Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

A relocation model of European manufacturing firms: cases from Italy and Sweden

Purpose The purpose of this paper is to deal with two major issues: what alternatives does a manufacturing company have when current office space use is not sufficient, or it exceeds its needs, following changes and business transformation; and second, what principal factors (in particular Facilities and Corporate Real Estate Management factors) must be taken into account in the decisionmaking process about possible relocation? The corporate real estate of manufacturing firms in the Western countries is very much similar to that of the service sector. When compared to property devoted to service activities only, the inertia of manufacturing companies is apparent only, because a large part of the premises are in fact offices that, to various extent, are connected to warehouses, laboratories, factories and manufacturing units that cannot be relocated. For this reason it is necessary to devise intermediate alternatives between staying on the current location or total relocation. Design/methodology/approach This paper is based on literature studies of company locations in a European and global context, with two independent surveys from two different geographical areas: northern Italy and Sweden. Despite the different aspects considered in the surveys, common conclusions can be made for a general understanding of how facilities management factors influence location. Findings The model described in this paper organizes location alternatives when space changes are required, especially by European manufacturing companies. Practical implications The model is a tool for decision makers when analysing and structuring their location needs. Originality/value The paper is a pioneering work of classification of intermediate alternatives of partial relocation

Die Bedeutung der Cryptosporidiose für die Kälbergesundheit in der Schweiz

Diarrhea in calves is one of the most important cattle diseases in Switzerland. The diagnosis and treatment of calf diarrhea represent a major challenge. Single-celled Cryptosporidium parasites are the most prevalent causative agents of calf diarrhea besides rotavirus in the first weeks of life, and are responsible for about 50% of diarrheal cases. Cryptosporidium parvum has been described as a cause of diarrhea in one to three weeks old calves since the 1970s. Oral ingestion of persistent environmental oocysts results in severe diarrhea lasting four to six days and shedding of large numbers of infectious oocysts. A tiny amount of 10 oocysts is already sufficient to cause disease. Detailed knowledge about the epidemiology and virulence of the different C. parvum strains is still lacking. In addition, current diagnostic tests cannot reliably distinguish between non-pathogenic (e.g. C. bovis) and pathogenic Cryptosporidium species. Until now, no effective therapeutic drug or vaccine against calf cryptosporidiosis has been found. Water-borne epidemics and the zoonotic potential of Cryptosporidium in immunodeficient patients are of great medical importance. The increasing number of cryptosporidiosis cases associated with high infant mortality in less industrialized and impoverished regions (including South-East Asia and sub-Saharan Africa) has intensified the research in recent years. The recent discoveries of new therapeutics against C. parvum may benefit calf medicine in the near future. This review article reports on these new developments, highlights calf cryptosporidiosis in Switzerland and draws attention to a new research project