Exploring the limits of the self consistent Born approximation for inelastic electronic transport

The non equilibrium Green function formalism is today the standard computational method for describing elastic transport in molecular devices. This can be extended to include inelastic scattering by the so called self-consistent Born approximation (SCBA), where the interaction of the electrons with the vibrations of the molecule is assumed to be weak and it is treated perturbatively. The validity of such an assumption and therefore of the SCBA is difficult to establish with certainty. In this work we explore the limitations of the SCBA by using a simple tight-binding model with the electron-phonon coupling strength $\rm{\alpha}$ chosen as a free parameter. As model devices we consider Au mono-atomic chains and a $\rm{H_2}$ molecule sandwiched between Pt electrodes. In both cases our self-consistent calculations demonstrate a breakdown of the SCBA for large $\rm{\alpha}$ and we identify a weak and strong coupling regime. For weak coupling our SCBA results compare closely with those obtained with exact scattering theory. However in the strong coupling regime large deviations are found. In particular we demonstrate that there is a critical coupling strength, characteristic of the materials system, beyond which multiple self-consistent solutions can be found depending on the initial conditions in the simulation. We attribute these features to the breakdown of the perturbative expansion leading to the SCBA.Comment: 12 pages, 16 figures, 1 Tabl

Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch

In many stochastic simulations of biochemical reaction networks, it is desirable to ``coarse-grain'' the reaction set, removing fast reactions while retaining the correct system dynamics. Various coarse-graining methods have been proposed, but it remains unclear which methods are reliable and which reactions can safely be eliminated. We address these issues for a model gene regulatory network that is particularly sensitive to dynamical fluctuations: a bistable genetic switch. We remove protein-DNA and/or protein-protein association-dissociation reactions from the reaction set, using various coarse-graining strategies. We determine the effects on the steady-state probability distribution function and on the rate of fluctuation-driven switch flipping transitions. We find that protein-protein interactions may be safely eliminated from the reaction set, but protein-DNA interactions may not. We also find that it is important to use the chemical master equation rather than macroscopic rate equations to compute effective propensity functions for the coarse-grained reactions.Comment: 46 pages, 5 figure

BeppoSAX observations of the X-ray pulsar MAXI J1409-619 in low state: discovery of cyclotron resonance features

The transient 500 s X-ray pulsar MAXI J1409-619 was discovered by the slit cameras aboard MAXI on October 17, 2010, and soon after accurately localized by Swift. We found that the source position was serendipitously observed in 2000 during BeppoSAX observations of the Galactic plane. Two sources are clearly detected in the MECS: one is consistent with the position of IGR J14043-6148 and the other one with that of MAXI J1409-619. We report on the analysis of this archival BeppoSAX/MECS observation integrated with newly analyzed observation from ASCA and a set of high-energy observations obtained from the offset fields of the BeppoSAX/PDS instrument. For the ON-source observation, the 1.8-100 keV spectrum is fit by an absorbed power law with a photon index Gamma = 0.87_{-0.19}^{+0.29}, corresponding to 2-10 and 15-100 keV unabsorbed fluxes of 2.7E-12 and 4E-11 erg/cm2/s, respectively, and a 2-10 keV luminosity of 7E+34 erg/s for a 15 kpc distance. For a PDS offset field observation, performed about one year later and showing a 15-100 keV flux of 7E-11 erg/cm2/s, we clearly pinpoint three spectral absorption features at 44, 73, and 128 keV, resolved both in the spectral fit and in the Crab ratio. We interpret these not harmonically spaced features as due to cyclotron resonances. The fundamental energy of 44 +/- 3 keV corresponds to a magnetic field strength at the neutron star surface of 3.8E12 (1+z) G, where z is the gravitational redshift. We discuss the nature of the source in the light of its possible counterpart.Comment: 10 pages, 9 figures. Expanded and revised version accepted for publication in ApJ Main Journa

post seismic relaxation and earthquake triggering in the southern adriatic region

SUMMARY An attempt at quantifying post-seismic relaxation triggered by decoupling earthquakes along the eastern thrusting border of the Adriatic plate (southern Dinarides) is carried out by finite element modelling, with a model constituted by an elastic lithosphere riding on a viscous asthenosphere. In particular, it is investigated the possibility that the above phenomenon is responsible for the fact that in the last two centuries most major earthquakes in the southern Dinarides (MS > 6) have been followed, within a few years, by intense, mainly tensional, earthquakes in southern Italy, i.e. the zone lying on the opposite margin of the Adriatic plate. This analysis has been applied to the last example of the supposed seismic interrelation, i.e. the triggering 1979 April 15 Montenegro event (MS= 6.7) and the presumably induced 1980 November 23 Irpinia earthquake in the southern Apennines (MS= 6.9). Results indicate that the strain induced in the southern Apennines by the triggering event has significant amplitude, since it largely exceeds the effect of earth tides, and the principal stress axes are consistent with those of southern Apenninic earthquakes. The order of magnitude of the time delay between the Montenegro and Irpinia events (1.6 yr) could be explained by assuming that earthquake triggering is most probable when the highest values of the induced strain rate reach the southern Apennines. In particular, this interpretation predicts the observed time delay when a model diffusivity of 400 m2 s−1 is assumed. The constraints that this diffusivity value may pose on the structural and rheological features of the crust–upper-mantle system in the study area are discussed. It is shown that the effects of the Montenegro event on the present velocity field are comparable to, though systematically lower than, the velocities suggested by geodetic observations in the Italian region. This suggests that geodynamic interpretations of geodetic data given without taking into account possible transient effects on the kinematic pattern, as those related to post-seismic relaxation, may be incorrect. Experiments carried out by tentatively simulating the presence of subducted lithosphere along the western margin of the Adriatic plate as a lateral variation of diffusivity, have shown that this structural feature may emphasize E–W tensional strains in the southern Apennines

The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

A systematic review of the safety information contained within the Summaries of Product Characteristics of medications licensed in the United Kingdom for Attention Deficit Hyperactivity Disorder. how does the safety prescribing advice compare with national guidance?

<p>Abstract</p> <p>Background</p> <p>The safety of paediatric medications is paramount and contraindications provide clear pragmatic advice. Further advice may be accessed through Summaries of Product Characteristics (SPCs) and relevant national guidelines. The SPC can be considered the ultimate independent guideline and is regularly updated. In 2008, the authors undertook a systematic review of the SPC contraindications of medications licensed in the United Kingdom (UK) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). At that time, there were fewer contraindications reported in the SPC for atomoxetine than methylphenidate and the specific contraindications varied considerably amongst methylphenidate formulations. In 2009, the European Medicines Agency (EMA) mandated harmonisation of methylphenidate SPCs. Between September and November 2011, there were three changes to the atomoxetine SPC that resulted in revised prescribing information. In addition, Clinical Guidance has also been produced by the National Institute for Health and Clinical Excellence (NICE) (2008), the Scottish Intercollegiate Guidelines Network (SIGN) (2009) and the British National Formulary for Children (BNFC).</p> <p>Methods</p> <p>An updated systematic review of the Contraindications sections of the SPCs of all medications currently licensed for treatment of ADHD in the UK was undertaken and independent statements regarding contraindications and relevant warnings and precautions were then compared with UK national guidance with the aim of assessing any disparity and potential areas of confusion for prescribers.</p> <p>Results</p> <p>As of November 2011, there were seven medications available in the UK for the treatment of ADHD. There are 15 contraindications for most formulations of methylphenidate, 14 for dexamfetamine and 5 for atomoxetine. Significant differences exist between the SPCs and national guidance part due to the ongoing reactive process of amending the former as new information becomes known. In addition, recommendations are made outside UK SPC licensed indications and a significant contraindication for methylphenidate (suicidal behaviours) is missing from both the NICE and SIGN guidelines. Particular disparity exists relating to monitoring for suicidal and psychiatric side effects. The BNFC has not yet been updated in line with the European Union (EU) Directive on methylphenidate; it does not include any contraindications for atomoxetine but describes contraindications for methylphenidate that are no longer in the SPC.</p> <p>Conclusion</p> <p>Clinicians seeking prescribing advice from critical independent sources of data, such as SPCs and national guidelines, may be confused by the disparity that exists. There are major differences between guidelines and SPCs and neither should be referred to in isolation. The SPC represents the most relevant source of safety data to aid prescribing of medications for ADHD as they present the most current safety data in line with increased exposure. National guidelines may need more regular updates.</p

Putting Children First: New Frontiers in the Fight Against Child Poverty in Africa

Despite important strides in the fight against poverty in the past two decades, child poverty remains widespread and persistent, particularly in Africa. Poverty in all its dimensions is detrimental for early childhood development and often results in unreversed damage to the lives of girls and boys, locking children and families into intergenerational poverty. This edited volume contributes to the policy initiatives aiming to reduce child poverty and academic understanding of child poverty and its solutions by bringing together applied research from across the continent. With the Sustainable Development Goals having opened up an important space for the fight against child poverty, not least by broadening its conceptualization to be multidimensional, this collection aims to push the frontiers by challenging existing narratives and exploring alternative understandings of the complexities and dynamics underpinning child poverty. Furthermore, it examines policy options that work to address this critical challenge.Comparative Research Programme on Poverty (CROP) at the University of Bergen.publishedVersio

A biologically plausible model of time-scale invariant interval timing

The temporal durations between events often exert a strong influence over behavior. The details of this influence have been extensively characterized in behavioral experiments in different animal species. A remarkable feature of the data collected in these experiments is that they are often time-scale invariant. This means that response measurements obtained under intervals of different durations coincide when plotted as functions of relative time. Here we describe a biologically plausible model of an interval timing device and show that it is consistent with time-scale invariant behavior over a substantial range of interval durations. The model consists of a set of bistable units that switch from one state to the other at random times. We first use an abstract formulation of the model to derive exact expressions for some key quantities and to demonstrate time-scale invariance for any range of interval durations. We then show how the model could be implemented in the nervous system through a generic and biologically plausible mechanism. In particular, we show that any system that can display noise-driven transitions from one stable state to another can be used to implement the timing device. Our work demonstrates that a biologically plausible model can qualitatively account for a large body of data and thus provides a link between the biology and behavior of interval timing

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)