Improving the Sensitivity of Screening Mammography in the South of the Netherlands

In this thesis I explore several factors that influence the sensitivity of screening mammography, with the aim to improve screening outcome in the southern breast cancer screening region of the Netherlands. This general introduction describes: - the background and implementation of mass breast cancer screening - trends of breast cancer incidence and mortality - the debate on screening - the relevance of this thesis - screening mammography sensitivity - methods and population - the outline of this thesi

Application of time-dependent density functional theory to optical activity

As part of a general study of the time-dependent local density approximation (TDLDA), we here report calculations of optical activity of chiral molecules. The theory automatically satisfies sum rules and the Kramers-Kronig relation between circular dichroism and optical rotatory power. We find that the theory describes the measured circular dichroism of the lowest states in methyloxirane with an accuracy of about a factor of two. In the chiral fullerene C_76 the TDLDA provides a consistent description of the optical absorption spectrum, the circular dichroism spectrum, and the optical rotatory power, except for an overall shift of the theoretical spectrum.Comment: 17 pages and 13 PostScript figure

Examination of Late Palaeolithic archaeological sites in northern Europe for the preservation of cryptotephra layers

We report the first major study of cryptotephra (non-visible volcanic ash layers) on Late Palaeolithic archaeological sites in northern Europe. Examination of 34 sites dating from the Last Termination reveals seven with identifiable cryptotephra layers. Preservation is observed in minerogenic and organic deposits, although tephra is more common in organic sediments. Cryptotephra layers normally occur stratigraphically above or below the archaeology. Nearby off-site palaeoclimate archives (peat bogs and lakes <0.3 km distant) were better locations for detecting tephra. However in most cases the archaeology can only be correlated indirectly with such cryptotephras. Patterns affecting the presence/absence of cryptotephra include geographic position of sites relative to the emitting volcanic centre; the influence of past atmospherics on the quantity, direction and patterns of cryptotephra transport; the nature and timing of local site sedimentation; sampling considerations and subsequent taphonomic processes. Overall, while tephrostratigraphy has the potential to improve significantly the chronology of such sites many limiting factors currently impacts the successful application

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX-XXX, XXXX)

Neanderthals in changing environments from MIS 5 to early MIS 4 in northern Central Europe:Integrating archaeological, (chrono)stratigraphic and paleoenvironmental evidence at the site of Lichtenberg

The resilience of Neanderthals towards changing climatic and environmental conditions, and especially towards severely cold climates in northern regions of central Europe, is still under debate. One way to address this is to investigate multi-layered occupation in different climatic intervals, using independently-compiled paleoenvironmental and chronological data. Unfortunately, most open-air sites on the northern European Plain lack a robust chronostratigraphy beyond the radiocarbon dating range, thereby often hampering direct links between human occupation and climate. Here we present the results of integrative research at the Middle Paleolithic open-air site of Lichtenberg, Northern Germany, comprising archaeology, luminescence dating, sedimentology, micromorphology, as well as pollen and phytolith analyses. Our findings clearly show Neanderthal presence in temperate, forested environments during the Mid-Eemian Interglacial, MIS 5e and the latest Brörup Interstadial, MIS 5c/GI 22 (Lichtenberg II). For the previously known occupation Lichtenberg I, we revise the chronology from the former early MIS 3 (57 ± 6 ka) to early MIS 4/GS 19 (71.3 ± 7.3 ka), with dominant cold steppe/tundra vegetation. The early MIS 4 occupation suggests that Neanderthals could adjust well to severely cold environments and implies recurring population in the region between MIS 5 and MIS 3. The artefact assemblages differ between the temperate and cold environment occupations regarding size, blank production, typology and tool use. We argue that this distinctness can partially be explained by different site functions and occupation duration, as well as the availability of large and high-quality flint raw material. Raw material availability is in turn governed by changing vegetation cover that hindered or fostered sediment redeposition as a provider of flint from the primary source of the glacial sediments nearby