Gene Regulation in The Human Immune System. Gene Expression Signatures of Th2 Cell Differentiation, Type 1 Diabetes, and Intrauterine Immune Adaptation

The human immune system is constantly interacting with the surrounding stimuli and microorganisms. However, when directed against self or harmless antigens, these vital defense mechanisms can cause great damage. In addition, the understanding the underlying mechanism of several human diseases caused by aberrant immune cell functions, for instance type 1 diabetes and allergies, remains far from being complete. In this Ph.D. study these questions were addressed using genome-wide transcriptomic analyses. Asthma and allergies are characterized by a hyperactive response of the T helper 2 (Th2) immune cells. In this study, the target genes of the STAT6 transcription factor in naïve human T cells were identified with RNAi for the first time. STAT6 was shown to act as a central activator of the genes expression upon IL-4 signaling, with both direct and indirect effects on Th2 cell transcriptome. The core transcription factor network induced by IL-4 was identified from a kinetic analysis of the transcriptome. Type 1 diabetes is an autoimmune disease influenced by both the genetic susceptibility of an individual and the disease-triggering environmental factors. To improve understanding of the autoimmune processes driving pathogenesis in the prediabetic phase in humans, a unique series of prospective whole-blood RNA samples collected from HLA-susceptible children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study was studied. Changes in different timewindows of the pathogenesis process were identified, and especially the type 1 interferon response was activated early and throughout the preclinical T1D. The hygiene hypothesis states that allergic diseases, and lately also autoimmune diseases, could be prevented by infections and other microbial contacts acquired in early childhood, or even prenatally. To study the effects of the standard of hygiene on the development of neonatal immune system, cord blood samples from children born in Finland (high standard of living), Estonia (rapid economic growth) and Russian Karelia (low standard of living) were compared. Children born in Russian Karelia deviated from Finnish and Estonian children in many aspects of the neonatal immune system, which was developmentally more mature in Karelia, resembling that of older infants. The results of this thesis offer significant new information on the regulatory networks associated with immune-mediated diseases in human. The results will facilitate understanding and further research on the role of the identified target genes and mechanisms driving the allergic inflammation and type 1 diabetes, hopefully leading to a new era of drug development.

Gene trio signatures as molecular markers to predict response to doxorubicin cyclophosphamide neoadjuvant chemotherapy in breast cancerpatients

In breast cancer patients submitted to neoadjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide, AC), expression of groups of three genes (gene trio signatures) could distinguish responsive from non-responsive tumors, as demonstrated by cDNA microarray profiling in a previous study by our group. In the current study, we determined if the expression of the same genes would retain the predictive strength, when analyzed by a more accessible technique (real-time RT-PCR). We evaluated 28 samples already analyzed by cDNA microarray, as a technical validation procedure, and 14 tumors, as an independent biological validation set. All patients received neoadjuvant chemotherapy (4 AC). Among five trio combinations previously identified, defined by nine genes individually investigated (BZRP, CLPTM1,MTSS1, NOTCH1, NUP210, PRSS11, RPL37A, SMYD2, and XLHSRF-1), the most accurate were established by RPL37A, XLHSRF-1based trios, with NOTCH1 or NUP210. Both trios correctly separated 86% of tumors (87% sensitivity and 80% specificity for predicting response), according to their response to chemotherapy (82% in a leave-one-out cross-validation method). Using the pre-established features obtained by linear discriminant analysis, 71% samples from the biological validation set were also correctly classified by both trios (72% sensitivity; 66% specificity). Furthermore, we explored other gene combinations to achieve a higher accuracy in the technical validation group (as a training set). A new trio, MTSS1, RPL37 and SMYD2, correctly classified 93% of samples from the technical validation group (95% sensitivity and 80% specificity; 86% accuracy by the cross-validation method) and 79% from the biological validation group (72% sensitivity and 100% specificity). Therefore, the combined expression of MTSS1, RPL37 and SMYD2, as evaluated by real-time RT-PCR, is a potential candidate to predict response to neoadjuvant doxorubicin and cyclophosphamide in breast cancer patients.

Essai sur l'origine de la gravure en bois et en taille-douce, et sur la connoissance des estampes des XVe et XVIe siècles, où il est parlé aussi de l'origine des cartes à jouer et des cartes géographiques. Tome 2 / , suivi de Recherches sur l'origine du papier de coton et de lin, sur la calligraphie depuis les plus anciens temps jusqu'à nos jours, sur les miniatures des anciens manuscrits, sur les filigranes des papiers des XIVe, XVe et XVIe siècles, ainsi que sur l'origine et le premier usage des signatures et des chiffres dans l'art de la typographie

Comprend : Mémoire sur l'origine et le premier usage des signatures et des chiffres dans l'art typographique ; Recherches sur l'origine et le premier usage des registres, des signatures, des réclames et des chiffres de page dans les livres imprimés ; Notice sur les éditions stéréotypes

Essai sur l'origine de la gravure en bois et en taille-douce, et sur la connoissance des estampes des XVe et XVIe siècles, où il est parlé aussi de l'origine des cartes à jouer et des cartes géographiques. Tome 1 / , suivi de Recherches sur l'origine du papier de coton et de lin, sur la calligraphie depuis les plus anciens temps jusqu'à nos jours, sur les miniatures des anciens manuscrits, sur les filigranes des papiers des XIVe, XVe et XVIe siècles, ainsi que sur l'origine et le premier usage des signatures et des chiffres dans l'art de la typographie

Comprend : Mémoire sur l'origine et le premier usage des signatures et des chiffres dans l'art typographique ; Recherches sur l'origine et le premier usage des registres, des signatures, des réclames et des chiffres de page dans les livres imprimés ; Notice sur les éditions stéréotypes

Album amicorum Chunradi Kechleri. II y a surtout des signatures recueillies à Bourges en 1584 et 1585

Gaignières.

Arrêt du grand conseil portant réglement pour les banquiers expéditionnaires et les signatures de cour de Rome

[Acte. 1725-03-27. Paris]

Album amicorum Jo. Huenich, Anthuerpiani. Ce volume renferme surtout des signatures recueillies à Constantinople en 1586.

Fonds non déterminé.

Ribbed moraines and subglacial geomorphological signatures of interior-sector palaeo-ice sheet dynamics

Transverse, subglacial bedforms (ribbed moraines) occur frequently in southern Keewatin, Nunavut, Canada, where they record a complex glacial history, including shifting centers of ice dispersal and fluctuating basal thermal regimes. Comprehensive mapping and quantitative morphometric analysis of the subglacial bedform archive in this sector reveals that ribbed moraines are spatially clustered by size and assume a broad range of visually distinct forms. Results suggest that end-member morphologies are consistent with a dichotomous polygenetic origin, and that a continuum of forms emerged through subsequent reshaping processes of variable intensity and duration. Translocation of mobile, immobile and quasi-mobile beds throughout the last glacial cycle conditioned the development of a subglacial deforming bed mosaic, and is likely responsible for the patchy zonation of palimpsest and inherited landscape signatures within this former core region of the Laurentide Ice Sheet. Comparison against field evidence collected from central Norway suggests that bedforming processes can be locally mediated by pre-existing topography.

Phytoplankton Pigment Signatures as a Biomarker in a Tropical Estuary

We are in the cutting edge of a new era of development without leaving any promises to next generation. But the scale and size of the problem are only partially blamed. The juggernaut of Globalisation has trampled upon whatever little hope we might have had making a quick transition to a less energy – intensive world. “Environment friendliness begins at home”. Our quest for productivity and profitability should progress simultaneous with our cooperative responsibility of leaving behind a clean and green earth for the generation to come. Climate change is the most pressing global environmental challenge being faced by humanity, with the quest for better productivity for our fragile ecosystem. It is too late to rely solely on reduction in Green house gas emissions to mitigate climate change although this is undoubtedly crucial. Coastal belts are more prone to these devastating impacts and its protection is an intensive filed of research. The present study describes how the colourful Carotenoids and Chlorophylls can be used in rapid hand on tool in conjunction with molecular biology to open sources and it also explores the fate of organic matter in the aquatic system and underlying sediments.

Signatures of Higher Functions of Brain Dynamics in Electroencephalogram: A Nonlinear Analysis

The brain with its highly complex structure made up of simple units,imterconnected information pathways and specialized functions has always been an object of mystery and sceintific fascination for physiologists,neuroscientists and lately to mathematicians and physicists. The stream of biophysicists are engaged in building the bridge between the biological and physical sciences guided by a conviction that natural scenarios that appear extraordinarily complex may be tackled by application of principles from the realm of physical sciences. In a similar vein, this report aims to describe how nerve cells execute transmission of signals ,how these are put together and how out of this integration higher functions emerge and get reflected in the electrical signals that are produced in the brain.Viewing the E E G Signal through the looking glass of nonlinear theory, the dynamics of the underlying complex system-the brain ,is inferred and significant implications of the findings are explored.

Remote Sensing the Signatures of Upwelling in South Eastern Arabian Sea

In this thesis, a variety of available satellite data products have been made use of to bring out a synergistic analysis on the upwelling phenomenon in SEAS. Basic concepts of remote sensing, upwelling and linked oceanography topics have been dealt in this work .Auxiliary data products utilized in this study are described in chapter 2. The climatological monthly variability of the upwelling signatures are detailed under chapter 3. Chapter 4 presents the forcing factors that trigger the upwelling process in SEAS. Chapter 5 describes the oceanic response to the forcing factors with respect to the SST cooling and CHLA blooms. Chapter 6 presents the heat budget of the region and the variability of heat budget terms with respect to upwelling. Chapter 7 describes the inter-annual variability of upwelling intensity in SEAS and the influence of climatic events on upwelling.

A Prototype for a Multimodal Biometric Security system based on Face and Audio Signatures

Any automatically measurable, robust and distinctive physical characteristic or personal trait that can be used to identify an individual or verify the claimed identity of an individual, referred to as biometrics, has gained significant interest in the wake of heightened concerns about security and rapid advancements in networking, communication and mobility. Multimodal biometrics is expected to be ultra-secure and reliable, due to the presence of multiple and independent—verification clues. In this study, a multimodal biometric system utilising audio and facial signatures has been implemented and error analysis has been carried out. A total of one thousand face images and 250 sound tracks of 50 users are used for training the proposed system. To account for the attempts of the unregistered signatures data of 25 new users are tested. The short term spectral features were extracted from the sound data and Vector Quantization was done using K-means algorithm. Face images are identified based on Eigen face approach using Principal Component Analysis. The success rate of multimodal system using speech and face is higher when compared to individual unimodal recognition systems

Biomarker pigment signatures in Cochin back water system e A tropical estuary south west coast of India

Sedimentary biomarker pigments around Cochin estuary situated in the southwest coast of India were determined by HPLC. Fucoxanthin, an indicator of diatom was observed to be the most abundant carotenoid pigment in the estuary. Dinoflagellate derived carotenoid pigment peridinin was confined in the southern part of estuary and zeaxanthin pigment indicative of cyanobacteria were more found in sites influenced by anthropogenic activities. One compound having close similarity to fucoxanthin was also detected. Alloxanthin (cryptophyceae), chl b (green algae), canthaxanthin, neoxanthin, lutein and peridinin isomer were also detected by spectra and corresponding algal class were identified. The highest concentration of chl a (11.01 mg g 1) found near to the anthropogenic affected area while the lowest chl a (0.65 mg g 1) was recorded in industrial area. Degradation products of chl a, such as pheophorbide and pheophytin were observed and principal mode of mechanism of degradation were derived. Higher pheopigments content than chl a, reflects a density trapping of dead cells and early degradation of phytopigments from grazing activities

“Unmixing” Tissue Gene Expression Signatures from Tumor Biopsies

Emergent molecular measurement methods, such as DNA microarray, qRTPCR, and many others, offer tremendous promise for the personalized treatment of cancer. These technologies measure the amount of specific proteins, RNA, DNA or other molecular targets from tumor specimens with the goal of “fingerprinting” individual cancers. Tumor specimens are heterogeneous; an individual specimen typically contains unknown amounts of multiple tissues types. Thus, the measured molecular concentrations result from an unknown mixture of tissue types, and must be normalized to account for the composition of the mixture. For example, a breast tumor biopsy may contain normal, dysplastic and cancerous epithelial cells, as well as stromal components (fatty and connective tissue) and blood and lymphatic vessels. Our diagnostic interest focuses solely on the dysplastic and cancerous epithelial cells. The remaining tissue components serve to “contaminate” the signal of interest. The proportion of each of the tissue components changes as a function of patient characteristics (e.g., age), and varies spatially across the tumor region. Because each of the tissue components produces a different molecular signature, and the amount of each tissue type is specimen dependent, we must estimate the tissue composition of the specimen, and adjust the molecular signal for this composition. Using the idea of a chemical mass balance, we consider the total measured concentrations to be a weighted sum of the individual tissue signatures, where weights are determined by the relative amounts of the different tissue types. We develop a compositional source apportionment model to estimate the relative amounts of tissue components in a tumor specimen. We then use these estimates to infer the tissuespecific concentrations of key molecular targets for sub-typing individual tumors. We anticipate these specific measurements will greatly improve our ability to discriminate between different classes of tumors, and allow more precise matching of each patient to the appropriate treatment