High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

ADAP is a possible negative regulator of glucosinolate biosynthesis in Arabidopsis thaliana based on clustering and gene expression analyses.

Glucosinolates (GSLs) are plant secondary metabolites consisting of sulfur and nitrogen, commonly found in Brassicaceae crops, such as Arabidopsis thaliana. These compounds are known for their roles in plant defense mechanisms against pests and pathogens. 'Guilt-by-association' (GBA) approach predicts genes encoding proteins with similar function tend to share gene expression pattern generated from high throughput sequencing data. Recent studies have successfully identified GSL genes using GBA approach, followed by targeted verification of gene expression and metabolite data. Therefore, a GSL co-expression network was constructed using known GSL genes obtained from our in-house database, SuCComBase. DPClusO was used to identify subnetworks of the GSL co-expression network followed by Fisher's exact test leading to the discovery of a potential gene that encodes the ARIA-interacting double AP2-domain protein (ADAP) transcription factor (TF). Further functional analysis was performed using an effective gene silencing system known as CRES-T. By applying CRES-T, ADAP TF gene was fused to a plant-specific EAR-motif repressor domain (SRDX), which suppresses the expression of ADAP target genes. In this study, ADAP was proposed as a negative regulator in aliphatic GSL biosynthesis due to the over-expression of downstream aliphatic GSL genes (UGT74C1 and IPMI1) in ADAP-SRDX line. The significant over-expression of ADAP gene in the ADAP-SRDX line also suggests the behavior of the TF that negatively affects the expression of UGT74C1 and IPMI1 via a feedback mechanism in A. thaliana.

Modulation of Toll-like receptor-mediated innate immunity in bovine intestinal epithelial cells by lactic acid bacteria isolated from feedlot cattle.

The ability of lactobacilli isolated from feedlot cattle environment to differentially modulate the innate immune response triggered by Toll-like receptors (TLRs) activation in bovine intestinal epithelial (BIE) cells was evaluated. BIE cells were stimulated with Lactobacillus mucosae CRL2069, Lactobacillus acidophilus CRL2074, Lactobacillus fermentum CRL2085 or Lactobacillus rhamnosus CRL2084 and challenged with heat-stable pathogen associated molecular patterns (PAMPs) from enterotoxigenic Escherichia coli (ETEC) to induce the activation of TLR4 or with polyinosinic:polycytidylic acid (poly(I:C)) to activate TLR3. Type I interferons, cytokines, chemokines and negative regulators of TLR signalling were studied by RT-PCR. L. mucosae CRL2069 significantly reduced the expression of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 in BIE cells in the context of TLR3 activation. L. mucosae CRL2069 also reduced the expression of tumour necrosis factor-α, IL-ß, MCP-1, and IL-8 in heat-stable ETEC PAMPs-challenged BIE cells. In addition, reduced expressions of IL-6, MCP-1, and IL-8 were found in BIE cells stimulated with L. rhamnosus CRL2084, although its effect was significantly lower than that observed for the CRL2069 strain. The reduced levels of pro-inflammatory factors in BIE cells induced by the CRL2069 and CRL2085 strains was related to their ability of increasing the expression of TLR negative regulators. L. mucosae CRL2069 significantly improved the expression of A20-binding inhibitor of NFκ-B activation 3 (ABIN-3), interleukin-1 receptor-associated kinase M (IRAK-M) and mitogen-activated protein kinase 1 (MKP-1) while L. rhamnosus CRL2084 augmented ABIN-3 expression in BIE cells. The results of this work suggest that among the studied strains, L. mucosae CRL2069 was able to regulate TLR3-mediated innate immune response and showed a remarkable capacity to modulate TLR4-mediated inflammation in BIE cells. The CRL2069 strain induce the up-regulation of three TLR negative regulators that would influence nuclear factor kB and mitogen-activated protein kinases signalling pathways while reducing the expression of pro-inflammatory cytokines and chemokines. Therefore, L. mucosae CRL2069 is an interesting immunobiotic candidate for the protection of the bovine host against TLR-mediated intestinal inflammatory damage.

Efficacy of pegfilgrastim administration in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil.

Chemotherapy is among the standard treatments for esophageal cancer. The docetaxel, 5-fluorouracil, and cisplatin (DCF) protocol yields a better response rate than 5-fluorouracil plus cisplatin. However, the incidence of side effects, such as febrile neutropenia and hematologic toxicity, is also significantly high with the DCF protocol. The granulocyte colony-stimulating factor and pegfilgrastim are prophylactically administered to prevent febrile neutropenia. This retrospective study evaluated the efficacy and safety of pegfilgrastim in patients receiving DCF therapy. Of the 65 patients who were administered DCF therapy in our hospital from 2011 through 2016, 21 received pegfilgrastim 24 hours or more after the end of chemotherapy. The protocol comprised 70 mg/m2 each of docetaxel and cisplatin on day 1 and 700 mg/m2 5-fluorouracil on days 1 to 5 via intravenous injection in a 3-week cycle. The primary endpoint was the rate of grade 3-4 neutropenia and febrile neutropenia. The mean patient age was 66.4 years. The incidence of grade 3 and 4 neutropenia was 14.2 % and 11.4 %, respectively, in the pegfilgrastim group and 31.9 % and 37.8 %, respectively, in the non-pegfilgrastim group. The incidence of febrile neutropenia in the pegfilgrastim group and non-pegfilgrastim group was 11.4 % and 40.3 %, respectively. Statistical analysis showed that the incidence of neutropenia and febrile neutropenia was significantly different (p<0.05) between the two groups. Pegfilgrastim prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer who are treated according to the DCF protocol.

Size-dependent uptake of electrically neutral amphipathic polymeric nanoparticles by cell-sized liposomes and an insight into their internalization mechanism in living cells.

Size-dependent uptake behaviors of electrically neutral amphipathic polymeric nanoparticles in cell-sized liposomes and living cells were investigated. Kinetic analyses and the particle size distribution suggested a size-dependent penetration mechanism (size threshold: 3.1 nm). The definite size-dependent uptake provides a new insight into the interactions between nanomaterials and living cells.

Measurement of urinary concentrations of the mycotoxins zearalenone and sterigmatocystin as biomarkers of exposure in mares.

Mycotoxins may affect animal health, including reproduction. Little is known about the clinical relevance of exposure of horses to contaminated feed. This study aimed at (i) monitoring the levels of the mycotoxins zearalenone (ZEN), with its metabolites α- and ß-zearalenol (α- and ß-ZOL), and sterigmatocystin (STC) in urine samples from thoroughbred mares in Japan and (ii) relating these findings to the potential effects on reproductive efficacy of breeding mares. Sixty-three urine samples of breeding mares from 59 breeding farms were used. Urine samples and reproductive records were collected from each mare when it was presented to the stallion station. Urinary concentrations of ZEN, α- and ß-ZOL, and STC were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). ZEN, α- and ß-ZOL were measurable in the urine of all examined mares, indicating the prevalence of ZEN in equine feeds. In seven of the 63 samples, STC was also detected at levels ranging from 1.3 to 18.0 pg/mg creatinine. No significant correlation between the concentrations of mycotoxins and pregnancy status was observed. In conclusion, measurement of mycotoxins in urine samples is a useful non-invasive method for monitoring the systemic exposure of mares to multiple mycotoxins.

Availability of immunocytochemistry using cocktail antibody targeting p63/cytokeratin14 for the differential diagnosis of fibroadenoma and ductal carcinoma in situ in fine needle aspiration cytology of the breast.

OBJECTIVE: The differential diagnosis of fibroadenoma (FA) and ductal carcinoma in situ (DCIS) has been problematic in fine needle aspiration biopsy (FNAC) because it has been difficult to differentiate between the "large epithelial clusters" associated with FA and those associated with DCIS. The purpose of this study was to prospectively validate the usefulness of immunocytochemical staining using cocktail antibody targeting p63/CK14 in the differential diagnosis of FA and DCIS. MATERIALS AND METHODS: Twenty patients diagnosed as having an uncertain malignant potential (indeterminate) for breast cancer on the basis of a FNAC finding were selected randomly: ten patients with FA and ten with DCIS. The cover glass on a specimen stained with the Papanicolaou stain on a glass slide was peeled off, and the specimen was restained by immunocytochemical staining of cocktail antibody targeting p63 and CK14. RESULTS: Six of the twenty patients were CK14-immunopositive: FA, 6; DCIS, 0. The remaining patients were CK14-immunonegative: FA, 4; DCIS, 10. The number of CK14-immunopositive DCIS patients was significantly different from that of FA patients (P=.0054). Eight out of the twenty patients were p63-immunopositive: FA, 8; DCIS, 0. The remaining patients were p63-immunonegative: FA, 2; DCIS, 10. The number of p63-immunopositive DCIS patients was significantly different from that of FA patients (P=.0004). CONCLUSIONS: Immunocytochemical staining using cocktail antibody targeting p63/CK14 was useful for the differential diagnosis of FA and DCIS in FNAC of the breast.

Chlorogenic acid supplementation during in vitro maturation improves maturation, fertilization and developmental competence of porcine oocytes.

Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid, and a phytochemical found in many fruits and beverages that acts as an antioxidant. The present study investigated the effects of CGA supplementation during in vitro maturation (IVM), on in vitro development of porcine oocytes, to improve the porcine in vitro production (IVP) system. Oocytes were matured either without (control) or with CGA (10, 50, 100 and 200 µM). Subsequently, the matured oocytes were fertilized and cultured in vitro for 7 day. The rates of maturation, fertilization and blastocyst formation of oocytes matured with 50 µM CGA were significantly (p < .05) higher than those of the control oocytes. Hydrogen peroxide (H2 O2 ) is one of the reactive oxygen species and induces DNA damage in porcine oocytes. When oocytes were matured with 1 mM H2 O2 to assess the protective effect of CGA, 50 µM CGA supplementation improved the maturation rate and the proportion of DNA-fragmented nuclei in oocytes compared with control oocytes matured without CGA. Moreover, when oocytes were matured with either 50 µM CGA (control) or caffeic acid (10, 50 and 100 µM), the rates of maturation, fertilization and the blastocyst formation of oocytes matured with 50 µM CGA were similar to those of oocytes matured with 10 and 50 µM caffeic acid. Our results suggest that CGA has comparable effects to caffeic acid, and IVM with 50 µM CGA is particularly beneficial to IVP of porcine embryos and protects oocytes from DNA damage induced by oxidative stress. Supplementation of CGA to the maturation medium has a potential to improve porcine IVP system.

Autophagy is required for cell survival under L-asparaginase-induced metabolic stress in acute lymphoblastic leukemia cells.

L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy. The autophagy is involved in reducing reactive oxygen species (ROS) level by eliminating injured mitochondria. Inhibition of autophagy enhances L-asparaginase-induced cytotoxicity and overcomes the acquired resistance to L-asparaginase in ALL cells. The ROS-p53-positive feedback loop is an essential mechanism of this synergistic cytotoxicity. Thus, our findings provide the rationale for the future development of combined treatment of L-asparaginase and anti-autophagy drug in ALL patients.

Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis.

Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.

How Zoophilic Japanese Encephalitis Vector Mosquitoes Feed on Humans.

Japanese encephalitis virus (JEV) is the most frequent cause of mosquito-borne encephalitis in Asian countries. Several culicine species are potential vectors. The primary JEV vectors feed mainly on cows (a dead-end host for JEV), pigs (an amplifying host), and, occasionally, humans (a dead-end host). It is essential to determine blood-feeding patterns to understand the transmission cycle of the disease. Here we review blood-feeding characteristics of the primary JEV vectors Culex tritaeniorhynchus, Culex vishnui, and Culex gelidus based on experimental works and field surveys conducted in Asian countries. Several studies showed that these JEV vectors have an innate preference for cows; however, the former two species often showed higher rates of blood-feeding on pigs than on cows, probably because pigs are more abundant than cows. On the other hand, the latter species Cx. gelidus fed mostly on cows. Thus, the first two species showed higher plasticity to compromise host availability than the last. By reviewing the available articles and based on our relevant studies, it may be deduced that JEV transmission cannot be reduced by zooprophylaxis. We emphasize the need of keeping cows away from the human residences to dampen the human risk of JEV. These primary JEV vector species exhibit pre-biting resting. The adaptive significance of this behavior remains to be unexplored, but it may have a function to avoid defensive attack of host animals. Application of recent quantitative analysis of gene expression in this phase may enable us to come up with novel vector control strategies.

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.

In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

Bone-peg grafting for osteochondritis dissecans of the humeral capitellum.

PURPOSE: To review the outcome of bone-peg grafting for osteochondritis dissecans (OCD) grade II lesions of the humeral capitellum. METHODS: Records of 10 male adolescent baseball players aged 10 to 15 (mean, 12.3) years who underwent bone-peg grafting for OCD grade II lesions of the humeral capitellum of the dominant arm were reviewed. The mean time from symptom onset to presentation was 11 (range, 1-36) months. The mean duration of conservative treatment was 5 (range, 1-25) months. The mean time from symptom onset to surgery was 17 (range, 3-39) months; it was >6 months in 6 patients. The mean size of the lesions was 13x14 mm. Patients were assessed for elbow pain, range of elbow and forearm motion, Timmerman- Andrews elbow score, return to sports activity level, and radiographic evidence of healing, osteoarthritic changes, and radial head hypertrophy. RESULTS: The mean follow-up period was 25 (range, 10-52) months. Postoperatively, elbow pain was absent in 6, mild in 2, and moderate in 2 patients. The mean range of elbow motion changed from 136º to 139° (p=0.80). The mean Timmerman-Andrews elbow score improved from 163 to 189 (p=0.014); it was excellent in 7, good in 2, and fair in one patient. The mean extent of lesion healing was 71% (range, 33-100%). Five patients achieved complete healing after a mean of 5.2 (range, 5-6) months and returned to sports at a competitive level. The other 5 achieved partial healing of 33 to 56% (mean, 41%) that occurred laterally but not medially. Two of them returned to sports at a competitive level: one changed the throwing side and another had radial head hypertrophy. The remaining 3 underwent arthroscopic debridement of the unhealed lesion at 5, 10, and 15 months. One patient developed secondary osteoarthritis and further underwent costal osteochondral autografting 10 months later. None of the 5 patients with partial healing versus 4 of the 5 patients with complete healing underwent surgery within 6 months of symptom onset. All 3 patients with a dot at the interface versus 2 of the 6 patients with a line at the interface between the fragment and the lesion on MRI had complete healing. CONCLUSION: Bone-peg grafting is a viable option for OCD grade II lesions of the humeral capitellum when performed within 6 months of symptom onset and when the interface between the fragment and the lesion appears as a dot (rather than a line) on MRI.

Hippocampal harms, protection and recovery following regular cannabis use.

Shifting policies towards legalisation of cannabis for therapeutic and recreational use raise significant ethical issues for health-care providers seeking evidence-based recommendations. We investigated whether heavy cannabis use is associated with persistent harms to the hippocampus, if exposure to cannabidiol offers protection, and whether recovery occurs with abstinence. To do this, we assessed 111 participants: 74 long-term regular cannabis users (with an average of 15.4 years of use) and 37 non-user healthy controls. Cannabis users included subgroups of participants who were either exposed to Δ9-tetrahydrocannabinol (THC) but not to cannabidiol (CBD) or exposed to both, and former users with sustained abstinence. Participants underwent magnetic resonance imaging from which three measures of hippocampal integrity were assessed: (i) volume; (ii) fractional anisotropy; and (iii) N-acetylaspartate (NAA). Three curve-fitting models across the entire sample were tested for each measure to examine whether cannabis-related hippocampal harms are persistent, can be minimised (protected) by exposure to CBD or recovered through long-term abstinence. These analyses supported a protection and recovery model for hippocampal volume (P=0.003) and NAA (P=0.001). Further pairwise analyses showed that cannabis users had smaller hippocampal volumes relative to controls. Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. Users exposed to CBD and former users did not differ from controls on any measure. Ongoing cannabis use is associated with harms to brain health, underpinned by chronic exposure to THC. However, such harms are minimised by CBD, and can be recovered with extended periods of abstinence.

Melatonin Supplementation During In Vitro Maturation and Development Supports the Development of Porcine Embryos.

Melatonin has been reported to improve the in vitro development of embryos in some species. This study was conducted to investigate the effect of melatonin supplementation during in vitro maturation (IVM) and development culture on the development and quality of porcine embryos. In the first experiment, when the in vitro fertilized embryos were cultured with different concentrations of melatonin (0, 10, 25 and 50 ng/ml) for 8 days, the blastocyst formation rate of embryos cultured with 25 ng/ml melatonin (10.7%) was significantly increased (p < 0.05) compared to the control embryos cultured without melatonin (4.2%). The proportion of DNA-fragmented nuclei in blastocysts derived from embryos cultured with 50 ng/ml melatonin was significantly lower (p < 0.05) than that of embryos cultured without melatonin (2.1% vs 7.2%). In the second experiment, when oocytes were cultured in the maturation medium supplemented with different concentrations of melatonin (0, 10, 25 and 50 ng/ml), fertilized and then cultured with 25 ng/ml melatonin for 8 days, there were no significant differences in the rates of cleavage and blastocyst formation among the groups. However, the proportions (2.7-5.4%) of DNA-fragmented nuclei in blastocysts derived from oocytes matured with melatonin were significantly decreased (p < 0.05) compared to those (8.9%) from oocytes matured without melatonin, irrespective of the concentration of melatonin. Our results suggest that supplementation of the culture media with melatonin (25 ng/ml) during IVM and development has beneficial effects on the developmental competence and quality of porcine embryos.

Effects of Dietary Contamination by Zearalenone and Its Metabolites on Serum Anti-Müllerian Hormone: Impact on the Reproductive Performance of Breeding Cows.

We investigated the effects of in vivo exposure to low zearalenone levels on the anti-Müllerian hormone endocrine levels and the reproductive performance of cattle. Urine and blood samples and reproductive records were collected from two Japanese Black breeding female cattle herds with dietary zearalenone contamination below the threshold levels (<1 ppm) at 30 days after calving. Urinary zearalenone, α-zearalenol and ß-zearalenol concentrations were measured by chromatography-tandem mass spectrometry, and serum anti-Müllerian hormone concentrations were determined along with serum biochemical parameters. Urinary concentrations of α-zearalenol were significantly higher (p < 0.05) in cattle in Herd 1 than in cattle in Herd 2, reflecting the different amounts of zearalenone in the diet of the two herds. Although the number of 5-mm and 10-mm follicles of the herds and their fertility after artificial insemination were similar, the serum anti-Müllerian hormone concentrations in herds 1 and 2 were 438.9 ± 48.6 pg/ml and 618.9 ± 80.0 pg/ml, respectively, with a trend towards a significant difference (p = 0.053), which may indicate differences in the antral follicle populations between herds. Thus, zearalenone intake from dietary feed, even when below the threshold zearalenone contamination level permitted in Japan, may affect the ovarian antral follicle populations, but not the fertility, of post-partum cows.

Direct heating of a laser-imploded core by ultraintense laser-driven ions.

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

Differences in risk factors for the onset of albuminuria and decrease in glomerular filtration rate in people with Type 2 diabetes mellitus: implications for the pathogenesis of diabetic kidney disease.

AIMS: To determine differences in predictors of albuminuria and decreased estimated GFR in Japanese people with Type 2 diabetes mellitus without chronic kidney disease. METHODS: This single-centre observational cohort study involved 1802 Japanese people with Type 2 diabetes with normoalbuminuria and estimated GFR ≥ 60 ml/min/1.73 m(2) (740 women; mean ± sd age 58 ± 12 years). Two separate outcomes were evaluated: onset of albuminuria ( ≥ 30 mg/g creatinine, albuminuria cohort; n = 1655) and decrease in estimated GFR ( < 60 ml/min/1.73 m(2) ; estimated GFR cohort; n = 1777). A Cox proportional hazards model was used to identify significant predictors for each outcome. RESULTS: During a median follow-up period of 6.9 years for the albuminuria cohort and 8.0 years for the estimated GFR cohort, 181 and 316 individuals reached the respective outcome. The 5-year cumulative incidence of albuminuria was 8.3%, and that of decreased estimated GFR was 10.4%. In the multivariate Cox model, greater urinary albumin-to-creatinine ratio, presence of diabetic retinopathy and higher HbA1c levels were associated with both outcomes. Unique risk factors for onset of albuminuria were male gender and higher uric acid levels; those for decreased estimated GFR were older age, greater systolic blood pressure, and lower baseline estimated GFR and HDL cholesterol levels. CONCLUSIONS: Identification of both common and distinct predictive factors for onset of albuminuria and decreased estimated GFR support the hypothesis that both common and distinct pathophysiological mechanisms are involved in the development of these two manifestations of chronic kidney disease in diabetes.

Host-plant dependent population genetics of the invading weevil Hypera postica.

Population genetics of invading pests can be informative for understanding their ecology. In this study, we investigated population genetics of the invasive alfalfa weevil Hypera postica in Fukuoka Prefecture, Japan. We analyzed mitochondrial tRNALeu-COII, nuclear EF-1α gene fragments, and Wolbachia infection in relation to three leguminous host plants: Vicia angustifolia, Vicia villosa, and a new host Astragalus sinicus cultivated as a honey source and green manure crop. A parsimony network generated from mitochondrial gene sequences uncovered two major haplotypic groups, Western and Egyptian. In contrast to reported Wolbachia infection of the Western strain in the United States, none of our analyzed individuals were infected. The absence of Wolbachia may contribute to the stable coexistence of mitochondrial strains through inter-strain reproductive compatibility. Hypera postica genetic variants for the mitochondrial and nuclear genes were associated neither with host plant species nor with two geographic regions (Hisayama and Kama) within Fukuoka. Mitochondrial haplogroups were incongruent with nuclear genetic variants. Genetic diversity at the nuclear locus was the highest for the populations feeding on V. angustifolia. The nuclear data for A. sinicus-feeding populations indicated past sudden population growth and extended Bayesian skyline plot analysis based on the mitochondrial and nuclear data showed that the growth of A. sinicus-feeding population took place within the past 1000 years. These results suggest a shorter history of A. sinicus as a host plant compared with V. angustifolia and a recent rapid growth of H. postica population using the new host A. sinicus.