Fractional Brownian motions ruled by nonlinear equations

In this note we consider generalized diffusion equations in which the diffusivity coefficient is not necessarily constant in time, but instead it solves a nonlinear fractional differential equation involving fractional Riemann–Liouville time-derivative. Our main contribution is to highlight the link between these generalised equations and fractional Brownian motion (fBm). In particular, we investigate the governing equation of fBm and show that its diffusion coefficient must satisfy an additive evolutive fractional equation. We derive in a similar way the governing equation of the iterated fractional Brownian motion

Probing the subtropical lowermost stratosphere and the tropical upper troposphere and tropopause layer for inorganic bromine

We report measurements of CH4 (measured in situ by the Harvard University Picarro Cavity Ringdown Spectrometer (HUPCRS) and NOAA Unmanned Aircraft System Chromatograph for Atmospheric Trace Species (UCATS) instruments), O3 (measured in situ by the NOAA dual-beam ultraviolet (UV) photometer), NO2, BrO (remotely detected by spectroscopic UV–visible (UV–vis) limb observations; see the companion paper of Stutz et al., 2016), and of some key brominated source gases in whole-air samples of the Global Hawk Whole Air Sampler (GWAS) instrument within the subtropical lowermost stratosphere (LS) and the tropical upper troposphere (UT) and tropopause layer (TTL). The measurements were performed within the framework of the NASA-ATTREX (National Aeronautics and Space Administration – Airborne Tropical Tropopause Experiment) project from aboard the Global Hawk (GH) during six deployments over the eastern Pacific in early 2013. These measurements are compared with TOMCAT/SLIMCAT (Toulouse Off-line Model of Chemistry And Transport/Single Layer Isentropic Model of Chemistry And Transport) 3-D model simulations, aiming at improvements of our understanding of the bromine budget and photochemistry in the LS, UT, and TTL. Changes in local O3 (and NO2 and BrO) due to transport processes are separated from photochemical processes in intercomparisons of measured and modeled CH4 and O3. After excellent agreement is achieved among measured and simulated CH4 and O3, measured and modeled [NO2] are found to closely agree with  ≤  15 ppt in the TTL (which is the detection limit) and within a typical range of 70 to 170 ppt in the subtropical LS during the daytime. Measured [BrO] ranges between 3 and 9 ppt in the subtropical LS. In the TTL, [BrO] reaches 0.5 ± 0.5 ppt at the bottom (150 hPa∕355 K∕14 km) and up to about 5 ppt at the top (70 hPa∕425 K∕18.5 km; see Fueglistaler et al., 2009 for the definition of the TTL used), in overall good agreement with the model simulations. Depending on the photochemical regime, the TOMCAT∕SLIMCAT simulations tend to slightly underpredict measured BrO for large BrO concentrations, i.e., in the upper TTL and LS. The measured BrO and modeled BrO ∕ Bryinorg ratio is further used to calculate inorganic bromine, Bryinorg. For the TTL (i.e., when [CH4]  ≥  1790 ppb), [Bryinorg] is found to increase from a mean of 2.63 ± 1.04 ppt for potential temperatures (θ) in the range of 350–360 K to 5.11 ± 1.57 ppt for θ  = 390 − 400 K, whereas in the subtropical LS (i.e., when [CH4]  ≤  1790 ppb), it reaches 7.66 ± 2.95 ppt for θ in the range of 390–400 K. Finally, for the eastern Pacific (170–90° W), the TOMCAT/SLIMCAT simulations indicate a net loss of ozone of −0.3 ppbv day−1 at the base of the TTL (θ  =  355 K) and a net production of +1.8 ppbv day−1 in the upper part (θ  =  383 K)

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

<p>Abstract</p> <p>Background</p> <p>The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.</p> <p>Methods</p> <p>We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes.</p> <p>Results</p> <p>HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells.</p> <p>Conclusions</p> <p>We have identified cells with possible defects in the MRN complex and S phase arrest, and a series of compounds that may preferentially target S phase-defective cells. We discuss limitations of the COMPARE program when attempting to identify compounds that selectively inhibit only a few cell lines.</p

Low Dosage of Histone H4 Leads to Growth Defects and Morphological Changes in Candida albicans

Chromatin function depends on adequate histone stoichiometry. Alterations in histone dosage affect transcription and chromosome segregation, leading to growth defects and aneuploidies. In the fungal pathogen Candida albicans, aneuploidy formation is associated with antifungal resistance and pathogenesis. Histone modifying enzymes and chromatin remodeling proteins are also required for pathogenesis. However, little is known about the mechanisms that generate aneuploidies or about the epigenetic mechanisms that shape the response of C. albicans to the host environment. Here, we determined the impact of histone H4 deficit in the growth and colony morphology of C. albicans. We found that C. albicans requires at least two of the four alleles that code for histone H4 (HHF1 and HHF22) to grow normally. Strains with only one histone H4 allele show a severe growth defect and unstable colony morphology, and produce faster-growing, morphologically stable suppressors. Segmental or whole chromosomal trisomies that increased wild-type histone H4 copy number were the preferred mechanism of suppression. This is the first study of a core nucleosomal histone in C. albicans, and constitutes the prelude to future, more detailed research on the function of histone H4 in this important fungal pathogen

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

Background: In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca2+ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results: Presynaptic Ca2+ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion: Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of medium-spiny neuron varicosities, the heterogeneous distribution of dopamine receptors on individual varicosities is likely to encode patterns in striatal information processing

Fractional Herglotz variational principles with generalized Caputo derivatives

We obtain Euler–Lagrange equations, transversality conditions and a Noether-like theorem for Herglotz-type variational problems with Lagrangians depending on generalized fractional derivatives. As an application, we consider a damped harmonic oscillator with time-depending mass and elasticity, and arbitrary memory effects

The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks

The accumulation of the human tumor suppressor 53BP1 at DNA damage sites requires the ubiquitin ligases RNF8 and RNF168. As 53BP1 recognizes dimethylated Lys20 in histone H4 (H4K20me2), the requirement for RNF8- and RNF168-mediated ubiquitylation has been unclear. Here we show that RNF8-mediated ubiquitylation facilitates the recruitment of the AAA-ATPase valosin-containing protein (VCP, also known as p97) and its cofactor NPL4 to sites of double-strand breaks. RIDDLE cells, which lack functional RNF168, also show impaired recruitment of VCP to DNA damage. The ATPase activity of VCP promotes the release of the Polycomb protein L3MBTL1 from chromatin, which also binds the H4K20me2 histone mark, thereby facilitating 53BP1 recruitment. Consistent with this, nematodes lacking the VCP orthologs CDC-48.1 or CDC-48.2, or cofactors UFD-1 or NPL-4, are highly sensitive to ionizing radiation. Our data suggest that human RNF8 and RNF168 promote VCP-mediated displacement of L3MBTL1 to unmask 53BP1 chromatin binding sites