Irreversibility and the Arrow of Time in a Quenched Quantum System

Irreversibility is one of the most intriguing concepts in physics. While microscopic physical laws are perfectly reversible, macroscopic average behavior has a preferred direction of time. According to the second law of thermodynamics, this arrow of time is associated with a positive mean entropy production. Using a nuclear magnetic resonance setup, we measure the nonequilibrium entropy produced in an isolated spin-1/2 system following fast quenches of an external magnetic field and experimentally demonstrate that it is equal to the entropic distance, expressed by the Kullback-Leibler divergence, between a microscopic process and its time-reverse. Our result addresses the concept of irreversibility from a microscopic quantum standpoint.

The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. © 2012 Biek et al.

ArnT proteins that catalyse the glycosylation of lipopolysaccharide share common features with bacterial N-oligosaccharyltransferases

ArnT is a glycosyltransferase that catalyses the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) to the lipid A moiety of the lipopolysaccharide. This is a critical modification enabling bacteria to resist killing by antimicrobial peptides. ArnT is an integral inner membrane protein consisting of 13 predicted transmembrane helices and a large periplasmic C-terminal domain. We report here the identification of a functional motif with a canonical consensus sequence DEXRYAX(5)MX(3)GXWX(9)YFEKPX(4)W spanning the first periplasmic loop, which is highly conserved in all ArnT proteins examined. Site-directed mutagenesis demonstrated the contribution of this motif in ArnT function, suggesting that these proteins have a common mechanism. We also demonstrate that the Burkholderia cenocepacia and Salmonella enterica serovar Typhimurium ArnT C-terminal domain is required for polymyxin B resistance in vivo. Deletion of the C-terminal domain in B. cenocepacia ArnT resulted in a protein with significantly reduced in vitro binding to a lipid A fluorescent substrate and unable to catalyse lipid A modification with L-Ara4N. An in silico predicted structural model of ArnT strongly resembled the tertiary structure of Campylobacter lari PglB, a bacterial oligosaccharyltransferase involved in protein N-glycosylation. Therefore, distantly related oligosaccharyltransferases from ArnT and PglB families operating on lipid and polypeptide substrates, respectively, share unexpected structural similarity that could not be predicted from direct amino acid sequence comparisons. We propose that lipid A and protein glycosylation enzymes share a conserved catalytic mechanism despite their evolutionary divergence.

Proton acceleration enhanced by a plasma jet in expanding foils undergoing relativistic transparency

Ion acceleration driven by the interaction of an ultraintense (2 × 10²⁰ W cm^-2) laser pulse with an ultrathin ( nm) foil target is experimentally and numerically investigated. Protons accelerated by sheath fields and via laser radiation pressure are angularly separated and identified based on their directionality and signature features (e.g. transverse instabilities) in the measured spatial-intensity distribution. A low divergence, high energy proton component is also detected when the heated target electrons expand and the target becomes relativistically transparent during the interaction. 2D and 3D particle-in-cell simulations indicate that under these conditions a plasma jet is formed at the target rear, supported by a self-generated azimuthal magnetic field, which extends into the expanded layer of sheath-accelerated protons. Electrons trapped within this jet are directly accelerated to super-thermal energies by the portion of the laser pulse transmitted through the target. The resulting streaming of the electrons into the ion layers enhances the energy of protons in the vicinity of the jet. Through the addition of a controlled prepulse, the maximum energy of these protons is demonstrated experimentally and numerically to be sensitive to the picosecond rising edge profile of the laser pulse.

Outlier SNP markers reveal fine-scale genetic structuring across European hake populations (Merluccius merluccius)

Shallow population structure is generally reported for most marine fish and explained as a consequence of high dispersal, connectivity and large population size. Targeted gene analyses and more recently genome-wide studies have challenged such view, suggesting that adaptive divergence might occur even when neutral markers provide genetic homogeneity across populations. Here, 381 SNPs located in transcribed regions were used to assess large- and fine-scale population structure in the European hake (Merluccius merluccius), a widely distributed demersal species of high priority for the European fishery. Analysis of 850 individuals from 19 locations across the entire distribution range showed evidence for several outlier loci, with significantly higher resolving power. While 299 putatively neutral SNPs confirmed the genetic break between basins (F(CT) = 0.016) and weak differentiation within basins, outlier loci revealed a dramatic divergence between Atlantic and Mediterranean populations (F(CT) range 0.275-0.705) and fine-scale significant population structure. Outlier loci separated North Sea and Northern Portugal populations from all other Atlantic samples and revealed a strong differentiation among Western, Central and Eastern Mediterranean geographical samples. Significant correlation of allele frequencies at outlier loci with seawater surface temperature and salinity supported the hypothesis that populations might be adapted to local conditions. Such evidence highlights the importance of integrating information from neutral and adaptive evolutionary patterns towards a better assessment of genetic diversity. Accordingly, the generated outlier SNP data could be used for tackling illegal practices in hake fishing and commercialization as well as to develop explicit spatial models for defining management units and stock boundaries.

Use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis

Mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the UK cattle industry. Here, we use high-density whole genome sequencing (WGS) in a defined sub-population of M. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. We show that despite low divergence among isolates, WGS can in principle expose contributions of under-sampled host populations to M. bovis transmission. However, we demonstrate that in our data such a signal is due to molecular type switching, which had been previously undocumented for M. bovis. Isolates from farms with a known history of direct cattle movement between them did not show a statistical signal of higher genetic similarity. Despite an overall signal of genetic isolation by distance, genetic distances also showed no apparent relationship with spatial distance among affected farms over distances <5 km. Using simulations, we find that even over the brief evolutionary timescale covered by our data, Bayesian phylogeographic approaches are feasible. Applying such approaches showed that M. bovis dispersal in this system is heterogeneous but slow overall, averaging 2 km/year. These results confirm that widespread application of WGS to M. bovis will bring novel and important insights into the dynamics of M. bovis spread and persistence, but that the current questions most pertinent to control will be best addressed using approaches that more directly integrate WGS with additional epidemiological data.

Behavioural reactivity of ewes and lambs during partial and total social isolation

This work investigated the differences in the reactivity of Sarda (primiparous n= 18, multiparous n= 17) and Dorset (multiparous n= 8) breeds of sheep and their singleton lambs to two challenging test situations involving a mother-lamb partial separation test and an isolation test. Non-parametric analysis used single behavioural variables and fear scores to evaluate the effect of parity, sex of lambs, and the association between mother-lamb behaviour. Amongst ewes, Dorset were characterised by a more calm temperament while Sarda (especially primiparous ewes) were more active in their response to challenge (i.e. more attempts to escape). As with their dams, lambs reflected to a certain extent this divergence and overall during isolation lamb fear score was on average significantly higher than dams. Correlations between measures of behavioural reactivity across tests were carried out to search for predictive measures of fear. A very strong correlation emerged linking vocalisation to locomotor activity. Vocalisation could be a good candidate as predictor factor of an active reaction of sheep to a fearful situation.

The η − µ / Inverse Gamma Composite Fading Model

In this paper we propose a new composite fadingmodel which assumes that the mean signal power of an η−µ signalenvelope follows an inverse gamma distribution. The inversegamma distribution has a simple relationship with the gammadistribution and can be used to model shadowed fading due to itssemi heavy-tailed characteristics. To demonstrate the utility of thenew η−µ / inverse gamma composite fading model, we investigatethe characteristics of the shadowed fading behavior observed inbody centric communications channels which are known to besusceptible to shadowing effects, particularly generated by thehuman body. It is shown that the η−µ / inverse gamma compositefading model provided an excellent fit to the measurement data.Moreover, using Kullback-Leibler divergence, the η −µ / inversegamma composite fading model was found to provide a better fitto the measured data than the κ − µ / inverse gamma compositefading model, for the communication scenarios considered here.

Buffered high charge spectrally-peaked proton beams in the relativistic-transparency regime

Spectrally-peaked proton beams of high charge (E_p ≈ 8 MeV, ΔE ≈ 4 MeV, N ≈ 50 nC ) have been observed from the interaction of an intense laser (>10¹⁹Wcm^-2) with ultrathinCHfoils, as measured by spectrally-resolved full beam profiles. These beams are reproducibly generated for foil thicknesses 5-100 nm, and exhibit narrowing divergence with decreasing target thickness down to ≈8° for 5 nm. Simulations demonstrate that the narrow energy spread feature is a result of buffered acceleration of protons. The radiation pressure at the front of the target results in asymmetric sheath fields which permeate throughout the target, causing preferential forward acceleration. Due to their higher chargeto-mass ratio, the protons outrun a carbon plasma driven in the relativistic transparency regime.

Comprehensive numerical modelling of the performance of a second harmonic generation stage coupled with a low-gain optical parametric amplifier

We present a comprehensive model for predicting the full performance of a second harmonic generation-optical parametric amplification system that aims at enhancing the temporal contrast of laser pulses. The model simultaneously takes into account all the main parameters at play in the system such as the group velocity mismatch, the beam divergence, the spectral content, the pump depletion, and the length of the nonlinear crystals. We monitor the influence of the initial parameters of the input pulse and the interdependence of the two related non-linear processes on the performance of the system and show its optimum configuration. The influence of the initial beam divergence on the spectral and the temporal characteristics of the generated pulse is discussed. In addition, we show that using a crystal slightly longer than the optimum length and introducing small delay between the seed and the pump ensures maximum efficiency and compensates for the spectral shift in the optical parametric amplification stage in case of chirped input pulse. As an example, calculations for bandwidth transform limited and chirped pulses of sub-picosecond duration in beta barium borate crystal are presented.

Guided post-acceleration of laser-driven ions by a miniature modular structure

All-optical approaches to particle acceleration are currently attracting a significant research effort internationally. Although characterized by exceptional transverse and longitudinal emittance, laser-driven ion beams currently have limitations in terms of peak ion energy, bandwidth of the energy spectrum and beam divergence. Here we introduce the concept of a versatile, miniature linear accelerating module, which, by employing laser-excited electromagnetic pulses directed along a helical path surrounding the laser-accelerated ion beams, addresses these shortcomings simultaneously. In a proof-of-principle experiment on a university-scale system, we demonstrate post-acceleration of laser-driven protons from a flat foil at a rate of 0.5 GeVm^-1, already beyond what can be sustained by conventional accelerator technologies, with dynamic beam collimation and energy selection. These results open up new opportunities for the development of extremely compact and cost-effective ion accelerators for both established and innovative applications.

Laser driven MeV proton beam focussing by auto-charged electrostatic lens configuration

Significant reduction of inherent large divergence of the laser driven MeV proton beams is achieved by strong (of the order of 10^9 V/m ) electrostatic focussing field generated in the confined region of a suitably shaped structure attached to the proton generating foil. The scheme exploits the positively charging of the target following an intense laser interaction. Reduction in the proton beam divergence, and commensurate increase in proton flux is observed while preserving the beam laminarity. The underlying mechanism has been established by the help of particle tracing simulations. Dynamic focussing power of the lens, mainly due to the target discharging, can also be exploited in order to bring up the desired chromaticity of the lens for the proton beams of broad energy range.

Shadowed Fading in Indoor Off-Body Communications Channels: A Statistical Characterization using the κ – μ / Gamma Composite Fading Model

This paper investigates the characteristics of the shadowed fading observed in off-body communications channels at 5.8 GHz. This is realized with the aid of the $\kappa-\mu$ / gamma composite fading model which assumes that the transmitted signal undergoes $\kappa-\mu$ fading which is subject to \emph{multiplicative} shadowing. Based on this, the total power of the multipath components, including both the dominant and scattered components, is subject to non-negligible variations that follow the gamma distribution. For this model, we present an integral form of the probability density function (PDF) as well as important analytic expressions for the PDF, cumulative distribution function, moments and moment generating function. In the case of indoor off-body communications, the corresponding measurements were carried out in the context of four explicit individual scenarios namely: line of sight (LOS) and non-LOS (NLOS) walking, rotational and random movements. The measurements were repeated within three different indoor environments and considered three different hypothetical body worn node locations. With the aid of these results, the parameters for the $\kappa-\mu$ / gamma composite fading model were estimated and analyzed extensively. Interestingly, for the majority of the indoor environments and movement scenarios, the parameter estimates suggested that dominant signal components existed even when the direct signal path was obscured by the test subject's body. Additionally, it is shown that the $\kappa-\mu$ / gamma composite fading model provides an adequate fit to the fading effects involved in off-body communications channels. Using the Kullback-Leibler divergence, we have also compared our results with another recently proposed shadowed fading model, namely the $\kappa-\mu$ / lognormal LOS shadowed fading model. It was found that the $\kappa-\mu$ / gamma composite fading model provided a better fit for the majority of the scenarios considered in this study.

Switched Diversity Techniques for Indoor Off-body Communications Channels: An Experimental Analysis and Modeling

This paper investigates the potential improvement in signal reliability for indoor off-body communications channels operating at 5.8 GHz using switched diversity techniques. In particular we investigate the performance of switch-and-stay combining (SSC), switch-and-examine combining (SEC) and switch-and-examine combining with post-examining selection (SECps) schemes which utilize multiple spatially separated antennas at the base station. During the measurements a test subject, wearing an antenna on his chest, performed a number of walking movements towards and then away from a uniform linear array. It was found that all of the considered diversity schemes provided a worthwhile signal improvement. However, the performance of the diversity systems varied according to the switching threshold that was adopted. To model the fading envelope observed at the output of each of the combiners, we have applied diversity specific equations developed under the assumption of Nakagami-$m$ fading. As a measure of the goodness-of-fit, the Kullback-Leibler divergence between the empirical and theoretical probability density functions (PDFs) was calculated and found to be close to 0. To assist with the interpretation of the goodness-of-fit achieved in this study, the standard deviation, $\sigma$, of a zero-mean, $\sigma^2$ variance Gaussian PDF used to approximate a zero-mean, unit variance Gaussian PDF is also presented. These were generally quite close to 1 indicating that the theoretical models provided an adequate fit to the measured data.