The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 10 (1842)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 11 (1843)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 14 (1844)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 6 (1841)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 8 (1842)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

2nd ser. v. 13 (1854)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

3rd ser. v. 4 (1859)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

3rd ser. v. 1 (1858)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

2nd ser. v. 9 (1852)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

2nd ser. v. 20 (1857)

The Annals and magazine of natural history; zoology, botany, and geology being a continuation of the Annals combined with Loudon and Charlesworth's Magazine of Natural History.

v. 17 (1846)

Numerical simulation of combined heat transfer phenomena (conduction, convection, and radiation). Application to he optimisation of thermal systems

Thermal systems interchanging heat and mass by conduction, convection, radiation (solar and thermal ) occur in many engineering applications like energy storage by solar collectors, window glazing in buildings, refrigeration of plastic moulds, air handling units etc. Often these thermal systems are composed of various elements for example a building with wall, windows, rooms, etc. It would be of particular interest to have a modular thermal system which is formed by connecting different modules for the elements, flexibility to use and change models for individual elements, add or remove elements without changing the entire code. A numerical approach to handle the heat transfer and fluid flow in such systems helps in saving the full scale experiment time, cost and also aids optimisation of parameters of the system. In subsequent sections are presented a short summary of the work done until now on the orientation of the thesis in the field of numerical methods for heat transfer and fluid flow applications, the work in process and the future work.

Identifying the neural correlates of executive functions in early cerebral microangiopathy: a combined VBM and DTI study.

Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry-VBM) and white matter (e.g., diffusion tensor imaging-DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics.

Combined clonotyping and gene signatures of individual tumor-reactive CD8 T-cells define their functional relevance following peptide vaccination in melanoma patients

Novel cancer vaccines are capableto efficiently induce and boost humantumor antigen specific T-cells. However,the properties of these CD8T-cells are only partially characterized.For in depth investigation ofT-cells following Melan-A/MART-1peptide vaccination in melanoma patients,we conducted a detailed prospectivestudy at the single cell level.We first sorted individual human naiveand effector CD8 T-cells from peripheralblood by flow cytometry, andtested a modified RT-PCR protocolincluding a global amplification ofexpressed mRNAs to obtain sufficientcDNAfromsingle cells.We successfullydetected the expression ofseveral specific genes of interest evendown to 106-fold dilution (equivalentto 10-5 cell). We then analyzed tumor-specific effector memory (EM)CD8T-cell subpopulations ex vivo, assingle cells from vaccinated melanomapatients. To elucidate the hallmarksof effective immunity the genesignatures were defined by a panel ofgenes related to effector functions(e.g. IFN-, granzyme B, perforin),and individual clonotypes were identifiedaccording to the expression ofdistinct T-cell receptors (TCR). Usingthis novel single cell analysis approach,we observed that T-cell differentiationis clonotype dependent,with a progressive restriction in TCRBV clonotype diversity from EMCD28pos to EMCD28neg subsets. However,the effector function gene imprintingis clonotype-independent,but dependent on differentiation,since it correlates with the subset oforigin (EMCD28pos or EMCD28neg). We also conducted a detailedcomparative analysis after vaccinationwith natural vs. analog Melan-Apeptide. We found that the peptideused for vaccination determines thefunctional outcome of individualT-cell clonotypes, with native peptideinducing more potent effector functions.Yet, selective clonotypic expansionwith differentiation was preservedregardless of the peptide usedfor vaccination. In summary, the exvivo single cell RT-PCR approach ishighly sensitive and efficient, andrepresents a reliable and powerfultool to refine our current view of molecularprocesses taking place duringT-cell differentiation.