Results of n-alkane biomarker analyses and paleoclimate reconstruction

The current study presents quantitative reconstructions of tree cover, annual precipitation and mean July temperature derived from the pollen record from Lake Billyakh (65°17'N, 126°47'E, 340 m above sea level) spanning the last ca. 50 kyr. The reconstruction of tree cover suggests presence of woody plants through the entire analyzed time interval, although trees played only a minor role in the vegetation around Lake Billyakh prior to 14 kyr BP (<5%). This result corroborates low percentages of tree pollen and low scores of the cold deciduous forest biome in the PG1755 record from Lake Billyakh. The reconstructed values of the mean temperature of the warmest month ~8-10 °C do not support larch forest or woodland around Lake Billyakh during the coldest phase of the last glacial between ~32 and ~15 kyr BP. However, modern cases from northern Siberia, ca. 750 km north of Lake Billyakh, demonstrate that individual larch plants can grow within shrub and grass tundra landscape in very low mean July temperatures of about 8 °C. This makes plausible our hypothesis that the western and southern foreland of the Verkhoyansk Mountains could provide enough moist and warm microhabitats and allow individual larch specimens to survive climatic extremes of the last glacial. Reconstructed mean values of precipitation are about 270 mm/yr during the last glacial interval. This value is almost 100 mm higher than modern averages reported for the extreme-continental north-eastern Siberia east of Lake Billyakh, where larch-dominated cold deciduous forest grows at present. This suggests that last glacial environments around Lake Billyakh were never too dry for larch to grow and that the summer warmth was the main factor, which limited tree growth during the last glacial interval. The n-alkane analysis of the Siberian plants presented in this study demonstrates rather complex alkane distribution patterns, which challenge the interpretation of the fossil records. In particular, extremely low n-alkane concentrations in the leaves of local coniferous trees and shrubs suggest that their contribution to the litter and therefore to the fossil lake sediments might be not high enough for tracing the Quaternary history of the needleleaved taxa using the n-alkane biomarker method.

Quantitative silicoflagellate data from the southern Indic Ocean from ODP Holes 188-1165B, 120-748B and 120-751A

In the modern marine environment the silicoflagellate genus Dictyocha is rare, or absent, south of the Antarctic polar front (APF); the genus Distephanus, in contrast, is dominant. In sediments recovered from ODP Site 1165, 1600 km south of the front, however, three intervals where Dictyocha is abundant are interpreted to represent Pliocene warm events. Comparison of our data with Ciesielski and Weaver's [1974] modern core top silicoflagellate relationship with sea surface temperature (SST) indicates that at Site 1165 mean annual SST was approximately 5°C at 3.7 Ma (event I), and approximately 4°C at 4.3-4.4 Ma (event II) and 4.55-4.8 Ma (event III). Event I represents a 5.5°C warming, and events II and III represents a 4.5°C warming relative to modern mean annual SST. Dictyocha is absent from other Site 1165 Pliocene intervals, which suggests that cooler SST (<2°C) prevailed. The warm events detected at Site 1165 may represent times when North Atlantic Deep Water production and ocean heat transport into the Southern Ocean exerted maximum influence.

Paleoclimate reconstruction from Miocene macroflora in Kazakhstan compiled from various publications

25 datasets (13 fossil leaf and pollen assemblages, 12 quantitative palaeoclimatic datasets) are provided in order to analyse Early Miocene palaeoclimate in Kazakhstan. The rich fossil record in Kazakhstan documents that during the Oligocene and Early Miocene this area in Central Eurasia was densely forested with warm-temperate deciduous trees and shrubs of the so-called "Turgayan flora". 29 fossil floras from 13 localities have been selected for a quantitative analysis of the Aquitanian (early Early Miocene) climate situation in Kazakhstan. The assessed mean annual temperatures generally place around 15 °C, while values of mean annual precipitation are of about 1000 mm. In combination with several other climate parameters estimated (temperatures of warmest and coldest months, precipitation rates of wettest, driest and warmest months), these data reflect uniform climatic conditions over several thousands of square kilometres. Data of temperature parameters show slight spatial differentiations, with generally cooler mean annual temperatures and higher seasonality (i.e. warmer summers and colder winters) in the north-eastern part of the study area compared with the south-western area around Lake Aral. As compared with palaeoclimate estimates for the European and East Asian Aquitanian, the central part of the Eurasian continent reveals evident signals of higher seasonality and slightly increased continentality.

Reconstruction and in silico analysis of the MAPK signaling pathways in the human blood fluke, Schistosoma japonicum

At present, little is known about signal transduction mechanisms in schistosomes, which cause the disease of schistosomiasis. The mitogen-activated protein kinase (MAPK) signaling pathways, which are evolutionarily conserved from yeast to Homo sapiens, play key roles in multiple cellular processes. Here, we reconstructed the hypothetical MAPK signaling pathways in Schistosoma japonicum and compared the schistosome pathways with those of model eukaryote species. We identified 60 homologous components in the S. japoncium MAPK signaling pathways. Among these, 27 were predicted to be full-length sequences. Phylogenetic analysis of these proteins confirmed the evolutionary conservation of the MAPK signaling pathways. Remarkably, we identified S. japonicum homologues of GTP-binding protein beta and alpha-I subunits in the yeast mating pathway, which might be involved in the regulation of different life stages and female sexual maturation processes as well in schistosomes. In addition, several pathway member genes, including ERK, JNK, Sja-DSP, MRAS and RAS, were determined through quantitative PCR analysis to be expressed in a stage-specific manner, with ERK, JNK and their inhibitor Sja-DSP markedly upregulated in adult female schistosomes. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

In-situ measurement and the reconstruction in 3D of femtosecond inscription induced complex permittivity modification in glass

We demonstrate a new approach to in-situ measurement of femtosecond laser pulse induced changes in glass enabling the reconstruction in 3D of the induced complex permittivity modification. The technique can be used to provide single shot and time resolved quantitative measurements with a micron scale spatial resolution.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Winter sea surface temperature reconstruction from planktic foraminiferal transfer functions in the northeastern Arabian Sea over the last two millennia

The Indian monsoon system is an important climate feature of the northern Indian Ocean. Small variations of the wind and precipitation patterns have fundamental influence on the societal, agricultural, and economic development of India and its neighboring countries. To understand current trends, sensitivity to forcing, or natural variation, records beyond the instrumental period are needed. However, high-resolution archives of past winter monsoon variability are scarce. One potential archive of such records are marine sediments deposited on the continental slope in the NE Arabian Sea, an area where present-day conditions are dominated by the winter monsoon. In this region, winter monsoon conditions lead to distinctive changes in surface water properties, affecting marine plankton communities that are deposited in the sediment. Using planktic foraminifera as a sensitive and well-preserved plankton group, we first characterize the response of their species distribution on environmental gradients from a dataset of surface sediment samples in the tropical and sub-tropical Indian Ocean. Transfer functions for quantitative paleoenvironmental reconstructions were applied to a decadal-scale record of assemblage counts from the Pakistan Margin spanning the last 2000?years. The reconstructed temperature record reveals an intensification of winter monsoon intensity near the year 100 CE. Prior to this transition, winter temperatures were >1.5°C warmer than today. Conditions similar to the present seem to have established after 450 CE, interrupted by a singular event near 950 CE with warmer temperatures and accordingly weak winter monsoon. Frequency analysis revealed significant 75-, 40-, and 37-year cycles, which are known from decadal- to centennial-scale resolution records of Indian summer monsoon variability and interpreted as solar irradiance forcing. Our first independent record of Indian winter monsoon activity confirms that winter and summer monsoons were modulated on the same frequency bands and thus indicates that both monsoon systems are likely controlled by the same driving force.

Sea surface temperature reconstruction based on planktonic foraminifera of surface sediments and sediment cores off Iberia

Quantitative and qualitative analyses of planktonic foraminiferal assemblages from 134 core-top sediment samples collected along the western Iberian margin were used to assess the latitudinal and longitudinal changes in surface water conditions and to calibrate a Sea Surface Temperature (SST) transfer function for this seasonal coastal upwelling region. Q-mode factor analysis performed on relative abundances yielded three factors that explain 96% of the total variance: factor 1 (50%) is exclusively defined by Globigerina bulloides, the most abundant and widespread species, and reflects the modern seasonal (May to September) coastal upwelling areas; factor 2 (32%) is dominated by Neogloboquadrina pachyderma (dextral) and Globorotalia inflata and seems to be associated with the Portugal Current, the descending branch of the North Atlantic Drift; factor 3 (14%) is defined by the tropical-sub-tropical species Globigerinoides ruber (white), Globigerinoides trilobus trilobus, and G. inflata and mirrors the influence of the winter-time eastern branch of the Azores Current. In conjunction with satellite-derived SST for summer and winter seasons integrated over an 18 year period the regional foraminiferal data set is used to calibrate a SST transfer function using Imbrie & Kipp, MAT and SIMMAX(ndw) techniques. Similar predicted errors (RMSEP), correlation coefficients, and residuals' deviation from SST estimated for both techniques were observed for both seasons. All techniques appear to underestimate SST off the southern Iberia margin, an area mainly occupied by warm waters where upwelling occurs only occasionally, and overestimate SST on the northern part of the west coast of the Iberia margin, where cold waters are present nearly all year round. The comparison of these regional calibrations with former Atlantic and North Atlantic calibrations for two cores, one of which is influenced by upwelling, reveals that the regional one attests more robust paleo-SSTs than for the other approaches.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

POSE ESTIMATION AND 3D RECONSTRUCTION USING SENSOR FUSION

A camera maps 3-dimensional (3D) world space to a 2-dimensional (2D) image space. In the process it loses the depth information, i.e., the distance from the camera focal point to the imaged objects. It is impossible to recover this information from a single image. However, by using two or more images from different viewing angles this information can be recovered, which in turn can be used to obtain the pose (position and orientation) of the camera. Using this pose, a 3D reconstruction of imaged objects in the world can be computed. Numerous algorithms have been proposed and implemented to solve the above problem; these algorithms are commonly called Structure from Motion (SfM). State-of-the-art SfM techniques have been shown to give promising results. However, unlike a Global Positioning System (GPS) or an Inertial Measurement Unit (IMU) which directly give the position and orientation respectively, the camera system estimates it after implementing SfM as mentioned above. This makes the pose obtained from a camera highly sensitive to the images captured and other effects, such as low lighting conditions, poor focus or improper viewing angles. In some applications, for example, an Unmanned Aerial Vehicle (UAV) inspecting a bridge or a robot mapping an environment using Simultaneous Localization and Mapping (SLAM), it is often difficult to capture images with ideal conditions. This report examines the use of SfM methods in such applications and the role of combining multiple sensors, viz., sensor fusion, to achieve more accurate and usable position and reconstruction information. This project investigates the role of sensor fusion in accurately estimating the pose of a camera for the application of 3D reconstruction of a scene. The first set of experiments is conducted in a motion capture room. These results are assumed as ground truth in order to evaluate the strengths and weaknesses of each sensor and to map their coordinate systems. Then a number of scenarios are targeted where SfM fails. The pose estimates obtained from SfM are replaced by those obtained from other sensors and the 3D reconstruction is completed. Quantitative and qualitative comparisons are made between the 3D reconstruction obtained by using only a camera versus that obtained by using the camera along with a LIDAR and/or an IMU. Additionally, the project also works towards the performance issue faced while handling large data sets of high-resolution images by implementing the system on the Superior high performance computing cluster at Michigan Technological University.