Independent particle descriptions of tunneling from a many-body perspective

Currents across thin insulators are commonly taken as single electrons moving across classically forbidden regions; this independent particle picture is well-known to describe most tunneling phenomena. Examining quantum transport from a different perspective, i.e., by explicit treatment of electron-electron interactions, we evaluate different single particle approximations with specific application to tunneling in metal-molecule-metal junctions. We find maximizing the overlap of a Slater determinant composed of single particle states to the many-body current-carrying state is more important than energy minimization for defining single particle approximations in a system with open boundary conditions. Thus the most suitable single particle effective potential is not one commonly in use by electronic structure methods, such as the Hartree-Fock or Kohn-Sham approximations.Comment: 4+ pages, 4 figures; accepted to Phys. Rev. B Rapid Communication

Correlated electron transport in molecular electronics

Theoretical and experimental values to date for the resistances of single molecules commonly disagree by orders of magnitude. By reformulating the transport problem using boundary conditions suitable for correlated many-electron systems, we approach electron transport across molecules from a new standpoint. Application of our correlated formalism to benzene-dithiol gives current-voltage characteristics close to experimental observations. The method can solve the open system quantum many-body problem accurately, treats spin exactly, and is valid beyond the linear response regime

C-60 as a Faraday cage

Endohedral fullerenes have been proposed for a number of technological uses, for example, as a nanoscale switch, memory bit and as qubits for quantum computation. For these technology applications, it is important to know the ease with which the endohedral atom can be manipulated using an applied electric field. We find that the Buckminsterfullerene (C-60) acts effectively as a small Faraday cage, with only 25% of the field penetrating the interior of the molecule. Thus influencing the atom is difficult, but as a qubit the endohedral atom should be well shielded from environmental electrical noise. We also predict how the field penetration should increase with the fullerene radius. (C) 2004 American Institute of Physics. (DOI: 10.1063/1.1640783

Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner

As described elsewhere in this Special Issue on biomarkers, much progress has been made in the detection of modified DNA within organisms at endogenous and exogenous levels of exposure to chemical species, including putative carcinogens and chemotherapeutic agents. Advances in the detection of damaged or unnatural bases have been able to provide correlations to support or refute hypotheses between the level of exposure to oxidative, alkylative, and other stresses, and the resulting DNA damage (lesion formation). However, such stresses can form a plethora of modified nucleobases, and it is therefore difficult to determine the individual contribution of a particular modification to alter a cell’s genetic fate, as measured in the form of toxicity by stalled replication past the damage, by subsequent mutation, and by lesion repair. Chemical incorporation of a modification at a specific site within a vector (site-specific mutagenesis) has been a useful tool to deconvolute what types of damage quantified in biologically relevant systems may lead to toxicity and/or mutagenicity, thereby allowing researchers to focus on the most relevant biomarkers that may impact human health. Here, we will review a sampling of the DNA modifications that have been studied by shuttle vector technique

The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond

The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli “adaptive response” protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1–8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins.National Institutes of Health (U.S.) (Grant P01 CA26731)National Institutes of Health (U.S.) (Grant R37 CA080024)National Institutes of Health (U.S.) (Grant P30 ES002109

Assessing and Manipulating The Illusion of Control of Video Poker Players

The present investigation explored the presence of illusory control in recreation-al video poker players. Using a multi-monitor computer which allowed for two different types of games to be presented concurrently, one on each monitor, players were allowed to freely choose which game they wished to play. One option allowed for the player to select the cards they wished to hold and discard, while the other option was designed such that the computer automatically se-lected the most probabilistically optimal sequence of cards to hold and discard. In the first experiment, two groups of ten participants were exposed to one of two rules (accurate or inaccurate) regarding the chances of winning. No differ-ences in response allocations between the games were found. In the second experiment, thirteen participants were sequentially exposed to a non-rule base-line followed by an inaccurate and subsequently accurate rule. Twelve of the thirteen players preferred the self-selecting game, and following the introduction of an experimenter given rule that was designed to strengthen the illusion (i.e., that the self-selecting option was better), most players increased their preference for this option. However, following the introduction of an experimenter given rule that attempted to weaken the illusion, only about half the participants fol-lowed that rule and reduced playing the self-selecting option. Variability across participants was able to be explained by examining each player’s verbal talk which was emitted overtly throughout the duration of the experiment. Implica-tions for understanding the illusion of control and the verbal behavior of gam-blers are presented

Non-universal Voronoi cell shapes in amorphous ellipsoid packings

In particulate systems with short-range interactions, such as granular matter or simple fluids, local structure plays a pivotal role in determining the macroscopic physical properties. Here, we analyse local structure metrics derived from the Voronoi diagram of configurations of oblate ellipsoids, for various aspect ratios $\alpha$ and global volume fractions $\phi_g$. We focus on jammed static configurations of frictional ellipsoids, obtained by tomographic imaging and by discrete element method simulations. In particular, we consider the local packing fraction $\phi_l$, defined as the particle's volume divided by its Voronoi cell volume. We find that the probability $P(\phi_l)$ for a Voronoi cell to have a given local packing fraction shows the same scaling behaviour as function of $\phi_g$ as observed for random sphere packs. Surprisingly, this scaling behaviour is further found to be independent of the particle aspect ratio. By contrast, the typical Voronoi cell shape, quantified by the Minkowski tensor anisotropy index $\beta=\beta_0^{2,0}$, points towards a significant difference between random packings of spheres and those of oblate ellipsoids. While the average cell shape $\beta$ of all cells with a given value of $\phi_l$ is very similar in dense and loose jammed sphere packings, the structure of dense and loose ellipsoid packings differs substantially such that this does not hold true. This non-universality has implications for our understanding of jamming of aspherical particles.Comment: 6 pages, 5 figure

Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning.

Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group (PcG) proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here, we explored the transcriptional response of genes associated with polycomb repressive complex (PRC) 1 (Ring1A, Ring1B, and Bmi1) and PRC2 (Ezh1, Ezh2, and Suz12), as well as additional transcriptional regulators Sirt1, Yy1, and Yy2, in a mouse model of status epilepticus (SE). Findings were contrasted to changes after SE in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed SE prompted an early (1 h) increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4, 8, and 24 h). Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12, and Yy2 relative to the normal injury response to SE. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes PcG gene expression following SE and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance

Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 ?l), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs

Mechanism of Repair of Acrolein- and Malondialdehyde-Derived Exocyclic Guanine Adducts by the α-Ketoglutarate/Fe(II) Dioxygenase AlkB

The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M[subscript 1]dG are formed when DNA is exposed to the reactive aldehydes acrolein and malondialdehyde (MDA). These lesions are believed to form the basis for the observed cytotoxicity and mutagenicity of acrolein and MDA. In an effort to understand the enzymatic pathways and chemical mechanisms that are involved in the repair of acrolein- and MDA-induced DNA damage, we investigated the ability of the DNA repair enzyme AlkB, an α-ketoglutarate/Fe(II) dependent dioxygenase, to process α-OH-PdG, γ-OH-PdG, and M[subscript 1]dG in both single- and double-stranded DNA contexts. By monitoring the repair reactions using quadrupole time-of-flight (Q-TOF) mass spectrometry, it was established that AlkB can oxidatively dealkylate γ-OH-PdG most efficiently, followed by M[subscript 1]dG and α-OH-PdG. The AlkB repair mechanism involved multiple intermediates and complex, overlapping repair pathways. For example, the three exocyclic guanine adducts were shown to be in equilibrium with open-ring aldehydic forms, which were trapped using (pentafluorobenzyl)hydroxylamine (PFBHA) or NaBH[subscript 4]. AlkB repaired the trapped open-ring form of γ-OH-PdG but not the trapped open-ring of α-OH-PdG. Taken together, this study provides a detailed mechanism by which three-carbon bridge exocyclic guanine adducts can be processed by AlkB and suggests an important role for the AlkB family of dioxygenases in protecting against the deleterious biological consequences of acrolein and MDA.National Institutes of Health (U.S.) (Grant R01 CA080024)National Institutes of Health (U.S.) (Grant R01 CA26731)National Institutes of Health (U.S.) (Center Grant P30 ES02109)National Institutes of Health (U.S.) (Training Grant T32 ES007020