Machine Learning Based Statistical Downscaling for Rainfall on Hawaiian Islands

M.S

Fixed-Parameter Algorithms for Graph Constraint Logic

Non-deterministic constraint logic (NCL) is a simple model of computation based on orientations of a constraint graph with edge weights and vertex demands. NCL captures PSPACE and has been a useful tool for proving algorithmic hardness of many puzzles, games, and reconfiguration problems. In particular, its usefulness stems from the fact that it remains PSPACE-complete even under severe restrictions of the weights (e.g., only edge-weights one and two are needed) and the structure of the constraint graph (e.g., planar AND/OR graphs of bounded bandwidth). While such restrictions on the structure of constraint graphs do not seem to limit the expressiveness of NCL, the building blocks of the constraint graphs cannot be limited without losing expressiveness: We consider as parameters the number of weight-one edges and the number of weight-two edges of a constraint graph, as well as the number of AND or OR vertices of an AND/OR constraint graph. We show that NCL is fixed-parameter tractable (FPT) for any of these parameters. In particular, for NCL parameterized by the number of weight-one edges or the number of AND vertices, we obtain a linear kernel. It follows that, in a sense, NCL as introduced by Hearn and Demaine is defined in the most economical way for the purpose of capturing PSPACE

Corticosterone Induces Rapid Spinogenesis via Synaptic Glucocorticoid Receptors and Kinase Networks in Hippocampus

BACKGROUND: Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100-1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2-0.4 µm) was increased even at low CORT levels (100-200 nM). The density of middle-head spines (0.4-0.5 µm) was increased at high CORT levels between 400-1000 nM. The density of large-head spines (0.5-1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect. CONCLUSIONS/SIGNIFICANCE: These results imply that stress levels of CORT (100-1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways

KLHDC10 Activates ASK1 by Suppressing PP5

Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here, we identified the kelch repeat protein, Slim, as an activator of ASK1 through a Drosophila misexpression screen. We also performed a proteomics screen and revealed that Kelch domain containing 10 (KLHDC10), a mammalian ortholog of Slim, interacted with Protein phosphatase 5 (PP5), which has been shown to inactivate ASK1 in response to ROS. KLHDC10 bound to the phosphatase domain of PP5 and suppressed its phosphatase activity. Moreover, KLHDC10 was required for H2O2-induced sustained activation of ASK1 and cell death in Neuro2A cells. These findings suggest that Slim/KLHDC10 is an activator of ASK1, contributing to oxidative stress-induced cell death through the suppression of PP5

Development of the photomultiplier tube readout system for the first Large-Sized Telescope of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is the next generation ground-based very high energy gamma-ray observatory. The Large-Sized Telescope (LST) of CTA targets 20 GeV -- 1 TeV gamma rays and has 1855 photomultiplier tubes (PMTs) installed in the focal plane camera. With the 23 m mirror dish, the night sky background (NSB) rate amounts to several hundreds MHz per pixel. In order to record clean images of gamma-ray showers with minimal NSB contamination, a fast sampling of the signal waveform is required so that the signal integration time can be as short as the Cherenkov light flash duration (a few ns). We have developed a readout board which samples waveforms of seven PMTs per board at a GHz rate. Since a GHz FADC has a high power consumption, leading to large heat dissipation, we adopted the analog memory ASIC "DRS4". The sampler has 1024 capacitors per channel and can sample the waveform at a GHz rate. Four channels of a chip are cascaded to obtain deeper sampling depth with 4096 capacitors. After a trigger is generated in a mezzanine on the board, the waveform stored in the capacitor array is subsequently digitized with a low speed (33 MHz) ADC and transferred via the FPGA-based Gigabit Ethernet to a data acquisition system. Both a low power consumption (2.64 W per channel) and high speed sampling with a bandwidth of $>$300 MHz have been achieved. In addition, in order to increase the dynamic range of the readout we adopted a two gain system achieving from 0.2 up to 2000 photoelectrons in total. We finalized the board design for the first LST and proceeded to mass production. Performance of produced boards are being checked with a series of quality control (QC) tests. We report the readout board specifications and QC results.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Regulation of NR4A nuclear receptors by p38

In Drosophila, the melanization reaction is an important defense mechanism against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the dopamine synthesis pathway, underlie the melanin synthesis by providing the melanin precursors dopa and dopamine, respectively. It has been shown that expression of Drosophila TH and Ddc is induced in various physiological and pathological conditions, including bacterial challenge; however, the mechanism involved has not been fully elucidated. Here, we show that ectopic activation of p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization in the Drosophila cuticle. This p38-dependent melanization was attenuated by knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate a promoter containing NR4A-binding elements, with this transactivation being, at least in part, dependent on the phosphorylation. This suggests an evolutionarily conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene induction through NR4As appears to function in the dopamine synthesis pathway and may be involved in immune and stress responses

Disturbance in Maternal Environment Leads to Abnormal Synaptic Instability during Neuronal Circuitry Development

Adverse maternal environment during gestation and lactation can have negative effects on the developing brain that persist into adulthood and result in behavioral impairment. Recent studies of human and animal models suggest epidemiological and experimental association between disturbances in maternal environments during brain development and the occurrence of neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, anxiety, depression, and neurodegenerative diseases. In this review, we summarize recent advances in understanding the effects of maternal metabolic and hormonal abnormalities on the developing brain by focusing on the dynamics of dendritic spine, an excitatory postsynaptic structure. We discuss the abnormal instability of dendritic spines that is common to developmental disorders and neurological diseases. We also introduce our recent studies that demonstrate how maternal obesity and hyperandrogenism leads to abnormal development of neuronal circuitry and persistent synaptic instability, which results in the loss of synapses. The aim of this review is to highlight the links between abnormal maternal environment, behavioral impairment in offspring, and the dendiric spine pathology of neuropsychiatric disorders

Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas

The objective of this study is to clarify clinical significance of theH3F3A K27Mmutation (H3K27M) and analyze the correlation between H3K27M, H3K27me3 status, and EZH2 expression and prognosis in spinal cord gliomas. Patients with spinal cord diffuse glioma regardless of World Health Organization (WHO) grade underwent genetic analysis forH3F3A, HIST1H3B,TERTpromoter,IDH1/2, andBRAF. H3K27me3 status and EZH2 expression were analyzed through immunohistochemistry. Thereafter, the association between H3K27M, H3K27me3 status, and EZH2 expression and prognosis was retrospectively analyzed using the log-rank test. A total of 26 cases, 5 with WHO grade 4, 9 with grade 3, and 12 with grade 2 glioma, were analyzed. Although WHO grade 2 cases tended to present favorable overall survival, the difference was not statistically significant. H3K27M, which was detected in four grade 4 cases (80%) and three grade 3 cases (33%), was not associated with prognosis among grade 3 and 4 cases. Among WHO grade 2-4 cases, the combination of retained H3K27me3 and negative EZH2 expression was correlated with favorable overall survival (p = 0.03). The combination of H3K27me3 status and EZH2 expression was considered as a potential prognostic marker in WHO grade 2-4 diffuse spinal cord gliomas

Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis

Purpose: We evaluated the sonographic findings of immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS). Methods: Nineteen patients with IgG4-SS and 12 healthy volunteers (controls) were enrolled. The following sonographic features were evaluated: (1) enlargement of the submandibular gland by measurement of the longitudinal diameter and thickness; (2) the contour texture of the submandibular gland (smooth or rough); (3) the internal echo texture, categorized into three sonographic patterns (homogeneous, multiple hypoechoic nodule, and diffuse hypoechoic); and (4) quantitative color Doppler signaling. Results: The longitudinal diameter and the thickness (mean ± SD) of the submandibular gland were significantly greater in patients than in controls (p = 0.005 and p < 0.001, respectively). Contour roughness was seen in 62.9 and 8.3 % of patients and controls (p < 0.001), respectively. Homogeneous echo textures alone were seen in controls, whereas multiple hypoechoic nodule patterns were seen in 60 % of the patients, and diffuse hypoechoic patterns were seen in 40 %. Color Doppler signaling (mean ± SD) was significantly higher in patients as compared with controls (p < 0.001). Conclusion: Patients could be distinguished from healthy volunteers using four distinctive sonographic findings, suggesting that ultrasonography would be a useful diagnostic tool for IgG4-SS