X-Ray Fluctuations from Locally Unstable Advection-Dominated Disks

The response of advection-dominated accretion disks to local disturbances is examined by one-dimensional numerical simulations. It is generally believed that advection-dominated disks are thermally stable. We, however, find that any disurbance added onto accretion flow at large radii does not decay so rapidly that it can move inward with roughly the free-fall velocity. Although disturbances continue to be present, the global disk structure will not be modified largely. This can account for persistent hard X-ray emission with substantial variations observed in active galactic nuclei and stellar black hole candidates during the hard state. Moreover, when the disturbance reaches the innermost parts, an acoustic wave emerges, propagating outward as a shock wave. The resultant light variation is roughly (time) symmetric and is quite reminiscent of the observed X-ray shots of Cygnus X-1.Comment: plain TeX, 11 pages, without figures; to be published in ApJ Lette

Diagonistic Apraxia: A Unique Case of Corpus Callosal Disconnection Syndrome and Neuromyelitis Optica Spectrum Disorder

Diagonistic apraxia is a corpus callosal disconnection syndrome. Callosal lesions in Neuromyelitis optica spectrum disorder (NMOSD) have been reported, but callosal disconnection syndrome are rare. A 48-year-old woman was treated for fever and a cough before hospitalization. Her fever abated immediately, but she had balance problems in walking and standing. She also had slurred speech. On neurological examination, she had diagonistic apraxia. Her left hand moved in an uncoordinated way when she moved her right hand: changing her clothes for example or using a knife and fork. She had to instruct her left hand to stop. She had dysarthria and her gait was wide-based. She also had many callosal disconnection syndrome symptoms such as alexia of left visual field, left ear extinction, crossed optic ataxia. Using FLAIR and DWI MRI, a mixture of low and high signals, a so-called “marbled pattern,” was seen in the corpus callosum. Since the patient was positive for anti-aquaporin-4 antibody, she was diagnosed with NMOSD. After two courses of steroid pulse therapy, the symptoms improved. Here we report diagonistic apraxia and other symptoms of callosal disconnection syndrome in anti-AQP4-positive NMOSD

Impaired cognitive modification for estimating time duration in Parkinson’s disease

Parkinson\u27s disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients’ ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD\u27s internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD

Prognostic value of plasminogen activator inhibitor-1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib

Background and AimsVascular endothelial growth factor-directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers. MethodsFrom September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4weeks after axitinib initiation. Bio-Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation. ResultsPatients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor-1 (PAI-1) level from pre-treatment to 4weeks after axitinib initiation compared with those with progressive disease (P = .022). The median progression-free survival (PFS) and median overall survival (OS) in patients with increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation were significantly shorter than those with decreased serum PAI-1 level (P = .027 and P = .026, respectively). Increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses (P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI-1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis (P = .026 and P = .010, respectively). ConclusionsThe initial change in serum PAI-1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC

gpt delta transgenic mice for in vivo genotoxicity assays: application for analysis of combined effects of radiation and chemicals

It is important to evaluate the combined effects of low–dose-rate or low-dose radiation with chemicals as humans are exposed to a variety of chemical agents. Here, we applied gpt delta transgenic genotoxicity assay to examine combined genotoxic effects of low-dose-rate radiation and 4-(methylnitrosamino)-1-(3-pyridy1)-1-butanone (NNK), the most carcinogenic tobacco-specific nitrosamine and a methylating agent, in the lung of mice. In this mouse model, base substitutions and deletions can be separately analyzed by gpt and Spi- selections, respectively. Female gpt delta mice were treated either with gamma-irradiation alone at a dose rate of 0.5, 1.0 or 1.5mGy/h for 22 h/day for 31 days or its combination with NNK at a dose of 2mg/mouse/day, i.p. for four consecutive days in the middle course of irradiation. In the gpt selection, the NNK treatments enhanced the mutation frequencies (MFs) significantly, but no obvious combined effects of gamma-irradiation were observable at any given radiation dose. In contrast, NNK treatments appeared to suppress the Spi- large deletions. In the Spi- selection, when NNK treatments were combined, the dose-response curve became bell-shaped where the highest radiation dose decreased substantially. These results suggest that NNK treatments may elicit an adaptive response that eliminates cells bearing radiation-induced double-strand breaks (DSBs) in DNA. We are currently examining the mechanisms underlying the apparent suppressive effects of methylating agent against radiation-induced DSBs with human cells in vitro.The 7th Japan-France Workshop on Radiation Biolog