NASA-UVA Light Aerospace Alloy and Structures Technology Program: LA(2)ST

The NASA-UVA Light Aerospace Alloy and Structures Technology (LA(2)ST) Program continues a high level of activity, with projects being conducted by graduate students and faculty advisors in the Departments of Materials Science and Engineering, Civil Engineering and Applied Mechanics, and Mechanical and Aerospace Engineering at the University of Virginia. This work is funded by the NASA-Langley Research Center under Grant NAG-1-745. We report on progress achieved between July 1 and December 31, 1992. The objective of the LA(2)ST Program is to conduct interdisciplinary graduate student research on the performance of next generation, light weight aerospace alloys, composites and thermal gradient structures in collaboration with NASA-Langley researchers. Specific technical objectives are presented for each research project. We generally aim to produce relevant data and basic understanding of material mechanical response, corrosion behavior, and microstructure; new monolithic and composite alloys; advanced processing methods; new solid and fluid mechanics analyses; measurement advances; and critically, a pool of educated graduate students for aerospace technologies

NASA-UVA light aerospace alloy and structures technology program

The report on progress achieved in accomplishing of the NASA-UVA Light Aerospace Alloy and Structures Technology Program is presented. The objective is to conduct interdisciplinary graduate student research on the performance of next generation, light weight aerospace alloys and associated thermal gradient structures in close collaboration with researchers. The efforts will produce basic understanding of material behavior, new monolithic and composite alloys, processing methods, solid and fluid mechanics analyses, measurement advances, and a pool of educated graduate students. The presented accomplishments include: research on corrosion fatigue of Al-Li-Cu alloy 2090; research on the strengthening effect of small In additions to Al-Li-Cu alloys; research on localized corrosion of Al-Li alloys; research on stress corrosion cracking of Al-Li-Cu alloys; research on fiber-matrix reaction studies (Ti-1100 and Ti-15-3 matrices containing SCS-6, SCS-9, and SCS-10 fibers); and research on methods for quantifying non-random particle distribution in materials that has led to generation of a set of computer programs that can detect and characterize clusters in particles

Persistence of apoptotic cells without autoimmune disease or inflammation in CD14−/− mice

Interaction of macrophages with apoptotic cells involves multiple steps including recognition, tethering, phagocytosis, and anti-inflammatory macrophage responses. Defective apoptotic cell clearance is associated with pathogenesis of autoimmune disease. CD14 is a surface receptor that functions in vitro in the removal of apoptotic cells by human and murine macrophages, but its mechanism of action has not been defined. Here, we demonstrate that CD14 functions as a macrophage tethering receptor for apoptotic cells. Significantly, CD14−/− macrophages in vivo are defective in clearing apoptotic cells in multiple tissues, suggesting a broad role for CD14 in the clearance process. However, the resultant persistence of apoptotic cells does not lead to inflammation or increased autoantibody production, most likely because, as we show, CD14−/− macrophages retain the ability to generate anti-inflammatory signals in response to apoptotic cells. We conclude that CD14 plays a broad tethering role in apoptotic cell clearance in vivo and that apoptotic cells can persist in the absence of proinflammatory consequences

Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3

double Holliday junction (dHJ) is a central intermediate of homologous recombination that can be processed to yield crossover or non-crossover recombination products. To preserve genomic integrity, cells possess mechanisms to avoid crossing over. We show that Saccharomyces cerevisiae Sgs1 and Top3 proteins are sufficient to migrate and disentangle a dHJ to produce exclusively non-crossover recombination products, in a reaction termed "dissolution." We show that Rmi1 stimulates dHJ dissolution at low Sgs1-Top3 protein concentrations, although it has no effect on the initial rate of Holliday junction (HJ) migration. Rmi1 serves to stimulate DNA decatenation, removing the last linkages between the repaired and template DNA molecules. Dissolution of a dHJ is a highly efficient and concerted alternative to nucleolytic resolution that prevents crossing over of chromosomes during recombinational DNA repair in mitotic cells and thereby contributes to genomic integrity

Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers.

Lipopolyamines (LPAs) are cationic lipids; they interact spontaneously with nucleic acids to form lipoplexes used for gene delivery. The main hurdle to using lipoplexes in gene therapy lies in their immunostimulatory properties, so far attributed to the nucleic acid cargo, while cationic lipids were considered as inert to the immune system. Here we demonstrate for the first time that di-C18 LPAs trigger pro-inflammatory responses through Toll-like receptor 2 (TLR2) activation, and this whether they are bound to nucleic acids or not. Molecular docking experiments suggest potential TLR2 binding modes reminiscent of bacterial lipopeptide sensing. The di-C18 LPAs share the ability of burying their lipid chains in the hydrophobic cavity of TLR2 and, in some cases, TLR1, at the vicinity of the dimerization interface; the cationic headgroups form multiple hydrogen bonds, thus crosslinking TLRs into functional complexes. Unravelling the molecular basis of TLR1 and TLR6-driven heterodimerization upon LPA binding underlines the highly collaborative and promiscuous ligand binding mechanism. The prevalence of non-specific main chain-mediated interactions demonstrates that potentially any saturated LPA currently used or proposed as transfection agent is likely to activate TLR2 during transfection. Hence our study emphasizes the urgent need to test the inflammatory properties of transfection agents and proposes the use of docking analysis as a preliminary screening tool for the synthesis of new non-immunostimulatory nanocarriers.MP would like to thank the FRIA-FNRS (F3/5/5-MCF/XH/FC-17514) for its financial support. NG and MG would like to thank the Wellcome Trust (WT100321/z/12/Z) for financial support. CL is grateful to the foundation Wiener Anspach and the Marie Curie Actions (TLR4-CAT PIEF-GA-2012-326481) for financial support

One-dimensional array of ion chains coupled to an optical cavity

We present a novel system where an optical cavity is integrated with a microfabricated planar-electrode ion trap. The trap electrodes produce a tunable periodic potential allowing the trapping of up to 50 separate ion chains aligned with the cavity and spaced by 160 μm in a one-dimensional array along the cavity axis. Each chain can contain up to 20 individually addressable Yb+ ions coupled to the cavity mode. We demonstrate deterministic distribution of ions between the sites of the electrostatic periodic potential and control of the ion–cavity coupling. The measured strength of this coupling should allow access to the strong collective coupling regime with lesssim10 ions. The optical cavity could serve as a quantum information bus between ions or be used to generate a strong wavelength-scale periodic optical potential.United States. Army Research OfficeNational Science Foundation (U.S.)National Science Foundation (U.S.). Graduate Research Fellowship Program (0645960)National Science Foundation (U.S.) (Interdisciplinary Quantum Information Science and Engineering (iQuISE) Program 0801525

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

Bioinspired Nanofeatured Substrates: Suitable Environment for Bone Regeneration.

Bone mimicking coatings provide a complex microenvironment in which material, through its inherent properties (such as nanostructure and composition), affects the commitment of stem cells into bone lineage and the production of bone tissue regulating factors required for bone healing and regeneration. Herein, a bioactive mineral/biopolymer composite made of calcium phosphate/chitosan and hyaluronic acid (CaP-CHI-HA) was elaborated using a versatile simultaneous spray coating of interacting species. The resulting CaP-CHI-HA coating was mainly constituted of bioactive, carbonated and crystalline hydroxyapatite with 277 ± 98 nm of roughness, 1 μm of thickness, and 2.3 ± 1 GPa of stiffness. After five days of culture, CaP-CHI-HA suggested a synergistic effect of intrinsic biophysical features and biopolymers on stem cell mechanobiology and nuclear organization, leading to the expression of an early osteoblast-like phenotype and the production of bone tissue regulating factors such as osteoprotegerin and vascular endothelial growth factor. More interestingly, amalgamation with biopolymers conferred to the mineral a bacterial antiadhesive property. These significant data shed light on the potential regenerative application of CaP-CHI-HA bioinspired coating in providing a suitable environment for stem cell bone regeneration and an ideal strategy to prevent implant-associated infections.journal article2017 Apr 122017 03 30importe

Improving a Solid-State Qubit through an Engineered Mesoscopic Environment.

A controlled quantum system can alter its environment by feedback, leading to reduced-entropy states of the environment and to improved system coherence. Here, using a quantum-dot electron spin as a control and probe, we prepare the quantum-dot nuclei under the feedback of coherent population trapping and observe their evolution from a thermal to a reduced-entropy state, with the immediate consequence of extended qubit coherence. Via Ramsey interferometry on the electron spin, we directly access the nuclear distribution following its preparation and measure the emergence and decay of correlations within the nuclear ensemble. Under optimal feedback, the inhomogeneous dephasing time of the electron, T_{2}^{*}, is extended by an order of magnitude to 39 ns. Our results can be readily exploited in quantum information protocols utilizing spin-photon entanglement and represent a step towards creating quantum many-body states in a mesoscopic nuclear-spin ensemble.We acknowledge financial support from the European Research Council ERC Consolidator Grant Agreement No. 617985 and the EPSRC National Quantum Technologies Program NQIT EP/M013243/1. G.E-M. acknowledges financial support from NSERC