A mass action model of a fibroblast growth factor signaling pathway and its simplification

We consider a kinetic law of mass action model for Fibroblast Growth Factor (FGF) signaling, focusing on the induction of the RAS-MAP kinase pathway via GRB2 binding. Our biologically simple model suffers a combinatorial explosion in the number of differential equations required to simulate the system. In addition to numerically solving the full model, we show that it can be accurately simplified. This requires combining matched asymptotics, the quasi-steady state hypothesis, and the fact subsets of the equations decouple asymptotically. Both the full and simplified models reproduce the qualitative dynamics observed experimentally and in previous stochastic models. The simplified model also elucidates both the qualitative features of GRB2 binding and the complex relationship between SHP2 levels, the rate SHP2 induces dephosphorylation and levels of bound GRB2. In addition to providing insight into the important and redundant features of FGF signaling, such work further highlights the usefulness of numerous simplification techniques in the study of mass action models of signal transduction, as also illustrated recently by Borisov and co-workers (Borisov et al. in Biophys. J. 89, 951–66, 2005, Biosystems 83, 152–66, 2006; Kiyatkin et al. in J. Biol. Chem. 281, 19925–9938, 2006). These developments will facilitate the construction of tractable models of FGF signaling, incorporating further biological realism, such as spatial effects or realistic binding stoichiometries, despite a more severe combinatorial explosion associated with the latter

Effect of Genotype and Environment on the Glycoalkaloid Content of Rare, Heritage, and Commercial Potato Varieties

peer-reviewedPotatoes accumulate toxic steroidal compounds that could be harmful for humans if consumed in high quantities and must be controlled. In this study, we were interested in assessing the levels and variation of glycoalkaloid content in 60 varieties of potato planted in 2 trial sites over 2 y. Total glycoalkaloid levels ranged from 4 to 957 mg/kg of dry weight in the flesh and from 150 to 8133 mg/kg in the skin, with the latter accumulating generally more α-chaconine than α-solanine. Contents in the flesh were below the safe limit for all varieties, but were generally above in the skin. Maximum values in each site and year of cultivation were found for varieties “Beauty of Hebron,” “May Queen,” and “Arran Pilot” in the skin and “Beauty of Hebron,” “International Kidney,” and “Congo” in the flesh. Year of cultivation had a significant effect on total glycoalkaloid content (P < 0.0001), with interactions between variety and site of cultivation and variety and year of cultivation also significant (P < 0.0001), implying that environmental effects seem to act differentially and could induce high levels in genetically predisposed varieties.Teagasc Walsh Fellowship Programm

Amendments to Federal Removal Statutes: Curtailing Adjudication of Diversity Cases or Bad Faith Causes of Action?

This student comment explores the problem facing Florida insurers preventing them from exercising their right to litigate bad faith causes of action in federal court. This article demonstrates how the federal removal statutes, and amendments thereto, have potentially precluded insurers from removing some bad faith actions from state to federal court under diversity jurisdiction. This article details the divergence in opinion among Florida’s Southern and Middle District Courts in interpreting the federal removal statutes and concludes with a prediction of how the split may be resolved by the Eleventh Circuit Court of Appeals

Response—Francis M. Gaffney

Does the social scientist have a role to play in helping judicial decision-makers make more effective and valid decisions? Even when this question is juxtaposed with the skepticism which has characterized the legal profession\u27s attitudes toward the social sciences, the answer would seem to be yes. The research reported here does not bear the imprint of youth, imprecision or changefulness. The studies by Grossman, Schmidhauser and Skogan are indicative of a vital point in the maturation process of any science, the stage at which basic hypotheses and notions are subjected to empirical validation. Those by Burnham, Cook and Fahey are characteristic of a maturing science which has achieved a sufficient degree of internal development to enable its practitioners to turn to problem oriented research. With these two activities going on simultaneously, there will undoubtedly be changes within the social sciences, but the changes that do occur will result in increased maturity. Given these trends within the social sciences, and the law\u27s desperate need for a reliable empirical base, these studies may well harbinger a productive exchange between law and the social sciences

Comparison of phenolic and flavonoid content and antioxidant activity in vitro among potato varieties.

Conference paperDiets rich in fruits and vegetables have been associated with a lower incidence of cancer and heart disease, which may be related to the antioxidant activity of bioactive compounds present in these foods. Phenolic compounds are potent antioxidants in vitro, of which flavonoids are of particular interest for their potential positive impact on health. Potatoes are one of the most consumed vegetables in the world and therefore an important source of phenolics. In Ireland they are the third most important crop with a farm gate value of approximately 45 million euros annually. The aim of this work was to evaluate the antioxidant activity of methanolic solutions extracted from the skin and flesh of potato tubers against the stable radical DPPH and analyze its relationship to the content of total phenolics and total flavonoids.Teagasc Walsh Fellowship Programm

A solute gradient in the tear meniscus I. A hypothesis to explain Marx's line

Marx's line is a line of mucosal staining behind the mucocutaneous junction. It can be demonstrated throughout life in all normal lids by staining with lissamine green and related dyes. Of all the body orifices, only the mucosae of the eye and mouth are directly exposed to the atmosphere. In this paper, we suggest that for the eye, this exposure leads to the formation of Marx's line. The tear meniscus thins progressively toward its apex, where it is pinned at the mucocutaneous junction of the lid. It also thins toward the black line, which segregates the meniscus from the tear film after the blink. We predict that, because of the geometry of the tear meniscus, evaporation generates a solute gradient across the meniscus profile in the anteroposterior plane, which peaks at the meniscus apices at the end of the interblink. One outcome would be to amplify the level of tear molarity at these sites so that they reach hyperosmolar proportions. Preliminary mathematical modeling suggests that dilution of this effect by advection and diffusion of solute away from the meniscus apex at the mucocutaneous junction will be restricted by spatial constraints, the presence of tear and surface mucins at this site, and limited fluid flow. We conclude that evaporative water loss from the tear meniscus may result in a physiological zone of hyperosmolar and related stresses to the occlusal conjunctiva, directly behind the mucocutaneous junction. We hypothesize that this stimulates a high epithelial cell turnover at this site, incomplete epithelial maturation, and a failure to express key molecules such as MUC 16 and galectin-3, which, with the tight junctions between surface epithelial cells, are necessary to seal the ocular surface and prevent penetration of dyes and other molecules into the epithelium. This is proposed as the basis for Marx's line. In Part II of this paper (also published in this issue of The Ocular Surface), we address additional pathophysiological consequences of this mechanism, affecting lid margins

Segmental Movement Compensations in Patients with Transtibial Amputation Identified Using Angular Momentum Separation

Patients with unilateral dysvascular transtibial amputation (TTA) adopt movement compensations that are required to maintain balance and achieve ambulation in the absence of ankle plantar flexion, and result in increased and asymmetric joint loading patterns. As a result, this population is at an increased risk of overuse injuries, such as low back pain (LBP). Clinical gait analysis is used to guide diagnostics in movement retraining following amputation, and is performed using instrumented (research based) or observational analyses (clinically based). However, instrumented analyses are currently impractical in most clinical settings due to expense and computational limitations. This dissertation presents the use of segmental angular momentum to describe movement compensations in patients with TTA, and assess their effects on the musculoskeletal system; which provides a potential platform applicable in both instrumented and observational settings. Ten patients with unilateral dysvascular TTA and two cohorts (patients with diabetes mellitus and healthy controls) completed one experimental study in which whole-body kinematics and core muscle demand were collected during walking and bilateral stepping tasks. Specific Aim 1 described the foundations of the separation of angular momentum into two components, translational (TAM) and rotational angular momentum (RAM) to describe movement coordination during healthy walking. Euler\u27s rotational laws were used to calculate segmental translational and rotational moments, which provide insight into the effort required to generate and arrest momentum by their relation to external forces and moments. Specific Aim 2 described trunk and pelvis movement compensations in patients with TTA during walking using TAM and RAM. Specific Aim 3 described the trunk translational and rotational moments in patients with TTA during step ambulation. Finally, Specific Aim 4 described the demand from the core musculature that supports trunk movement compensations in patients with TTA during step ambulation. The results from these Specific Aims indicate that patients with TTA generate larger amounts of TAM and RAM, which were caused by larger translational and rotational trunk moments and demand from core muscles, than healthy controls. These compensations alter the low back loading patterns, which may be reduced by targeted strengthening and retraining motor control compensations to better support trunk movements