) than the satisfied group.</p> <p>Conclusion</p> <p>We found that elderly people with a lower LSI score, regardless of gender, were at risk of increased mortality from all causes, and low LSI score was also associated with cardiovascular mortality.</p

The Distribution of Dust and Gas in Elliptical Galaxies

Results from IRAS and recent optical CCD surveys are examined to discuss the distribution and origin of dust and ionized gas in elliptical galaxies. In strong contrast with the situation among spiral galaxies, masses of dust in elliptical galaxies as derived from optical extinction are an order of magnitude LOWER than those derived from IRAS data. I find that this dilemma can be resolved by assuming the presence of a diffusely distributed component of dust which is not detectable in optical data. The morphology of dust lanes and their association with ionized gas in elliptical galaxies argues for an external origin of BOTH components of the ISM.Comment: Invited talk given at conference on "NEW EXTRAGALACTIC PERSPECTIVES IN THE NEW SOUTH AFRICA: Changing Perceptions of the Morphology, Dust Content and Dust-Gas Ratios in Galaxies", Held in Johannesburg, South Africa, during January 22-26, 1996. Proceedings will be edited by D.L. Block and published by Kluwer, Dordrecht, The Netherlands. uuencoded, gzipped LaTeX file of 8 pages; figures included as PostScript files (enclosed). Uses crckapb.sty (enclosed) and psfig.st

Differential effects of saturated versus unsaturated dietary fatty acids on weight gain and myocellular lipid profiles in mice

OBJECTIVE: In conditions of continuous high-fat (HF) intake, the degree of saturation of the fatty acids (FAs) in the diet might have a crucial role in the onset of obesity and its metabolic complications. In particular, the FA composition of the diet might influence the storage form of lipids inside skeletal muscle. The aim of the present study was to examine whether the FA composition of HF diets differentially affects weight gain and accumulation of myocellular triacylglycerol (TAG) and diacylglycerol (DAG). Furthermore, we examined whether the FA composition of the diet was reflected in the composition of the myocellular lipid intermediates.DESIGN: C57Bl6 mice were fed HF diets (45% energy) mainly containing palm oil (PO), cocoa butter (CB), olive oil (OO) or safflower oil (SO; n=6 per group) for 8 weeks. A low-fat diet (10% energy, PO) was used as control. Body weight was monitored weekly. At the end of the dietary intervention, myocellular TAG and DAG content and profiles were measured.RESULTS: We here show that HF_CB prevented weight gain after 8 weeks of HF feeding. Furthermore, the HF diet rich in SO prevented the accumulation of both myocellular TAG and DAG. Interestingly, the FA composition of DAG and TAG in skeletal muscle was a reflection of the dietary FA composition.CONCLUSION: Already after a relatively short period, the dietary FA intake relates to the FA composition of the lipid metabolites in the muscle. A diet rich in polyunsaturated FAs seems to prevent myocellular lipid accumulation.<br/

Tuning hardness in calcite by incorporation of amino acids

Structural biominerals are inorganic/organic composites that exhibit remarkable mechanical properties. However, the structure–property relationships of even the simplest building unit—mineral single crystals containing embedded macromolecules—remain poorly understood. Here, by means of a model biomineral made from calcite single crystals containing glycine (0–7 mol%) or aspartic acid (0–4 mol%), we elucidate the origin of the superior hardness of biogenic calcite. We analysed lattice distortions in these model crystals by using X-ray diffraction and molecular dynamics simulations, and by means of solid-state nuclear magnetic resonance show that the amino acids are incorporated as individual molecules. We also demonstrate that nanoindentation hardness increased with amino acid content, reaching values equivalent to their biogenic counterparts. A dislocation pinning model reveals that the enhanced hardness is determined by the force required to cut covalent bonds in the molecules

Evaluation of pyrene sorption–desorption on tropical soils

Sorption–desorption processes control soil-pollutant interactions. These processes determine the extent of pyrene transport in soils. Understanding sorption characteristics of pyrene is necessary in ascertaining its fate in soil. Laboratory batch experiments were conducted to study the sorptions–desorption of pyrene on eight soils from varying tropical agro-ecological zones (AEZs). The results showed that pyrene sorptions equilibria were attained within 720 min. Solution pH had a reciprocal effect on pyrene sorptions. Sorption was exothermic and increased with pyrene concentration in solution. The quantities of pyrene sorbed by each soil as well as the hysteresis were proportional to the percentage organic matter, and to some degree, the clay mineralogy. Sorption isotherms showed distributed reactivity involving several linear and non-linear isotherms. The present investigation showed that pyrene is likely to be more available to biota and reach the aquifer faster in low organic matter soils than those with relatively higher organic matter and more so in warmer climes