Metal stopping reagents facilitate discontinuous activity assays of the de novo purine biosynthesis enzyme PurE

The conversion of 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynthesis: microbes and nonmetazoan eukaryotes use class I PurEs while animals use class II PurEs. Class I PurEs are therefore a potential antimicrobial target; however, no enzyme activity assay is suitable for high throughput screening (HTS). Here we report a simple chemical quench that fixes the PurE substrate/product ratio for 24 h, as assessed by the Bratton-Marshall assay (BMA) for diazotizable amines. The ZnSO4 stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile product by BMA or other HTS method

Effects of ultraviolet radiation on metabolic rate and fitness of Aedes albopictus and Culex pipiens mosquitoes

Natural and anthropogenic changes (e.g., land use change, pollution) will alter many environmental factors in the coming years, including the amount of solar radiation reaching the earth’s surface. Alterations in solar radiation exposure is likely to impact the ecologies of many living organisms, including invertebrates that inhabit aquatic habitats. In this study, we assessed the effect of UV-B radiation on the metabolic rates and fitness (survival, development time, body size) of Aedes albopictus and Culex pipiens mosquitoes and the activity of their microbial food resources in experimental aquatic microcosms. We exposed single-species cohorts of newly hatched Ae. albopictus and Cx. pipiens larvae and a control treatment with no larvae to three UV-B conditions that mimicked those in full-sun and shade in the field and to a control condition with no UV-B radiation. Our results indicated that UV-B radiation affected the metabolic rates of both Ae. albopictus and Cx. pipiens larvae, with significantly higher rates found in full-sun compared to shade and no-UV conditions, 8 and 15 days after exposure began. Ae. albopictus and Cx. pipiens survival was also affected by UV-B radiation condition, with significantly lower survival in full-sun compared to shade and no UV-B conditions. Microbial metabolic rates were consistently significantly lower in full-sun compared to shade and no-UV conditions, especially at 8 days of exposure. These results show that UV-B radiation at levels found in open spaces showed strong and important impacts on the metabolic rates and survival of Ae. albopictus and Cx. pipiens larvae. Decreased survival of Ae. albopictus and Cx. pipiens with higher UV-B radiation levels may be caused by both direct exposure to radiation as well as the indirect effects of reduced microbial food, resulting in greater metabolic demands and stress. Negative impacts of UV-B radiation on the survival of Ae. albopictus and Cx. pipiens are likely to have important implications for the distribution and abundance of these mosquitoes, and the transmission of pathogens that these two broadly distributed mosquitoes vector

Supersaturating silicon with transition metals by ion implantation and pulsed laser melting

We investigate the possibility of creating an intermediate band semiconductor by supersaturating Si with a range of transition metals (Au, Co, Cr, Cu, Fe, Pd, Pt, W, and Zn) using ion implantation followed by pulsed laser melting (PLM). Structural characterization shows evidence of either surface segregation or cellular breakdown in all transition metals investigated, preventing the formation of high supersaturations. However, concentration-depth profiling reveals that regions of Si supersaturated with Au and Zn are formed below the regions of cellular breakdown. Fits to the concentration-depth profile are used to estimate the diffusive speeds, v D, of Au and Zn, and put lower bounds on v D of the other metals ranging from 10² to 10⁴ m/s. Knowledge of v D is used to tailor the irradiation conditions and synthesize single-crystal Si supersaturated with 10¹⁹ Au/cm³ without cellular breakdown. Values of v D are compared to those for other elements in Si. Two independent thermophysical properties, the solute diffusivity at the melting temperature, D s(T m), and the equilibrium partition coefficient, k e, are shown to simultaneously affect v D. We demonstrate a correlation between v D and the ratio D s(T m)/k e ⁰·⁶⁷, which is exhibited for Group III, IV, and V solutes but not for the transition metals investigated. Nevertheless, comparison with experimental results suggests that D s(T m)/k e ⁰·⁶⁷ might serve as a metric for evaluating the potential to supersaturate Si with transition metals by PLM.Research at Harvard was supported by The U.S. Army Research Office under contracts W911NF-12-1-0196 and W911NF-09-1-0118. M.T.W. and T.B.’s work was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under Grant No. W911NF-10-1-0442, and the National Science Foundation (NSF) Faculty Early Career Development Program ECCS-1150878 (to T.B.). M.J.S., J.T.S., M.T.W., T.B., and S.G. acknowledge a generous gift from the Chesonis Family Foundation and support in part by the National Science Foundation (NSF) and the Department of Energy (DOE) under NSF CA No. EEC- 1041895. S.C. and J.S.W.’s work was supported by The Australian Research Council. J.M. was supported by a National Research Council Research Associateship

Supersaturating silicon with transition metals by ion implantation and pulsed laser melting

We investigate the possibility of creating an intermediate band semiconductor by supersaturating Si with a range of transition metals (Au, Co, Cr, Cu, Fe, Pd, Pt, W, and Zn) using ion implantation followed by pulsed laser melting (PLM). Structural characterization shows evidence of either surface segregation or cellular breakdown in all transition metals investigated, preventing the formation of high supersaturations. However, concentration-depth profiling reveals that regions of Si supersaturated with Au and Zn are formed below the regions of cellular breakdown. Fits to the concentration-depth profile are used to estimate the diffusive speeds, v [subscript D], of Au and Zn, and put lower bounds on v [subscript D] of the other metals ranging from 10[superscript 2] to 10[superscript 4] m/s. Knowledge of v [subscript D] is used to tailor the irradiation conditions and synthesize single-crystal Si supersaturated with 10[superscript 19] Au/cm[superscript 3] without cellular breakdown. Values of v [subscript D] are compared to those for other elements in Si. Two independent thermophysical properties, the solute diffusivity at the melting temperature, D [subscript s](T [subscript m]), and the equilibrium partition coefficient, k [subscript e], are shown to simultaneously affect v [subscript D]. We demonstrate a correlation between v [subscript D] and the ratio D [subscript s](T [subscript m])/k [subscript e] [superscript 0.67], which is exhibited for Group III, IV, and V solutes but not for the transition metals investigated. Nevertheless, comparison with experimental results suggests that D [subscript s](T [subscript m])/k [subscript e] [superscript 0.67] might serve as a metric for evaluating the potential to supersaturate Si with transition metals by PLM.National Science Foundation (U.S.) (Faculty Early Career Development Program ECCS-1150878)Chesonis Family FoundationUnited States. Army Research Laboratory (United States. Army Research Office Grant W911NF-10-1-0442)National Science Foundation (U.S.) (United States. Dept. of Energy NSF CA EEC-1041895

Deactivation of metastable single-crystal silicon hyperdoped with sulfur

Silicon supersaturated with sulfur by ion implantation and pulsed laser melting exhibits broadband optical absorption of photons with energies less than silicon's band gap. However, this metastable, hyperdoped material loses its ability to absorb sub-band gap light after subsequent thermal treatment. We explore this deactivation process through optical absorption and electronic transport measurements of sulfur-hyperdoped silicon subject to anneals at a range of durations and temperatures. The deactivation process is well described by the Johnson-Mehl-Avrami-Kolmogorov framework for the diffusion-mediated transformation of a metastable supersaturated solid solution, and we find that this transformation is characterized by an apparent activation energy of E[subscript A] = 1.7 ± 0.1  eV. Using this activation energy, the evolution of the optical and electronic properties for all anneal duration-temperature combinations collapse onto distinct curves as a function of the extent of reaction. We provide a mechanistic interpretation of this deactivation based on short-range thermally activated atomic movements of the dopants to form sulfur complexes.Center for Clean Water and Clean Energy at MIT and KFUPMNational Science Foundation (U.S.) (Energy, Power, and Adaptive Systems Grant Contract ECCS-1102050)National Science Foundation (U.S.) (United States. Dept. of Energy Contract EEC-1041895

TgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite Toxoplasma gondii

New drugs to control infection with the protozoan parasite Toxoplasma gondii are needed as current treatments exert toxic side effects on patients. Approaches to develop novel compounds for drug development include screening of compound libraries and targeted inhibition of essential cellular pathways. We identified two distinct compounds that display inhibitory activity against the parasite's replicative stage: F3215-0002, which we previously identified during a compound library screen, and I-BET151, an inhibitor of bromodomains, the "reader" module of acetylated lysines. In independent studies, we sought to determine the targets of these two compounds using forward genetics, generating resistant mutants and identifying the determinants of resistance with comparative genome sequencing. Despite the dissimilarity of the two compounds, we recovered resistant mutants with nonsynonymous mutations in the same domain of the same gene, TGGT1_254250, which we found encodes a protein that localizes to the parasite mitochondrion (designated TgPRELID after the name of said domain). We found that mutants selected with one compound were cross resistant to the other compound, suggesting a common mechanism of resistance. To further support our hypothesis that TgPRELID mutations facilitate resistance to both I-BET151 and F3215-0002, CRISPR (clustered regularly interspaced short palindromic repeat)/CAS9-mediated mutation of TgPRELID directly led to increased F3215-0002 resistance. Finally, all resistance mutations clustered in the same subdomain of TgPRELID. These findings suggest that TgPRELID may encode a multidrug resistance factor or that I-BET151 and F3215-0002 have the same target(s) despite their distinct chemical structures. IMPORTANCE We report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite Toxoplasma gondii. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the development of new therapies for toxoplasmosis and other related parasitic diseases

Anomalous Purcell decay of strongly driven inhomogeneous emitters coupled to a cavity

We perform resonant fluorescence lifetime measurements on a nanocavity-coupled erbium ensemble as a function of cavity-laser detuning and pump power. Our measurements reveal an anomalous suppression of the ensemble decay lifetime at zero cavity detuning and high pump fluence. We capture qualitative aspects of this decay rate suppression using a Tavis-Cummings model of non-interacting spins coupled to a common cavity.Comment: 4 figure

Engineering Analysis Studies for Preliminary Design of Lightweight Cryogenic Hydrogen Tanks in UAV Applications

A series of engineering analysis studies were conducted to investigate the potential application of nanoclay-enhanced graphite/epoxy composites and polymer cross-linked silica aerogels in cryogenic hydrogen storage tank designs. This assessment focused on the application of these materials in spherical tank designs for unmanned aeronautic vehicles with mission durations of 14 days. Two cryogenic hydrogen tank design concepts were considered: a vacuum-jacketed design and a sandwiched construction with an aerogel insulating core. Analyses included thermal and structural analyses of the tank designs as well as an analysis of hydrogen diffusion to specify the material permeability requirements. The analyses also provided material property targets for the continued development of cross-linked aerogels and nanoclay-enhanced graphite/epoxy composites for cryogenic storage tank applications. The results reveal that a sandwiched construction with an aerogel core is not a viable design solution for a 14-day mission. A vacuum-jacketed design approach was shown to be far superior to an aerogel. Aerogel insulation may be feasible for shorter duration missions. The results also reveal that the application of nanoclay-enhanced graphite/epoxy should be limited to the construction of outer tanks in a vacuum-jacketed design, since a graphite/epoxy inner tank does not provide a significant weight savings over aluminum and since the ability of nanoclay-enhanced graphite/epoxy to limit hydrogen permeation is still in question

Inclusive Jet Production, Parton Distributions, and the Search for New Physics

Jet production at the Tevatron probes some of the smallest distance scales currently accessible. A gluon distribution that is enhanced at large x compared to previous determinations provides a better description of the Run 1b jet data from both CDF and D0. However, considerable uncertainty still remains regarding the gluon distribution at high x. In this paper, we examine the effects of this uncertainty, and of the remaining uncertainties in the NLO QCD theory, on jet cross section comparisons to Run 1b data. We also calculate the range of contributions still possible from any new physics. Predictions are also made for the expanded kinematic range expected for the ongoing Run 2 at the Tevatron and for the LHC.Comment: 50 pages, 31 figures, RevTe

Purcell enhancement of erbium ions in TiO2_{2} on silicon nanocavities

Isolated solid-state atomic defects with telecom optical transitions are ideal quantum photon emitters and spin qubits for applications in long-distance quantum communication networks. Prototypical telecom defects such as erbium suffer from poor photon emission rates, requiring photonic enhancement using resonant optical cavities. Many of the traditional hosts for erbium ions are not amenable to direct incorporation with existing integrated photonics platforms, limiting scalable fabrication of qubit-based devices. Here we present a scalable approach towards CMOS-compatible telecom qubits by using erbium-doped titanium dioxide thin films grown atop silicon-on-insulator substrates. From this heterostructure, we have fabricated one-dimensional photonic crystal cavities demonstrating quality factors in excess of $5\times10^{4}$ and corresponding Purcell-enhanced optical emission rates of the erbium ensembles in excess of 200. This easily fabricated materials platform represents an important step towards realizing telecom quantum memories in a scalable qubit architecture compatible with mature silicon technologies.Comment: 3 figure