Ablation of kynurenine 3-monooxygenase rescues plasma inflammatory cytokine levels in the R6/2 mouse model of Huntington's disease

Kynurenine 3-monooxygenase (KMO) regulates the levels of neuroactive metabolites in the kynurenine pathway (KP), dysregulation of which is associated with Huntington’s disease (HD) pathogenesis. KMO inhibition leads to increased levels of neuroprotective relative to neurotoxic metabolites, and has been found to ameliorate disease-relevant phenotypes in several HD models. Here, we crossed KMO knockout mice to R6/2 HD mice to examine the effect of KMO depletion in the brain and periphery. KP genes were dysregulated in peripheral tissues from R6/2 mice and KMO ablation normalised levels of a subset of these. KP metabolites were also assessed, and KMO depletion led to increased levels of neuroprotective kynurenic acid in brain and periphery, and dramatically reduced neurotoxic 3-hydroxykunurenine levels in striatum and cortex. Notably, the increased levels of pro-inflammatory cytokines TNFa, IL1β, IL4 and IL6 found in R6/2 plasma were normalised upon KMO deletion. Despite these improvements in KP dysregulation and peripheral inflammation, KMO ablation had no effect upon several behavioural phenotypes. Therefore, although genetic inhibition of KMO in R6/2 mice modulates several metabolic and inflammatory parameters, these do not translate to improvements in primary disease indicators—observations which will likely be relevant for other interventions targeted at peripheral inflammation in HD

Electron scattering on molecular nitrogen: common gas, uncommon cross sections

We discuss peculiar features of electron scattering on the N2 molecule and the N2+ ion, that are important for modeling plasmas, Earth’s and other planets’ atmospheres. These features are, among others: the resonant enhancement of the vibrational excitation in the region of the shape resonance around 2.4 eV, the resonant character of some of electronic excitation channels (and high values of these cross sections, both for triplet and singlet states), high cross section for the dissociation into neutrals, high cross sections for elastic scattering (and electronic transitions) on metastable states. For the N2+ ion we discuss both dissociation and the dissociative ionization, leading to the formation of atoms in excited states, and dissociative recombination which depends strongly on the initial vibrational state of the ion. We conclude that the theory became an indispensable completion of experiments, predicting many of partial cross sections and their physical features. We hope that the data presented will serve to improve models of nitrogen plasmas and atmospheres. Graphical abstract: [Figure not available: see fulltext.]

Cross Sections for Electron Collisions with NO, N2O, and NO2

Cross section data are compiled from the literature for electron collisions with oxides of nitrogen (NxOy) molecules: the species nitric oxide (NO), nitrous oxide (N2O), and nitrogen dioxide (NO2) are explicitly considered. Cross sections are collected and reviewed for total scattering, elastic scattering, momentum transfer, excitations of rotational, vibrational, and electronic states, dissociation, ionization, and dissociative attachment. For each of these processes, the recommended values of the cross sections are presented. The literature has been surveyed up to the end of 2017. These results are supplemented by a reanalysis of the swarm measurements for NO and newly calculated cross sections for rotational excitation of N2O and for rotational excitation and electronic excitation of NO2

On All-loop Integrands of Scattering Amplitudes in Planar N=4 SYM

We study the relationship between the momentum twistor MHV vertex expansion of planar amplitudes in N=4 super-Yang-Mills and the all-loop generalization of the BCFW recursion relations. We demonstrate explicitly in several examples that the MHV vertex expressions for tree-level amplitudes and loop integrands satisfy the recursion relations. Furthermore, we introduce a rewriting of the MHV expansion in terms of sums over non-crossing partitions and show that this cyclically invariant formula satisfies the recursion relations for all numbers of legs and all loop orders.Comment: 34 pages, 17 figures; v2: Minor improvements to exposition and discussion, updated references, typos fixe

RNAi-mediated silencing of the Bmi-1 gene causes growth inhibition and enhances doxorubicin-induced apoptosis in MCF-7 cells

The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1 /S phase transition. The number of target cells was found to increase in phase G 0 /G 1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer

Tuning ultrafast electron thermalization pathways in a van der Waals heterostructure

Ultrafast electron thermalization - the process leading to Auger recombination, carrier multiplication via impact ionization and hot carrier luminescence - occurs when optically excited electrons in a material undergo rapid electron-electron scattering to redistribute excess energy and reach electronic thermal equilibrium. Due to extremely short time and length scales, the measurement and manipulation of electron thermalization in nanoscale devices remains challenging even with the most advanced ultrafast laser techniques. Here, we overcome this challenge by leveraging the atomic thinness of two-dimensional van der Waals (vdW) materials in order to introduce a highly tunable electron transfer pathway that directly competes with electron thermalization. We realize this scheme in a graphene-boron nitride-graphene (G-BN-G) vdW heterostructure, through which optically excited carriers are transported from one graphene layer to the other. By applying an interlayer bias voltage or varying the excitation photon energy, interlayer carrier transport can be controlled to occur faster or slower than the intralayer scattering events, thus effectively tuning the electron thermalization pathways in graphene. Our findings, which demonstrate a novel means to probe and directly modulate electron energy transport in nanoscale materials, represent an important step toward designing and implementing novel optoelectronic and energy-harvesting devices with tailored microscopic properties.Comment: Accepted to Nature Physic

Cross Sections for Electron Collisions with Acetylene

Cross section data are compiled from the literature for electron collisions with the acetylene (HCCH) molecule. Cross sections are collected and reviewed for total scattering, elastic scattering, momentum transfer, excitations of rotational and vibrational states, dissociation, ionization, and dissociative attachment. The data derived from swarm experiments are also considered. For each of these processes, the recommended values of the cross sections are presented. The literature has been surveyed through early 2016

Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems