Positron emission tomography for staging of oesophageal and gastroesophageal malignancy.

Positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) was prospectively investigated as a means of detecting metastatic disease in patients with oesophageal tumours and compared with computerized tomography (CT), with the surgical findings as a gold standard. Twenty-six patients with a malignant tumour of the oesophagus or gastroesophageal junction underwent CT and PET of the chest and the abdomen. Seven patients underwent laparoscopy to establish resectability. Fifteen patients underwent laparotomy without prior laparoscopy. Four patients did not undergo surgery. The primary tumour was visualized in 81% of patients with CT and in 96% with PET. Neither CT nor PET were suited to assess the extent of wall invasion. Surgically assessed nodal status corresponded in 62% with CT and in 90% with PET. Distant metastases were found in five patients with CT and in eight with PET. The diagnostic accuracy of CT in determining resectability was 65% and for PET 88%. For CT and PET together this was 92%. The present study indicates that FDG-PET can be of importance for staging patients with oesophageal tumours. PET has a higher sensitivity for nodal and distant metastases and a higher accuracy for determining respectability than CT. PET and CT together would have decreased ill-advised surgery by 90%

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

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

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

Power laws in microrheology experiments on living cells: comparative analysis and modelling

We compare and synthesize the results of two microrheological experiments on the cytoskeleton of single cells. In the first one, the creep function J(t) of a cell stretched between two glass plates is measured after applying a constant force step. In the second one, a micrometric bead specifically bound to transmembrane receptors is driven by an oscillating optical trap, and the viscoelastic coefficient $G_e(\omega)$ is retrieved. Both $J(t)$ and $G_e(\omega)$ exhibit power law behavior: $J(t)= A(t/t_0)^\alpha$ and $\bar G_e(\omega)\bar = G_0 (\omega/\omega_0)^\alpha$, with the same exponent $\alpha\approx 0.2$. This power law behavior is very robust ; $\alpha$ is distributed over a narrow range, and shows almost no dependance on the cell type, on the nature of the protein complex which transmits the mechanical stress, nor on the typical length scale of the experiment. On the contrary, the prefactors $A_0$ and $G_0$appear very sensitive to these parameters. Whereas the exponents $\alpha$ are normally distributed over the cell population, the prefactors $A_0$ and $G_0$ follow a log-normal repartition. These results are compared with other data published in the litterature. We propose a global interpretation, based on a semi-phenomenological model, which involves a broad distribution of relaxation times in the system. The model predicts the power law behavior and the statistical repartition of the mechanical parameters, as experimentally observed for the cells. Moreover, it leads to an estimate of the largest response time in the cytoskeletal network: $\tau_m \approx 1000$ s.Comment: 47 pages, 14 figures // v2: PDF file is now Acrobat Reader 4 (and up) compatible // v3: Minor typos corrected - The presentation of the model have been substantially rewritten (p. 17-18), in order to give more details - Enhanced description of protocols // v4: Minor corrections in the text : the immersion angles are estimated and not measured // v5: Minor typos corrected. Two references were clarifie

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al