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Atmospheric gravity waves (GWs) during the February 2018 sudden stratospheric warming (SSW) event are simulated using the T639L340 whole neutral atmosphere general circulation model. Their characteristic morphology around the drastically evolving polar vortex is revealed by three‐dimensional (3D) visualization and ray‐tracing analyses. The 3D morphology of simulated GWs is described for the three key days that represent the pre‐SSW conditions, the mature stage for the vortex splitting, and the late SSW. The combination of strong winds along the polar vortex edge and underneath the tropospheric winds with similar wind directions consist of the deep waveguide for the upward‐propagating GWs, forming GW hot spots in the middle atmosphere. The GW hot spots associated with the development of the SSW are limited to North America and Greenland, and they include the typical upward‐propagating orographic GWs with relatively long vertical wavelengths. Different types of characteristic GW signatures are also recognized around the Canadian sub‐vortex (CV). GWs having short vertical wavelengths form near the surface and obliquely propagate over long distances along the CV winds. The non‐orographic GWs with short vertical wavelengths form in the middle stratosphere through the spontaneous adjustment of flow imbalance around the CV. Those GWs cyclonically ascend into the mesosphere along CV winds. Plain Language Summary: Atmospheric gravity waves (GWs) have three‐dimensional (3D) phase structures and propagate three‐dimensionally from their sources. Examples include flow over mountains, convection, fronts, and dynamically imbalanced flow systems. For the first time, we simulated and visualized their 3D global morphology from the surface to an altitude of ∼100 km by focusing on the February 2018 sudden stratospheric warming event, when the stratospheric polar vortex split into two sub‐vortices. The most interesting findings in the 3D and ray‐tracing analyses are the formation of narrow GW hotspots along the south to east rim of the Canadian sub‐vortex (CV) and the cyclonical ascent of GWs around the edge of the CV. Key Points: Gravity waves during the 2018 sudden stratospheric warming were simulated using a whole neutral atmosphere general circulation modelThree‐dimensional visualization analyses revealed their characteristic morphology around the dramatically evolving polar vortexPaths of gravity waves near the Canadian sub‐vortex were estimated by ray tracing, highlighting long‐distance gravity wave propagation [ABSTRACT FROM AUTHOR]

Tropical tropospheric responses to a sudden stratospheric warming (SSW) event that occurred over Antarctica in September 2019 have been investigated by conducting a series of ensemble forecast experiments. Comparative examinations between the normal forecast and the partially nudged forecast, whose stratospheric circulation is constrained to a reanalysis, reveal a significant enhancement/suppression in the convective activity (upwelling/downwelling) over the northern/southern part of the tropics. Such an acceleration of the Hadley circulation is set up by thermal structural changes in the upper troposphere and lower stratosphere. The tropical cooling caused by the enhanced Brewer‐Dobson circulation destabilizes the environment there and stimulates deep cumulus convections. In this case, the southern area of the Asian monsoon region is particularly sensitive. Although details of the triggered response depend on the adopted cumulus parameterization scheme, a boosting tendency of the convective upwelling via the SSW is robust. Plain Language Summary: A rare Antarctic sudden stratospheric warming (SSW) event that occurred in September 2019 provides an opportunity to investigate its impact on convective activity in the tropics. By comparing the normal forecast and a "perfect stratosphere" forecast, this study confirmed the robust influence of the SSW on the cumulus convection over the Northern Hemisphere tropics. In other words, the Antarctic SSW could enhance the probability of extreme weather in boreal summer to early autumn, including the genesis and development of tropical cyclones. Therefore, this process of the teleconnection between the Antarctic stratosphere and the tropical troposphere has the potential to be a valuable source of extended‐range predictability in practical seasonal forecasts. Key Points: Enhancement in the tropical convective activity during the 2019 Antarctic sudden warming is confirmed by ensemble nudging integrationsEnhanced Brewer‐Dobson circulation is linked to Hadley cells via thermal structure changes in the upper troposphere and lower stratosphereFor certain parameterizations, the large stratospheric effect is observed in cumulus convections at the south of the Asian monsoon zone [ABSTRACT FROM AUTHOR]

The observational impacts of satellite data assimilation on extended‐range forecasts of sudden stratospheric warmings (SSWs) are investigated by conducting ensemble forecast experiments. We use two Japanese novel reanalysis products: the Japanese 55‐year reanalysis (JRA‐55) and its subset that assimilates conventional observations only (JRA‐55C). A comparative examination on the reproducibility for SSWs between the two ensemble forecasts reveals that the impact of satellite observations is significant for forecasts starting 5 days before the SSW onset, with 20% less accuracy in the JRA‐55C forecasts. Moreover, some of forecasts of vortex‐splitting SSWs show a sudden appearance of deep difference, which lasts over a few months in the lower stratosphere and significantly affects the surface climate. These results highlight an important role of mesospheric and upper stratospheric circulations on the onset and development of SSWs. Plain Language Summary: Satellite observations are valuable for producing initial conditions for numerical weather prediction (NWP) systems, especially over the upper stratosphere that typical upper‐air observations cannot cover. However, many NWP models suffer from biases associated with unresolved processes. This study explores how the NWP system benefited from satellite data in forecasting the breakdown events of stratospheric polar vortexes/sudden stratospheric warmings (SSWs) by making many forecasts from typical initial conditions, both with and without satellite data. Due to unresolved bias over the upper stratosphere, some forecasts from no‐satellite initial conditions miss the onset of SSWs and subsequent anomalous tropospheric conditions. Thus, the deteriorated grasp of the upper atmosphere in the absence of satellite observations degrades the deterministic predictability of extreme stratospheric events and following downward‐propagating signals. Key Points: Mesospheric and upper stratospheric initial conditions play an important role in forecasting the onset and development of sudden warmingsThe 5‐day lead capture rate of the onset of major sudden stratospheric warmings degrades about 20% if satellite data are not assimilatedThe absence of satellite observations could also affect the extended‐range forecast skill related to downward‐propagating signals [ABSTRACT FROM AUTHOR]

Oncolytic virotherapy is a novel treatment involving replication‐competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 108 to 5.0 × 109 TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group‐ Common Terminology Criteria for Adverse Events (VCOG‐CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti‐reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post‐treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well‐tolerated and can be given safely to tumour‐bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours. [ABSTRACT FROM AUTHOR]

Background: SRC kinase (SRC proto-oncogene, non-receptor tyrosine kinase) is a promising target for the treatment of solid cancers including human melanoma. Bosutinib (Bosu), a SRC inhibitor, has already been applied to the treatment of human chronic myelogenous leukemia and also has been assessed its safety in dogs. Aim: The aim of this study was to clarify a novel anti-tumour mechanism of Bosu in canine and human melanoma cells. Materials and Methods: The canine and human melanoma cells were treated with Bosu and its effects were evaluated by the cell viability, the protein expression levels such as caspase-3 and LC3, Annexin V/Propidium iodide staining, and confocal immunostaining. Results: Bosu induced the massive caspase-independent cell death, and blocked autophagy flux, which resulted from lysosomal dysfunction. Lysosomal dysfunction caused by Bosu was due to lysosomal membrane permeabilization (LMP), which resulted in the release of lysosomal hydrolases including cathepsin B. Conclusion: Our data suggest that Bosu induces the cell death through induction of LMP in melanoma cells and is a promising therapeutic agent for treatment of melanoma in both dogs and humans. [ABSTRACT FROM AUTHOR]

Background and Objective The barrier function of long junctional epithelium is thought to be important after periodontal initial therapy and periodontal surgery. Although the difference between long junctional epithelium and normal junctional epithelium regarding their resistance to destruction of periodontal tissue has been investigated, the mechanism still remains unclear. Using our rat experimental periodontitis model in which loss of attachment and resorption of alveolar bone is induced by the formation of immune complexes, we investigated the resistance of periodontal tissue containing long junctional epithelium and normal junctional epithelium to destruction. Material and Methods Rats were divided into four groups. In the immunized long junctional epithelium (I-LJE) group, rats were immunized with lipopolysaccharide (LPS), and curettage and root planing procedures were performed on the palatal gingiva of the maxillary first molars to obtain reattachment by long junctional epithelium. In the immunized normal junctional epithelium (I-JE) group, rats were immunized without curettage and root planing procedures. In the nonimmunized long junctional epithelium (nI-LJE) group, rats were not immunized but curettage and root-planing procedures were performed. In the control group, neither immunization nor curettage and root-planing was performed. In all rats, periodontal inflammation was induced by topical application of LPS into the palatal gingival sulcus of maxillary first molars. The rats were killed at baseline and after the third and fifth applications of LPS. Attachment loss and the number of inflammatory cells and osteoclasts in the four groups were compared histopathologically and histometrically. Results After the third application of LPS in the I- LJE group, attachment loss showed a greater increase than in control and nI-LJE groups, and inflammatory cell infiltration and osteoclasts were increased more than in the other groups. After the fifth application of LPS, attachment loss was greater and there was a higher degree of inflammatory cell infiltration in nI- LJE and I- LJE groups than in control and I- JE groups. Conclusion Our findings suggest that the destruction of periodontal tissue is increased in tissue containing long junctional epithelium compared with normal junctional epithelium and that the immunized condition accelerates the destruction by forming immune complexes. [ABSTRACT FROM AUTHOR]

MicroRNA ( miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein ( CREB)/microphthalmia-associated transcription factor ( MITF)/ RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development. [ABSTRACT FROM AUTHOR]

The cover image, by Shunsuke Noguchi et al., is based on the Original Article Analysis of microRNA-203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells, DOI: . [ABSTRACT FROM AUTHOR]

Reovirus is a potent oncolytic virus in many human neoplasms that has reached phase II and III clinical trials. Our laboratory has previously reported the oncolytic effects of reovirus in canine mast cell tumour ( MCT). In order to further explore the potential of reovirus in veterinary oncology, we tested the susceptibility of reovirus in 10 canine lymphoma cell lines. Reovirus-induced cell death, virus replication and infectivity were confirmed in four cell lines with variable levels of susceptibility. The level of Ras activation varied among the cell lines with no correlation with reovirus susceptibility. Reovirus-susceptible cell lines underwent apoptosis as proven by propidium iodide ( PI) staining, Annexin V- FITC/ PI assay, cleavage of PARP and inhibition of cell death by caspase inhibitor. A single intratumoral injection of reovirus suppressed the growth of canine lymphoma subcutaneous tumour in NOD/ SCID mice. Unlike canine MCT, canine lymphoma is less susceptible to reovirus. [ABSTRACT FROM AUTHOR]

Malignant melanoma ( MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs ( miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA-microarray assay and quantitative RT- PCR. Importantly, a decreased expression of miR-203 was significantly associated with a shorter survival time. Also, miR-203 and -205 were markedly down-regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR-205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR-203 is a new prognostic factor in canine oral MMs and that miR-205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells. [ABSTRACT FROM AUTHOR]

Fascin-1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin-1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin-1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas ( P < 0.05). In addition, strong fascin-1 staining was associated with a significantly shortened survival time ( P < 0.05). The results of this study suggest that fascin-1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin-1 may represent a new strategy for the treatment of canine melanoma. [ABSTRACT FROM AUTHOR]

SUMMARY The seismic structural response is affected by temporal and spatial variations in strong ground motion. It can be evaluated through the fault-structure system: the fault mechanism, wave propagation through the crust, amplification near the surface, and soil-structure interaction. To analyze this system at high resolution and accuracy, we previously proposed a new multiscale analysis method and numerically verified its validity. However, the problem of the extremely large computation cost of constructing a three-dimensional numerical model and solving the discretized governing equations still remains. Here, we introduce a new method to resolve these difficulties. By combining this new method with our multiscale analysis, we developed a tool for fault-structure system analysis. The accuracy of this tool is verified by comparing it to a Green's function solution. Finally, we demonstrate the potential utility of the method by estimating the seismic response of a large and complex underground highway junction in a given earthquake scenario. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and purpose: Mutations in the valosin-containing protein ( VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). Despite an increasing number of clinical reports, only one Asian family with IBMPFD has been described. Methods: To characterize patients with VCP mutations, we screened a total of 152 unrelated Asian families who were suspected to have rimmed vacuolar myopathy. Results: We identified VCP mutations in seven patients from six unrelated Asian families. Five different missense mutations were found, including a novel p.Ala439Pro substitution. All patients had adult-onset progressive muscle wasting with variable involvement of axial, proximal, and distal muscles. Two of seven patients were suggested to have mild brain involvement including cerebellar ataxia, and only one showed radiological findings indicating a change in bone. Findings from skeletal muscle indicated mixed neurogenic and myogenic changes, fibers with rimmed vacuoles, and the presence of cytoplasmic and nuclear inclusions. These inclusions were immunopositive for VCP, ubiquitin, transactivation response DNA-binding protein 43, and also histone deacetylase 6 (HDAC6), of which function is regulated by VCP. Evidence of early nuclear and mitochondrial damage was also characteristic. Conclusions: Valosin-containing protein mutations are not rare in Asian patients, and gene analysis should be considered for patients with adult-onset rimmed vacuolar myopathy with neurogenic changes. A wide variety of central and peripheral nervous system symptoms coupled with rare bone abnormalities may complicate diagnosis. [ABSTRACT FROM AUTHOR]

Background: The authors investigated the impact of the genetic polymorphisms cytochrome P450 (CYP) family 2, subfamily D, polypeptide 6, allele 10 (CYP2D6 10) and CYP family 2, subfamily C, polypeptide 19, allele 2, 3 (CYP2C19 2, 3) on disease recurrence in patients with breast cancer who received adjuvant tamoxifen and evaluated the impact of those polymorphisms on endometrial thickness, bone mineral density (BMD), and serum total cholesterol levels.Methods: Patients with primary breast cancer (n=173) who had hormone receptor-positive tumors and who also received adjuvant tamoxifen were included in the current study. Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 were analyzed.Results: Recurrence-free survival (RFS) rates did not differ significantly between patients with the CYP2D6 10/10 genotype (n=40) and patients with the CYP2D6 wild-type (wt)/wt or wt/10 genotype (n=133) or between patients with the CYP2C19 2/2, 2/3, or 3/3 genotypes (n=41) and patients with the CYP2C19 wt/wt, wt/2, or wt/3 genotype (n=132). Multivariate analysis indicated that, even after adjustment for well established prognostic factors, these CYP2D6 or CYP2C19 genotypes were not associated significantly with the RFS rate. Moreover, these genotypes did not affect endometrial thickness, BMD, or total cholesterol levels 1 year after the start of tamoxifen treatment.Conclusions: Neither the CYP2D6 10/10 genotype nor the CYP2C19 genotype is likely to have a clinically significant impact on prognosis, endometrial thickness, BMD, or total cholesterol levels in Japanese patients with breast cancer who are treated with adjuvant tamoxifen. [ABSTRACT FROM AUTHOR]

The article reports on the study conducted by J. N. Negishi and colleagues on the influence of intercepted subsurface flow to road runoff and sediment transport in Singapore. Researchers monitored the hydrological and sediment fluxes in a tropical headwater catchment wherein the 3 year old logging road caused substantial Hortonian overland flow (HOF) and intercepted subsurface flow (ISSF). They discovered that the management of unpaved roads in mountainous catchments characterize by soil horizons and prevailing stormflow generation process are conducive to the occurrence of ISSF along the road wherein drainage ditches do not exist. Aside from HOF and associated surface erosion, they found that roads cut into hillslopes intercept subsurface flow.

Hydrological responses in a zero-order basin (ZOB), a portion of whose discharge emerged via preferential flow through soil pipes, were examined over a 2-year period in Peninsular Malaysia to elucidate primary stormflow generation processes. Silicon (Si) and specific conductance (EC) in various runoff components were also measured to identify their sources. ZOB flow response was dependent on antecedent precipitation amount; runoff increased linearly with precipitation during events >20 mm in relatively wet antecedent moisture conditions. Runoff derived from direct precipitation falling onto saturated areas accounted for <0.2% of total ZOB flow volume during the study period, indicating the predominance of subsurface pathways in ZOB flow. ZOB flow (high EC and low Si) was distinct from perennial baseflow via bedrock seepage (low EC and high Si) 5 m downstream of the ZOB outlet. Pipe flow responded quickly to ZOB flow rate and was characterized by a threshold flow capacity unique to each pipe. Piezometric data and pipe flow records demonstrated that pipes located deeper in the soil initiated first, followed by those at shallower depths; initiation of pipe flow corresponded to shallow groundwater rise above the saprolite-soil interface. Chemical signatures of pipe flow were similar to each other and to the ZOB flow, suggesting that the sources were well-mixed soil-derived shallow groundwater. Based upon the volume of pipe flow during storms, the combined contribution of the pipes monitored accounted for 48% of total ZOB flow during the study period. Our results suggest that shallow groundwater, possibly facilitated by preferential flow accreted above the saprolite--soil interface, provides dominant stormflow, and that soil pipes play an important role in the rapid delivery of solute-rich water to the stream system. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection not only causes chronic liver diseases but shows extrahepatic manifestations as oral lichen planus (OLP) and oral cancer. To elucidate the direct relationships among these diseases and HCV infection, we investigated the detection of positive- and negative-strand HCV-RNA from serum, OLP (n=19), and oral cancer (n=17) tissues. We used a sensitive reverse transcription to polymerase chain reaction (RT-PCR) method, and analyzed sequences from the HCV El/E2 region of the genome from serum and tissue. Positive and negative HCV-RNA strands were observed in 13 (92.9%) and 3 (21.4%) OLP tissues, respectively. In oral cancer tissues, positive HCV-RNA strands were detected in all tissues from anti-HCV positive patients. Negative HCV-RNA strands were observed in 5 of 7 (71.4%) patient's tissues. Furthermore, it was confirmed that the sequence from one of each OLP and oral cancer patient differed between serum and tissue HCV-RNA. These results may indicate that HCV persists and replicates in these lesions, suggesting a pathological role for HCV, although the mechanisms are unclear. [ABSTRACT FROM AUTHOR]

We studied the incidence of GBV-C infection in patients with oral cancer or oral lichen planus (OLP). Subjects included 38 patients with oral cancer and 34 patients with OLP from whom serum was collected to detect GBV-C-RNA using reverse transcription (RT) "nested" PCR. GBV-C-RNA was positive in 1 (2.6%) oral cancer patient and 3 (8.8%) OLP patients. All 4 GBV-C-positive patients were also positive both for the antibody for hepatitis C virus (anti-HCV) and HCV-RNA, indicating simultaneous infection with GBV-C and HCV. In conclusion, GBV-C infection was found in 5.5% (4/72) of oral cancer or OLP patients and all patients infected with GBV-C also had HCV infection. This suggests that GBV-C infection is unlikely to play an important role in the pathogenesis of oral cancer and OLP. [ABSTRACT FROM AUTHOR]

Experimental studies of acute inflammation of the tracheobronchial lumen of rats suggest that protease inhibitor increases in tracheobronchial secretions in order to control inflammation. Recent studies have shown that the polyvalent protease inhibitor, Miraclid, derived from human urine, is useful for treating DIC and acute pancreatitis. In view of this information, local administration of Miraclid was expected to diminish acute inflammation of the respiratory tract by creating a favorable balance in the protease-antiprotease system. Before the chemotherapeutic use of locally administered Miraclid, the inhibitory activity of Miraclid on various proteases was first estimated in vitro. Administration of Miraclid by means of ultrasonic nebulization was then investigated in rats. The results can be summarized as follows. 1. During ultrasonic nebulization, the inhibitory activity of Miraclid on protease was decreased by means of mechanical stimulation in comparison to the activity before nebulization. 2. Compared to administration of physiological saline into the tracheobronchial lumen, administration of Miraclid by means of ultrasonic nebulization decreased the fibrinolytic activity in tracheobronchial secretions. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the revision of the cytological diagnosis of central nervous system (CNS) relapse into aseptic meningitis in a patient with leukemia.

The article discusses common pathological mechanisms in mouse models for muscular dystrophies. Expression profiling distinguishes severly affected dystrophin- and sarcoglyan-deficient mice from mildly affected dysferlin-deficient mice and control mice. Inflammation and remodeling of the extracellular matrix, sarcomere, and cytoskeleton are also evident in dysferlin-deficient mice, though present at lower levels, in agreement with the later age of onset and the earlier stage of the disease analyzed.

Electrical resistance values are reported for soaps of various moisture contents. Marked changes in resistance were found at 40-50°C. Below this temperature the logarithm of conductivity is a linear function of inverse temperature, and the slope of the curve is practically independent of water content. Above 40° resistance is markedly affected by the water content of the soap. For soaps containing 12-30% water, heating and cooling curves show definite maxima and minima in electrical resistance values. This effect is less obvious in soaps containing more than 30% water. The phase transition points estimated from resistance measurements are in good agreement with those deduced from other physical measurements. [ABSTRACT FROM AUTHOR]

An abstract of the article "Visibility grade classification for fetoscopic laser surgery for TTTS: relationship between visibility grade and necessity for irrigation technique," by T. Murakoshi and colleagues is presented.