Penetrating particle ANalyzer (PAN)

PAN is a scientific instrument suitable for deep space and interplanetary missions. It can precisely measure and monitor the flux, composition, and direction of highly penetrating particles ($> \sim$100 MeV/nucleon) in deep space, over at least one full solar cycle (~11 years). The science program of PAN is multi- and cross-disciplinary, covering cosmic ray physics, solar physics, space weather and space travel. PAN will fill an observation gap of galactic cosmic rays in the GeV region, and provide precise information of the spectrum, composition and emission time of energetic particle originated from the Sun. The precise measurement and monitoring of the energetic particles is also a unique contribution to space weather studies. PAN will map the flux and composition of penetrating particles, which cannot be shielded effectively, precisely and continuously, providing valuable input for the assessment of the related health risk, and for the development of an adequate mitigation strategy. PAN has the potential to become a standard on-board instrument for deep space human travel. PAN is based on the proven detection principle of a magnetic spectrometer, but with novel layout and detection concept. It will adopt advanced particle detection technologies and industrial processes optimized for deep space application. The device will require limited mass (~20 kg) and power (~20 W) budget. Dipole magnet sectors built from high field permanent magnet Halbach arrays, instrumented in a modular fashion with high resolution silicon strip detectors, allow to reach an energy resolution better than 10\% for nuclei from H to Fe at 1 GeV/n

Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line

The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.This work was supported by R01DA021336 and K99DA029635

Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J)-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15). Transcription activator-like effector nucleases (TALENs)-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention and treatment of substance abuse and possibly other psychiatric disorders

The Evolution of Private Equity: Corporate Restructuring in the UK, c.1945-2010

The paper analyses the role of private equity in restructuring the UK corporate economy. It develops a theoretical synthesis to show that the evolution of the PE industry and firms in which it invested were governed by the relations of corporate governance between investor and investee companies. Effective governance relations were a necessary condition for success and complement firm specific resources to create competitive advantage. Four case studies are used to show the contrasting effects of these determining factors, ICFC and Slater Walker, and the two waves of buy-out centred restructuring that developed with the maturity of the PE industry after 1980. In contrast to the evolutionary approach, the periodisations utilised in this study show that structural breaks associated with points of institutional reform are also necessary to make firm specific resource and governance determinants of competitive advantage operable

Branching dendrites with resonant membrane: a “sum-over-trips” approach

Dendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the “sum-over-trips” approach (Abbott et al. in Biol Cybernetics 66, 49–60 1991). To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an Ih current contributes to a voltage overshoot at the soma

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Noncontact conductivity and dielectric measurement for high throughput roll-to-roll nanomanufacturing

Advances in roll-to-roll processing of graphene and carbon nanotubes have at last led to the continuous production of high-quality coatings and filaments, ushering in a wave of applications for flexible and wearable electronics, woven fabrics, and wires. These applications often require specific electrical properties, and hence precise control over material micro- and nanostructure. While such control can be achieved, in principle, by closed-loop processing methods, there are relatively few noncontact and nondestructive options for quantifying the electrical properties of materials on a moving web at the speed required in modern nanomanufacturing. Here, we demonstrate a noncontact microwave method for measuring the dielectric constant and conductivity (or geometry for samples of known dielectric properties) of materials in a millisecond. Such measurement times are compatible with current and future industrial needs, enabling real-time materials characterization and in-line control of processing variables without disrupting production

The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions

Vascular homoeostasis, development and disease critically depend on the regulation of endothelial cell-cell junctions. Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion. Pacsin2 concentrates at focal adherens junctions (FAJs) that are experiencing unbalanced actomyosin-based pulling. FAJs move in response to differences in local cytoskeletal geometry and pacsin2 is recruited consistently to the trailing end of fast-moving FAJs via a mechanism that requires an intact F-BAR domain. Photoconversion, photobleaching, immunofluorescence and super-resolution microscopy reveal polarized dynamics, and organization of junctional proteins between the front of FAJs and their trailing ends. Interestingly, pacsin2 recruitment inhibits internalization of the VE-cadherin complex from FAJ trailing ends and is important for endothelial monolayer integrity. Together, these findings reveal a novel junction protective mechanism during polarized trafficking of VE-cadherin, which supports barrier maintenance within dynamic endothelial tissue