Borrelia burgdorferi membranes are the primary targets of reactive oxygen species

Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle

Graphene based superconducting quantum point contacts

We investigate the Josephson effect in the graphene nanoribbons of length $L$ smaller than the superconducting coherence length and an arbitrary width $W$. We find that in contrast to an ordinary superconducting quantum point contact (SQPC) the critical supercurrent $I_c$ is not quantized for the nanoribbons with smooth and armchair edges. For a low concentration of the carriers $I_c$ decreases monotonically with lowering $W/L$ and tends to a constant minimum for a narrow nanoribbon with $W\lesssim L$. The minimum $I_c$ is zero for the smooth edges but $e\Delta_{0}/\hbar$ for the armchair edges. At higher concentrations of the carriers this monotonic variation acquires a series of peaks. Further analysis of the current-phase relation and the Josephson coupling strength $I_cR_N$ in terms of $W/L$ and the concentration of carriers revels significant differences with those of an ordinary SQPC. On the other hand for a zigzag nanoribbon we find that, similar to an ordinary SQPC, $I_c$ is quantized but to the half-integer values $(n+1/2)4e\Delta_{0}/\hbar$.Comment: 8 pages, 5 figure

Klein tunneling in graphene: optics with massless electrons

This article provides a pedagogical review on Klein tunneling in graphene, i.e. the peculiar tunneling properties of two-dimensional massless Dirac electrons. We consider two simple situations in detail: a massless Dirac electron incident either on a potential step or on a potential barrier and use elementary quantum wave mechanics to obtain the transmission probability. We emphasize the connection to related phenomena in optics, such as the Snell-Descartes law of refraction, total internal reflection, Fabry-P\'erot resonances, negative refraction index materials (the so called meta-materials), etc. We also stress that Klein tunneling is not a genuine quantum tunneling effect as it does not necessarily involve passing through a classically forbidden region via evanescent waves. A crucial role in Klein tunneling is played by the conservation of (sublattice) pseudo-spin, which is discussed in detail. A major consequence is the absence of backscattering at normal incidence, of which we give a new shorten proof. The current experimental status is also thoroughly reviewed. The appendix contains the discussion of a one-dimensional toy model that clearly illustrates the difference in Klein tunneling between mono- and bi-layer graphene.Comment: short review article, 18 pages, 14 figures; v3: references added, several figures slightly modifie

Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behçet Disease

Introduction: The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genomewide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended metaanalysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our

Being, Becoming and the Undivided Universe: A Dialogue between Relational Blockworld and the Implicate Order Concerning the Unification of Relativity and Quantum Theory

In this paper two different approaches to unification will be compared, Relational Blockworld (RBW) and Hiley's implicate order. Both approaches are monistic in that they attempt to derive matter and spacetime geometry 'at once' in an interdependent and background independent fashion from something underneath both quantum theory and relativity. Hiley's monism resides in the implicate order via Clifford algebras and is based on process as fundamental while RBW's monism resides in spacetimematter via path integrals over graphs whereby space, time and matter are co-constructed per a global constraint equation. RBW's monism therefore resides in being (relational blockworld) while that of Hiley's resides in becoming (elementary processes). Regarding the derivation of quantum theory and relativity, the promises and pitfalls of both approaches will be elaborated. Finally, special attention will be paid as to how Hiley's process account might avoid the blockworld implications of relativity and the frozen time problem of canonical quantum gravity.Comment: 33 pages, 7 figures. Revised to include modified Regge calculus results. Accepted for publication in Foundations of Physics. arXiv admin note: substantial text overlap with arXiv:1106.333

Subclinical Thyroid Dysfunction and Fracture Risk: A Meta-analysis

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.http://www.sciencedirect.com/science/article/B6SYS-4S50K2J-1/1/7d11c902193bfa3f1f57030572f7034