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Endovascular therapy for stroke is generally avoided if the cerebral infarction is large. In a trial conducted in Japan, the percentage of patients who had a good functional outcome at 90 days was higher with endovascular therapy than with medical care, but there were more cerebral hemorrhages with endovascular therapy.

The spongy moth Lymantria dispar L. is a major forest pest causing substantial economic damage in Holarctic region. Lymantria dispar multiple nucleopolyhedrovirus isolates (LdMNPVs) have demonstrated significant potential as biological control agents against this pest. In this study we evaluated the virulence of six LdMNPV isolates against five L. dispar populations (including subspecies dispar , asiatica , japonica ) and L. umbrosa . Bioassay results revealed significant differences in susceptibility among the larvae, with the Krasnodar L. dispar population exhibiting notably higher susceptibility to LdMNPV infection than the Novosibirsk population, despite their shared host plant species. The non-local isolate LdMNPV-27/0 was more effective against Krasnodar larvae than the local LdMNPV-KR isolate. The LdMNPV-KG from Kyrgyzstan had minimal effect on larvae from Novosibirsk population but reduced survival in Krasnodar population. Our analyses indicated that virulence is predominantly determined by isolate-specific characteristics rather than the host population’s origin or subspecies classification. Genomic analysis of novel LdMNPV sequences (LdMNPV-KR, -KG, and -BibJ) detected differences in genome sizes, gene composition, and specific mutations, including the absence of the enhancing factor-1 gene in the LdMNPV-BibJ isolate. Phylogenetic analysis confirmed the clustering of isolates into distinct clades reflecting their geographic origin and evolutionary history. Our findings suggest that LdMNPV’s efficacy is primarily influenced by isolate-specific traits rather than by host origin or subspecies. The results contribute to a better understanding of genetic diversity of LdMNPV and offer valuable information for the development of more effective biological pest control strategies against L. dispar populations worldwide—irrespective of geographic or host subspecies variations—provided that the most effective isolate is selected for such an application.

BackgroundEvidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this in uncommon cancers and Asian populations.MethodsWe utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.ResultsThe multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (Ptrend < 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years’ follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.ConclusionOur consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer.

Populations of Japanese macaques were significantly reduced in most areas from the 1900s to the 1960s and then recovered mainly in the northeastern part of Honshu. A drastic reduction in population size reduces genetic variability through a bottleneck effect. Demographic expansion after the reduction that accumulates new mutations can reduce the bottleneck effects or drive the recovery of genetic variability. We examined the genetic status of a small island population (Kinkazan Island) and a larger mainland population (southern Tohoku) of Japanese macaques that experienced recent demographic bottlenecks and recovery using eight microsatellite loci. The two populations were significantly genetically different from each other. The Kinkazan population exhibited lower genetic variability, remarkable evidence of bottleneck (i.e., significant heterozygosity excess and lower frequency of rare alleles), and a considerably smaller effective population size based on genetic data than based on the current census size. These results indicate that the genetic status has not completely recovered from the demographic bottleneck despite a full recovery in census size on Kinkazan Island. New mutations might rarely have accumulated because of the small carrying capacity of the island. Therefore, the genetic variability of the population would have been restrained by the severe bottleneck size, small carrying capacity, and long-term isolation. On the other hand, the bottleneck effect seems to be limited in the southern Tohoku population considering higher genetic variability, non-significant heterozygosity excess in many mutation conditions, and the highest frequency of rare alleles.

The seasonal cycle accounts for a dominant mode of total column CO2 (XCO2) annual variability and is connected to CO2 uptake and release; it thus represents an important quantity to test the accuracy of the measurements from space. We quantitatively evaluate the XCO2 seasonal cycle of the Greenhouse Gases Observing Satellite (GOSAT) observations from the Atmospheric CO2 Observations from Space (ACOS) retrieval system and compare average regional seasonal cycle features to those directly measured by the Total Carbon Column Observing Network (TCCON). We analyse the mean seasonal cycle amplitude, dates of maximum and minimum XCO2, as well as the regional growth rates in XCO2 through the fitted trend over several years. We find that GOSAT/ACOS captures the seasonal cycle amplitude within 1.0 ppm accuracy compared to TCCON, except in Europe, where the difference exceeds 1.0 ppm at two sites, and the amplitude captured by GOSAT/ACOS is generally shallower compared to TCCON. This bias over Europe is not as large for the other GOSAT retrieval algorithms (NIES v02.21, RemoTeC v2.35, UoL v5.1, and NIES PPDF-S v.02.11), although they have significant biases at other sites. We find that the ACOS bias correction partially explains the shallow amplitude over Europe. The impact of the co-location method and aerosol changes in the ACOS algorithm were also tested and found to be few tenths of a ppm and mostly non-systematic. We find generally good agreement in the date of minimum XCO2 between ACOS and TCCON, but ACOS generally infers a date of maximum XCO2 2–3 weeks later than TCCON. We further analyse the latitudinal dependence of the seasonal cycle amplitude throughout the Northern Hemisphere and compare the dependence to that predicted by current optimized models that assimilate in situ measurements of CO2. In the zonal averages, models are consistent with the GOSAT amplitude to within 1.4 ppm, depending on the model and latitude. We also show that the seasonal cycle of XCO2 depends on longitude especially at the mid-latitudes: the amplitude of GOSAT XCO2 doubles from western USA to East Asia at 45–50° N, which is only partially shown by the models. In general, we find that model-to-model differences can be larger than GOSAT-to-model differences. These results suggest that GOSAT/ACOS retrievals of the XCO2 seasonal cycle may be sufficiently accurate to evaluate land surface models in regions with significant discrepancies between the models.

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 10 19  W/cm 2 ), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.

The Atacama Millimeter/submillimeter Array (ALMA) Phasing Project (APP) has developed and deployed the hardware and software necessary to coherently sum the signals of individual ALMA antennas and record the aggregate sum in Very Long Baseline Interferometry (VLBI) Data Exchange Format. These beamforming capabilities allow the ALMA array to collectively function as the equivalent of a single large aperture and participate in global VLBI arrays. The inclusion of phased ALMA in current VLBI networks operating at (sub)millimeter wavelengths provides an order of magnitude improvement in sensitivity, as well as enhancements in u-v coverage and north-south angular resolution. The availability of a phased ALMA enables a wide range of new ultra-high angular resolution science applications, including the resolution of supermassive black holes on event horizon scales and studies of the launch and collimation of astrophysical jets. It also provides a high-sensitivity aperture that may be used for investigations such as pulsar searches at high frequencies. This paper provides an overview of the ALMA Phasing System design, implementation, and performance characteristics.

While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches. Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation. A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3-2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83-7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2-10.5%; RR: 1.56, 95% CI: 1.38-1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2-11.3%; RR: 1.60, 95% CI: 1.42-1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses. Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained. Dormant lung cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor (TKI) treatment. In terms of mechanism, we found that a negative regulator of ERBB signaling, MIG6/ERRFI1/RALT/Gene33, was induced by hypoxia both in vitro and in vivo . MIG6 expression prevented heterodimer formation of ERBB family RTKs, and suppressed their downstream signaling. Knockdown of MIG6 enhanced tumor cell growth under hypoxic conditions, and promoted the phosphorylation of ERK and AKT via increased EGFR-HER3 binding. Critically, sensitivity to an EGFR-TKI, as well as to irradiation under hypoxic conditions, was increased in MIG6 knockdown cells. The expression of MIG6 was partly correlated with a pS6 negative zone in patient tumors. Analyses of tumor sections from 68 patients with activating EGFR mutations showed that patients with high MIG6 expression showed significantly shorter survival after EGFR-TKI treatment than other groups. Collectively, our data suggest that dormant cancer cells with a high MIG6 expression level might be one of the causes of EGFR-TKI resistance in EGFR mutant lung cancer cells.

Background/Objectives: Epidemiologic evidence on the relationship between antioxidant vitamin intake and stroke is limited. We aimed to investigate the association between dietary intake of antioxidant vitamins and the incidence of total stroke and ischemic stroke. Subjects/Methods: The subjects were 82 044 Japanese men and women aged 45–74 years under the Japan Public Health Center-based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was done using a food frequency questionnaire. During 983 857 person-years of follow-up until the end of 2009 we documented 3541 incident total strokes and 2138 ischemic strokes. Results: Dietary intakes of α-carotene, β-carotene, α-tocopherol and vitamin C were not inversely associated with the incidence of total stroke and ischemic stroke adjustment for cardiovascular risk factors and selected lifestyle variables. When stratified by current smoking status, the inverse association between dietary vitamin C intake and incidence of total stroke observed among non-smokers but not smokers, with respective multivariable hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95% confidence interval (CI), 0.68–0.96; P -trend=0.03) among non-smokers; and 1.03 (0.84–1.25; P -trend=0.55) among smokers. As for ischemic stroke, the corresponding multivariable hazard ratios were 0.76 (0.60–0.96; P -trend=0.02) among non-smokers; and 1.00 (0.78–1.28; P -trend=0.61) among smokers. Conclusions: Dietary vitamin C intake was inversely associated with the incidence of total stroke and ischemic stroke among non-smokers.