MicroRNA regulation of CD8+ T cell responses.

MicroRNAs (miRNAs) are a class of short noncoding RNAs that play critical roles in the regulation of a broad range of biological processes. Like transcription factors, miRNAs exert their effects by modulating the expression of networks of genes that operate in common or convergent pathways. CD8+ T cells are critical agents of the adaptive immune system that provide protection from infection and cancer. Here, we review the important roles of miRNAs in the regulation of CD8+ T cell biology and provide perspectives on the broader emerging principles of miRNA function

Flexible Receptor Docking Method Development and Molecular Dynamics Studies Towards Targeting Dynamic Protein Surfaces.

Protein-protein interactions are integral for cellular function, playing a huge role in processes such as cell signaling and transcription regulation. Targeting these essential interactions with small molecule inhibitors is important from a biochemical and pharmaceutical perspective. This dissertation contains chapters on multidisciplinary, collaborative approaches to investigate transcription regulation as well as MHC Class I assembly, which is involved in the immune response. During these projects I applied a variety of computational tools and developed a new docking methodology in CHARMM (CDOCKER). This new version of CDOCKER incorporates receptor flexibility through maintaining selected side-chains in an all-atom representation, while the rest of the receptor is represented as a grid. This version of CDOCKER includes a newly implemented sampling protocol that leads to docking accuracy that is competitive with and even exceeds that of other commonly used docking software in redocking trials. This docking methodology was applied to identify a putative ATP binding on calreticulin (CRT), a chaperone key to MHC Class I assembly and the immune response. This work was a collaborative effort with the Raghavan research group at the University of Michigan and was the first demonstration that CRT both binds and catalyzes ATP. We added further automated functionality to the CDOCKER method to investigate small- molecules covalently bound to receptors in collaboration with the Mapp research group at the University of Michigan. The tethering method was able to stabilize the dynamic surface of GACKIX for crystallization and modeled small-molecules that were identified experimentally but were unable to be crystalized. Finally, we employed Gō-like models to investigate the allosteric signaling between the two binding sites on GACKIX. These studies demonstrated the positive allostery arises from the first peptide paying the entropic cost of binding for the second peptide. The developments in docking methodology within CHARMM allow for targeting of fluid receptors such as GACKIX. A multidisciplinary approach to investigate complex cellular processes such as transcription regulation or the immune response takes advantage of the strengths of the different approaches and leads to advancements in understanding of the process at different size scales, atomistic to in vitro and even in vivo.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116710/1/gagnonj_1.pd

X,Y,Z-Waves: Extended Structures in Nonlinear Lattices

Motivated by recent experimental and theoretical results on optical X-waves, we propose a new type of waveforms in 2D and 3D discrete media -- multi-legged extended nonlinear structures (ENS), built as arrays of lattice solitons (tiles or stones, in the 2D and 3D cases, respectively). First, we study the stability of the tiles and stones analytically, and then extend them numerically to complete ENS forms for both 2D and 3D lattices. The predicted patterns are relevant to a variety of physical settings, such as Bose-Einstein condensates in deep optical lattices, lattices built of microresonators, photorefractive crystals with optically induced lattices (in the 2D case) and others.Comment: 4 pages, 4 figure

Angular position of nodes in the superconducting gap of YBCO

The thermal conductivity of a YBCO single crystal has been studied as a function of the relative orientation of the crystal axes and a magnetic field rotating in the Cu-O planes. Measurements were carried out at several temperatures below T_c and at a fixed field of 30 kOe. A four-fold symmetry characteristic of a superconducting gap with nodes at odd multiples of 45 degrees in k-space was resolved. Experiments were performed to exclude a possible macroscopic origin for such a four-fold symmetry such as sample shape or anisotropic pinning. Our results impose an upper limit of 10% on the weight of the s-wave component of the essentially d-wave superconducting order parameter of YBCO.Comment: 10 pages, 4 figure

Exact Soliton-like Solutions of the Radial Gross-Pitaevskii Equation

We construct exact ring soliton-like solutions of the cylindrically symmetric (i.e., radial) Gross- Pitaevskii equation with a potential, using the similarity transformation method. Depending on the choice of the allowed free functions, the solutions can take the form of stationary dark or bright rings whose time dependence is in the phase dynamics only, or oscillating and bouncing solutions, related to the second Painlev\'e transcendent. In each case the potential can be chosen to be time-independent.Comment: 8 pages, 7 figures. Version 2: stability analysis of the dark solutio

Dense Quark Matter Conductivity in Ultra-Intense Magnetic Field

Heavy-ion collisions generate a huge magnetic field of the order of $10^{18} G$ for the duration of about 0.2 fm/c. This time may become an order of magnitude longer if the electrical conductivity of quark matter is large. We calculate the conductivity in the regime of high density and show that contrary to naive expectations it only weakly depends on the MF.Comment: 3 pages, 0 figure

Contaminant (PAHs, OCs, PCBs and trace metals) concentrations are declining in axial tissue of sand flathead (Platycephalus bassensis) collected from an urbanised catchment (Port Phillip Bay, Australia)

© 2016 Elsevier Ltd. Concentrations of PAHs, OCs, PCBs and trace metals were determined in the white muscle of sand flathead Platycephalus bassensis collected at 6 locations in Port Phillip Bay during 2015. No PAHs, OCs or PCBs were detected in the white muscle of sand flathead at any of the locations, however measurable levels of As, Cu, Hg, Se and Zn were detected at all sites. Only As and Hg exhibited regional difference in white muscle concentrations, with As present only in a non-toxic organic form and Hg measured at levels that are comparable to levels reported in reference sites in other studies. All contaminants detected in the white muscle of sand flathead collected in Port Phillip Bay in 2015 were below Australian Food Standards guideline values, and by world standards, the Port Phillip Bay sand flathead population is considered minimally contaminated. Furthermore, tissue contaminant concentrations appear to be decreasing over time

Triplanar Model for the Gap and Penetration Depth in YBCO

YBaCuO_7 is a trilayer material with a unit cell consisting of a CuO_2 bilayer with a CuO plane of chains in between. Starting with a model of isolated planes coupled through a transverse matrix element, we consider the possibility of intra as well as interplane pairing within a nearly antiferromagnetic Fermi liquid model. Solutions of a set of three coupled BCS equations for the gap exhibit orthorhombic symmetry with s- as well as d-wave contributions. The temperature dependence and a-b in plane anisotropy of the resulting penetration depth is discussed and compared with experiment.Comment: To appear in Physical Review B1 01Mar97; 12 pages with 10 figures; RevTeX+eps

The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers

INTRODUCTION: Appraising the quality of studies included in systematic reviews combining qualitative and quantitative evidence is challenging. To address this challenge, a critical appraisal tool was developed: the Mixed Methods Appraisal Tool (MMAT). The aim of this paper is to present the enhancements made to the MMAT. DEVELOPMENT: The MMAT was initially developed in 2006 based on a literature review on systematic reviews combining qualitative and quantitative evidence. It was subject to pilot and interrater reliability testing. A revised version of the MMAT was developed in 2018 based on the results from usefulness testing, a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts to identify core criteria. TOOL DESCRIPTION: The MMAT assesses the quality of qualitative, quantitative, and mixed methods studies. It focuses on methodological criteria and includes five core quality criteria for each of the following five categories of study designs: (a) qualitative, (b) randomized controlled, (c) nonrandomized, (d) quantitative descriptive, and (e) mixed methods. CONCLUSION: The MMAT is a unique tool that can be used to appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more efficient appraisal