This paper describes the safety, efficacy and operability of the world's first malaria vaccine (RTS, S/AS01) in latest field pilot studies and the recommendations from the WHO expert group for its ...use. In addition, further studies to examine the associations of inoculation rate and full-dose rate with the reduction in morbidity and mortality of malaria among target children and explore the scientific evidence for seasonable preventive vaccination with 5 doses and more among children at ages of below 5 years are recommended.
A modified distinct element Voronoi method, which we refer to as “Trigon” logic, is proposed for use in both two and three-dimensional modelling. A rock material is represented by an assembly of ...triangular (in 2D) or tetrahedral (in 3D) blocks bonded through their contacts. To evaluate the ability of the proposed Trigon logic in simulating brittle fracture, a series of unconfined and confined compression and Brazilian tests is performed illustrating the sample failure mechanisms under two and three dimensional conditions. Typical failure fracture patterns (damage) experienced by brittle rock are explicitly simulated including axial tensile failure under unconfined compression, shear failure under confined compression, and tensile crack extension during indirect tension (Brazilian) testing. A ‘damage parameter’ D and a ‘damage intensity’ D21 measure are proposed to allow the evaluation of the simulated rock damage in a more quantitative manner. At the mine opening scale, the process of roof shear failure is successfully captured using the Trigon logic. In comparison with the conventional Voronoi model, the proposed Trigon model is less mesh-sensitive and predicts both a more realistic friction angle and failure pattern under varied loading conditions.
•Develop a novel UDEC ‘Trigon’ logic to explicitly simulate brittle fracture in both 2 and 3 dimensions.•Proposed a ‘damage parameter’ to quantitatively evaluate simulated rock damage.•The ‘Trigon’ logic can capture various fracture patterns under different loading conditions.
Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, ...depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the ID edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle ...distribution and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24(+) sub-population possessed stem cell-like characteristics of remaining quiescence and more chemoresistant compared with CD24(-) fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 x 10(3) CD24(+) cells was able to form tumor xenografts in nude mice, whereas equal number of CD24(-) cells remained nontumorigenic. We also found that CD24(+) cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, beta-catenin, Bmi-1, Oct4, Oct3/4, Notch1 and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24(-) cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.
The megacity of Beijing has experienced frequent severe fine particle pollution during the last decade. Although the sources and formation mechanisms of aerosol particles have been extensively ...investigated on the basis of ground measurements, real-time characterization of aerosol particle composition and sources above the urban canopy in Beijing is rare. In this study, we conducted real-time measurements of non-refractory submicron aerosol (NR-PM1) composition at 260 m at the Beijing 325 m meteorological tower (BMT) from 10 October to 12 November 2014, by using an aerosol chemical speciation monitor (ACSM) along with synchronous measurements of size-resolved NR-PM1 composition near ground level using a high-resolution time-of-flight aerosol mass spectrometer (HR–ToF–AMS). The NR-PM1 composition above the urban canopy was dominated by organics (46 %), followed by nitrate (27 %) and sulfate (13 %). The high contribution of nitrate and high NO3− / SO42− mass ratios illustrates an important role of nitrate in particulate matter (PM) pollution during the study period. The organic aerosol (OA) was mainly composed of secondary OA (SOA), accounting for 61 % on an average. Different from that measured at the ground site, primary OA (POA) correlated moderately with SOA, likely suggesting a high contribution from regional transport above the urban canopy. The Asia–Pacific Economic Cooperation (APEC) summit with strict emission controls provides a unique opportunity to study the impacts of emission controls on aerosol chemistry. All aerosol species were shown to have significant decreases of 40–80 % during APEC from those measured before APEC, suggesting that emission controls over regional scales substantially reduced PM levels. However, the bulk aerosol composition was relatively similar before and during APEC as a result of synergetic controls of aerosol precursors. In addition to emission controls, the routine circulations of mountain–valley breezes were also found to play an important role in alleviating PM levels and achieving the "APEC blue" effect. The evolution of vertical differences between 260 m and the ground level was also investigated. Our results show complex vertical differences during the formation and evolution of severe haze episodes that are closely related to aerosol sources and boundary-layer dynamics.
Prostate cancer (PCa) is considered to be a frequently diagnosed cancer in males with high mortality worldwide, but the molecular mechanism responsible for prostate tumorigenesis and progression ...remains unclear. Increasing evidence has shown that microRNAs (miRNAs) play an important role in PCa. In this review, we focus on the current advances about the role of miRNAs in regulating tumorigenesis and progression of PCa, mainly in suppressing or promoting PCa growth and metastasis, and maintaining the pluripotency of PCa stem cells (PCSC). More studies on miRNAs will provide a better understanding of their regulatory mechanisms in PCa.
Epithelial-to-mesenchymal transition (EMT), marked by the dissolution of cell-cell junctions, loss of cell polarity and increased cell motility, is one of the essential steps for prostate cancer ...metastasis. However, the underlying mechanism has not been fully explored. We report in this study that Shp2 is upregulated in prostate cancers and is associated with a poor disease outcome, namely tumor metastasis and shortened patient survival. Overexpression of wild-type Shp2 or an oncogenic Shp2 mutant leads to increased prostate cancer cell proliferation, colony and sphere formation, and in vivo tumor formation. Opposite effects are seen in Shp2-knockdown cells. Moreover, Shp2 promotes in vitro migration and in vivo metastasis of prostatic tumor cells. Mechanistically, Shp2 interacts with PAR3 (partitioning-defective 3) via its Src homology-2 domain. Ectopic expression of Shp2 attenuates the phosphorylation of PAR3 and the formation of the PAR3/PAR6/atypical protein kinase C polarity protein complex, resulting in disrupted cell polarity, dysregulated cell-cell junctions and increased EMT. These findings provide a novel mechanism by which oncogenic signal-transduction molecules regulate cell polarity and induction of EMT.
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