Correcting the polarization effect in low frequency Dielectric Spectroscopy

We demonstrate a simple and robust methodology for measuring and analyzing the polarization impedance appearing at interface between electrodes and ionic solutions, in the frequency range from 1 to $10^6$ Hz. The method assumes no particular behavior of the electrode polarization impedance and it only makes use of the fact that the polarization effect dies out with frequency. The method allows a direct and un-biased measurement of the polarization impedance, whose behavior with the applied voltages and ionic concentration is methodically investigated. Furthermore, based on the previous findings, we propose a protocol for correcting the polarization effect in low frequency Dielectric Spectroscopy measurements of colloids. This could potentially lead to the quantitative resolution of the $\alpha$-dispersion regime of live cells in suspension

A New Galactic Extinction Map of the Cygnus Region

We have made a Galactic extinction map of the Cygnus region with 5' spatial resolution. The selected area is 80^\circ to 90^\circ in the Galactic longitude and -4^\circ to 8^\circ in the Galactic latitude. The intensity at 140 \mum is derived from the intensities at 60 and 100 \mum of the IRAS data using the tight correlation between 60, 100, and 140 \mum found in the Galactic plane. The dust temperature and optical depth are calculated with 5' resolution from the 140 and 100 \mum intensity, and Av is calculated from the optical depth. In the selected area, the mean dust temperature is 17 K, the minimum is 16 K, and the maximum is 30 K. The mean Av is 6.5 mag, the minimum is 0.5 mag, and the maximum is 11 mag. The dust temperature distribution shows significant spatial variation on smaller scales down to 5'. Because the present study can trace the 5'-scale spatial variation of the extinction, it has an advantage over the previous studies, such as the one by Schlegel, Finkbeiner, & Davis, who used the COBE/DIRBE data to derive the dust temperature distribution with a spatial resolution of 1^\circ. The difference of Av between our map and Schlegel et al.'s is \pm 3 mag. A new extinction map of the entire sky can be produced by applying the present method.Comment: 27 pages, 14 figures, accepted for publication in Ap

Attouch-Th\'era duality revisited: paramonotonicity and operator splitting

The problem of finding the zeros of the sum of two maximally monotone operators is of fundamental importance in optimization and variational analysis. In this paper, we systematically study Attouch-Th\'era duality for this problem. We provide new results related to Passty's parallel sum, to Eckstein and Svaiter's extended solution set, and to Combettes' fixed point description of the set of primal solutions. Furthermore, paramonotonicity is revealed to be a key property because it allows for the recovery of all primal solutions given just one arbitrary dual solution. As an application, we generalize the best approximation results by Bauschke, Combettes and Luke [J. Approx. Theory 141 (2006), 63-69] from normal cone operators to paramonotone operators. Our results are illustrated through numerous examples

Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress:from mouse to man

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression

The mPower Study, Parkinson Disease Mobile Data Collected Using Researchkit

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health

Evaluating 5-nitrofurans as trypanocidal agents

The nitroheterocycle nifurtimox, as part of a nifurtimox-eflornithine combination therapy, represents one of a limited number of treatments targeting Trypanosoma brucei, the causative agent of human African trypanosomiasis. The mode of action of this prodrug involves an initial activation reaction catalysed by a type I nitroreductase (NTR), an enzyme found predominantly in prokaryotes, leading to the formation of a cytotoxic unsaturated open chain nitrile metabolite. Here, we evaluate the trypanocidal activity of a library of other 5-nitrofurans against bloodstream form T. brucei as a preliminary step in the identification of additional nitroaromatic compounds that could potentially partner eflornithine. Biochemical screening against purified enzyme revealed that all 5-nitrofurans were effective substrates for TbNTR with the preferred compounds having apparent kcat/KM values approximately 50-fold greater than nifurtimox. For several compounds, in vitro reduction by this nitroreductase yielded products characterized by mass spectroscopy as either unsaturated or saturated open chain nitriles. When tested against bloodstream form T. brucei, many of the derivatives displayed significant growth inhibitory properties with the most potent compounds generating IC50 values around 200 nM. The anti-parasitic activity of the most potent agents was demonstrated to be NTR dependent as parasites having reduced levels of the enzyme displayed resistance to the compounds while parasites over expressing TbNTR showed hypersensitivity. We conclude that other members of the 5-nitrofurans class of nitroheterocycles have potential to treat human African trypanosomiasis perhaps as an alternative partner prodrug to nifurtimox in the next generation of eflornithine-based combinational therapies

Rescue of Murine F508del CFTR Activity in Native Intestine by Low Temperature and Proteasome Inhibitors

Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correctors) or at enhancing the open probability of the CFTR chloride channel (CFTR potentiators). Preventing premature breakdown of F508del CFTR is an alternative or additional strategy, which is investigated in this study. We established an ex vivo assay for murine F508del CFTR rescue in native intestinal epithelium that can be used as a pre-clinical test for candidate therapeutics. Overnight incubation of muscle stripped ileum in modified William's E medium at low temperature (26°C), and 4 h or 6 h incubation at 37°C with different proteasome inhibitors (PI: ALLN, MG-132, epoxomicin, PS341/bortezomib) resulted in fifty to hundred percent respectively of the wild type CFTR mediated chloride secretion (forskolin induced short-circuit current). The functional rescue was accompanied by enhanced expression of the murine F508del CFTR protein at the apical surface of intestinal crypts and a gain in the amount of complex-glycosylated CFTR (band C) up to 20% of WT levels. Sustained rescue in the presence of brefeldin A shows the involvement of a post-Golgi compartment in murine F508del CFTR degradation, as was shown earlier for its human counterpart. Our data show that proteasome inhibitors are promising candidate compounds for improving rescue of human F508del CFTR function, in combination with available correctors and potentiators

Adenosine A(2B) receptor agonism inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in ApoE deficient mice

Biopharmaceutic