Measuring fine molecular structures with luminescence signal from an alternating current scanning tunneling microscope

In scanning tunneling microscopy induced luminescence (STML), the photon counting is measured to reflect the single-molecule properties, e.g., the first molecular excited state. The energy of the first excited state is typically determined by a rising position of the photon counting as a function of the bias voltage between the tip and the substrate. It remains a challenge to determine the precise rise position of the current due to the possible experimental noise. In this work, we propose an alternating current version of STML to resolve the fine structures in the photon counting measurement. The measured photon counting and the current at the long-time limit show a sinusoidal oscillation. The zero-frequency component of the current shows knee points at the precise voltage as the fraction of the detuning between the molecular gap and the DC component of bias voltage. We propose to measure the energy level with discontinuity of the first derivative of such zero-frequency component. The current method will extend the application of STML in terms of measuring molecular properties

ChromSorter PC: A database of chromosomal regions associated with human prostate cancer

BACKGROUND: Our increasing use of genetic and genomic strategies to understand human prostate cancer means that we need access to simplified and integrated information present in the associated biomedical literature. In particular, microarray gene expression studies and associated genetic mapping studies in prostate cancer would benefit from a generalized understanding of the prior work associated with this disease. This would allow us to focus subsequent laboratory studies to genomic regions already related to prostate cancer by other scientific methods. We have developed a database of prostate cancer related chromosomal information from the existing biomedical literature. The input material was based on a broad literature search with subsequent hand annotation of information relevant to prostate cancer. DESCRIPTION: The database was then analyzed for identifiable trends in the whole scale literature. We have used this database, named ChromSorter PC, to present graphical summaries of chromosomal regions associated with prostate cancer broken down by age, ethnicity and experimental method. In addition we have placed the database information on the human genome using the Generic Genome Browser tool that allows the visualization of the data with respect to user generated datasets. CONCLUSIONS: We have used this database as an additional dataset for the filtering of genes identified through genetics and genomics studies as warranting follow-up validation studies. We would like to make this dataset publicly available for use by other groups. Using the Genome Browser allows for the graphical analysis of the associated data . Additional material from the database can be obtained by contacting the authors ([email protected])

Study on damage mechanism and treatment of water sprayed roof in Jurassic stratum roadway

The roof of the Jurassic main coal seam in western China generally contained low level weak rich water layer, which led to the long-term watering of the roof of the coal roadway especially the roof anchor cable hole and the reduction of the roof surrounding rock strength and the roof support effect, and affected the safety of the coal roadway roof. In order to study the damage mechanism and control measures of the water sprayed roof, the No.414106 auxiliary transportation water spraying area of Yangjiacun Coal Mine of Shuangxin Mining in Inner Mongolia was taken as the research object. Through field investigation and roof drilling sampling, it could be seen that there were obvious water conducting cracks in the area 4m above the roof of the roadway in the synclinal area. The water flowing from the anchor cable hole was in a linear water spraying state. The roof surrounding rock had a large degree of deflection, and some anchor cable anchorage sections were separated from the surrounding rock. The mineral composition analysis and water physical test showed that the clay minerals in the roof sandy mudstone contain up to 73% kaolinite, and the softening coefficient is 0.162, which had obvious water softening characteristics. At the initial stage, the roof of the coal roadway in the water spraying area was mainly destroyed by hydrostatic pressure, and the water softening property reduced the mechanical properties of the fracture structural plane, which led to the expansion of the size of the surrounding rock fractures in shear under the action of hydrostatic pressure. In the later stage, the roof surrounding rock was mainly destroyed by hydrodynamic pressure, which was mainly manifested in the deformation and expansion of fracture structural plane, displacement of fracture fillings, piping, etc. The destruction speed of roof surrounding rock was gradually accelerated. The whole process of surrounding rock of water drenching roadway roof from ground pressure appearance deformation and crack softening expansion to piping corrosion failure was analyzed. According to the main forms of the surrounding rock failure of roof drilling (physical softening, seepage failure, suction corrosion expansion failure, scouring deformation failure), it was divided into four different stages. The criteria for determining the development stage of roof failure of roadway drenching water had been formed with the main forms of roof drilling surrounding rock failure, the flow state of the roof anchor cable hole, roof surrounding rock fracture development characteristics and water control reinforcement principles as the key indicators. Combined with the site conditions, the 414106 auxiliary transportation water spraying area was the Ⅲ stage of the development of spraying roof damage. The structural form of anchor cable sealing grouting (drainage) and the principle of “deep hole drainage + shallow water sealing + deep reinforcement + high pressures support” were proposed for the roof of the roadway in the spraying area. An integrated reinforcement scheme of anchoring, sealing and grouting, which combined the reinforcement of high pre-tightened long anchor cables and sealing and grouting on the roof of the roadway in the water-spraying area, had been formulated. According to the field industrial test and rock pressure monitoring, the effect of roof water control and surrounding rock reinforcement was achieved

The ancient mammalian KRAB zinc finger gene cluster on human chromosome 8q24.3 illustrates principles of C2H2 zinc finger evolution associated with unique expression profiles in human tissues

<p>Abstract</p> <p>Background</p> <p>Expansion of multi-C2H2 domain zinc finger (ZNF) genes, including the Krüppel-associated box (KRAB) subfamily, paralleled the evolution of tetrapodes, particularly in mammalian lineages. Advances in their cataloging and characterization suggest that the functions of the KRAB-ZNF gene family contributed to mammalian speciation.</p> <p>Results</p> <p>Here, we characterized the human 8q24.3 ZNF cluster on the genomic, the phylogenetic, the structural and the transcriptome level. Six (ZNF7, ZNF34, ZNF250, ZNF251, ZNF252, ZNF517) of the seven locus members contain exons encoding KRAB domains, one (ZNF16) does not. They form a paralog group in which the encoded KRAB and ZNF protein domains generally share more similarities with each other than with other members of the human ZNF superfamily. The closest relatives with respect to their DNA-binding domain were ZNF7 and ZNF251. The analysis of orthologs in therian mammalian species revealed strong conservation and purifying selection of the KRAB-A and zinc finger domains. These findings underscore structural/functional constraints during evolution. Gene losses in the murine lineage (ZNF16, ZNF34, ZNF252, ZNF517) and potential protein truncations in primates (ZNF252) illustrate ongoing speciation processes. Tissue expression profiling by quantitative real-time PCR showed similar but distinct patterns for all tested ZNF genes with the most prominent expression in fetal brain. Based on accompanying expression signatures in twenty-six other human tissues ZNF34 and ZNF250 revealed the closest expression profiles. Together, the 8q24.3 ZNF genes can be assigned to a cerebellum, a testis or a prostate/thyroid subgroup. These results are consistent with potential functions of the ZNF genes in morphogenesis and differentiation. Promoter regions of the seven 8q24.3 ZNF genes display common characteristics like missing TATA-box, CpG island-association and transcription factor binding site (TFBS) modules. Common TFBS modules partly explain the observed expression pattern similarities.</p> <p>Conclusions</p> <p>The ZNF genes at human 8q24.3 form a relatively old mammalian paralog group conserved in eutherian mammals for at least 130 million years. The members persisted after initial duplications by undergoing subfunctionalizations in their expression patterns and target site recognition. KRAB-ZNF mediated repression of transcription might have shaped organogenesis in mammalian ontogeny.</p

Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

BACKGROUND: Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. RESULTS: Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using tissue microarrays to demonstrate a significant association between downregulated protein expression and tumorigenesis, a process that is the reverse of what is seen in the presence of Selenium. CONCLUSIONS: Thus the outlined process demonstrates similar baseline and selenium induced gene expression profiles between rat and human prostate cancers, and provides a method for identifying testable functional pathways for the action of Selenium's chemopreventive properties in prostate cancer

Why do authoritarian regimes provide public goods? Policy communities, external shocks and ideas in China’s rural social policy making

Recent research on authoritarian regimes argues that they provide public goods in order to prevent rebellion. This essay shows that the ‘threat of rebellion’ alone cannot explain Chinese party-state policies to extend public goods to rural residents in the first decade of the twenty-first century. Drawing on theories of policy making, it argues that China’s one-party regime extended public goods to the rural population under the influence of ideas and policy options generated by policy communities of officials, researchers, international organisations and other actors. The party-state centre adopted and implemented these ideas and policy options when they provided solutions to external shocks and supported economic development goals. Explanations of policies and their outcomes in authoritarian political systems need to include not only ‘dictators’ but also other actors, and the ideas they generate

Mitigating NO_x emissions does not help alleviate wintertime particulate pollution in Beijing-Tianjin-Hebei (BTH), China

Stringent mitigation measures have reduced wintertime PM_(2.5) concentrations by 42.2% from 2013 to 2018 in the BTH. The observed nitrate aerosols have not exhibited a significant decreasing trend and constituted a major fraction (about 20%) of the total PM_(2.5), although the surface-measured NO₂ level has decreased by over 20%. It still remains elusive about contributions of nitrogen oxides (NO_x) emissions mitigation to the nitrate and PM_(2.5) level. The WRF-Chem model simulations of a persistent haze episode in January 2019 in the BTH reveal that NO_x emissions mitigation does not help lower wintertime nitrate and PM_(2.5) concentrations under current conditions in the BTH, because the substantial O₃ increase induced by NO_x mitigation offsets the HNO₃ loss and enhances sulfate and secondary organic aerosols formation. Our results are further consolidated by occurrence of the severe PM pollution in the BTH during the COVID-19 outbreak with a significant reduction of NO₂

Mitigating NO_x emissions does not help alleviate wintertime particulate pollution in Beijing-Tianjin-Hebei (BTH), China

Stringent mitigation measures have reduced wintertime PM_(2.5) concentrations by 42.2% from 2013 to 2018 in the BTH. The observed nitrate aerosols have not exhibited a significant decreasing trend and constituted a major fraction (about 20%) of the total PM_(2.5), although the surface-measured NO₂ level has decreased by over 20%. It still remains elusive about contributions of nitrogen oxides (NO_x) emissions mitigation to the nitrate and PM_(2.5) level. The WRF-Chem model simulations of a persistent haze episode in January 2019 in the BTH reveal that NO_x emissions mitigation does not help lower wintertime nitrate and PM_(2.5) concentrations under current conditions in the BTH, because the substantial O₃ increase induced by NO_x mitigation offsets the HNO₃ loss and enhances sulfate and secondary organic aerosols formation. Our results are further consolidated by occurrence of the severe PM pollution in the BTH during the COVID-19 outbreak with a significant reduction of NO₂

Large-scale field phenotyping using backpack LiDAR and CropQuant-3D to measure structural variation in wheat

Plant phenomics bridges the gap between traits of agricultural importance and genomic information. Limitations of current field-based phenotyping solutions include mobility, affordability, throughput, accuracy, scalability, and the ability to analyze big data collected. Here, we present a large-scale phenotyping solution that combines a commercial backpack Light Detection and Ranging (LiDAR) device and our analytic software, CropQuant-3D, which have been applied jointly to phenotype wheat (Triticum aestivum) and associated 3D trait analysis. The use of LiDAR can acquire millions of 3D points to represent spatial features of crops, and CropQuant-3D can extract meaningful traits from large, complex point clouds. In a case study examining the response of wheat varieties to three different levels of nitrogen fertilization in field experiments, the combined solution differentiated significant genotype and treatment effects on crop growth and structural variation in the canopy, with strong correlations with manual measurements. Hence, we demonstrate that this system could consistently perform 3D trait analysis at a larger scale and more quickly than heretofore possible and addresses challenges in mobility, throughput, and scalability. To ensure our work could reach non-expert users, we developed an open-source graphical user interface for CropQuant-3D. We, therefore, believe that the combined system is easy-to-use and could be used as a reliable research tool in multi-location phenotyping for both crop research and breeding. Furthermore, together with the fast maturity of LiDAR technologies, the system has the potential for further development in accuracy and affordability, contributing to the resolution of the phenotyping bottleneck and exploiting available genomic resources more effectively

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020