Paradoxes in carcinogenesis: New opportunities for research directions

<p>Abstract</p> <p>Background</p> <p>The prevailing paradigm in cancer research is the somatic mutation theory that posits that cancer begins with a single mutation in a somatic cell followed by successive mutations. Much cancer research involves refining the somatic mutation theory with an ever increasing catalog of genetic changes. The problem is that such research may miss paradoxical aspects of carcinogenesis for which there is no likely explanation under the somatic mutation theory. These paradoxical aspects offer opportunities for new research directions that should not be ignored.</p> <p>Discussion</p> <p>Various paradoxes related to the somatic mutation theory of carcinogenesis are discussed: (1) the presence of large numbers of spatially distinct precancerous lesions at the onset of promotion, (2) the large number of genetic instabilities found in hyperplastic polyps not considered cancer, (3) spontaneous regression, (4) higher incidence of cancer in patients with xeroderma pigmentosa but not in patients with other comparable defects in DNA repair, (5) lower incidence of many cancers except leukemia and testicular cancer in patients with Down's syndrome, (6) cancer developing after normal tissue is transplanted to other parts of the body or next to stroma previously exposed to carcinogens, (7) the lack of tumors when epithelial cells exposed to a carcinogen were transplanted next to normal stroma, (8) the development of cancers when Millipore filters of various pore sizes were was inserted under the skin of rats, but only if the holes were sufficiently small. For the latter paradox, a microarray experiment is proposed to try to better understand the phenomena.</p> <p>Summary</p> <p>The famous physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." The same viewpoint should apply to cancer research. It is easy to ignore this piece of wisdom about the means to advance knowledge, but we do so at our peril.</p

Integrating the weight of history into the alignment framework: the case of distributed generation technologies

Whereas a centralized energy supply system is still dominant today, the energy sector is currently witnessing the development of small-scale and more geographically dispersed generation units, so-called distributed generation technologies. So-called "alignment framework" proposes a very useful approach to look at this evolution. Yet, we argue in this paper that this framework does not fully take into account the inertia associated with past technological and institutional choices that may hinder future changes. Relying on the concept of socio-technical lock-in, we illustrate this point with the case of the diffusion of distributed generation technologies. Based on this analysis, we propose an adaptation of the alignment framework to integrate these elements

Late Pleistocene/Early Holocene Migratory Behavior of Ungulates Using Isotopic Analysis of Tooth Enamel and Its Effects on Forager Mobility

Zooarchaeological and paleoecological investigations have traditionally been unable to reconstruct the ethology of herd animals, which likely had a significant influence on the mobility and subsistence strategies of prehistoric humans. In this paper, we reconstruct the migratory behavior of red deer (Cervus elaphus) and caprids at the Pleistocene-Holocene transition in the northeastern Adriatic region using stable oxygen isotope analysis of tooth enamel. The data show a significant change in δ18O values from the Pleistocene into the Holocene, as well as isotopic variation between taxa, the case study sites, and through time. We then discuss the implications of seasonal faunal availability as determining factors in human mobility patterns

Pastoralism in northern Peru during pre-Hispanic times: insights from the Mochica Period (100-800 AD) based on stable isotopic analysis of domestic camelids.

Llama (Lama glama) and alpaca (Vicugna pacos) are the only large domesticated animals indigenous to the Americas. Pastoralism occupies a fundamental economic, social and religious role in Andean life. Today, camelid livestock are confined to the ecozone of the puna (above 3,500 masl), while their presence on the Pacific coast during pre-Hispanic times is attested by archaeological skeletal remains. This study aims to document herding practices on the northern Peruvian coast during the Early Intermediate Period (200 BC-600 AD) by gaining insights into diet, location of breeding and mobility of archaeological camelids from the funerary and ritual contexts of two Mochica sites, Uhle Platform in Huacas de Moche and El Brujo. The three first early years and the long-term life histories of the animals were documented by the combined bulk analysis of bone collagen (δ(13)C col and δ(15)N col) and bone structural carbonate (δ(13)C bone and δ(18)O bone) and the serial analysis of structural carbonate of molar tooth enamel (δ(13)C enamel and δ(18)O enamel). Mochica camelids were bred in the low and/or middle valleys, unlike their modern counterparts, who are restricted to highland puna C3 pastures. Archaeological camelids had diverse and complex life histories, usually with substantial maize foddering. An ontogenetic switch in diet and possible residential mobility during the course of life were identified for some specimens. Although the inference of geographic origin from δ(18)O bone and δ(18)O enamel values was limited because of the lack of understanding of the influence of environmental and biological factors, tooth enamel analysis has great potential for exploring camelid herding practices and Andean pastoralism. Our study suggested that Mochica herders adapted their practices to the difficult lowland environment and that herding practices were varied and not restricted to breeding at higher altitudes. The role of maize in different aspects of the economic life of the Mochicas is also underlined