The relation between thermal tolerance and latitudinal distribution was studied with 30 drosophilid species collected from the cool-temperate region (Sap-poro), the warm-temperate region (Tokyo and ...Kyoto) and the subtropical region (Iriomote island) in Japan. In addition, intraspecific variation was examined for five species collected from two localities. The subtropical strains of Scaptodrosophila coracina, Drosophila bizonata and D. daruma were less tolerant to cold than their temperate strains. However, the difference of cold toler- ance between these two geographic strains was much smaller than the difference between the species restricted to the subtropical region and those occurring in the temperate region. In D. auraria and D. suzukii, no difference was observed in thermal tolerance between their cool- and warm-temperate strains. Thus, geographic variation in thermal tolerance within species was low or negligible. Interspecific comparisons by phylogenetic independent contrasts revealed that species which had the northern boundaries of their distributions at higher latitudes were generally more tolerant to cold than those which had their boundaries at lower latitudes. However, the data for some species did not agree with this trend. The use of man-protected warm places for overwintering, competition or predation would also affect their distributions. It also appeared that species which had their southern boundaries at higher latitudes were generally more cold-tolerant. The acquisition of cold tolerance may lower a fly's capacity to compete, survive or reproduce in warmer climates. On the other hand, no relation was observed between heat tolerance and latitudinal distribution. Heat tolerance was higher in species inhabiting openlands or the forest canopy than in those inhabiting the forest understorey.
In this largest phase II trial with advanced thymic carcinoma (TC), carboplatin and paclitaxel (CbP) showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, ...which is the current standard treatment of TC. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.
Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC.
The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m2) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05.
Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%–53%; P = 0.031). The median PFS was 7.5 (6.2–12.3) months, while OS did not reach the median value. Major adverse event was grade 3–4 neutropenia in 34 patients (87%). There was no treatment-related death.
In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy and the kidney: health and disease Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi ...
Nephrology, dialysis, transplantation,
09/2014, Volume:
29, Issue:
9
Journal Article
Peer reviewed
Open access
Macroautophagy is a highly evolutionally conserved degradation process by which cytosolic materials (including macromolecules such as proteins and lipids) and damaged organelles are broken down to ...their basic components. The role of autophagy is not only the elimination of materials, but it also serves as a dynamic recycling system that produces new components and energy for cellular renovation and homeostasis. The association of autophagy with the organ physiology and pathogenesis of various disorders such as neurodegenerative diseases, cancer, infection and inflammatory bowel disease has been revealed in recent years. Autophagy also plays an essential role in cellular homeostasis in kidney and counteracts age-related stress and kidney diseases. Here, we critically review the current evidence regarding autophagy in the kidney, in particular as assessed with tissue- or cell lineage-specific autophagy-deficient mice. Better insight into the mechanisms underlying renoprotective roles of autophagy will pave the way toward novel therapies for kidney diseases.
The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse ...event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2-0.3 mg kg(-1) per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Seismic wave extractions have been performed using ambient noise records observed by distributed acoustic sensing (DAS) technology. Extractions of microseisms can be investigated at a local scale ...using such DAS records observed in the ocean. Here, we show P and Scholte wave extractions from ambient seafloor noise observed by DAS along a submarine cable deployed off Cape Muroto in the Nankai subduction zone, Japan. The P waves can be observed at a frequency band of 0.1–0.3 Hz and up to a distance of 8 km. The distance at which the P waves can be observed is controlled by the P incident angle and the DAS sensitivity to the observable apparent velocity. Effective extractions of P and Scholte waves, corresponding to large intensity of wave‐wave interaction at the sea surface, are performed, indicating that the waves are originated from pressure field at the sea surface.
Plain Language Summary
The density of seismic observations on land is typically higher than that in the ocean. However, higher‐density observations in both land and ocean regions can be made using the recently developed distributed acoustic sensing (DAS). In this study, we focus on the waves persistently propagating through the Earth, which are excited by ocean swell and are called microseisms. Ocean swell at the sea surface primarily excites surface waves: however, P and S waves excited by ocean swell, especially during tropical storms, were observed on a global scale. Because this indicates that body waves may be locally excited by sea surface disturbances, we investigate the problem using DAS records. Our results show that large amplitudes of P waves occur when an atmospheric low pressure passes through Japan, and those amplitudes become weak when the wave‐wave interaction intensity at the ocean surface is weak. Although many previous studies at global or regional scales have indicated that microseisms are originated from fluid disturbances at the sea surface, the current study observed the excitation of P and surface waves right beneath the sea surface disturbances.
Key Points
P waves were extracted from ambient seafloor noise records observed by distributed acoustic sensing (DAS) at a frequency band of 0.1–0.3 Hz and up to a distance of 8 km
Extraction of P waves depends on weather conditions, particularly for wave‐wave interaction intensity at the sea surface
The distance at which the P waves emerge is controlled by the P incident angle and the DAS sensitivity to apparent velocities
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Edoxaban, an oral direct factor Xa inhibitor, has proven antithrombotic efficacy. In a multicenter, phase II study, 264 total hip arthroplasty (THA) patients randomly received edoxaban 15 or ...30 mg once daily or enoxaparin 2000 IU (20-mg) twice daily for 11–14 days. Thromboembolic event incidences were 3.8% (3/78), 2.8% (2/72), and 4.1% (3/74) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively ( P = 1.00). Edoxaban-induced prolongation of prothrombin time, international normalized ratio, and activated partial thromboplastin time were proportional to plasma edoxaban concentration. Major or clinically relevant non-major bleeding incidences were 2.2% (2/89), 1.2% (1/85), and 2.3% (2/87) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively ( P = 1.00). Once-daily edoxaban showed similar efficacy and safety to enoxaparin for prevention of thromboembolic events in patients undergoing THA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The relationship between electron energy flux and the characteristic energy of electron distributions in the main auroral loss cone bridges the gap between predictions made by theory and measurements ...just recently available from Juno. For decades such relationships have been inferred from remote sensing observations of the Jovian aurora, primarily from the Hubble Space Telescope, and also more recently from Hisaki. However, to infer these quantities, remote sensing techniques had to assume properties of the Jovian atmospheric structure - leading to uncertainties in their profile. Juno's arrival and subsequent auroral passes have allowed us to obtain these relationships unambiguously for the first time, when the spacecraft passes through the auroral acceleration region. Using Juno /Jupiter Energetic particle Detector Instrument (JEDI), an energetic particle instrument, we present these relationships for the 30-kiloelectronvolts to 1-megaelectronvolts electron population. Observations presented here show that the electron energy flux in the loss cone is a nonlinear function of the characteristic or mean electron energy and supports both the predictions from Knight (1973, https://doi.org/10.1016/0032-0633(73)90093-7) and magnetohydrodynamic turbulence acceleration theories (e.g., Saur et al., 2003, https://doi.org/10.1029/2002GL015761). Finally, we compare the in situ analyses of Juno with remote Hisaki observations and use them to help constrain Jupiter's atmospheric profile. We find a possible solution that provides the best agreement between these data sets is an atmospheric profile that more efficiently transports the hydrocarbons to higher altitudes. If this is correct, it supports the previously published idea (e.g., Parkinson et al., 2006, https://doi.org/10.1029/2005JE002539) that precipitating electrons increase the hydrocarbon eddy diffusion coefficients in the auroral regions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper describes the plasma distribution solver (PDS), a theoretical model that determines plasma number density and pressure profiles along a magnetic field line of magnetized planets. The PDS ...computes velocity distribution functions of each particle species at an arbitrary point along a field line to meet the force balance and the accessibility. The number density, mean flow velocity, and pressure calculated by taking the zero‐th, first‐, second‐order moments of the velocity distribution functions enable us to obtain field‐aligned profiles of the quantities strictly consistent with the assumed ionospheric/magnetospheric boundary conditions. The spatial distribution of physical quantities, such as Alfvén speed and plasma β, was also obtained from the PDS results. We applied the PDS to the Jupiter‐Io system. When the temperature anisotropy is presented for the ion species originated from Io, the ion species other than protons, especially O+, can hardly reach mid‐to‐high latitudes. The number density of electrons which satisfy the charge neutrality with ions is also reduced compared to the case when the temperature is assumed to be isotropic. From these differences in the number density profile, we found the change of the boundary position, which characterizes dispersive Alfvén waves from the relation between the plasma β and the mass ratio between electrons and ions.
Key Points
We developed a solver to calculate the number density and the plasma pressure profiles along the magnetic field line of planets
These profiles satisfy the ionospheric/magnetospheric boundary conditions strictly
The profiles are derived from the velocity distribution of electrons and multi‐species ions, considering the accessibility of particles
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Temperature dependence of spin relaxation process in a Cu wire has been studied by means of nonlocal spin-valve measurements. The spin-diffusion length of the Cu wire is found to take maximum at the ...characteristic temperature, below which the spin-diffusion length is reduced. The mechanism of the reduction can be explained by considering the spin-flip scattering due to the oxidized surface of the Cu wire. The thickness dependence of the characteristic temperature supports the interpretation with the surface oxidation.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
A mesoscopic multi-terminal superconducting Nb strip with a spin injection terminal has been developed. We investigate the influence of spin polarization on the relaxation process of the ...quasiparticle in the superconducting Nb. The position dependence of the nonlocal voltage provides the quasiparticle relaxation length. The relaxation length for the spin-polarized quasiparticle is found to show a 12.5% increase from that for the un-polarized quasiparticle. This demonstration opens a new avenue for utilization of the spin current in a superconducting device.
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