Ceragenins are cholic acid-derived antimicrobial agents that mimic the activity of endogenous antimicrobial peptides. Ceragenins target bacterial membranes, yet the consequences of these interactions have not been fully elucidated. The role of the outer membrane in allowing access of the ceragenins to the cytoplasmic membrane of Gram-negative bacteria was studied using the ML-35p mutant strain of Escherichia coli that has been engineered to allow independent monitoring of small-molecule flux across the inner and outer membranes. The ceragenins CSA-8, CSA-13, and CSA-54 permeabilize the outer membrane of this bacterium, suggesting that the outer membrane does not play a major role in preventing the access of these agents to the cytoplasmic membrane. However, only the most potent of these ceragenins, CSA-13, was able to permeabilize the inner membrane. Interestingly, neither CSA-8 nor CSA-54 caused inner membrane permeabilization over a 30-min period, even at concentrations well above those required for bacterial toxicity. To further assess the role of membrane interactions, we measured membrane depolarization in Gram-positive bacteria with different membrane lipid compositions, as well as in Gram-negative bacteria. We found greatly increased membrane depolarization at the minimal bactericidal concentration of the ceragenins for bacterial species containing a high concentration of phosphatidylethanolamine or uncharged lipids in their cytoplasmic membranes. Although membrane lipid composition affected bactericidal efficiency, membrane depolarization was sufficient to cause lethality, providing that agents could access the cytoplasmic membrane. Consequently, we propose that in targeting bacterial cytoplasmic membranes, focus be placed on membrane depolarization as an indicator of potency.

CSA-13 retained potent antibacterial activity against S. aureus over the course of 30 serial passages. Resistance generated in Gram-negative bacteria correlates with modifications to the outer membranes of these organisms and was not stable outside of the presence of the antimicrobial.

The activation, differentiation and subsequent effector functions of CD4 T cells depend on interactions with a multitude of MHCII-expressing antigen presenting cells (APCs). To evaluate the individual contribution of various APCs to CD4 T cell function, we have designed a new murine tool for selective in vivo expression of MHCII in subsets of APCs. Conditional expression of MHCII in B cells was achieved using a cre-loxP approach. After intravenous or subcutaneous priming, partial proliferation and activation of CD4 T cells was observed in mice expressing MHCII only by B cells. Restricting MHCII expression to B cells constrained secondary CD4 T cell responses in vivo, as demonstrated in a CD4 T cell-dependent model of autoimmunity, EAE. These results highlight the limitations of B cell antigen presentation during initiation and propagation of CD4 T cell function in vivo using a novel system to study individual APCs by the conditional expression of MHCII.

Multiple GaN nanowires produced by thermal chemical vapor deposition were employed as gas sensors for detection of hydrogen at concentrations from 200–1500 ppm in N2 at 300 K. Palladium coating of the wires improved the sensitivity by a factor of up to 11 at low ppm concentrations relative to uncoated controls. The GaN nanowires showed relative responses of ∼7.4% at 200 ppm and ∼9.1% at 1500 ppm H2 in N2 after a 10 min exposure. Upon removal of hydrogen from the measurement ambient, ∼90% of the initial GaN conductance was recovered within 2 min. Temperature dependent measurements showed a larger relative response and shorter response time at elevated temperature. The adsorption activation energy of the sensor was 2.2 kcal mol−1 at 3000 ppm H2 in N2. These sensors exhibit low power consumption (<0.6 mW) at 300 K.

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These properties of the PCL can be used to assess the utility of graft choices and operative techniques for PCL reconstruction and may partly explain limited differences in the outcomes of single-bundle compared with double-bundle reconstruction techniques for the PCL.

We report on the growth and characterization of high-quality GaN nanowires for hydrogen sensors. We grew the GaN nanowires by catalytic chemical vapor deposition (CVD) using gold thin films as a catalyst on a Si wafer with an insulating SiO 2 layer. Structural characterization of the as-grown nanowires by several methods shows that the nanowires are single-crystal wurtzite GaN. Photoluminescence measurements under 325 nm excitation show a near-band-edge emission peak around $3.4 eV. The hydrogen sensors are fabricated by contacting the as-grown GaN nanowires by source and drain electrodes and coating them with a thin layer of Pd. Hydrogen sensing experiments using the fabricated devices show high sensitivity response (ppm detection limit at room temperature) and excellent recovery. This work opens up the possibility of using high-quality GaN nanowire networks for hydrogen sensing applications.