Publications

<div><p>Mammalian Peptidoglycan Recognition Proteins (PGRPs) are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS), a mechanism of killing that was also postulated, and later refuted, for several bactericidal antibiotics. Here, using whole genome expression arrays, qRT-PCR, and biochemical tests we show that in both <i>Escherichia coli</i> and <i>Bacillus subtilis</i> PGRPs induce a transcriptomic signature characteristic of oxidative stress, as well as correlated biochemical changes. However, induction of ROS was required, but not sufficient for PGRP killing. PGRPs also induced depletion of intracellular thiols and increased cytosolic concentrations of zinc and copper, as evidenced by transcriptome changes and supported by direct measurements. Depletion of thiols and elevated concentrations of metals were also required, but by themselves not sufficient, for bacterial killing. Chemical treatment studies demonstrated that efficient bacterial killing can be recapitulated only by the simultaneous addition of agents leading to production of ROS, depletion of thiols, and elevation of intracellular metal concentrations. These results identify a novel mechanism of bacterial killing by innate immunity proteins, which depends on synergistic effect of oxidative, thiol, and metal stress and differs from bacterial killing by antibiotics. These results offer potential targets for developing new antibacterial agents that would kill antibiotic-resistant bacteria.</p></div>

We report the integration of inorganic nanotubes into metal-oxide-solution field effect transistors (FETs) which exhibit rapid field effect modulation of ionic conductance. Surface functionalization, analogous to doping in semiconductors, can switch the nanofluidic transistors from p-type to ambipolar and n-type field effect transistors. Transient study reveals the kinetics of field effect modulation is controlled by ion-exchange step. Nanofluidic FETs have potential implications in subfemtoliter analytical technology and large-scale nanofluidic integration.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Prediction of the accumulated pitting corrosion damage in aluminum-lithium (Al-Li) is of great importance due to the wide application of these alloys in the aerospace industry. The Point Defect Model (PDM) is arguably one of the most well-developed techniques for evaluating the electrochemical behavior of passive metals. In this paper, the passivity breakdown and pitting corrosion performance of AA 2098-T851 was investigated using the PDM with the potentiodynamic polarization (PDP) technique in NaCl solutions at different scan rates, Cl− concentrations and pH. Both the PDM predictions and experiments reveal linear relationships between the critical breakdown potential (Ec) of the alloy and various independent variables, such as a C l − and pH. Optimization of the PDM of the near-normally distributed Ec as measured in at least 20 replicate experiments under each set of conditions, allowing for the estimation of some of the critical parameters on barrier layer generation and dissolution, such as the critical areal concentration of condensed cation vacancies (ξ) at the metal/barrier layer interface and the mean diffusivity of the cation vacancy in the barrier layer (D). With these values obtained—using PDM optimization—in one set of conditions, the Ec distribution can be predicted for any other set of conditions (combinations of a Cl − , pH and T). The PDM predictions and experimental observations in this work are in close agreement.

Abstract Most Type I superluminous supernovae (SLSNe-I) reported to date have been identified by their high peak luminosities and spectra lacking obvious signs of hydrogen. We demonstrate that these events can be distinguished from normal-luminosity SNe (including Type Ic events) solely from their spectra over a wide range of light-curve phases. We use this distinction to select 19 SLSNe-I and four possible SLSNe-I from the Palomar Transient Factory archive (including seven previously published objects). We present 127 new spectra of these objects and combine these with 39 previously published spectra, and we use these to discuss the average spectral properties of SLSNe-I at different spectral phases. We find that Mn ii most probably contributes to the ultraviolet spectral features after maximum light, and we give a detailed study of the O ii features that often characterize the early-time optical spectra of SLSNe-I. We discuss the velocity distribution of O ii , finding that for some SLSNe-I this can be confined to a narrow range compared to relatively large systematic velocity shifts. Mg ii and Fe ii favor higher velocities than O ii and C ii , and we briefly discuss how this may constrain power-source models. We tentatively group objects by how well they match either SN 2011ke or PTF12dam and discuss the possibility that physically distinct events may have been previously grouped together under the SLSN-I label.

Fructose feeding increases hepatic de novo lipogenesis (DNL) and is associated with nonalcoholic fatty liver disease. Little is known, however, about individual variation in susceptibility to fructose stimulation of DNL. In this three-period crossover study, 17 healthy male subjects were enrolled to evaluate the within- and between-subject variability of acute fructose feeding on hepatic fractional DNL. During each assessment, [1- 13 C 1 ]acetate was infused to measure DNL in the fasting state and during fructose feeding. Subjects randomly received a high dose of fructose (10 mg·kg fat-free mass −1 ·min −1 ) on two occasions and a low dose (5 mg·kg fat-free mass −1 ·min −1 ) on another. Fructose solutions were administered orally every 30 min for 9.5 h. Ten subjects completed all three study periods. DNL was assessed as the fractional contribution of newly synthesized palmitate into very-low-density lipoprotein triglycerides using mass isotopomer distribution analysis. Mean fasting DNL was 5.3 ± 2.8%, with significant within- and between-subject variability. DNL increased dose dependently during fructose feeding to 15 ± 2% for low- and 29 ± 2% for high-dose fructose. The DNL response to high-dose fructose was very reproducible within an individual ( r = 0.93, P < 0.001) and independent of fasting DNL. However, it was variable between individuals and significantly correlated to influx of unlabeled acetyl-CoA ( r = 0.7, P < 0.001). Unlike fasting DNL, fructose-stimulated DNL is a robust and reproducible measure of hepatic lipogenic activity for a given individual and may be a useful indicator of metabolic disease susceptibility and treatment response.