Neutron Energy Spectrum Measurements with a Compact Liquid Scintillation Detector on EAST

A neutron detector based on EJ301 liquid scintillator has been employed at EAST to measure the neutron energy spectrum for D-D fusion plasma. The detector was carefully characterized in different quasi-monoenergetic neutron fields generated by a 4.5 MV Van de Graaff accelerator. In recent experimental campaigns, due to the low neutron yield at EAST, a new shielding device was designed and located as close as possible to the tokamak to enhance the count rate of the spectrometer. The fluence of neutrons and gamma-rays was measured with the liquid neutron spectrometer and was consistent with 3He proportional counter and NaI (Tl) gamma-ray spectrometer measurements. Plasma ion temperature values were deduced from the neutron spectrum in discharges with lower hybrid wave injection and ion cyclotron resonance heating. Scattered neutron spectra were simulated by the Monte Carlo transport Code, and they were well verified by the pulse height measurements at low energies.Comment: 19 pages,10 figures, 1 tabl

Accident prediction based on integrated design consistency with the lower number of vehicles/traffic volumes (due to health disaster/covid-19)

Purpose: Malaysia is one of the developing countries that facing high road accident in Asia. The most common accident happens is between motorcyclist and cars. A motorcyclist is 17 times more dangerous than passenger cars. Analysis shows the three main types of accidents in Malaysia is collision with passenger cars, collisions with other motorcycles and single-motorcycle accidents. Road accidents keep rising in Malaysia, because lacks of road geometric design consistency where the drivers make mistakes errors due to the road geometric features. Design/methodology/approach: The study was conducted at F0050 from km 21 until km 25. By using GPS (DG -200), the continuous speed profile data were using new analysis method to develop road design consistency profile of motorcycle and cars and determined the value of the index the integrated road design consistency (IC). Findings: The developments of consistency model are based on parameter: the bounded area between the profile and the average speed, standard deviation of speed along a segment. Hence, use ACAD software for develops consistency model’s profile. The integrated-consistency model is the impact of the speed profile on design consistency in traffic and safety evaluations. The highest areas of an accident at km 24 are justified based on the design consistency of the area and integrated design consistency model between of car and motorcycle is poor design. The study shows that crashes and fatalities are fully effected by traffic volumes but road design performances and driving behaviour. Research limitations/implications: However, the traffic volumes are relatively low at the whole country regarding to the Movement Control Order (MCO) due to the pandemic COVID-19 since March 2020. In contrast with the reduction of the volumes, number of crashes still shows relatively high. Therefore, it shows that crashes and fatalities are influenced by other factors. Geometric factors such as access point, tangent length, curve length, shoulder width and lane width are influencing for an operating speed profile for a developed of tangents and curves of motorcycle and cars. Practical implications: Result of this study can be used as references to solve accident problems in Malaysia. Paper type: This study is categorised as a case study

Loss‐of‐Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia

Background and aims: Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC. Approach and results: From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia-inducible factor-1α and fat mass and obesity-associated protein-mediated N6 -methyladenosine modification through transcriptional and posttranscriptional regulation, respectively. Analysis of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration-approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd-5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd-5 in preclinical patient-derived xenograft models of HCC. Conclusions: Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC

RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer

Objective: Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood. Design: We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models. Results: We identified a novel RNA-binding protein, RALY (also known as hnRNPCL2), that is highly associated with colorectal tumour aggressiveness. RALY acts as a key regulatory component in the Drosha complex, and promotes the post-transcriptional processing of a specific subset of miRNAs (miR-483, miR-676 and miR-877). These miRNAs systematically downregulate the expression of the metabolism-associated genes (ATP5I, ATP5G1, ATP5G3 and CYC1) and thereby reprogramme mitochondrial metabolism in the cancer cell. Analysis of The Cancer Genome Atlas (TCGA) reveals that increased levels of RALY are associated with poor prognosis in the patients with CRC expressing low levels of mitochondrion-associated genes. Mechanistically, induced processing of these miRNAs is facilitated by their N6-methyladenosine switch under reactive oxygen species (ROS) stress. Inhibition of the m6A methylation abolishes the RALY recognition of the terminal loop of the pri-miRNAs. Knockdown of RALY inhibits colorectal tumour growth and progression in vivo and in organoid models. Conclusions: Collectively, our results reveal a critical metabolism-centric role of RALY in tumour progression, which may lead to cancer therapeutics targeting RALY for treating CRC

Analysis of the dermatophyte Trichophyton rubrum expressed sequence tags

BACKGROUND: Dermatophytes are the primary causative agent of dermatophytoses, a disease that affects billions of individuals worldwide. Trichophyton rubrum is the most common of the superficial fungi. Although T. rubrum is a recognized pathogen for humans, little is known about how its transcriptional pattern is related to development of the fungus and establishment of disease. It is therefore necessary to identify genes whose expression is relevant to growth, metabolism and virulence of T. rubrum. RESULTS: We generated 10 cDNA libraries covering nearly the entire growth phase and used them to isolate 11,085 unique expressed sequence tags (ESTs), including 3,816 contigs and 7,269 singletons. Comparisons with the GenBank non-redundant (NR) protein database revealed putative functions or matched homologs from other organisms for 7,764 (70%) of the ESTs. The remaining 3,321 (30%) of ESTs were only weakly similar or not similar to known sequences, suggesting that these ESTs represent novel genes. CONCLUSION: The present data provide a comprehensive view of fungal physiological processes including metabolism, sexual and asexual growth cycles, signal transduction and pathogenic mechanisms

Identifying a few foot-and-mouth disease virus signature nucleotide strings for computational genotyping

<p>Abstract</p> <p>Background</p> <p>Serotypes of the Foot-and-Mouth disease viruses (FMDVs) were generally determined by biological experiments. The computational genotyping is not well studied even with the availability of whole viral genomes, due to uneven evolution among genes as well as frequent genetic recombination. Naively using sequence comparison for genotyping is only able to achieve a limited extent of success.</p> <p>Results</p> <p>We used 129 FMDV strains with known serotype as training strains to select as many as 140 most serotype-specific nucleotide strings. We then constructed a linear-kernel Support Vector Machine classifier using these 140 strings. Under the leave-one-out cross validation scheme, this classifier was able to assign correct serotype to 127 of these 129 strains, achieving 98.45% accuracy. It also assigned serotype correctly to an independent test set of 83 other FMDV strains downloaded separately from NCBI GenBank.</p> <p>Conclusion</p> <p>Computational genotyping is much faster and much cheaper than the wet-lab based biological experiments, upon the availability of the detailed molecular sequences. The high accuracy of our proposed method suggests the potential of utilizing a few signature nucleotide strings instead of whole genomes to determine the serotypes of novel FMDV strains.</p

The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

<p>Abstract</p> <p>Background</p> <p>Conidia are considered to be the primary cause of infections by <it>Trichophyton rubrum</it>.</p> <p>Results</p> <p>We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the <it>Saccharomyces </it>Genome Database (SGD). A number of homologues of <it>Saccharomyces cerevisiae </it>genes related to signalling pathways and some important cellular processes were found to be involved in <it>T. rubrum </it>germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions.</p> <p>Conclusion</p> <p>Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of <it>T. rubrum</it>.</p