The Freeness and Minimal Free Resolutions of Modules of Differential Operators of a Generic Hyperplane Arrangement

Let A be a generic hyperplane arrangement composed of r hyperplanes in an n-dimensional vector space, and S the polynomial ring in n variables. We consider the S-submodule D(m)(A) of the nth Weyl algebra of homogeneous differential operators of order m preserving the defining ideal of A. We prove that if n \geq 3, r > n,m > r - n + 1, then D(m)(A) is free (Holm's conjecture). Combining this with some results by Holm, we see that D(m)(A) is free unless n \geq 3, r > n,m < r - n + 1. In the remaining case, we construct a minimal free resolution of D(m)(A) by generalizing Yuzvinsky's construction for m = 1. In addition, we construct a minimal free resolution of the transpose of the m-jet module, which generalizes a result by Rose and Terao for m = 1.Comment: 20 page

12(S)-Hydroxyeicosatetraenoic acid induces cAMP production via increasing intracellular calcium concentration

AbstractWe have found that a 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), induces cAMP production in human normal fibroblast TIG-1 cells. This phenomenon was not observed in other cells tested including human embryonic kidney HEK293 cells. We have speculated that this specific response might be influenced by the kinds of isoform of adenylyl cyclase (AC) present in cells. We found that TIG-1 cells specifically expressed type VIII AC. As type VIII AC is known to be activated by an increase of calcium concentration, we determined the change of intracellular Ca2+ concentration after the addition of 12-HETE. It was elevated not only in TIG-1 cells, but also HEK293 cells, which did not respond to 12-HETE to produce cAMP. The addition of a calcium ionophore elevated the concentration of intracellular cAMP in TIG-1 cells, but it was without effect in HEK293 cells. To show that the expression of this particular isoform of AC is responsible for the positive response to 12-HETE, we transfected this AC isoform into HEK293 cells. The type VIII AC-transfected cells, in contrast to the mock-transfected ones, became very responsive to 12-HETE to produce cAMP. Taken all together the data would strongly suggest that 12-HETE specifically activates type VIII AC via increasing intracellular Ca2+ concentration

Does respiratory drive modify the cerebral vascular response to changes in end‐tidal carbon dioxide?

What is the central question of this study? An interaction exists between the regulatory systems of respiration and cerebral blood flow (CBF), because of the same mediator (carbon dioxide, CO ) for both physiological systems. The present study examined whether the traditional method for determining cerebrovascular reactivity to CO (cerebrovascular reactivity; CVR) is modified by changes in respiration. What is the main finding and its importance? CVR was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may under- or over-estimate CVR determined by traditional methods in healthy adults.The cerebral vasculature is sensitive to changes in the arterial partial pressure of carbon dioxide (CO ). This physiological mechanism has been well established as a cerebrovascular reactivity to CO (CVR). However, arterial CO may not be an independent variable in the traditional method to assess CVR since the cerebral blood flow (CBF) response is partly affected by the activation of respiratory drive or higher centers in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, ten young healthy subjects performed hyper- or hypo-ventilation to change end-tidal CO (P CO ) under different concentrations of CO gas inhalation (0, 2.0, 3.5%). We measured middle cerebral artery mean blood flow velocity (MCAVm) by transcranial Doppler to identify the CBF response to change in P CO during each condition. At each F CO condition, P CO was significantly altered by changes in ventilation, and MCA Vm changed accordingly. However, the relationship between changes in MCV Vm and P CO as a response curve of CVR was reset upwards and downwards by hypo- and hyper-ventilation, respectively, compared with CVR during normal-ventilation. The findings of the present study may provide the possibility that an alteration in respiration under- or over-estimates CVR determined by the traditional methods

A Retrospective Study of Canine Idiopathic Epilepsy in Referral Centers in Japan

Idiopathic epilepsy (IE) is one of the most common neurologic disorder in dogs. The aim of this study was to describe the clinical data of dogs with IE in Japan and to search for predisposing factors of IE for further investigation. Medical records and clinical information of dogs diagnosed with IE at 2 referral centers between April 2013 and March 2016 were retrospectively reviewed. It was conducted according to the consensus statement published by International Veterinary Epilepsy Task Force. A total of 70 dogs were used with a median (range) weight of 5.15 (1.85–79.85) kg and age at initial epileptic seizure onset of 4.2 (0.3–11.8) years. Fortyfour dogs were male, and 26 were female. Toy Poodles were over-represented in the present study indicating that this breed may be predisposed to IE and would be a candidate for gene study to elucidate the cause of IE in dogs

Direct measurement of radial strain in the inner-half layer of the left ventricular wall in hypertensive patients

SummaryBackgroundTwo-dimensional speckle tracking echocardiography (2D-STE) is a novel technology that directly measures regional left ventricular (LV) wall contraction. This study aimed to directly measure inner-layer thickening (radial strain) of the LV using 2D-STE, and to examine the relationship between radial strain and the degree of hypertrophy.MethodsThe study enrolled 63 untreated hypertensive patients with normal geometry (N group, n=32) or concentric hypertrophy (CH group, n=31), classified according to LV mass index (LVMI) and relative wall thickness (RWT). Thirty normotensive subjects (C group, n=30) served as controls. Radial strain (ɛ) in the inner half (ɛi) and all layers of the LV wall (ɛa) were calculated from the LV short-axis view by 2D-STE.ResultsLV ejection fraction did not differ significantly among the groups. However, ɛi and ɛa were significantly lower in the CH group compared with the C and N groups (p<0.01). A ratio of ɛi to ɛa was significantly lower in the CH group compared with the C and N groups (p<0.01). A multivariate regression model that included midwall fractional shortening, E/e′, LVMI, RWT, and LV ejection fraction showed that LVMI (p=0.002) and RWT (p=0.014) were independent predictors (R2=0.59) of ɛi.ConclusionRadial strain in the inner half layer of the LV wall decreases in parallel with the degrees of LV concentricity and hypertrophy in hypertensive patients. Radial strain in the inner half layer may identify subtle systolic dysfunction even in hypertensive patients with preserved LV chamber function

Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer

金沢大学がん研究所Purpose: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). Experimental Design: Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. Results: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. Conclusions: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC. ©2010 AACR

Long interspersed nuclear element-1 hypomethylation is a potential biomarker for the prediction of response to oral fluoropyrimidines in microsatellite stable and CpG island methylator phenotype-negative colorectal cancer

金沢大学がん研究所We investigated the clinical value of methylation of long interspersed nuclear element-1 (LINE-1) for the prognosis of colorectal cancer (CRC) and for the survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1 methylation in tumor DNA was measured by quantitative methylation-specific PCR in 155 samples of stage II and stage III CRC. The presence of microsatellite instability and CpG island methylator phenotype (CIMP) were assessed and 131 microsatellite stable/CIMP- cases were selected for survival analysis, of which 77 patients had received postoperative adjuvant chemotherapy with oral fluoropyrimidines. The CRC cell lines were used to investigate possible mechanistic links between LINE-1 methylation and effects of 5-fluorouracil (5-FU). High LINE-1 methylation was a marker for better prognosis in patients treated by surgery alone. Patients with low LINE-1 methylation who were treated with adjuvant chemotherapy survived longer than those treated by surgery alone, suggestive of a survival benefit from the use of oral fluoropyrimidines. In contrast, a survival benefit from chemotherapy was not observed for patients with high LINE-1 methylation. The CRC cell lines treated with 5-FU showed increased expression of LINE-1 mRNA. This was associated with upregulation of the phospho-histone H2A.X in cells with low LINE-1 methylation, but not in cells with high LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A.X, a marker of DNA damage, was inhibited by knockdown of LINE-1. These results suggest that LINE-1 methylation is a novel predictive marker for survival benefit from adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. This finding could be important for achieving personalized chemotherapy. © 2010 Japanese Cancer Association

Study on the reusability of fluorescent nuclear track detectors using optical bleaching

Fluorescent nuclear track detectors (FNTDs) based on Al${_2}$O${_3}$:C,Mg crystals are luminescent detectors that can be used for dosimetry and detection of charged particles and neutrons. These detectors can be utilised for imaging applications where a reasonably high track density, approximately of the order of 1 $\times$ $10^4$ tracks in an area of 100 $\times$ 100 $\mu$m$^2$, is required. To investigate the reusability of FNTDs for imaging applications, we present an approach to perform optical bleaching under the required track density conditions. The reusability was assessed through seven irradiation-bleaching cycles. For the irradiation, the studied FNTD was exposed to alpha-particles from an $^{241}$Am radioactive source. The optical bleaching was performed by means of ultraviolet laser light with a wavelength of 355 nm. Three dedicated regions on a single FNTD with different accumulated track densities and bleaching conditions were investigated. After every irradiation-bleaching cycle, signal-to-noise ratio was calculated to evaluate FNTD performance. It is concluded that FNTDs can be reused at least seven times for applications where accumulation of a high track density is required

Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

In 2007 and 2008 in Myanmar, we detected influenza viruses A (H3N2) that exhibited reduced sensitivity to both zanamivir and amantadine. These rare and naturally occurring viruses harbored a novel Q136K mutation in neuraminidase and S31N mutation in M2

Trials for Risk Assessment of Japanese Encephalitis Based on Serologic Surveys of Wild Animals

Flavivirus Encephaliti