Maintaining a High Degree of Research Productivity at a PUI as Your Career Advances

In this perspective, two experienced academic administrators who are computational chemists discuss strategies for how to maintain an active research program at a pre- dominately undergraduate institution as your career progresses. More responsibility equates to less time for research, so planning for research to remain a priority is essential. We all have the same amount of time, so figuring out how to use yours bet- ter is the key to remaining active. Professional organizations such as Council on Undergraduate Research, consortia of computational chemists such as Molecular Education and Research Consortium in computational chemistRY and Midwest Undergraduate Computational Chemistry Consortium, and attendance at profes- sional conferences can help sustain your research program. Collaborations with fac- ulty at other institutions provide a particularly effective accountability mechanism as well. Perhaps the best way to improve your productivity is to become a better men- tor to your undergraduate students. Building a research group that is fun and exciting develops a culture that sustains itself and provides the momentum necessary to maintain progress toward scientific goals

Backbone conformational flexibility of the lipid modified membrane anchor of the human N-Ras protein investigated by solid-state NMR and molecular dynamics simulation

AbstractThe lipid modified human N-Ras protein, implicated in human cancer development, is of particular interest due to its membrane anchor that determines the activity and subcellular location of the protein. Previous solid-state NMR investigations indicated that this membrane anchor is highly dynamic, which may be indicative of backbone conformational flexibility. This article aims to address if a dynamic exchange between three structural models exist that had been determined previously. We applied a combination of solid-state nuclear magnetic resonance (NMR) methods and replica exchange molecular dynamics (MD) simulations using a Ras peptide that represents the terminal seven amino acids of the human N-Ras protein. Analysis of correlations between the conformations of individual amino acids revealed that Cys 181 and Met 182 undergo collective conformational exchange. Two major structures constituting about 60% of all conformations could be identified. The two conformations found in the simulation are in rapid exchange, which gives rise to low backbone order parameters and nuclear spin relaxation as measured by experimental NMR methods. These parameters were also determined from two 300 ns conventional MD simulations, providing very good agreement with the experimental data

Dynamical approach to chains of scatterers

Linear chains of quantum scatterers are studied in the process of lengthening, which is treated and analysed as a discrete dynamical system defined over the manifold of scattering matrices. Elementary properties of such dynamics relate the transport through the chain to the spectral properties of individual scatterers. For a single-scattering channel case some new light is shed on known transport properties of disordered and noisy chains, whereas translationally invariant case can be studied analytically in terms of a simple deterministic dynamical map. The many-channel case was studied numerically by examining the statistical properties of scatterers that correspond to a certain type of transport of the chain i.e. ballistic or (partially) localised.Comment: 16 pages, 7 figure

All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0–20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0–22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0–22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0–18:1PC) bilayers. They were run in the absence and presence of 20 mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, ̅ = 0.152). EPA-PC (̅ = 0.131) is most disordered, while DPA-PC ( ̅ = 0.140) is least disordered. DHA-PC (̅ = 0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (̅ = 0.169), DHA-PC (̅ = 0.178) and DPA-PC (̅ = 0.182) is increased less than in OA-PC (̅ = 0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy

α-Tocopherol is well designed to protect polyunsaturated fatty acids

poster abstractPolyunsaturated fatty acids (PUFA) are an influential constituent in cell membranes, but are extremely vulnerable to oxidation. The presumptive role for α-tocopherol (α-toc), the molecular form of vitamin E retained by the human body, is to protect PUFA-containing lipids from oxidation. To investigate whether α-toc preferentially interacts with PUFA in support of this function, we performed MD simulations on lipid bilayers composed of 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22-6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) in the presence of α-toc. SDPC with docosahexaenoic acid (DHA) for the sn-2 chain is polyunsaturated, while SOPC with oleic acid (OA) for the sn-2 chain serves as a monounsaturated control. The simulations were run at 37 °C under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-toc molecules and 2165 water molecules. In qualitative agreement with our results from solid state 2H NMR and neutron scattering experiments, the simulations show that α-toc increases order inside the bilayer and that the chromanol headgroup sits near the surface in both SDPC and SOPC. Analyses of the density distribution of the lipid chains relative to α-toc show that the α-toc’s chromanol headgroup, the part of the molecule that protects against oxidation, would have more chance to interact with PUFA chains than saturated chains. A major prediction from our simulations is that α-toc undergoes flip-flop across the bilayer and that the rate is an order of magnitude greater in SDPC than SOPC. This is a remarkable finding that reveals a possible mechanism by which the chromanol group would not only wait at the membrane surface but would also patrol the membrane interior to meet lipid radicals and terminate the chain reaction by which lipid peroxidation proceeds

Interaction of α-tocopherol with a polyunsaturated lipid studied by MD simulations

poster abstractPolyunsaturated phospholipids are essential components of neural membranes and their effect on membrane architecture is proposed to be the molecular origin of a myriad of health benefits. A downside of polyunsaturated phospholipids is that they are highly susceptible to oxidation due to the presence of multiple double bonds. α-Tocopherol is the most biologically active component in a family of phenolic compounds that comprise vitamin E, which is the major lipid soluble antioxidant in cell membranes. To investigate whether α-tocopherol preferentially interacts with polyunsaturated phospholipids to optimize protection against oxidation, we performed MD simulations on 1-stearoyl-2-docosahexaenoylphosphatiylcholine (SDPC, 18:0-22:6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) bilayers containing α-tocopherol. SDPC with a docosahexaenoyl sn-2 chain is polyunsaturated, while SOPC with an oleoyl sn-2 chain serves as a monounsaturated control. The simulations were run under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-tocopherol molecules and 2165 water molecules. We discovered significant differences between the two systems. Analysis of the simulations indicates that the α-tocopherol has a strong interaction with the polyunsaturated fatty acid. The flip-flop of α-tocopherol across the bilayer is also much faster in SDPC than in SOPC. Solid state NMR, neutron scattering and complementary experiments are now underway to test the predictions from the MD simulations

Soundsense: Sonifying pryroelectric sensor data for an interactive media event

Presented at the 11th International Conference on Auditory Display (ICAD2005)Collaborations between artists, engineers, and scientists often occur when creating new media works. These interdisciplinary efforts must overcome the ideals and practical-limitations inherent in both artistic and research pursuits. In turn, successful projects may truly be greater than the sum of their parts, enabling each collaborator to gain insight into their own work. soundSense, a cooperative effort between engineers, composers, and other specialists, sonifies pyroelectic sensor data to create a novel interactive-media event. Signals generated by multiplexing pyroelectric detectors inform datadriven audio and visual displays articulating – in real-time – the presence and motion of individuals within the sensed space

Statistical auditing and randomness test of lotto k/N-type games

One of the most popular lottery games worldwide is the so-called ``lotto k/N''. It considers N numbers 1,2,...,N from which k are drawn randomly, without replacement. A player selects k or more numbers and the first prize is shared amongst those players whose selected numbers match all of the k randomly drawn. Exact rules may vary in different countries. In this paper, mean values and covariances for the random variables representing the numbers drawn from this kind of game are presented, with the aim of using them to audit statistically the consistency of a given sample of historical results with theoretical values coming from a hypergeometric statistical model. The method can be adapted to test pseudorandom number generators.Comment: 10 pages, no figure

Failure Processes in Elastic Fiber Bundles

The fiber bundle model describes a collection of elastic fibers under load. the fibers fail successively and for each failure, the load distribution among the surviving fibers change. Even though very simple, the model captures the essentials of failure processes in a large number of materials and settings. We present here a review of fiber bundle model with different load redistribution mechanism from the point of view of statistics and statistical physics rather than materials science, with a focus on concepts such as criticality, universality and fluctuations. We discuss the fiber bundle model as a tool for understanding phenomena such as creep, and fatigue, how it is used to describe the behavior of fiber reinforced composites as well as modelling e.g. network failure, traffic jams and earthquake dynamics.Comment: This article has been Editorially approved for publication in Reviews of Modern Physic