Biological and Chemical Physics Commons^™

Vibrational Microspectroscopy For Cancer Screening, Fiona Lyng, Ines Ramos, Ola Ibrahim, Hugh Byrne

Articles

Vibrational spectroscopy analyses vibrations within a molecule and can be used to characterise a molecular structure. Raman spectroscopy is one of the vibrational spectroscopic techniques, in which incident radiation is used to induce vibrations in the molecules of a sample, and the scattered radiation may be used to characterise the sample in a rapid and non-destructive manner. Infrared (IR) spectroscopy is a complementary vibrational spectroscopic technique based on the absorption of IR radiation by the sample. Molecules absorb specific frequencies of the incident light which are characteristic of their structure. IR and Raman spectroscopy are sensitive to subtle biochemical changes …

Multivariate Statistical Methodologies Applied In Biomedical Raman Spectroscopy: Assessing The Validity Of Partial Least Squares Regression Using Simulated Model Datasets, Mark E. Keating, Haq Nawaz, Franck Bonnier, Hugh Byrne

Articles

Raman spectroscopy is fast becoming a valuable analytical tool in a number of biomedical scenarios, most notably disease diagnostics. Importantly, the technique has also shown increasing promise in the assessment of drug interactions on a cellular and subcellular level, particularly when coupled with multivariate statistical analysis. However, an important consideration, both with Raman spectroscopy and the associated statistical methodologies, is the accuracy of these techniques and more specifically the sensitivities which can be achieved and ultimately the limits of detection of the various methods. The purpose of this study is thus the construction of a model simulated data set with …

"Probing The Transition State Region In Catalytic Co Oxidation On Ru" Data Files, H. Öström, H. Öberg, H. Xin, Jerry L. Larue, M. Beye, M. Dell'angela, J. Gladh, M. L. Ng, J. A. Sellberg, S. Kaya, G. Mercurio, D. Nordlund, W. F. Schlotter, A. Föhlisch, M. Wolf, W. Wurth, M. Persson, J. K. Nørskov, F. Abild-Pedersen, H. Ogasawara, L. G. M. Pettersson, A. Nilsson

Biology, Chemistry, and Environmental Sciences Faculty Data Sets

Femtosecond x-ray laser pulses are used to probe the CO oxidation reaction on Ru initiated by an optical laser pulse. On a timescale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and O on the surface allowing the reactants to collide and, with a transient close to a picosecond (ps), new electronic states appear in the O K-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond-formation between CO and O with a distribution of OC—O bond lengths close to the transition state (TS). After …

Probing The Transition State Region In Catalytic Co Oxidation On Ru, H. Öström, H. Öberg, H. Xin, Jerry L. Larue, M. Beye, M. Dell'angela, J. Gladh, M. L. Ng, J. A. Sellberg, S. Kaya, G. Mercurio, D. Nordlund, M. Hantschmann, F. Hieke, D. Kühn, W. F. Schlotter, G. L. Dakovski, J. J. Turner, M. P. Minitti, A. Mitra, S. P. Moeller, A. Föhlisch, M. Wolf, W. Wurth, M. Persson, J. K. Nørskov, F. Abild-Pedersen, H. Ogasawara, L. G. M. Pettersson, A. Nilsson

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Femtosecond x-ray laser pulses are used to probe the CO oxidation reaction on Ru initiated by an optical laser pulse. On a timescale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and O on the surface allowing the reactants to collide and, with a transient close to a picosecond (ps), new electronic states appear in the O K-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond-formation between CO and O with a distribution of OC—O bond lengths close to the transition state (TS). After …

Advantages Of A Finite Extensible Nonlinear Elastic Potential In Lattice Boltzmann Simulations, Tai-Hsien Wu, Dewei Qi

The Hilltop Review

A new structure, generalized lattice nonlinear spring model (GLNSM), which adopts non-linear FENE-LJ potential instead of harmonic potential, has been coupled with lattice Boltzmann simulation for solving fluid-solid interaction problem. In this article, a significant work is the relationship between the GLNSM (FENE-LJ potential) and Young’s modulus has been described in detail. A validation has also been presented to prove that GLNSM is reliable.

New Methods For Measuring Transient Interactions Between Proteins And Curved Membranes, Philip P. Cheney

Electronic Theses and Dissertations

Variations in the physical deformation of the plasma membrane play a significant role in the sorting and behavior of the proteins that occupy it. Determining the interplay between membrane curvature and protein behavior required the development and thorough characterization of a model plasma membrane with well defined and localized regions of curvature. This model system consists of a fluid lipid bilayer that is supported by a dye-loaded polystyrene nanoparticle patterned glass substrate. As the physical deformation of the supported lipid bilayer is essential to our understanding of the behavior of the protein occupying the bilayer, extensive characterization of the structure …

Spatial Analyses On Seismo-Ionospheric Precursors Observed By Gim Tec And Demeter During The 2008 M8.0wenchuan Earthquake, Jann-Yenq Liu, Yuh-Ing Chen, Cheng-Chi Huang, Michel Parrot, Sergey Pulintets, Dimitar Ouzounov

Mathematics, Physics, and Computer Science Faculty Articles and Research

An abstract of the "Spatial analyses on seismo-ionospheric precursors observed by GIM TEC and DEMETER during the 2008 M8.0Wenchuan earthquake" paper presented at EGU General Assembly in 2015.

Elasticity Of Differentiated And Undifferentiated Human Neuroblastoma Cells Characterized By Atomic Force Microscopy, Shijia Zhao, Alexander B. Stamm, Jeong Soon Lee, Alexei Gruverman, Jung Yul Lim, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Human neuroblastoma (SH-SY5Y) cells, with its ability to differentiate into neurons, have been widely used as the in vitro cell culture model for neuroscience research, especially in studying the pathogenesis of Parkinson’s disease (PD) and developing therapeutic strategies. Cellular elasticity could potentially serve as a biomarker to quantitatively distinguish undifferentiated and differentiated SH-SY5Y cells. The goal of this work is to characterize the retinoic acid (RA) induced alternations of elastic properties of SH-SY5Y cells using atomic force microscopy (AFM). The elasticity was measured at multiple points of a single cell. Results have shown that the differentiation of SH-SY5Y cell led …

Enhanced Nanopore Detection Via Diffusion Gradients And Optical Tweezers, Kyle T. Brady

Theses and Dissertations

Nanopore-based resistive pulse sensing represents an important class of single-molecule measurements. It provides information about many molecules of interest (i.e. DNA, proteins, peptides, clusters, polymers, etc.) without the need for labeling. Two experiments that are especially well suited for studying with nanopore sensors are DNA sequencing and DNA-protein force measurements. This thesis will describe progress that has been made in both areas.

DNA sequencing has become an active area of research for stochastic single-molecule sensing, with many researchers striving for the ultimate goal of single-molecule de novo DNA sequencing. One intriguing method towards that goal involves the use of a …

A Principle Of Economy Predicts The Functional Architecture Of Grid Cells, Xue-Xin Wei, Jason Prentice, Vijay Balasubramanian

Publications and Research

Grid cells in the brain respond when an animal occupies a periodic lattice of ‘grid fields’ during navigation. Grids are organized in modules with different periodicity. We propose that the grid system implements a hierarchical code for space that economizes the number of neurons required to encode location with a given resolution across a range equal to the largest period. This theory predicts that (i) grid fields should lie on a triangular lattice, (ii) grid scales should follow a geometric progression, (iii) the ratio between adjacent grid scales should be √e for idealized neurons, and lie between 1.4 and 1.7 …

Antimicrobial Properties Of Nano-Silver: A Cautionary Approach To Ionic Interference, Kate Sheehy, Alan Casey, Anna Murphy, Gordon Chambers

Articles

Hypothesis: Metallic nanoparticles such as nano-silver have found many applications as alternative antimicrobials in recent years. However methods for determining their proposed antimicrobial activity have received little attention to date. The disk diffusion assay is commonly used as a demonstration of antimicrobial properties and is a regular feature in synthetic nanoparticle papers. The aim of this study was to assess its effectiveness in demonstrating the ‘‘nanoparticle specific’’ antimicrobial properties in the absence of ionic contributions from unreacted reducing agents and or impurities. Experiments: The disk diffusion assay was carried out on a range of silver nanoparticles, both in-house synthesised and …

Competitive Evaluation Of Data Mining Algorithms For Use In Cassification Of Leukocyte Subtypes With Raman Microspectroscopy, Adrian Maguire, I. Vega-Carrascal, Jane Bryant, Lisa White, Orla Howe, Fiona Lyng, Aidan Meade

Articles

Raman microspectroscopy has been investigated for some time for use in label-free cell sorting devices. These approaches require coupling of the Raman spectrometer to complex data mining algorithms for identification of cellular subtypes such as the leukocyte subpopulations of lymphocytes and monocytes. In this study, three distinct multivariate classification approaches, (PCA-LDA, SVMs and Random Forests) are developed and tested on their ability to classify the cellular subtype in extracted peripheral blood mononuclear cells (T-cell lymphocytes from myeloid cells), and are evaluated in terms of their respective classification performance. A strategy for optimisation of each of the classification algorithm is presented …

Small Quantum Dots Conjugated To Nanobodies As Immunofluorescence Probes For Nanometric Microscopy, Yong Wang, En Cai, Tobias Rosenkranz, Pinghua Ge, Kai Wen Teng, Sung Jun Lim, Andrew M. Smith, Hee Jung Chung, Frederick Sachs, William N. Green, Philip Gottlieb, Paul R. Selvin

Physics Faculty Publications and Presentations

Immunofluorescence, a powerful technique to detect specific targets using fluorescently labeled antibodies, has been widely used in both scientific research and clinical diagnostics. The probes should be made with small antibodies and high brightness. We conjugated GFP binding protein (GBP) nanobodies, small single-chain antibodies from llamas, with new ∼7 nm quantum dots. These provide simple and versatile immunofluorescence nanoprobes with nanometer accuracy and resolution. Using the new probes we tracked the walking of individual kinesin motors and measured their 8 nm step sizes; we tracked Piezo1 channels, which are eukaryotic mechanosensitive channels; we also tracked AMPA receptors on living neurons. …

Rational Design Of Small-Molecule Stabilizers Of Spermine Synthase Dimer By Virtual Screening And Free Energy-Based Approach, Zhe Zhang, Virginie Martiny, David Lagorce, Yoshihiko Ikeguchi, Emil Alexov, Maria A. Miteva

Publications

Snyder-Robinson Syndrome (SRS) is a rare mental retardation disorder which is caused by the malfunctioning of an enzyme, the spermine synthase (SMS), which functions as a homo-dimer. The malfunctioning of SMS in SRS patients is associated with several identified missense mutations that occur away from the active site. This investigation deals with a particular SRS-causing mutation, the G56S mutation, which was shown computationally and experimentally to destabilize the SMS homo-dimer and thus to abolish SMS enzymatic activity. As a proof-of-concept, we explore the possibility to restore the enzymatic activity of the malfunctioning SMS mutant G56S by stabilizing the dimer through …

Protein Nano-Object Integrator: Generating Atomic-Style Objects For Use In Molecular Biophysics, Nicholas Smith

All Theses

As researchers obtain access to greater and greater amounts of computational power, focus has shifted towards modeling macroscopic objects while still maintaining atomic-level details. The Protein Nano-Object Integrator (ProNOI) presented here has been designed to provide a streamlined solution for creating and designing macro-scale objects with atomic-level details to be used in molecular simulations and tools. To accomplish this, two different interfaces were developed: a Protein Data Bank (PDB), PDB-focused interface for generating regularly-shaped three-dimensional atomic objects and a 2D image-based interface for tracing images with irregularly shaped objects and then extracting three-dimensional models from these images. Each interface is …

Problm Web Server: Protein And Membrane Placement And Orientation Package, Taylor Kimmett, Nicholas Smith, Shawn Witham, Marharyta Petukh, Subhra Sarkar, Emil Alexov

Publications

The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of …

Binding Of Solvated Peptide (Eplqlkm) With A Graphene Sheet Via Simulated Coarse-Grained Approach, Somayyeh Sheikholeslami, R. B. Pandey, Nadiya Dragneva, Wely Floriano, Oleg Rubel, Stephen A. Barr, Zhifeng Kuang, Rajiv Berry, Rajesh Naik, Barry Farmer

Faculty Publications

Binding of a solvated peptide A1 (¹E ²P ³L ⁴Q ⁵L ⁶K ⁷M) with a graphene sheet is studied by a coarse-grained computer simulation involving input from three independent simulated interaction potentials in hierarchy. A number of local and global physical quantities such as energy, mobility, and binding profiles and radius of gyration of peptides are examined as a function of temperature (T). Quantitative differences (e.g., the extent of binding within a temperature range) and qualitative similarities are observed in results from three simulated potentials. Differences in variations of both local and …

Does Protein Folding Exhibit Self-Organized Criticality?, Addison Wisthoff

Senior Theses

Proteins are known to fold into tertiary structures that determine their functionality in living organisms. By understanding the general features of this folding process, that are independent of specific proteins, folding can be better understood. Self-organized critical systems exhibit behavior that scales with system size. In this project, I wrote a simulation of a simplistic three-dimensional cubic lattice protein model. The model consisted of only two different types of amino acids, one being hydrophobic and the other hydrophilic, known as the HP model. To identify self-organized criticality in proteins, there must be clear signs of power law behavior in the …

A Novel P.Leu(381)Phe Mutation In Presenilin 1 Is Associated With Very Early Onset And Unusually Fast Progressing Dementia As Well As Lysosomal Inclusions Typically Seen In Kufs Disease, Natalia Dolzhanskaya, Michael A. Gonzalez, Fiorella Sperziani, Shannon Stefl, Jeffrey Messing, Guang Y. Wen, Emil Alexov, S Stephan Zuchner, Milen Velinov

Publications

Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However his brain autopsy demonstrated typical changes of Alzheimer disease.

On The Modeling Of Polar Component Of Solvation Energy Using Smooth Gaussian-Based Dielectric Function, Lin Li, Chuan Li, Emil Alexov

Publications

Traditional implicit methods for modeling electrostatics in biomolecules use a two-dielectric approach: a biomolecule is assigned low dielectric constant while the water phase is considered as a high dielectric constant medium. However, such an approach treats the biomolecule-water interface as a sharp dielectric border between two homogeneous dielectric media and does not account for inhomogeneous dielectric properties of the macromolecule as well. Recently we reported a new development, a smooth Gaussian-based dielectric function which treats the entire system, the solute and the water phase, as inhomogeneous dielectric medium (J Chem Theory Comput. 2013 Apr 9; 9(4): 2126-2136.). Here we examine …