Copying and Evolution of Neuronal Topology

We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance

External borrowing issue in Ottoman Empire (1854-1876 term)

WOS: 000444369900004By the beginning of the Nineteenth century, foreign borrowing was put on the agenda since it was understood that fiscal structure of the state could not be sustained by internal dynamics; yet, foreign borrowing did not materialize in that period. The state, which could not afford increasing war expenditures during Crimean war in 1853, borrowed from abroad for the first time in 1854. After this initial borrowing from England and France, foreign borrowing was started to be seen as a state policy by the state, who signed several debt treaties in succession. The newspapers that started to emerge in the Ottoman state in that period penned articles regarding borrowing policy of the state. In these newspapers, there were no direct criticisms regarding borrowing per se, rather the state was criticized mainly on the grounds that it borrowed money when it was in trouble, not to make investments. This study explains foreign borrowings made by the Ottoman State from 1854 and analyzes the views of the intellectuals of the period regarding them