Laboratory assessment of antibacterial activity of zwitterionic 7-methoxyimino cephalosporins

Zwitterionic 7-methoxyimino cephalosporins (cefpirome, cefepime, cefclidin, DQ2556, FKO37 and SCE2787) possess a variable substitution at C3 which contains a quarernary nitrogen. These cephalosporins display low affinities for Class I /7-lactamase and rapid penetration through the outer membrane of Gram-negative bacilli, so that an increased number of periplasmic β-lactam molecules interact with PBP's per unit of time. As a consequence, the new zitterionic compounds remain active against some, but not all, ceftazidime-resistant Enterobacteriaceae producing high levels of Class Iβlactamase or Bush type 2bβlactamases. Antipseudomonas activities are generally similar to that of ceftazidime except that cefclidin is more active. The new zwitterionic compounds, especially cefpirome and FK037, express greater antistaphylococcal potency than does ceftazidime. A variety of animal models including meningitis and endocarditis have confirmed the potential of these compounds in-vivo. On the basis of structural and antibacterial characteristics, the expression ‘forth generation' is acceptable to describe the zwitterionic 7-methoxyimino cephalosporin

Characterizing Scales of Genetic Recombination and Antibiotic Resistance in Pathogenic Bacteria Using Topological Data Analysis

Pathogenic bacteria present a large disease burden on human health. Control of these pathogens is hampered by rampant lateral gene transfer, whereby pathogenic strains may acquire genes conferring resistance to common antibiotics. Here we introduce tools from topological data analysis to characterize the frequency and scale of lateral gene transfer in bacteria, focusing on a set of pathogens of significant public health relevance. As a case study, we examine the spread of antibiotic resistance in Staphylococcus aureus. Finally, we consider the possible role of the human microbiome as a reservoir for antibiotic resistance genes.Comment: 12 pages, 6 figures. To appear in AMT 2014 Special Session on Advanced Methods of Interactive Data Mining for Personalized Medicin

Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in J774 macrophages

J774 macrophage-like cells express organic anion transporters that promote the efflux of fluoroquinolone antibiotics such as norfloxacin (NFX) from these cells. Gemfibrozil (GFZ) blocks organic anion transport in J774 cells, thereby facilitating the intracellular accumulation of NFX (Cao, C., H.C. Neu, and S.C. Silverstein. 1991. J. Cell Biol. 115:467a [Abstr.]). To determine whether GFZ enhances the efficacy of fluoroquinolone antibiotics against intracellular bacterial pathogens, J774 cells were infected with Listeria monocytogenes and incubated in medium containing a fluoroquinolone antibiotic in the presence or absence of GFZ. Intracellular growth of L. monocytogenes was evaluated by lysing J774 cells and assaying for colony-forming units of Listeria. GFZ intensified the bacteriostatic effect of 4 micrograms/ml NFX and rendered 8 micrograms/ml bactericidal for L. monocytogenes. GFZ had a similar potentiating effect when used in combination with 2 micrograms/ml ciprofloxacin (CFX). CFX plus GFZ was bactericidal for intracellular L. monocytogenes. Treatment of J774 cells with NFX plus GFZ markedly reduced the cytotoxic effect of the bacteria on these cells. Over 55% of cells treated with 8 micrograms/ml NFX alone were dead 16 h after infection, whereas only 5% of cells treated with 8 micrograms/ml NFX plus GFZ were dead at 16 h. Similarly, GFZ potentiated the ability of 2 micrograms/ml to protect J774 cells against the cytocidal effect of Listeria. NFX in combination with GFZ limited cell-to-cell spread of L. monocytogenes. In antibiotic-free medium, > 99% of J774 cells contained intracellular L. monocytogenes at 14 h after infection. NFX alone in the medium did not change this outcome. However, 4 micrograms/ml NFX plus GFZ decreased bacterial spread by approximately 40% at 24 h postinfection, and 8 micrograms/ml NFX plus GFZ prevented all spread beyond the initially infected cell population. These results suggest that GFZ could be used clinically to enhance the efficacy of fluoroquinolone and of other anionic antibiotics against bacteria that grow and/or reside within macrophages and/or other cells

Cumulant Expansions and the Spin-Boson Problem

The dynamics of the dissipative two-level system at zero temperature is studied using three different cumulant expansion techniques. The relative merits and drawbacks of each technique are discussed. It is found that a new technique, the non-crossing cumulant expansion, appears to embody the virtues of the more standard cumulant methods.Comment: 26 pages, LaTe

Scanning Electron Microscopy Study of Biofilms on Silicone Voice Prosthesis

Patients after laryngectomy often receive silicone made voice prostheses fot speech rehabilitation. The prosthesis is inserted in a shunt between the trachea and the digestive tract. As the prosthesis is placed in a nonsterile environment it becomes rapidly colonized by microorganisms eventually leading to failure and frequent exchange of the implant. In this study, explanted Groningen Button silicone voice prostheses were used to investigate by scanning electron microscopy the biofilm developing on the implant. Two main types of microbial colonization forms could be distinguished. Firstly, macroscopically visible, single colonies dominating on the esophagus side of the prosthesis were found, which were built up of mainly yeast cells. Secondly, thin microbial films on the areas in between were seen in which bacteria were the dominating organisms. In both colonization forms, mixed biofilms of mainly cocci and yeasts could also be found

Chemical vapor deposition and infiltration for the production of tungsten fiber reinforced tungsten composite material

Contribution submission to the conference Regensburg 2016Chemical vapor deposition and infiltration for the productionof tungsten fiber reinforced tungsten composite material —∙Martin Aumann1, Jan Willem Coenen1, Hanns Gietl2, TillHoeschen2, Johann Riesch2, Klaus Schmid2, Rudolf Neu2, andChristian Linsmeier1 — 1Forschungszentrum Juelich GmbH, Institutfür Energie- und Klimaforschung, 52425 Juelich — 2Max-Planck-Institut für Plasmaphysik, 85748 GarchingDue to its high melting point, high corrosion resistance and its preferableproperties in terms of hydrogen retention, tungsten is a promisingcandidate in future nuclear fusion devices. However, the mechanicalbehavior of tungsten is crucial, as it is inherently brittle at room temperature.As possibility to overcome this brittleness, a composite materialcan be formed, which shows pseudo-ductility and therefore avoidscatastrophic failure of the material. A possibility to produce such aWf/W-composite is chemical vapor deposition and chemical vapor infiltration,where tungsten is deposited on small tungsten wires throughthe reaction of WF6 and H2. With ongoing infiltration time, pores areformed between the fibers, which decrease in size through the chemicalreaction. For better process understanding, a pore model was established,which solves the mass balance inside the pore and the resultingpore diameter simultaneously. It shows a significant difference in diameterfor longer infiltration times. This behavior shall be proved inexperiments with an experimental pore, which is similar to the simulatedone. Furthermore also kinetic investigations on the chemicalsurface reaction are carried out to increase the process understanding.Part: MMType: Vortrag;TalkTopic: Transport (Diffusion, Leitfähigkeit,Wärme)/ Transport (Diffusion,conductivity, heat)Email: [email protected]

Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure

Optical signatures of silicon-vacancy spins in diamond

Colour centres in diamond have emerged as versatile tools for solid-state quantum technologies ranging from quantum information to metrology, where the nitrogen-vacancy centre is the most studied to date. Recently, this toolbox has expanded to include novel colour centres to realize more efficient spin-photon quantum interfaces. Of these, the silicon-vacancy centre stands out with highly desirable photonic properties. The challenge for utilizing this centre is to realize the hitherto elusive optical access to its electronic spin. Here we report spin-tagged resonance fluorescence from the negatively charged silicon-vacancy centre. Our measurements reveal a spin-state purity approaching unity in the excited state, highlighting the potential of the centre as an efficient spin-photon quantum interface