Abstract
Small integration timesteps for a small fraction of the particles become a bottleneck for future galaxy simulations with a higher resolution, especially for massively parallel computing. As ...we increase the resolution, we must resolve physics on a smaller timescale while the total integration time is fixed as the universe age. The small timesteps for a small fraction of the particles worsen the scalability. More specifically, the regions affected by supernovae (SN) have the smallest timestep in the whole galaxy. Using a Hamiltonian splitting method, we calculate the SN regions with small timesteps using a few thousand CPU cores but integrate the entire galaxy using a shared timestep. For this approach, we need to pick up particles in regions, which will be affected by SN (the target particles) by the next global step (the integration timestep for the entire galaxy) in advance. In this work, we developed the deep learning model to predict the region where the shell due to a supernova explosion expands during one global step. In addition, we identify the target particles using image processing of the density distribution predicted by our deep learning model. Our algorithm could identify the target particles better than the method based on the analytical solution. This particle selection method using deep learning and the Hamiltonian splitting method will improve the performance of galaxy simulations with extremely high resolution.
Succinate is a building block compound that the U.S. Department of Energy (DOE) has declared as important in biorefineries, and it is widely used as a commodity chemical. Here, we identified the two ...genes increasing succinate production of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Succinate was excreted under dark, anaerobic conditions, and its production level increased by knocking out ackA, which encodes an acetate kinase, and by overexpressing sigE, which encodes an RNA polymerase sigma factor. Glycogen catabolism and organic acid biosynthesis were enhanced in the mutant lacking ackA and overexpressing sigE, leading to an increase in succinate production reaching five times of the wild-type levels. Our genetic and metabolomic analyses thus demonstrated the effect of genetic manipulation of a metabolic enzyme and a transcriptional regulator on succinate excretion from this cyanobacterium with the data based on metabolomic technique.
Light-based methods are being further developed to meet the growing demands for food in the agricultural industry. Optical imaging is a rapid, non-destructive, and accurate technology that can ...produce consistent measurements of product quality compared to conventional techniques. In this research, a novel approach for seed quality prediction is presented. In the proposed approach two advanced optical imaging techniques based on chlorophyll fluorescence and chemometric-based multispectral imaging were employed. The chemometrics encompassed principal component analysis (PCA) and quadratic discrimination analysis (QDA). Among plants that are relevant as both crops and scientific models, tomato, and carrot were selected for the experiment. We compared the optical imaging techniques to the traditional analytical methods used for quality characterization of commercial seedlots. Results showed that chlorophyll fluorescence-based technology is feasible to discriminate cultivars and to identify seedlots with lower physiological potential. The exploratory analysis of multispectral imaging data using a non-supervised approach (two-component PCA) allowed the characterization of differences between carrot cultivars, but not for tomato cultivars. A Random Forest (RF) classifier based on Gini importance was applied to multispectral data and it revealed the most meaningful bandwidths from 19 wavelengths for seed quality characterization. In order to validate the RF model, we selected the five most important wavelengths to be applied in a QDA-based model, and the model reached high accuracy to classify lots with high-and low-vigor seeds, with a correct classification from 86 to 95% in tomato and from 88 to 97% in carrot for validation set. Further analysis showed that low quality seeds resulted in seedlings with altered photosynthetic capacity and chlorophyll content. In conclusion, both chlorophyll fluorescence and chemometrics-based multispectral imaging can be applied as reliable proxies of the physiological potential in tomato and carrot seeds. From the practical point of view, such techniques/methodologies can be potentially used for screening low quality seeds in food and agricultural industries.
Although neocortical GABAergic (γ-aminobutyric acidergic) interneurons have been the focus of intense study, especially in the rat, a consensus view of the functional diversity and organization of ...inhibitory cortical neurons has not yet been achieved. To better analyze GABAergic neurons in the rat, we used a bacterial artificial chromosome (BAC) construct and established 2 lines of transgenic rats that coexpress Venus, a yellow fluorescent protein, with the vesicular GABA transporter. The brain GABA content from both transgenic lines was similar to the level found in wild-type rats. In the frontal cortex, Venus was expressed in >95% of GABAergic neurons, most of which also expressed at least one of 6 biochemical markers, including α-actitin-2, which preferentially labeled late-spiking neurogliaform cells. Taking advantage of the fact that Venus expression allows for targeted recording from all classes of nonpyramidal cells, irrespective of their somatic morphologies, we demonstrated that fast-spiking neurons, which were heterogeneous in somatic size as well as vertical dendritic projection, had relatively uniform horizontal dimensions, suggesting a cell type–specific columnar input territory. Our data demonstrate the benefits of VGAT-Venus rats for investigating GABAergic circuits, as well as the feasibility of using BAC technology in rats to label subsets of specific, genetically defined neurons.
The identification of chemicals that modulate plant development and adaptive responses to stresses has attracted increasing attention for agricultural applications. Recent basic studies have ...identified functional amino acids that are essential for plant organogenesis, indicating that amino acids can regulate plant growth. In this study, we newly identified 2-aminopimelic acid (2APA), a nonproteinogenic amino acid, as a novel bioactive compound involved in root morphogenesis. This biological effect was confirmed in several plant species. Our phenotypic analysis revealed that the bioactive 2APA is an l-form stereoisomer. Overall, our study identified a promising root growth regulator and provided insight into the intricate metabolism related to root morphology.
We describe an outbreak of Bacillus cereus bacteremia that occurred at Jichi Medical University Hospital in 2006. This study aimed to identify the source of this outbreak and to implement appropriate ...control measures. We reviewed the charts of patients with blood cultures positive for B. cereus, and investigated B. cereus contamination within the hospital environment. Genetic relationships among B. cereus isolates were analyzed. Eleven patients developed B. cereus bacteremia between January and August 2006. The hospital linens and the washing machine were highly contaminated with B. cereus, which was also isolated from the intravenous fluid. All of the contaminated linens were autoclaved, the washing machine was cleaned with a detergent, and hand hygiene was promoted among the hospital staff. The number of patients per month that developed new B. cereus bacteremia rapidly decreased after implementing these measures. The source of this outbreak was B. cereus contamination of hospital linens, and B. cereus was transmitted from the linens to patients via catheter infection. Our findings demonstrated that bacterial contamination of hospital linens can cause nosocomial bacteremia. Thus, blood cultures that are positive for B. cereus should not be regarded as false positives in the clinical setting.
PREMISE OF THE STUDY:
Autopolyploidy, or whole‐genome duplication, is a recurrent phenomenon in plant evolution. Its existence can be inferred from the presence of massive levels of genetic ...redundancy revealed by comparative plant phylogenomics. Whole‐genome duplication is theoretically associated with evolutionary novelties such as the development of new metabolic reactions and therefore contributes to the evolution of new plant metabolic profiles. However, very little is yet known about the impact of autopolyploidy on the metabolism of recently formed autopolyploids. This study provides a better understanding of the relevance of this evolutionary process.
METHODS:
In this study, we compared the metabolic profiles of wild diploids, wild autotetraploids, and artificial autotetraploids of Arabidopsis thaliana using targeted ultra‐high performance liquid chromatography‐triple quadrupole‐ mass spectrometry (UPLC‐QqQ‐MS) metabolomics.
KEY RESULTS:
We found that wild and artificial A. thaliana autotetraploids display different metabolic profiles. Furthermore, wild autotetraploids display unique metabolic profiles associated with their geographic origin.
CONCLUSIONS:
Autopolyploidy might help plants adapt to challenging environmental conditions by allowing the evolution of novel metabolic profiles not present in the parental diploids. We elaborate on the causes and consequences leading to these distinct profiles.
Alpha-satellite DNA (AS) is a main DNA component of primate centromeres, consisting of tandemly repeated units of ~170 bp. The AS of humans contains sequences organized into higher-order repeat (HOR) ...structures, in which a block of multiple repeat units forms a larger repeat unit and the larger units are repeated tandemly. The presence of HOR in AS is widely thought to be unique to hominids (family Hominidae; humans and great apes). Recently, we have identified an HOR-containing AS in the siamang, which is a small ape species belonging to the genus Symphalangus in the family Hylobatidae. This result supports the view that HOR in AS is an attribute of hominoids (superfamily Hominoidea) rather than hominids. A single example is, however, not sufficient for discussion of the evolutionary origin of HOR-containing AS. In the present study, we developed an efficient method for detecting signs of large-scale HOR and demonstrated HOR of AS in all the three other genera. Thus, AS organized into HOR occurs widely in hominoids. Our results indicate that (i) HOR-containing AS was present in the last common ancestor of hominoids or (ii) HOR-containing AS emerged independently in most or all basal branches of hominoids. We have also confirmed HOR occurrence in centromeric AS in the Hylobatidae family, which remained unclear in our previous study because of the existence of AS in subtelomeric regions, in addition to centromeres, of siamang chromosomes.
The gap between Japan and both the United States (US) and the European Union (EU) with regard to access to new drugs is becoming a major issue in Japan. We analyzed the time lags involved in new drug ...application (NDA) and biological license application submissions in Japan, the US, and the EU in order to identify the causes of delayed access. The time lag related to submission of applications (“submission lag”) was longer for in‐licensed products and for non‐Japanese companies. Factors related to costs of clinical studies and potential volumes of sales were not associated with the submission lag. A bridging strategy (extrapolative use of foreign clinical data in the clinical data package based on International Conference on Harmonisation guideline E5) seemed to reduce submission lag, but the association between the two diminished when the cause‐and‐effect relationship was specifically investigated. These results suggest that multinational companies are likely to place more emphasis on the choice of development strategies that successfully lead to their goal rather than on direct costs and expected sales when deciding to introduce their pharmaceutical products in Japan. Our findings indicate that the clinical development guidances that helps pharmaceutical companies decide on investment and strategies are also the key to narrowing the gap in access to new drugs.
Clinical Pharmacology & Therapeutics (2010) 87 2, 212–218. doi:10.1038/clpt.2009.215
Contents
The regulation of granulosa cell proliferation is complex, and it is essential for normal follicular development in mammals. The aim of this study was to examine the expression of cyclins ...and their inhibitors in the granulosa cells of follicles at different developmental stages. Follicles were classified into three groups: oestrogen‐inactive dominant follicles (EIDs), oestrogen‐active dominant follicles (EADs) and pre‐ovulatory follicles (POs). The expression of CCND2 (cyclin D2) mRNA was significantly higher in granulosa cells from EADs and POs than in those from EIDs. The expression of CCND3 (cyclin D3) mRNA was significantly higher in granulosa cells from EADs than in those from other follicles. CCND1 (cyclin D1), CCNE1 (cyclin E1) and CCNE2 (cyclin E2) mRNA expression did not differ among the different follicular stages. The expression of CDKN1A (p21cip1) and CDKN1B (p27kip1) mRNA was significantly higher in granulosa cells from EIDs and POs, respectively, than in those from other follicles. Expression of CDKN2D (p19INK4d) mRNA did not differ among the different follicular stages. Taken together, our study suggested that cyclins and their inhibitors are associated with granulosa cell proliferation at specific follicular developmental stages.
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