Bedford, MA, United States
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Shelton C.L.,University of Cincinnati | Shelton C.L.,United Medical Systems | Conrady D.G.,United Medical Systems | Conrady D.G.,Beryllium | And 2 more authors.
Biochemical Journal | Year: 2017

Staphylococcus epidermidis is an opportunistic pathogen that can form robust biofilms that render the bacteria resistant to antibiotic action and immune responses. Intercellular adhesion in S. epidermidis biofilms is mediated by the cell wall-associated accumulation-associated protein (Aap), via zinc-mediated self-assembly of its B-repeat region. This region contains up to 17 nearly identical sequence repeats, with each repeat assumed to be functionally equivalent. However, Aap B-repeats exist as two subtypes, defined by a cluster of consensus or variant amino acids. These variable residues are positioned near the zinc-binding (and dimerization) site and the stability determinant for the B-repeat fold. We have characterized four B-repeat constructs to assess the functional relevance of the two Aap B-repeat subtypes. Analytical ultracentrifugation experiments demonstrated that constructs with the variant sequence show reduced or absent Zn2+-induced dimerization. Likewise, circular dichroism thermal denaturation experiments showed that the variant sequence could significantly stabilize the fold, depending on its location within the construct. Crystal structures of three of the constructs revealed that the side chains from the variant sequence form an extensive bonding network that can stabilize the fold. Furthermore, altered distribution of charged residues between consensus and variant sequences changes the electrostatic potential in the vicinity of the Zn2+-binding site, providing a mechanistic explanation for the loss of zinc-induced dimerization in the variant constructs. These data suggest an assembly code that defines preferred oligomerization modes of the B-repeat region of Aap and a slip-grip model for initial contact followed by firm intercellular adhesion during biofilm formation. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.


Appleby T.C.,Gilead Sciences | Perry J.K.,Gilead Sciences | Murakami E.,Gilead Sciences | Barauskas O.,Gilead Sciences | And 9 more authors.
Science | Year: 2015

Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A β loop and a C-terminal membrane-anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3′ terminus, and vacate the active-site cavity during elongation.We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site. © 2015, American Association for the Advancement of Science. All rights reserved.


Gelinas A.D.,SomaLogic | Davies D.R.,Beryllium | Janjic N.,SomaLogic
Current Opinion in Structural Biology | Year: 2016

Understanding the structural rules that govern specific, high-affinity binding characteristic of aptamer-protein interactions is important in view of the increasing use of aptamers across many applications. From the modest number of 16 aptamer-protein structures currently available, trends are emerging. The flexible phosphodiester backbone allows folding into precise three-dimensional structures using known nucleic acid motifs as scaffolds that orient specific functional groups for target recognition. Still, completely novel motifs essential for structure and function are found in modified aptamers with diversity-enhancing side chains. Aptamers and antibodies, two classes of macromolecules used as affinity reagents with entirely different backbones and composition, recognize protein epitopes of similar size and with comparably high shape complementarity. © 2016.


Patent
Northern Illinois University and Beryllium | Date: 2016-03-09

Antibacterial and antimalarial IspF inhibitor compounds and compositions are described. Methods include administering described compounds and compositions to treat bacterial or parasitic infections and to inhibit parasite or bacterial growth.


Manufacturers add product variants in one product family to meet customers' different preferences. Components could be shared and reused to reduce costs. Demand and demand variance change with different sale prices under the stochastic and price-sensitive demand environment. Demand uncertainty has significant effects on costs and profits of the supply chain. With a numerical example involving a product family of cordless drills, a model is used to investigate the effect of supplier profit rate, cost reduction, and component commonality on the supply chain performance. Results show that saving in upstream suppliers due to component commonality could be passed to the manufacturer, retailer, and customers with appropriate coordination models such as quantity discount. With reduced procedure cost, a win-win pricing strategy for one supplier is to increase its profit at a rate while sell its products at a cheaper sale price based on the cost mark-up method considering the demand uncertainty from buyers or downstream suppliers in the supply chain. Copyright © 2011 Inderscience Enterprises Ltd.


Zhang T.,Beryllium
Yejin Fenxi/Metallurgical Analysis | Year: 2013

The beryllium copper intermediate alloy sample was dissolved by nitric acid to determine the content of aluminum. The pH of solution was adjusted to 6-7 using ammonia water. The iron and aluminum were precipitated in form of hydroxide. After filtration and washing, they were separated from matrix copper. The precipitation was dissolved with hydrochloric acid. In HAc-NaAc buffer solution at pH 5.0, aluminum reacted with 8-hydroxyquinoline to form complex, which was extracted with chloroform. The maximum absorption wavelength of complex was at 393 nm, and the apparent molar absorptivity was 6.45×103 L·mol-1·cm-1. In chloroform coloring solution, the Beer's law was obeyed for aluminum ion with mass concentration of 0-4000 μg/L. The interference ions such as iron and copper were removed by cupron-chloroform extraction before coloring. This method was applicable for the determination of 0.0002%-0.5% aluminum in beryllium copper intermediate alloy. The results were consistent with those obtained by ICP-AES. The recoveries of standard addition were 98%-102%.


Patent
Beryllium | Date: 2012-02-16

The beryllium content of beryllium aluminum alloys suitable for investment casting which contain a small but suitable amount of silver can be significantly reduced without adversely affecting their thermal or investment casting properties by including significantly more silicon in the alloy than done in the past.


Trademark
Beryllium | Date: 2014-01-23

Protein Reagents for Scientific or Research Use. Software Systems for Scientific or Research Use. Research, development, testing, management and consulting services in fields of drug discovery, health care and life sciences.


Trademark
Beryllium | Date: 2014-01-23

Protein Reagents for Scientific or Research Use. Software Systems for Scientific or Research Use. Research, development, testing, management and consulting services in fields of drug discovery, health care and life sciences.


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