Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI

Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half‐life in vivo. In a rational design strategy, we obtained an X‐ray structure of lead mannosides and then designed mannosides with improved drug‐like properties. We show that cyclizing the carboxamide onto the biphenyl B‐ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2‐methyl‐4‐(1‐oxo‐1,2‐dihydroisoquinolin‐7‐yl)phenyl α‐d ‐mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N‐Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22 , as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria‐mediated hemagglutination and prevent biofilm formation by UPEC with single‐digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date.     

PMMA composites of single‐walled carbon nanotubes‐graft‐PMMA

To facilitate the dispersion of single‐walled carbon nanotubes (SWCNT) into poly(methyl methacrylate) (PMMA), SWCNT were functionalized with a RAFT chain transfer agent, and PMMA was grafted from the SWCNT by reversible addition–fragmentation transfer (RAFT) polymerization to give SWCNT‐g‐PMMA containing 6 wt % PMMA. SWCNT‐g‐PMMA in the form of small bundles was dispersed into PMMA matrices. The SWCNT‐g‐PMMA filler increased the glass transition temperature (T_g) of the composite when the matrix molecular weight M_n was less than the graft molecular weight, but not when the matrix M_n was equal to or greater than the graft M_n. The threshold of electrical conductivity of the composites as a function of weight percent SWCNT increased from 0.2% when matrix M_n was less than graft M_n to about 1% when matrix M_n was greater than graft M_n. Dynamic mechanical analyses of the composites having graft M_n less than or equal to matrix M_n showed broader rubbery plateaus with increased SWCNT content but no significant differences between samples with different grafted PMMAs. The results indicate that lower M_n matrix wets the SWCNT‐g‐PMMA whereas higher M_n matrix does not wet the SWCNT‐g‐PMMA. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39884.     

Polycrystalline Silicon-Film™ Thin-film Solar Cells: Advanced Products

Thin-film polycrystalline silicon has the potential to achieve the cost reduction and performance improvement necessary for large-scale electricity markets. Reduced cost is achieved by capitalizing on the benefits of thin films grown on low-cost, large-area substrates. Improved efficiency is realized, in spite of reduced material quality, by incorporating enhanced optical absorption and back-surface passivation. The cornerstone of AstroPower's thin-film solar cell technology is the Silicon-Film™ process: a method for the manufacture of solar cell-quality, polycrystalline films of silicon on a variety of low-cost, supporting substrates. Three thin-film solar cell designs, based on this technology, are currently under development. This paper presents the key design features of these three products and briefly reviews the current status of the development of the key technologies that comprise the advanced thin-film solar cell products.     

Polybrominated diphenyl ethers in the sediments of the Great Lakes. 3. Lakes Ontario and Erie

Sediment cores were taken in 2002 in Lakes Ontario and Erie at four locations. A total of 48 sediment samples were characterized, dated using 210Pb, and analyzed for 10 congeners of polybrominated diphenyl ethers (PBDEs) including BDE209 as well as 39 congeners of polychlorinated biphenyls (PCBs). The surficial concentrations of nine tri- through hepta-BDE congeners (sigma9PBDE) are 4.85 and 6.33 ng g(-1), at sampling sites ON40 and ON30 in Lake Ontario, and 1.83 and 1.95 ng g(-1) at ER37 and ER09 in Lake Erie, respectively, based on dry sediment weight. The surficial BDE209 concentrations are 242 and 211 ng g(-1) at ON40 and ON30 and 50 and 55 ng g(-1) at ER37 and ER09. The sigma(9-) PBDEs fluxes to the sediment around 2002 are 147 and 195 pg cm(-2) year(-1) at ON40 and ON30 and 136 and 314 pg cm(-2) year(-1) at ER37 and ER09, respectively. The fluxes of BDE209 are 6.5 and 7.3 ng cm(-2) year(-1) at ON30 and ON40 and 3.7 and 8.9 ng cm(-2) year(-1) at ER37 and ER09, respectively. Dramatic increases in PBDE concentrations and fluxes upward toward the sediment surface and the present time are evident at both locations in Lake Ontario, while PCBs concentrations peak in the middle of sediment cores around the dated time of 1970s and 1960s. For both locations of Lake Erie, the increasing trends of both PBDEs and PCBs from the bottom to the surficial segments were distorted by sediment mixing. BDE209 is the most abundant congener among PBDEs in the sediments, constituting about 96 and 91% of the total PBDEs on mass basis in Lakes Ontario and Erie, respectively.     

The effect of iron on the corrosion characteristics of 90-10 cupro nickel in quiescent 3·4%NaCl solution

The corrosion resistance of 90-10 cupro nickel is very much dependent on small amounts of added Fe. It has been found that in quiescent 3·4%NaCl solution, corrosion rate decreases with increasing Fe and that both solutionized and precipitated Fe are effective. The corrosion product films were essentially similar in all alloys tested being mainly Cu₂O and Cu₂(OH)₃Cl. A complex Fe phase was identified on a 1·5wt.%Fe alloy which had undergone heat treatment to precipitate most of the Fe. A modification of the defect structure of Cu₂O increasing the electronic resistance of the corrosion product film is proposed as responsible for the increased corrosion resistance in cases where Fe is in solid solution. A complex Fe phase, which was found to have a high ionic resistance, was found responsible for the increased corrosion resistance of the precipitated alloy. The results are discussed with reference to current theories of corrosion product doping.     

Validation of scales measuring attitudes, self-efficacy, and intention related to smoking among middle school students.

Attitudes toward smoking, self-efficacy to avoid smoking, and smoking intention, widely cited correlates of youth smoking prevention, are often measured in large-scale youth tobacco surveys. The psychometric properties of these scales have not been well studied among middle school youth. We examined the factorial, discriminate, and convergent validity of these scales among sixth to eighth graders from a convenience sample of 22 Texas middle schools (51.2% female; 51.21% White, 32.1% Hispanic, 16.9% African American, and 8.8% Other; 67.8% nonsmokers, 21.9% experimental smokers; 3.3% former smokers; and 7.6% current smokers). Confirmatory factor analysis and invariance testing suggest that smoking attitudes, self-efficacy, and intention have evidence of construct validity in this multiethnic sample, and the scales are appropriate to assess these constructs among middle school adolescents. Additional studies are needed to establish additional evidence of validity of these constructs in other middle school samples and other subgroups (e.g. current, experimental, and former smokers). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hadamard tensors and lower bounds on multiparty communication complexity

We develop a new method for estimating the discrepancy of tensors associated with multiparty communication problems in the “Number on the Forehead” model of Chandra, Furst, and Lipton. We define an analog of the Hadamard property of matrices for tensors in multiple dimensions and show that any k-party communication problem represented by a Hadamard tensor must have Ω(n/2 ^k ) multiparty communication complexity. We also exhibit constructions of Hadamard tensors. This allows us to obtain Ω(n/2 ^k ) lower bounds on multiparty communication complexity for a new class of explicitly defined Boolean functions.     

The fluid-filling system for the Borexino solar neutrino detector

The system for controlled filling of the nested flexible scintillator containment vessels in the Borexino solar neutrino detector is described. The design and operation principles of pressure and shape monitoring systems are presented for gas filling, gas displacement by water, and water displacement by scintillator. System specifications for safety against overstressing the flexible nylon vessels are defined as well as leak-tightness and cleanliness requirements. The fluid-filling system was a major engineering challenge for the Borexino detector.     

Information modelling in the construction industry: The information engineering approach

Modelling of knowledge in the construction industry is a cumbersome task because of the large amount of data involved and the lack of automated information-modelling tools. Adoption of a method and an automated CASE (Computer-Aided Software Engineering) tool could eliminate many problems encountered in the development of information systems in the construction industry. In particular, this approach may help to assess the information requirements and define strategies for such information systems. The Information Engineering Method (IEM) is introduced to illustrate hoar the conceptual models may be improved by using this method. Additionally Texas Instruments' Information Engineering Facility (IEF?) CASE tool is described to illustrate the advantages of automating such a method. The introduction of conceptual modelling in the construction industry using data and process models should lead to a better structuring of information. This should result in the development of well defined and structured, not ad hoc, applications. This conceptual modelling approach using information engineering is currently being used at the University of Salford to study the potential development of an integrated database (design, procurement and management of construction) for the construction industry. The case study describes the information analysis phase of the procurement process included towards the end of this paper.