Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of Nuclear factor (erythroid-derived 2)-like 2

Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury. In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours. In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection. These data provide a new molecular mechanism for the potential application of Argon as a neuroprotectant in HIE

A fast high-order method to calculate wakefield forces in an electron beam

In this paper we report on a high-order fast method to numerically calculate wakefield forces in an electron beam given a wake function model. This method is based on a Newton-Cotes quadrature rule for integral approximation and an FFT method for discrete summation that results in an $O(Nlog(N))$ computational cost, where $N$ is the number of grid points. Using the Simpson quadrature rule with an accuracy of $O(h^4)$, where $h$ is the grid size, we present numerical calculation of the wakefields from a resonator wake function model and from a one-dimensional coherent synchrotron radiation (CSR) wake model. Besides the fast speed and high numerical accuracy, the calculation using the direct line density instead of the first derivative of the line density avoids numerical filtering of the electron density function for computing the CSR wakefield force

A Neural Network Approach to Context-Sensitive Generation of Conversational Responses

We present a novel response generation system that can be trained end to end on large quantities of unstructured Twitter conversations. A neural network architecture is used to address sparsity issues that arise when integrating contextual information into classic statistical models, allowing the system to take into account previous dialog utterances. Our dynamic-context generative models show consistent gains over both context-sensitive and non-context-sensitive Machine Translation and Information Retrieval baselines.Comment: A. Sordoni, M. Galley, M. Auli, C. Brockett, Y. Ji, M. Mitchell, J.-Y. Nie, J. Gao, B. Dolan. 2015. A Neural Network Approach to Context-Sensitive Generation of Conversational Responses. In Proc. of NAACL-HLT. Pages 196-20

Frame-Independence of Exclusive Amplitudes in the Light-Front Quantization

While the particle-number-conserving convolution formalism established in the Drell-Yan-West reference frame is frequently used to compute exclusive amplitudes in the light-front quantization, this formalism is limited to only those frames where the light-front helicities are not changed and the good (plus) component of the current remains unmixed. For an explicit demonstration of such criteria, we present the relations between the current matrix elements in the two typical reference frames used for calculations of the exclusive amplitudes, i.e. the Drell-Yan-West and Breit frames and investigate both pseudoscalar and vector electromagnetic currents in detail. We find that the light-front helicities are unchanged and the good component of the current does not mix with the other components of the current under the transformation between these two frames. Thus, the pseudoscalar and vector form factors obtained by the diagonal convolution formalism in both frames must indeed be identical. However, such coincidence between the Drell-Yan-West and Breit frames does not hold in general. We give an explicit example in which the light-front helicities are changed and the plus component of the current is mixed with other components under the change of reference frame. In such a case, the relationship between the frames should be carefully analyzed before the established convolution formalism in the Drell-Yan-West frame is used.Comment: 14 pages, 4 figure

Gluon contribution to the structure function g_2(x,Q^2)

We calculate the one-loop twist-3 gluon contribution to the flavor-singlet structure function g_2(x,Q^2) in polarized deep-inelastic scattering and find that it is dominated by the contribution of the three-gluon operator with the lowest anomalous dimension (for each moment N). The similar property was observed earlier for the nonsinglet distributions, although the reason is in our case different. The result is encouraging and suggests a simple evolution pattern of g_2(x,Q^2) in analogy with the conventional description of twist-2 parton distributions.Comment: 26 pages, Latex style, 4 figures (two references added, a few typos corrected

Evolution equation for the structure function g_2(x,Q^2)

We perform an extensive study of the scale dependence of flavor-singlet contributions to the structure function g_2(x,Q^2) in polarized deep-inelastic scattering. We find that the mixing between quark-antiquark-gluon and three-gluon twist-3 operators only involves the three-gluon operator with the lowest anomalous dimension and is weak in other cases. This means, effectively, that only those three-gluon operators with the lowest anomalous dimension for each moment are important, and allows to formulate a simple two-component parton-like description of g_2(x,Q^2) in analogy with the conventional description of twist-2 parton distributions. The similar simplification was observed earlier for the nonsinglet distributions, although the reason is in our case different.Comment: 53 pages, 10 figures, LaTeX styl

Poincare Invariant Algebra From Instant to Light-Front Quantization

We present the Poincare algebra interpolating between instant and light-front time quantizations. The angular momentum operators satisfying SU(2) algebra are constructed in an arbitrary interpolation angle and shown to be identical to the ordinary angular momentum and Leutwyler-Stern angular momentum in the instant and light-front quantization limits, respectively. The exchange of the dynamical role between the transverse angular mometum and the boost operators is manifest in our newly constructed algebra.Comment: 21 pages, 3 figures, 1 tabl

Stimulation of an α1-adrenergic receptor downregulates ecto-5′ nucleotidase activity on the apical membrane of RPE cells

The purines ATP and adenosine play an important role in the communication between the photoreceptors and the retinal pigment epithelium (RPE). While the RPE is known to release ATP into subretinal space, the source of extracellular adenosine is unclear. In other tissues, ecto-nucleotidases mediate the consecutive dephosphorylation of ATP to AMP, and AMP is converted to adenosine by ecto-5′ nucleotidase (CD73). This study identifies ecto-5′ nucleotidase on RPE cells and investigates modulation of enzyme activity. The RPE was the most active site of 5′AMP dephosphorylation in the posterior rat eye. The ecto-5′ nucleotidase inhibitor αβmADP prevented the production adenosine by the apical membrane of the bovine RPE. Cultured human ARPE-19 cells expressed mRNA and protein for ecto-5′ nucleotidase. The production of phosphate from 5′AMP by ARPE-19 cells was inhibited by αβmADP, but the ecto-alkaline phosphatase inhibitor levamisole had no effect. Degradation of 5′AMP was blocked by norepinephrine, epinephrine and phenylephrine, with inhibition by antagonists prazosin and corynanthine implicating the α1 adrenergic receptor. The block of enzyme activity by norepinephrine was rapid, occurring within 1 min, and was similar at both 4 and 37°C, consistent with cleavage of the enzyme from its GPI anchor. HPLC measurements indicated norepinephrine reduced levels of adenosine in the bath. In the apical face of the bovine-RPE eyecup, norepinephrine reduced the production of phosphate from 5′AMP, suggesting that both receptor and enzyme face sub-retinal space. In conclusion, RPE cells express ecto-5′ nucleotidase, with activity on the apical membrane, and stimulation of α-1 adrenergic receptors downregulates activity. As epinephrine is released at light onset, and adenosine can inhibit phagocytosis, the corresponding decrease in subretinal adenosine levels may contribute to the enhanced the phagocytosis of rod outer segments that occurs at this time

Distinct Expression Pattern and Post-Transcriptional Regulation of Cell Cycle Genes in the Glandular Epithelia of Avian Ovarian Carcinomas

The cell cycle system is controlled in a timely manner by three groups of cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors. Abnormal alterations of cell cycle regulatory mechanisms are a common feature of many diseases including numerous tumor types such as ovarian cancer. Although a variety of cell cycle regulatory genes are well known in mammalian species including human and mice, they are not well studied in avian species, especially in laying hens which are recognized as an excellent animal model for research relevant to human ovarian carcinogenesis. Therefore, in the present study, we focused on comparative expression and regulation of expression of candidate genes which might be involved in the cell cycle program in surface epithelial ovarian cancer in laying hens. Our current results indicate that expression levels of cell cycle gene transcripts are greater in cancerous as compared to normal ovaries. In particular, cyclin A2 (CCNA2), CCND1, CCND2, CCND3, CCNE2, cyclin dependent kinase 1 (CDK1), CDK3, CDK5, cyclin dependent kinases inhibitor 1A (CDKN1A) and CDKN1B were upregulated predominantly in the glandular epithelia of cancerous ovaries from laying hens. Further, several microRNAs (miRs), specifically miR-1798, miR-1699, miR-223 and miR-1744 were discovered to influence expression of CCND1, CCNE2, CDK1, and CDK3 mRNAs, respectively, via their 3'-UTR which suggests that post-transcriptional regulation of gene expression influences their expression in laying hens. Moreover, miR-1626 influenced CDKN1A expression and miR-222, miR-1787 and miR-1812 regulated CDKN1B expression via their 3'-UTR regions. Collectively, results of the present study demonstrate increased expression of cell cycle-related genes in cancerous ovaries of laying hens and indicate that expression of these genes is post-transcriptionally regulated by specific microRNAs

Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption

Inosine monophosphate dehydrogenase (IMPDH) is a pivotal enzyme in the de novo pathway of guanine nucleotide biosynthesis. Inhibitors of this enzyme decrease intracellular guanine nucleotide levels by 50-80% and have potential as anti-neoplastic agents. Both mycophenolic acid (MPA) and AVN-944 are highly specific inhibitors of IMPDH that cause cell cycle arrest or apoptosis in lymphocytes and leukemic cell lines. We have examined the mechanisms by which these two agents cause cytotoxicity. Both MPA and AVN-944 inhibit the growth of K562 cells, and induce apoptosis in Raji B and CCRF-CEM T cells. Both compounds strikingly inhibit RNA synthesis within 2 h of exposure. Depletion of guanine nucleotides by MPA and AVN-944 also causes an early and near-complete reduction in levels of the 45S precursor rRNA synthesis and the concomitant translocation of nucleolar proteins including nucleolin, nucleophosmin, and nucleostemin from the nucleolus to the nucleoplasm. This efflux correlates temporally with the sustained induction of p53 in cell lines with wild type p53. We conclude that inhibition of IMPDH causes a primary reduction in rRNA synthesis and secondary nucleolar disruption and efflux of nucleolar proteins that most likely mediate cell cycle arrest or apoptosis. The ability of AVN-944 to induce apoptosis in a number of leukemic cell lines supports its potential utility in the treatment of hematologic malignancies