Differential expression analysis for sequence count data via mixtures of negative binomials

The recent advent of Next-generation sequencing technologies has revolutionized the way of analyzing the genome. This innovation allows to get deeper information at a lower cost and in less time, and provides data that are discrete measurements. One of the most important applications with these data is the differential analysis, that is investigating if one gene exhibit a different expression level in correspondence of two (or more) biological conditions (such as disease states, treatments received and so on). As for the statistical analysis, the final aim will be statistical testing and for modeling these data the Negative Binomial distribution is considered the most adequate one especially because it allows for "over dispersion". However, the estimation of the dispersion parameter is a very delicate issue because few information are usually available for estimating it. Many strategies have been proposed, but they often result in procedures based on plug-in estimates, and in this thesis we show that this discrepancy between the estimation and the testing framework can lead to uncontrolled first-type errors. We propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Afterwards, three consistent statistical tests are developed for differential expression analysis. We show that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it is the best one in reaching the nominal value for the first-type error, while keeping elevate power. The method is finally illustrated on prostate cancer RNA-seq data.

Statistical shape modeling of pathological scoliotic vertebrae: A comparative analysis

Statistical shape models (SSMs) have been used widely as a basis for segmenting and interpreting complex anatomical structures. The robustness of these models are sensitive to the registration procedures, i.e., establishment of a dense correspondence across a training data set. In this work, two SSMs based on the same training data set of scoliotic vertebrae, and registration procedures were compared. The first model was constructed based on the original binary masks without applying any image pre- and post-processing, and the second was obtained by means of a feature preserving smoothing method applied to the original training data set, followed by a standard rasterization algorithm. The accuracies of the correspondences were assessed quantitatively by means of the maximum of the mean minimum distance (MMMD) and Hausdorf distance (H(D)). Anatomical validity of the models were quantified by means of three different criteria, i.e., compactness, specificity, and model generalization ability. The objective of this study was to compare quasi-identical models based on standard metrics. Preliminary results suggest that the MMMD distance and eigenvalues are not sensitive metrics for evaluating the performance and robustness of SSMs.

Multi-Scale Modeling for Image Analysis of Brain Tumor Studies

Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multi-scale, multi-physics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlasbased segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.

The scholarly networks of Albrecht von Haller and the Economic Society of Bern – a multi-level network analysis

Here, by the example of the transfer of cultivated plants in the context of the correspondence networks of Albrecht von Haller and the Economic Society, a multi-level network analysis is suggested. By a multi-level procedure, the chronological dynamics, the social structure, the spatial distribution and the functional networking are analyzed one after the other. These four levels of network analysis do not compete with each other but are mutually supporting. This aims at a deeper understanding of how these networks contributed to an international transfer of knowledge in the 18th century.

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

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.

A climatological analysis of high-precipitation events in Dronning Maud Land, Antarctica, and associated large-scale atmospheric conditions

The link between high precipitation in Dronning Maud Land (DML), Antarctica, and the large-scale atmospheric circulation is investigated using ERA-Interim data for 1979–2009. High-precipitation events are analyzed at Halvfarryggen situated in the coastal region of DML and at Kohnen Station located in its interior. This study further includes a comprehensive comparison of high precipitation in ERA-Interim with precipitation data from the Antarctic Mesoscale Prediction System (AMPS) and snow accumulation measurements from automatic weather stations (AWSs), with the limitations of such a comparison being discussed. The ERA-Interim and AMPS precipitation data agree very well. However, the correspondence between high precipitation in ERA-Interim and high snow accumulation at the AWSs is relatively weak. High-precipitation events at both Halvfarryggen and Kohnen are typically associated with amplified upper level waves. This large-scale atmospheric flow pattern is preceded by the downstream development of a Rossby wave train from the eastern South Pacific several days before the precipitation event. At the surface, a cyclone located over the Weddell Sea is the main synoptic ingredient for high precipitation both at Halvfarryggen and at Kohnen. A blocking anticyclone downstream is not a requirement for high precipitation per se, but a larger share of blocking occurrences during the highest-precipitation days in DML suggests that these blocks strengthen the vertically integrated water vapor transport (IVT) into DML. A strong link between high precipitation and the IVT perpendicular to the local orography suggests that IVT could be used as a “proxy” for high precipitation, in particular over DML's interior.

Bulk chemical analysis of sediments ODP Hole 110-671B and 110-672A

Chemical analyses for calcium carbonate, organic carbon, and major constituents (Al, Ti, Ca, Mg, K, Fe) of bulk sediments collected in Hole 671B have been carried out. Organic carbon contents in Pleistocene through middle Miocene sediments above the zone of decollement are very low (<0.1%); below the decollement considerably higher concentrations of organic carbon occur (up to 1 %). Changes in Ti/Al and Fe/Al ratios are minor, but K/Al and Mg/Al ratios show clear trends with the age of the sediments. Preliminary comparisons of these ratios with mineralogic information on clays indicate good correspondence with clay abundances. Calculations of the mass flux of magnesium from the overlying ocean into the pore fluids suggest that addition of magnesium to the sediments is difficult to detect, especially in the absence of a background reference concentration.

Late Pliocene dinoflagellate cyst and diatom analysis from a high resolution sequence in DSDP Site 594, Chatham Rise, south west Pacific

A high resolution mixed carbonate and siliciclastic sequence from DSDP Site 594 contains a detailed record of climate change in the late Pliocene. The sequence can be accurately dated by the LAD of Nitzschia weaveri, the LAD of Thalassiosira insigna, the LAD of T. vulnifica and the LAD of T. kolbei diatom datums. Carbonate content and delta18O signatures provide added resolution and place the sequence between isotope stage 100 and 92. The sequence contains well-preserved and diverse dinoflagellate cyst floras. Use of principal component (PCA) and canonical correspondence analyses (CCA) identifies changes in the assemblages that principally reflect warming and cooling trends. Species association with warmer climates included Impagidinium patulum, I. paradoxum and I. sp. cf. paradoxum while those from cooler climates include Invertecysta tabulata and I. velorum. CCA is shown to be a valuable method of determining the past environmental preferences of extinct species such as I. tabulata.

GIS analysis for the study of rural depopulation: the Kingdom of Valencia (Tomas Lopez 1789)

One of the more aspects that have shaped the landscape is the human impact. The human impact has the clearest indicator of the density of settlements in a particular geographic region. In this paper we study all settlements shown on the map of the Kingdom of Valencia, Spain Geographic Atlas (AGE) of Tomas Lopez (1788), and their correspondence with the current ones. To meet this goal we have developed a specific methodology, the systematic study of all existing settlements in historical cartography. This will determine which have disappeared and which have been renamed. The material used has been the historical cartography of Tomas Lopez, part of the AGE (1789), the Kingdom of Valencia (1789), sheets numbers (78, 79, 80 and 81); Current mapping of the provinces of Alicante, Valencia, Castellon, Teruel, Tattagona and Cuenca; As main software ArcGis V.9.3. The steps followed in the methodology are as follows: 1. Check the scale of the maps. Analyze the possible use of a spherical earth model. 2. Geo-reference of maps with latitude and longitude framework. Move the historical longitude origin to the origin longitude of modern cartography. 3 Digitize of all population settlements or cities. 4 Identify historic settlements or cities corresponding with current ones. 5. If the maps have the same orientation and scale, replace the coordinate transformation of historical settlements with a new one, by a translation in latitude and longitude equal to the calculated mean value of all ancient map points corresponding to the new. 6. Calculation of absolute accuracy of the two maps, i.e. the linear distance between the points of both maps. 7 draw in the GIS, the settlements without correspondence, in the current coordinates, and with a circle of mean error of the sheet, in order to locate their current location. If there are actual settlements exist within this circle, they are candidates to be the searched settlements. We analyzed more than 2000 settlements represented in the Atlas of Tomas Lopez of the Kingdom of Valencia (1789), of which almost 14.5% have no correspondence with the existing settlements. The rural landscape evolution of the Valencia, oldest kingdom of Valencia, one can say that can be severely affected by the anthropization suffered in the period from 1789 to the present, since 70% of existing settlements actually have appeared after Tomas Lopez¿s cartography, dated on 1789

GIS for cartographic accuracy analysis of settlements in the province of Madrid (AGE Tomas Lopez 1804).

Purpose: In this paper we study all settlements shown on the map of the Province of Madrid, sheet number 1 of AGE (Atlas Geográfico de España of Tomas Lopez 1804) and their correspondence with the current ones. This map is divided in to zones: Madrid and Almonacid de Zorita. Method: The steps followed in the methodology are as follow: 1. Geo-reference of maps with latitude and longitude framework. Move the historical longitude origin to the origin longitude of modern cartography. 2 Digitize of all population settlements or cities (97 on Madrid and 42 on Almonacid de Zorita), 3 Identify historic settlements or cities corresponding with current ones. 4. If the maps have the same orientation and scale, replace the coordinate transformation of historical settlements with a new one, by a translation in latitude and longitude equal to the calculated mean value of all ancient map points corresponding to the new. 5. Calculation of absolute accuracy of the two maps. 6 draw in the GIS, the settlements accuracy. Result: It was found that all AGE settlements have good correspondence with current, ie only 27 settlements lost in Madrid and 2 in Almonacid. The average accuracy is 2.3 and 5.7 km to Madrid and Almonacid de Zorita respectively. Discussion & Conclusion: The final accuracy map obtained shows that there is less error in the middle of the map. This study highlights the great work done by Tomas Lopez in performing this mapping without fieldwork. This demonstrates the great value that has been the work of Tomas Lopez in the history of cartography.

Analysis of linear trade models and relation to scale economies

We discuss linear Ricardo models with a range of parameters. We show that the exact boundary of the region of equilibria of these models is obtained by solving a simple integer programming problem. We show that there is also an exact correspondence between many of the equilibria resulting from families of linear models and the multiple equilibria of economies of scale models.

On the absorbance changes in the photocycle of the photoactive yellow protein: A quantum-chemical analysis

Spectral changes in the photocycle of the photoactive yellow protein (PYP) are investigated by using ab initio multiconfigurational second-order perturbation theory at the available structures experimentally determined. Using the dark ground-state crystal structure [Genick, U. K., Soltis, S. M., Kuhn, P., Canestrelli, I. L. & Getzoff, E. D. (1998) Nature (London) 392, 206–209], the ππ* transition to the lowest excited state is related to the typical blue-light absorption observed at 446 nm. The different nature of the second excited state (nπ*) is consistent with the alternative route detected at 395-nm excitation. The results suggest the low-temperature photoproduct PYPHL as the most plausible candidate for the assignment of the cryogenically trapped early intermediate (Genick et al.). We cannot establish, however, a successful correspondence between the theoretical spectrum for the nanosecond time-resolved x-ray structure [Perman, B., Šrajer, V., Ren, Z., Teng, T., Pradervand, C., et al. (1998) Science 279, 1946–1950] and any of the spectroscopic photoproducts known up to date. It is fully confirmed that the colorless light-activated intermediate recorded by millisecond time-resolved crystallography [Genick, U. K., Borgstahl, G. E. O., Ng, K., Ren, Z., Pradervand, C., et al. (1997) Science 275, 1471–1475] is protonated, nicely matching the spectroscopic features of the photoproduct PYPM. The overall contribution demonstrates that a combined analysis of high-level theoretical results and experimental data can be of great value to perform assignments of detected intermediates in a photocycle.

Cost-analysis engineering;

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