A Wavelet Analysis of Pliopleistocene Climate Indicators: A New View of Periodicity Evolution

Wavelet analysis offers an alternative to Fourier based time-series analysis, and is particularly useful when the amplitudes and periods of dominant cycles are time dependent. We analyse climatic records derived from oxygen isotopic ratios of marine sediment cores with modified Morlet wavelets. We use a normalization of the Morlet wavelets which allows direct correspondence with Fourier analysis. This provides a direct view of the oscillations at various frequencies, and illustrates the nature of the time-dependence of the dominant cycles.

In human basophils, IL-3 selectively induces RANKL expression that is modulated by IgER-dependent and IgER-independent stimuli

BACKGROUND Receptor activator of NF-κB ligand (RANKL) is expressed as either surface (hRANKL1, hRANKL2) or soluble (hRANKL3) form. RANKL is involved in multifaceted processes of immunoregulation and bone resorption such as they occur in rheumatoid arthritis (RA). Interestingly, activated basophils, which are effector cells in allergic inflammation, contribute to the progress of collagen-induced arthritis (CIA), a mouse model for RA. Here, we investigate under which conditions human basophils express RANKL. METHODS Among other stimuli, basophils were cultured with IL-3 alone. Alternatively, as a secondary stimulus, IgER-dependent or IgER-independent agents were added simultaneously either with IL-3 or after prolonged IL-3 culturing. Expression of RANKL protein and mRNA was analyzed by flow cytometry, ELISA, and real-time PCR. A coculture system was applied to investigate biological activity of basophil-derived RANKL. RESULTS We show that in human basophils, IL-3 but no other stimulus induces de novo expression of soluble and surface RANKL, of which the latter enhances survival of MoDC. Upon simultaneous stimulation, IgER cross-linking reduces surface RANKL expression, while IgER-independent stimuli have no effect. This is in contrast to consecutive stimulation, as triggering with both IgER-dependent and IgER-independent stimuli enhances RANKL expression, particularly in its soluble form. Real-time PCR analysis shows that RANKL expression is mainly regulated at the mRNA level. CONCLUSION This study identifies IL-3 as a potent inducer of RANKL expression in human basophils, suggesting them to interact with bone physiology and activation of immune cells. IgER-dependent and IgER-independent stimuli modulate the IL-3-mediated RANKL expression in a time- and stimulus-dependent fashion.

A space-time analysis of reported shigellosis and salmonellosis cases in Texas from 2000 to 2004

Background. The purpose of this study was to describe the risk factors and demographics of persons with salmonellosis and shigellosis and to investigate both seasonal and spatial variations in the occurrence of these infections in Texas from 2000 to 2004, utilizing time series analyses and the geographic information system digital mapping methods. ^ Methods. Spatial Analysis: MapInfo software was used to map the distribution of age-adjusted rates of reported shigellosis and salmonellosis in Texas from 2000–2004 by zip codes. Census data on above or below poverty level, household income, highest level of educational attainment, race, ethnicity, and urban/rural community status was obtained from the 2000 Decennial Census for each zip code. The zip codes with the upper 10% and lower 10% were compared using t-tests and logistic regression to determine whether there were any potential risk factors. ^ Temporal analysis. Seasonal patterns in the prevalence of infections in Texas from 2000 to 2003 were determined by performing time-series analysis on the numbers of cases of salmonellosis and shigellosis. A linear regression was also performed to assess for trends in the incidence of each disease, along with auto-correlation and multi-component cosinor analysis. ^ Results. Spatial analysis: Analysis by general linear model showed a significant association between infection rates and age, with young children aged less than 5 and those aged 5–9 years having increased risk of infection for both disease conditions. The data demonstrated that those populations with high percentages of people who attained a higher than high school education were less likely to be represented in zip codes with high rates of shigellosis. However, for salmonellosis, logistic regression models indicated that when compared to populations with high percentages of non-high school graduates, having a high school diploma or equivalent increased the odds of having a high rate of infection. ^ Temporal analysis. For shigellosis, multi-component cosinor analyses were used to determine the approximated cosine curve which represented a statistically significant representation of the time series data for all age groups by sex. The shigellosis results show 2 peaks, with a major peak occurring in June and a secondary peak appearing around October. Salmonellosis results showed a single peak and trough in all age groups with the peak occurring in August and the trough occurring in February. ^ Conclusion. The results from this study can be used by public health agencies to determine the timing of public health awareness programs and interventions in order to prevent salmonellosis and shigellosis from occurring. Because young children depend on adults for their meals, it is important to increase the awareness of day-care workers and new parents about modes of transmission and hygienic methods of food preparation and storage. ^

Reference list of 120 datasets from time series station Payerne used for exploratory search

The analysis of time-dependent data is an important problem in many application domains, and interactive visualization of time-series data can help in understanding patterns in large time series data. Many effective approaches already exist for visual analysis of univariate time series supporting tasks such as assessment of data quality, detection of outliers, or identification of periodically or frequently occurring patterns. However, much fewer approaches exist which support multivariate time series. The existence of multiple values per time stamp makes the analysis task per se harder, and existing visualization techniques often do not scale well. We introduce an approach for visual analysis of large multivariate time-dependent data, based on the idea of projecting multivariate measurements to a 2D display, visualizing the time dimension by trajectories. We use visual data aggregation metaphors based on grouping of similar data elements to scale with multivariate time series. Aggregation procedures can either be based on statistical properties of the data or on data clustering routines. Appropriately defined user controls allow to navigate and explore the data and interactively steer the parameters of the data aggregation to enhance data analysis. We present an implementation of our approach and apply it on a comprehensive data set from the field of earth bservation, demonstrating the applicability and usefulness of our approach.

A second order in time modified Lagrange-Galerkin finite element method for the incompressible Navier-Stokes equations

We introduce a second order in time modified Lagrange--Galerkin (MLG) method for the time dependent incompressible Navier--Stokes equations. The main ingredient of the new method is the scheme proposed to calculate in a more efficient manner the Galerkin projection of the functions transported along the characteristic curves of the transport operator. We present error estimates for velocity and pressure in the framework of mixed finite elements when either the mini-element or the $P2/P1$ Taylor--Hood element are used.

Análisis de sistemas dinámicos y complejos en la Liga Profesional de Balonmano de España = Complex and dynamical systems analysis in Spanish Professional Handball League

El propósito de esta tesis fue estudiar el rendimiento ofensivo de los equipos de balonmano de élite cuando se considera el balonmano como un sistema dinámico complejo no lineal. La perspectiva de análisis dinámica dependiente del tiempo fue adoptada para evaluar el rendimiento de los equipos durante el partido. La muestra general comprendió los 240 partidos jugados en la temporada 2011-2012 de la liga profesional masculina de balonmano de España (Liga ASOBAL). En el análisis posterior solo se consideraron los partidos ajustados (diferencia final de goles ≤ 5; n = 142). El estado del marcador, la localización del partido, el nivel de los oponentes y el periodo de juego fueron incorporados al análisis como variables situacionales. Tres estudios compusieron el núcleo de la tesis. En el primer estudio, analizamos la coordinación entre las series temporales que representan el proceso goleador a lo largo del partido de cada uno de los dos equipos que se enfrentan. Autocorrelaciones, correlaciones cruzadas, doble media móvil y transformada de Hilbert fueron usadas para el análisis. El proceso goleador de los equipos presentó una alta consistencia a lo largo de todos los partidos, así como fuertes modos de coordinación en fase en todos los contextos de juego. Las únicas diferencias se encontraron en relación al periodo de juego. La coordinación en los procesos goleadores de los equipos fue significativamente menor en el 1er y 2º periodo (0–10 min y 10–20 min), mostrando una clara coordinación creciente a medida que el partido avanzaba. Esto sugiere que son los 20 primeros minutos aquellos que rompen los partidos. En el segundo estudio, analizamos los efectos temporales (efecto inmediato, a corto y a medio plazo) de los tiempos muertos en el rendimiento goleador de los equipos. Modelos de regresión lineal múltiple fueron empleados para el análisis. Los resultados mostraron incrementos de 0.59, 1.40 y 1.85 goles para los periodos que comprenden la primera, tercera y quinta posesión de los equipos que pidieron el tiempo muerto. Inversamente, se encontraron efectos significativamente negativos para los equipos rivales, con decrementos de 0.50, 1.43 y 2.05 goles en los mismos periodos respectivamente. La influencia de las variables situacionales solo se registró en ciertos periodos de juego. Finalmente, en el tercer estudio, analizamos los efectos temporales de las exclusiones de los jugadores sobre el rendimiento goleador de los equipos, tanto para los equipos que sufren la exclusión (inferioridad numérica) como para los rivales (superioridad numérica). Se emplearon modelos de regresión lineal múltiple para el análisis. Los resultados mostraron efectos negativos significativos en el número de goles marcados por los equipos con un jugador menos, con decrementos de 0.25, 0.40, 0.61, 0.62 y 0.57 goles para los periodos que comprenden el primer, segundo, tercer, cuarto y quinto minutos previos y posteriores a la exclusión. Para los rivales, los resultados mostraron efectos positivos significativos, con incrementos de la misma magnitud en los mismos periodos. Esta tendencia no se vio afectada por el estado del marcador, localización del partido, nivel de los oponentes o periodo de juego. Los incrementos goleadores fueron menores de lo que se podría esperar de una superioridad numérica de 2 minutos. Diferentes teorías psicológicas como la paralización ante situaciones de presión donde se espera un gran rendimiento pueden ayudar a explicar este hecho. Los últimos capítulos de la tesis enumeran las conclusiones principales y presentan diferentes aplicaciones prácticas que surgen de los tres estudios. Por último, se presentan las limitaciones y futuras líneas de investigación. ABSTRACT The purpose of this thesis was to investigate the offensive performance of elite handball teams when considering handball as a complex non-linear dynamical system. The time-dependent dynamic approach was adopted to assess teams’ performance during the game. The overall sample comprised the 240 games played in the season 2011-2012 of men’s Spanish Professional Handball League (ASOBAL League). In the subsequent analyses, only close games (final goal-difference ≤ 5; n = 142) were considered. Match status, game location, quality of opposition, and game period situational variables were incorporated into the analysis. Three studies composed the core of the thesis. In the first study, we analyzed the game-scoring coordination between the time series representing the scoring processes of the two opposing teams throughout the game. Autocorrelation, cross-correlation, double moving average, and Hilbert transform were used for analysis. The scoring processes of the teams presented a high consistency across all the games as well as strong in-phase modes of coordination in all the game contexts. The only differences were found when controlling for the game period. The coordination in the scoring processes of the teams was significantly lower for the 1st and 2nd period (0–10 min and 10–20 min), showing a clear increasing coordination behavior as the game progressed. This suggests that the first 20 minutes are those that break the game-scoring. In the second study, we analyzed the temporal effects (immediate effect, short-term effect, and medium-term effect) of team timeouts on teams’ scoring performance. Multiple linear regression models were used for the analysis. The results showed increments of 0.59, 1.40 and 1.85 goals for the periods within the first, third and fifth timeout ball possessions for the teams that requested the timeout. Conversely, significant negative effects on goals scored were found for the opponent teams, with decrements of 0.59, 1.43 and 2.04 goals for the same periods, respectively. The influence of situational variables on the scoring performance was only registered in certain game periods. Finally, in the third study, we analyzed the players’ exclusions temporal effects on teams’ scoring performance, for the teams that suffer the exclusion (numerical inferiority) and for the opponents (numerical superiority). Multiple linear regression models were used for the analysis. The results showed significant negative effects on the number of goals scored for the teams with one less player, with decrements of 0.25, 0.40, 0.61, 0.62, and 0.57 goals for the periods within the previous and post one, two, three, four and five minutes of play. For the opponent teams, the results showed positive effects, with increments of the same magnitude in the same game periods. This trend was not affected by match status, game location, quality of opposition, or game period. The scoring increments were smaller than might be expected from a 2-minute numerical playing superiority. Psychological theories such as choking under pressure situations where good performance is expected could contribute to explain this finding. The final chapters of the thesis enumerate the main conclusions and underline the main practical applications that arise from the three studies. Lastly, limitations and future research directions are described.

Rho-dependent Regulation of Cell Spreading by the Tetraspan Membrane Protein Gas3/PMP22

Gas3/PMP22 plays a crucial role in regulating myelin formation and maintenance, and different genetic alterations in gas3/PMP22 are responsible for a set of human peripheral neuropathies. We have previously demonstrated that Gas3/PMP22 could regulate susceptibility to apoptosis in NIH3T3 cells but not in REF 52 cells. In this report we demonstrate that when the apoptotic response triggered by gas3/PMP22 was counteracted by Bcl-2 coexpression, morphological changes were observed. Time-lapse analysis confirmed that Gas3/PMP22 can modulate cell spreading, and this effect was strengthened after inhibition of phosphoinositide 3-kinase. Using the active form of the small GTPase RhoA, we have been able to dissect the different Gas3/PMP22 biological activities. RhoA counteracted the Gas3/PMP22-dependent morphological response but was unable to neutralize the apoptotic response. Treatment of NIH3T3 cells with cytotoxic necrotizing factor 1, which activates endogenous Rho, also counteracted Gas3/PMP22-mediated cell shape and spreading changes. Treatment of REF 52 cells, which are unresponsive to Gas3/PMP22 overexpression, with the C3 exoenzyme, inhibiting Rho activity, renders REF 52 cells responsive to Gas3/PMP22 overexpression for cell shape and spreading changes. Finally, assembly of stress fibers and focal adhesions complexes, in response to lysophosphatidic acid–induced endogenous Rho activation, was impaired in Gas3/PMP22-overexpressing cells. We hypothesize that cell shape and spreading regulated by Gas3/PMP22 through the Rho GTPase might have an important role during Schwann cells differentiation and myelinization.

The analysis of economic time series.

"Originally published as Monograph no.6 of the Cowles Commission for Research in Economics."

Seasonal analysis of economic time series /

Mode of access: Internet.

Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil

Aim To develop a population pharmacokinetic model for mycophenolic acid in adult kidney transplant recipients, quantifying average population pharmacokinetic parameter values, and between- and within-subject variability and to evaluate the influence of covariates on the pharmacokinetic variability. Methods Pharmacokinetic data for mycophenolic acid and covariate information were previously available from 22 patients who underwent kidney transplantation at the Princess Alexandra Hospital. All patients received mycophenolate mofetil 1 g orally twice daily. A total of 557 concentration-time points were available. Data were analysed using the first-order method in NONMEM (version 5 level 1.1) using the G77 FORTRAN compiler. Results The best base model was a two-compartment model with a lag time (apparent oral clearance was 271 h(-1), and apparent volume of the central compartment 981). There was visual evidence of complex absorption and time-dependent clearance processes, but they could not be successfully modelled in this study. Weight was investigated as a covariate, but no significant relationship was determined. Conclusions The complexity in determining the pharmacokinetics of mycophenolic acid is currently underestimated. More complex pharmacokinetic models, though not supported by the limited data collected for this study, may prove useful in the future. The large between-subject and between-occasion variability and the possibility of nonlinear processes associated with the pharmacokinetics of mycophenolic acid raise questions about the value of the use of therapeutic monitoring and limited sampling strategies.

Flow field analysis of some mixing and conveying screw element regions, within a closely intermeshing, co-rotating twin-screw extruder.

Grafting of antioxidants and other modifiers onto polymers by reactive extrusion, has been performed successfully by the Polymer Processing and Performance Group at Aston University. Traditionally the optimum conditions for the grafting process have been established within a Brabender internal mixer. Transfer of this batch process to a continuous processor, such as an extruder, has, typically, been empirical. To have more confidence in the success of direct transfer of the process requires knowledge of, and comparison between, residence times, mixing intensities, shear rates and flow regimes in the internal mixer and in the continuous processor.The continuous processor chosen for the current work in the closely intermeshing, co-rotating twin-screw extruder (CICo-TSE). CICo-TSEs contain screw elements that convey material with a self-wiping action and are widely used for polymer compounding and blending. Of the different mixing modules contained within the CICo-TSE, the trilobal elements, which impose intensive mixing, and the mixing discs, which impose extensive mixing, are of importance when establishing the intensity of mixing. In this thesis, the flow patterns within the various regions of the single-flighted conveying screw elements and within both the trilobal element and mixing disc zones of a Betol BTS40 CICo-TSE, have been modelled using the computational fluid dynamics package Polyflow. A major obstacle encountered when solving the flow problem within all of these sets of elements, arises from both the complex geometry and the time-dependent flow boundaries as the elements rotate about their fixed axes. Simulation of the time dependent boundaries was overcome by selecting a number of sequential 2D and 3D geometries, used to represent partial mixing cycles. The flow fields were simulated using the ideal rheological properties of polypropylene and characterised in terms of velocity vectors, shear stresses generated and a parameter known as the mixing efficiency. The majority of the large 3D simulations were performed on the Cray J90 supercomputer situated at the Rutherford-Appleton laboratories, with pre- and postprocessing operations achieved via a Silicon Graphics Indy workstation. A mechanical model was constructed consisting of various CICo-TSE elements rotating within a transparent outer barrel. A technique has been developed using coloured viscous clays whereby the flow patterns and mixing characteristics within the CICo-TSE may be visualised. In order to test and verify the simulated predictions, the patterns observed within the mechanical model were compared with the flow patterns predicted by the computational model. The flow patterns within the single-flighted conveying screw elements in particular, showed good agreement between the experimental and simulated results.

Temporal finite elements in the dynamic analysis of structures

This thesis demonstrates that the use of finite elements need not be confined to space alone, but that they may also be used in the time domain, It is shown that finite element methods may be used successfully to obtain the response of systems to applied forces, including, for example, the accelerations in a tall structure subjected to an earthquake shock. It is further demonstrated that at least one of these methods may be considered to be a practical alternative to more usual methods of solution. A detailed investigation of the accuracy and stability of finite element solutions is included, and methods of applications to both single- and multi-degree of freedom systems are described. Solutions using two different temporal finite elements are compared with those obtained by conventional methods, and a comparison of computation times for the different methods is given. The application of finite element methods to distributed systems is described, using both separate discretizations in space and time, and a combined space-time discretization. The inclusion of both viscous and hysteretic damping is shown to add little to the difficulty of the solution. Temporal finite elements are also seen to be of considerable interest when applied to non-linear systems, both when the system parameters are time-dependent and also when they are functions of displacement. Solutions are given for many different examples, and the computer programs used for the finite element methods are included in an Appendix.

Microarray analysis of expression of cell death-associated genes in spinal cord cells with cyclic tensile strain

Previous studies have described alterations in gene expression following spinal cord injury, but this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile strain on cultured spinal cord cells from E15 Sprague-Dawley rats. Microarray analysis of gene expression and categorization of identified genes were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. The application of cyclic tensile strain reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. GO analysis identified candidate genes related to apoptosis (44) and to response to stimulus (17). KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated and validated by RT-PCR analysis. Spinal cord cells undergo cell death in response to cyclic tensile strain, which were dose- and time-dependent, with upregulation of various genes, in particular of the MAPK pathway.

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30-60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BACKGROUND: The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.

METHODS: A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.

RESULTS: In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I(2)=0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I(2)=67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04).

CONCLUSION: In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.