Chemical research projects office functions accomplishments programs

Basic and applied research in the fields of polymer chemistry, polymeric composites, chemical engineering, and biophysical chemistry is summarized. Emphasis is placed on fire safety and human survivability as they relate to commercial and military aircraft, high-rise buildings, mines and rapid transit transportation. Materials systems and other fire control systems developed for aerospace applications and applied to national domestic needs are described along with bench-scale and full-scale tests conducted to demonstrate the improvements in performance obtained through the utilization of these materials and fire control measures

Evidence for the evolutionary steps leading to mecA-mediated ß-lactam resistance in staphylococci

The epidemiologically most important mechanism of antibiotic resistance in Staphylococcus aureus is associated with mecA–an acquired gene encoding an extra penicillin-binding protein (PBP2a) with low affinity to virtually all β-lactams. The introduction of mecA into the S. aureus chromosome has led to the emergence of methicillin-resistant S. aureus (MRSA) pandemics, responsible for high rates of mortality worldwide. Nonetheless, little is known regarding the origin and evolution of mecA. Different mecA homologues have been identified in species belonging to the Staphylococcus sciuri group representing the most primitive staphylococci. In this study we aimed to identify evolutionary steps linking these mecA precursors to the β-lactam resistance gene mecA and the resistance phenotype. We sequenced genomes of 106 S. sciuri, S. vitulinus and S. fleurettii strains and determined their oxacillin susceptibility profiles. Single-nucleotide polymorphism (SNP) analysis of the core genome was performed to assess the genetic relatedness of the isolates. Phylogenetic analysis of the mecA gene homologues and promoters was achieved through nucleotide/amino acid sequence alignments and mutation rates were estimated using a Bayesian analysis. Furthermore, the predicted structure of mecA homologue-encoded PBPs of oxacillin-susceptible and -resistant strains were compared. We showed for the first time that oxacillin resistance in the S. sciuri group has emerged multiple times and by a variety of different mechanisms. Development of resistance occurred through several steps including structural diversification of the non-binding domain of native PBPs; changes in the promoters of mecA homologues; acquisition of SCCmec and adaptation of the bacterial genetic background. Moreover, our results suggest that it was exposure to β-lactams in human-created environments that has driven evolution of native PBPs towards a resistance determinant. The evolution of β-lactam resistance in staphylococci highlights the numerous resources available to bacteria to adapt to the selective pressure of antibiotics

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

Florida marine biotechnology: research, development and training capabilities to advance science and commerce

The level of activity and interest in “marine biotechnology” among Florida university faculty and allied laboratory scientists is reported in this document. The information will be used to (1) promote networking and collaboration in research and education, (2) inform industry of possible academic partners, (3) identify contacts interested in potential new sources of funding, and (4) assist development of funding for a statewide marine biotechnology research, training and development program. This document is the first of its kind. Institutions of higher learning were given the opportunity to contribute both an overview of campus capabilities and individual faculty Expressions of Scientific Interest. They are listed in the table of contents. (104pp.

Substructures in hydrodynamical cluster simulations

The abundance and structure of dark matter subhalos has been analyzed extensively in recent studies of dark matter-only simulations, but comparatively little is known about the impact of baryonic physics on halo substructures. We here extend the SUBFIND algorithm for substructure identification such that it can be reliably applied to dissipative hydrodynamical simulations that include star formation. This allows, in particular, the identification of galaxies as substructures in simulations of clusters of galaxies, and a determination of their content of gravitationally bound stars, dark matter, and hot and cold gas. Using a large set of cosmological cluster simulations, we present a detailed analysis of halo substructures in hydrodynamical simulations of galaxy clusters, focusing in particular on the influence both of radiative and non-radiative gas physics, and of non-standard physics such as thermal conduction and feedback by galactic outflows. We also examine the impact of numerical nuisance parameters such as artificial viscosity parameterizations. We find that diffuse hot gas is efficiently stripped from subhalos when they enter the highly pressurized cluster atmosphere. This has the effect of decreasing the subhalo mass function relative to a corresponding dark matter-only simulation. These effects are mitigated in radiative runs, where baryons condense in the central subhalo regions and form compact stellar cores. However, in all cases, only a very small fraction, of the order of one percent, of subhalos within the cluster virial radii preserve a gravitationally bound hot gaseous atmosphere. (abridged)Comment: improved manuscript, to appear in MNRA

Social interactions in the Burkholderia cepacia complex : biofilms and quorum sensing

Burkholderia cepacia complex bacteria are opportunistic pathogens that cause respiratory tract infections in susceptible patients, mainly people with cystic fibrosis. There is convincing evidence that B. cepacia complex bacteria can form biofilms, not only on abiotic surfaces (e.g., glass and plastics), but also on biotic surfaces such as epithelial cells, leading to the suggestion that biofilm formation plays a key role in persistent infection of cystic fibrosis lungs. This article presents an overview of the molecular mechanisms involved in B. cepacla complex biofilm formation, the increased resistance of sessile B. cepacia complex cells and the role of quorum sensing in B. cepacia complex biofilm formation

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel