Time series classification with ensembles of elastic distance measures

Several alternative distance measures for comparing time series have recently been proposed and evaluated on time series classification (TSC) problems. These include variants of dynamic time warping (DTW), such as weighted and derivative DTW, and edit distance-based measures, including longest common subsequence, edit distance with real penalty, time warp with edit, and move–split–merge. These measures have the common characteristic that they operate in the time domain and compensate for potential localised misalignment through some elastic adjustment. Our aim is to experimentally test two hypotheses related to these distance measures. Firstly, we test whether there is any significant difference in accuracy for TSC problems between nearest neighbour classifiers using these distance measures. Secondly, we test whether combining these elastic distance measures through simple ensemble schemes gives significantly better accuracy. We test these hypotheses by carrying out one of the largest experimental studies ever conducted into time series classification. Our first key finding is that there is no significant difference between the elastic distance measures in terms of classification accuracy on our data sets. Our second finding, and the major contribution of this work, is to define an ensemble classifier that significantly outperforms the individual classifiers. We also demonstrate that the ensemble is more accurate than approaches not based in the time domain. Nearly all TSC papers in the data mining literature cite DTW (with warping window set through cross validation) as the benchmark for comparison. We believe that our ensemble is the first ever classifier to significantly outperform DTW and as such raises the bar for future work in this area

Use of 18O Labels to Monitor Deamidation during Protein and Peptide Sample Processing

Nonenzymatic deamidation of asparagine residues in proteins generates aspartyl (Asp) and isoaspartyl (isoAsp) residues via a succinimide intermediate in a neutral or basic environment. Electron capture dissociation (ECD) can differentiate and quantify the relative abundance of these isomeric products in the deamidated proteins. This method requires the proteins to be digested, usually by trypsin, into peptides that are amenable to ECD. ECD of these peptides can produce diagnostic ions for each isomer; the c· + 58 and z − 57 fragment ions for the isoAsp residue and the fragment ion ((M + nH)(n−1)+· − 60) corresponding to the side-chain loss from the Asp residue. However, deamidation can also occur as an artifact during sample preparation, particularly when using typical tryptic digestion protocols. With 18O labeling, it is possible to differentiate deamidation occurring during trypsin digestion which causes a +3 Da (18O1 + 1D) mass shift from the pre-existing deamidation, which leads to a +1-Da mass shift. This paper demonstrates the use of 18O labeling to monitor three rapidly deamidating peptides released from proteins (calmodulin, ribonuclease A, and lysozyme) during the time course of trypsin digestion processes, and shows that the fast (̃4 h) trypsin digestion process generates no additional detectable peptide deamidations

Long-Lived Electron Capture Dissociation Product Ions Experience Radical Migration via Hydrogen Abstraction

To explore the mechanism of electron capture dissociation (ECD) of linear peptides, a set of 16-mer peptides were synthesized with deuterium labeled on the α-carbon position of four glycines. The ECD spectra of these peptides showed that such peptides exhibit a preference for the radical to migrate to the α-carbon position on glycine via hydrogen (or deuterium) abstraction before the final cleavage and generation of the detected product ions. The data show c-type fragment ions, ions corresponding to the radical cation of the c-type fragments, c·, and they also show c·-1 peaks in the deuterated peptides only. The presence of the c·-1 peaks is best explained by radical-mediated scrambling of the deuterium atoms in the long-lived, metastable, radical intermediate complex formed by initial electron capture, followed by dissociation of the complex. These data suggest the presence of at least two mechanisms, one slow, one fast. The abundance of H· and −CO losses from the precursor ion changed upon deuterium labeling indicating the presence of a kinetic isotope effect, which suggests that the values reported here represent an underestimation of radical migration and H/D scrambling in the observed fragments

Sex-Specific Correlations of Individual Heterozygosity, Parasite Load, and Scalation Asymmetry in a Sexually Dichromatic Lizard

Heterozygosity-fitness correlations (HFCs) provide insights into the genetic bases of individual fitness variation in natural populations. However, despite decades of study, the biological significance of HFCs is still under debate. In this study, we investigated HFCs in a large population of the sexually dimorphic lizard Takydromus viridipunctatus (Lacertidae). Because of the high prevalence of parasitism from trombiculid mites in this lizard, we expect individual fitness (i.e., survival) to decrease with increasing parasite load. Furthermore, because morphological asymmetry is likely to influence individuals\u27 mobility (i.e., limb asymmetry) and male biting ability during copulation (i.e., head asymmetry) in this species, we also hypothesize that individual fitness should decrease with increasing morphological asymmetry. Although we did not formally test the relationship between morphological asymmetry and fitness in this lizard, we demonstrated that survival decreased with increasing parasite load using a capture-mark-recapture data set. We used a separate sample of 140 lizards to test the correlations between individual heterozygosity (i.e., standardized mean d2 and HL based on 10 microsatellite loci) and the two fitness traits (i.e., parasite load and morphological asymmetry). We also evaluated and excluded the possibility that single-locus effects produced spurious HFCs. Our results suggest male-only, negative correlations between individual heterozygosity and parasite load and between individual heterozygosity and asymmetry, suggesting sex-specific, positive HFCs. Male T. viridipunctatus with higher heterozygosity tend to have lower parasite loads (i.e., higher survival) and lower asymmetry, providing a rare example of HFC in reptiles

Alcohol consumption and leukocyte telomere length.

The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation

Theory of photoluminescence spectral line shapes of semiconductor nanocrystals

Single-molecule photoluminescence (PL) spectroscopy of semiconductor nanocrystals (NCs) reveals the nature of exciton-phonon interactions in NCs. Understanding the narrow line shapes at low temperatures and the significant broadening as temperature increases remains an open problem. Here, we develop an atomistic model to describe the PL spectrum of NCs, accounting for excitonic effects, phonon dispersion relations, and exciton-phonon couplings. We use single-molecule PL measurements on CdSe/CdS core-shell NCs from T=4 to T=290K to validate our model and find that the slightly-asymmetric main peak at low temperatures is comprised of a narrow zero-phonon line (ZPL) and several acoustic phonon sidebands. Furthermore, we identify the distinct CdSe optical modes that give rise to the optical phonon sidebands. As the temperature increases, the spectral width shows a stronger dependence on temperature, which we demonstrated to be correlated with frequency shifts and mode-mixing, reflected as higher-order exciton-phonon couplings (Duschinsky rotations). We also model the PL dependence on core size and shell thickness and provide strategies for the design of NCs with narrow linewidths at elevated temperatures

Induction of Heme Oxygenase-1 Expression Inhibits Platelet-Dependent Thrombosis

Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative stress. Although some studies implicate HO-1 in modulating thrombosis after vascular injury, the impact of HO-1 on the rate of clot formation in vivo is poorly defined. This study examined the potential function of HO-1 in regulating platelet-dependent arterial thrombosis. Platelet-rich thrombi were induced in C57BL/6J mice by applying 10% ferric chloride to the exposed carotid artery. Mean occlusion time of wild-type mice (n = 10) was 14.6 ± 1.0 min versus 12.9 ± 0.6 min for HO-1-/- mice (n = 11, p = 0.17). However, after challenge with hemin, mean occlusion time was significantly longer in wild-type mice (16.3 ± 1.2 min, n = 15) than HO-1-/- mice (12.0 ± 1.0 min, n = 9; p = 0.021). Hemin administration induced an approximately twofold increase in oxidative stress, measured as plasma thiobarbituric acid reactive substances. Immunohistochemical analysis revealed that hemin induced a robust increase in HO-1 expression within the carotid arterial wall. Ex vivo blood clotting within a collagen-coated perfusion chamber was studied to determine whether the accelerated thrombosis observed in HO-1-/- mice was contributed to by effects on the blood itself. Under basal conditions, mean clot formation during perfusion of blood over collagen did not differ between wild-type mice and HO-1-/- mice. However, after hemin challenge, mean clot formation was significantly increased in HO-1-/- mice compared with wild-type controls. These results suggest that, under basal conditions, HO-1 does not exert a significant effect on platelet-dependent clot formation in vivo. However, under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1. Enhanced HO-1 expression in response to oxidative stress may represent an adaptive response mechanism to down-regulate platelet activation under prothrombotic conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63386/1/1523086041361677.pd