Unraveling the intricacies of spatial organization of the ErbB receptors and downstream signaling pathways

Faced with the complexity of diseases such as cancer which has 1012 mutations, altering gene expression, and disrupting regulatory networks, there has been a paradigm shift in the biological sciences and what has emerged is a much more quantitative field of biology. Mathematical modeling can aid in biological discovery with the development of predictive models that provide future direction for experimentalist. In this work, I have contributed to the development of novel computational approaches which explore mechanisms of receptor aggregation and predict the effects of downstream signaling. The coupled spatial non-spatial simulation algorithm, CSNSA is a tool that I took part in developing, which implements a spatial kinetic Monte Carlo for capturing receptor interactions on the cell membrane with Gillespies stochastic simulation algorithm, SSA, for temporal cytosolic interactions. Using this framework we determine that receptor clustering significantly enhances downstream signaling. In the next study the goal was to understand mechanisms of clustering. Cytoskeletal interactions with mobile proteins are known to hinder diffusion. Using a Monte Carlo approach we simulate these interactions, determining at what cytoskeletal distribution and receptor concentration optimal clustering occurs and when it is inhibited. We investigate oligomerization induced trapping to determine mechanisms of clustering, and our results show that the cytoskeletal interactions lead to receptor clustering. After exploring the mechanisms of clustering we determine how receptor aggregation effects downstream signaling. We further proceed by implementing the adaptively coarse grained Monte Carlo, ACGMC to determine if \u27receptor-sharing\u27 occurs when receptors are clustered. In our proposed \u27receptor-sharing\u27 mechanism a cytosolic species binds with a receptor then disassociates and rebinds a neighboring receptor. We tested our hypothesis using a novel computational approach, the ACGMC, an algorithm which enables the spatial temporal evolution of the system in three dimensions by using a coarse graining approach. In this framework we are modeling EGFR reaction-diffusion events on the plasma membrane while capturing the spatial-temporal dynamics of proteins in the cytosol. From this framework we observe \u27receptor-sharing\u27 which may be an important mechanism in the regulation and overall efficiency of signal transduction. In summary, I have helped to develop predictive computational tools that take systems biology in a new direction.\u2

Solutions for IPv6-based mobility in the EU project MobyDick

Proceedings of the WTC 2002, 18th World Telecommunications Congress, Paris, France, 22 -27 September, 2002.Mobile Internet technology is moving towards a packet-based or, more precisely, IPv6-based network. Current solutions on Mobile IPv6 and other related QoS and AAA matters do not offer the security and quality users have come to take for granted. The EU IST project Moby Dick has taken on the challenge of providing a solution that integrates QoS, mobility and AAA in a heterogeneous access environment. This paper focuses on the mobility part of the project, describes and justifies the handover approach taken, shows how QoS-aware and secure handover is achieved, and introduces the project's paging concept. It shows that a transition to a fully integrated IP-RAN and IP-Backbone has become a distinct option for the future.Publicad

Working from Home During the COVID-19 Pandemic: Tips and Strategies to Maintain Productivity & Connectedness

Due to the COVID-19 Pandemic many workers are shifting from coming into their workplace to working from home. This may be a new challenge for many workers. Successfully working from home can present unique challenges, from how to focus with at-home distractions, to trying to be productive, trying to communicate well with team members from afar, and childcare. Here at the Transitions to Adulthood Center for Research, many of our faculty and staff have years of experience mastering the art of remote work and have put together a list of their top 5 tips and tricks to navigating this strange new world. An American Sign language (ASL) translation video of the tip sheet is available

Methodology for DSC calibration in high heating rates

Despite the large use of differential scanning calorimetry (DSC) technique in advanced polymer materials characterization, the new methodology called DSC in high heating rates was developed. The heating rate during conventional DSC experiments varying from 10 to 20ºC.min-¹, sample mass from 10 to 15mg and standard aluminum sample pan weighting, approximately, 27mg. In order to contribute to a better comprehension of DSC behavior in different heating rates, this work correlates as high heating rate influences to the thermal events in DSC experiments. Samples of metallic standard (In, Pb, Sn and Zn) with masses varying from 0.570mg to 20.9mg were analyzed in multiples sample heating rate from 4 to 324°C. min-¹. In order to make properly all those experiments, a precise and careful temperature and enthalpy calibrations were performed and deeply discussed. Thus, this work shows a DSC methodology able to generate good and reliable results on experiments under any researcher choice heating rates to characterize the advanced materials used, for example, for aerospace industry. Also it helps the DSC users to find in their available instruments, already installed, a better and more accurate DSC test results, improving in just one shot the analysis sensitivity and resolution. Polypropylene melting and enthalpy thermal events are also studied using both the conventional DSC method and high heating rate method

Áreas de lazer no Aeroporto Internacional Afonso Pena em Sao José dos Pinhais

Orientador : Michelle Cardoso CostaMonografia (especializaçao) - Universidade Federal do Paraná, Setor de Ciencias Humanas Letras e Artes, Curso de Especializaçao em Planejamento e Gestao do TurismoInclui bibliografi