Lehigh University

About: Lehigh University is a education organization based out in Bethlehem, Pennsylvania, United States. It is known for research contribution in the topics: Catalysis & Fracture mechanics. The organization has 12684 authors who have published 26550 publications receiving 770061 citations.

Sequence determinants of protein phase behavior from a coarse-grained model.

Abstract: Membraneless organelles important to intracellular compartmentalization have recently been shown to comprise assemblies of proteins which undergo liquid-liquid phase separation (LLPS). However, many proteins involved in this phase separation are at least partially disordered. The molecular mechanism and the sequence determinants of this process are challenging to determine experimentally owing to the disordered nature of the assemblies, motivating the use of theoretical and simulation methods. This work advances a computational framework for conducting simulations of LLPS with residue-level detail, and allows for the determination of phase diagrams and coexistence densities of proteins in the two phases. The model includes a short-range contact potential as well as a simplified treatment of electrostatic energy. Interaction parameters are optimized against experimentally determined radius of gyration data for multiple unfolded or intrinsically disordered proteins (IDPs). These models are applied to two systems which undergo LLPS: the low complexity domain of the RNA-binding protein FUS and the DEAD-box helicase protein LAF-1. We develop a novel simulation method to determine thermodynamic phase diagrams as a function of the total protein concentration and temperature. We show that the model is capable of capturing qualitative changes in the phase diagram due to phosphomimetic mutations of FUS and to the presence or absence of the large folded domain in LAF-1. We also explore the effects of chain-length, or multivalency, on the phase diagram, and obtain results consistent with Flory-Huggins theory for polymers. Most importantly, the methodology presented here is flexible so that it can be easily extended to other pair potentials, be used with other enhanced sampling methods, and may incorporate additional features for biological systems of interest.

Driving in young adults with attention deficit hyperactivity disorder: knowledge, performance, adverse outcomes, and the role of executive functioning.

Abstract: Past studies find that attention deficit hyperactivity disorder (ADHD) creates a higher risk for adverse driving outcomes. This study comprehensively evaluated driving in adults with ADHD by comparing 105 young adults with the disorder (age 17-28) to 64 community control (CC) adults on five domains of driving ability and a battery of executive function tasks. The ADHD group self-reported significantly more traffic citations, particularly for speeding, vehicular crashes, and license suspensions than the CC group, with most of these differences corroborated in the official DMV records. Cognitively, the ADHD group was less attentive and made more errors during a visual reaction task under rule-reversed conditions than the CC group. The ADHD group also obtained lower sceres on a test of driving rules and decision-making but not on a simple driving simulator. Both self- and other-ratings showed the CC group employed safer routine driving habits than the ADHD group. Relationships between the cognitive and driving measures and the adverse outcomes were limited or absent, calling into question their use in screening ADHD adults for driving risks. Several executive functions also were significantly yet modestly related to accident frequency and total traffic violations after controlling for severity of ADHD. These results are consistent with earlier studies showing significant driving problems are associated with ADHD. This study found that these driving difficulties were not a function of comorbid oppositional defiant disorder, depression, anxiety, or frequency of alcohol or illegal drug use. Findings to date argue for the development of interventions to reduce driving risks among adults with ADHD.

Life-cycle performance, management, and optimisation of structural systems under uncertainty: accomplishments and challenges 1

Abstract: Our knowledge to model, analyse, design, maintain, monitor, manage, predict and optimise the life-cycle performance of structures and infrastructures under uncertainty is continually growing. However, in many countries, including the United States, the civil infrastructure is no longer within desired levels of performance and safety. Decisions regarding civil infrastructure systems should be supported by an integrated reliability-based life-cycle multi-objective optimisation framework by considering, among other factors, the likelihood of successful performance and the total expected cost accrued over the entire life-cycle. The primary objective of this paper is to highlight recent accomplishments in the life-cycle performance assessment, maintenance, monitoring, management and optimisation of structural systems under uncertainty. Challenges are also identified.

Ultrawide-bandwidth slow-light system based on THz plasmonic graded metallic grating structures.

Abstract: We explore a novel mechanism for slowing down THz waves based on metallic grating structures with graded depths, whose dispersion curves and cutoff frequencies are different at different locations. Since the group velocity of spoof surface plasmons at the cutoff frequency is extremely low, THz waves are actually stopped at different positions for different frequencies. The separation between stopped waves can be tuned by changing the grade of the grating depths. This structure offers the advantage of reducing the speed of the light over an ultrawide spectral band, and the ability to operate at various temperatures, but demands a stringent requirement for the temperature stability.

Reflections on the 2010 AMR Decade Award: Whither the Promise? Moving Forward with Entrepreneurship As a Science of the Artificial

Abstract: In this article we speak of roads taken and paths yet to be traversed Over the past decade, entrepreneurship researchers have accumulated considerable work related to opportunities Here we outline new possibilities opened up by that work and seek to recast entrepreneurship as a science of the artificial in three ways: understanding opportunities as made as well as found, moving beyond new combinations to transformations, and developing a new nexus around actions and interactions