Judicial disagreement need not be political: dissent on the Estonian Supreme Court

I investigate the non-unanimous decisions of judges on the Estonian Supreme Court. I argue that since judges on the court enjoy high de jure independence, dissent frequently, and are integrated in the normal judicial hierarchy, the Estonian Supreme Court is a crucial case for the presumption that judicial disagreement reveals policy preferences. I analyse dissenting opinions using an ideal point response model. Examining the characteristics of cases which discriminated with respect to the recovered dimension, I show that this dimension cannot be interpreted as a meaningful policy dimension, but instead reflects disagreement about the proper scope of constitutional redress

Statistical approach to the analysis of cell desynchronization data

Experimental measurements on semi-synchronous tumor cell populations show that after a few cell cycles they desynchronize completely, and this desynchronization reflects the intercell variability of cell-cycle duration. It is important to identify the sources of randomness that desynchronize a population of cells living in a homogeneous environment: for example, being able to reduce randomness and induce synchronization would aid in targeting tumor cells with chemotherapy or radiotherapy. Here we describe a statistical approach to the analysis of the desynchronization measurements that is based on minimal modeling hypotheses, and can be derived from simple heuristics. We use the method to analyze existing desynchronization data and to draw conclusions on the randomness of cell growth and proliferation

Thresholds, long delays and stability from generalized allosteric effect in protein networks

Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation are well known to play a pivotal role in the intracellular transduction of activation and death signals. A protein can have multiple sites where chemical groups can reversibly attach in processes such as phosphorylation or nitrosylation. A microscopic description of these processes must take into account the intrinsic probabilistic nature of the underlying reactions. We apply combinatorial considerations to standard enzyme kinetics and in this way we extend to the dynamic regime a simplified version of the traditional models on the allosteric regulation of protein functions. We link a generic modification chain to a downstream Michaelis\u2013Menten enzymatic reaction and we demonstrate numerically that this accounts both for thresholds and long time delays in the conversion of the substrate by the enzyme. The proposed mechanism is stable and robust and the higher the number of modification sites, the greater the stability. We show that a high number of modification sites converts a fast reaction into a slow process, and the slowing down depends on the number of sites and may span many orders of magnitude; in this way multisite modification of proteins stands out as a general mechanism that allows the transfer of information from the very short time scales of enzyme reactions (milliseconds) to the long time scale of cell response (hours)

Plant lectins as carriers for oral drugs: is wheat germ agglutinin a suitable candidate?

Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. 3H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 AM, c0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and timedependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis