The increasing severity of droughts/floods and worsening air quality from increasing aerosols in Asia monsoon regions are the two gravest threats facing over 60% of the world population living in ...Asian monsoon regions. These dual threats have fueled a large body of research in the last decade on the roles of aerosols in impacting Asian monsoon weather and climate. This paper provides a comprehensive review of studies on Asian aerosols, monsoons, and their interactions. The Asian monsoon region is a primary source of emissions of diverse species of aerosols from both anthropogenic and natural origins. The distributions of aerosol loading are strongly influenced by distinct weather and climatic regimes, which are, in turn, modulated by aerosol effects. On a continental scale, aerosols reduce surface insolation and weaken the land‐ocean thermal contrast, thus inhibiting the development of monsoons. Locally, aerosol radiative effects alter the thermodynamic stability and convective potential of the lower atmosphere leading to reduced temperatures, increased atmospheric stability, and weakened wind and atmospheric circulations. The atmospheric thermodynamic state, which determines the formation of clouds, convection, and precipitation, may also be altered by aerosols serving as cloud condensation nuclei or ice nuclei. Absorbing aerosols such as black carbon and desert dust in Asian monsoon regions may also induce dynamical feedback processes, leading to a strengthening of the early monsoon and affecting the subsequent evolution of the monsoon. Many mechanisms have been put forth regarding how aerosols modulate the amplitude, frequency, intensity, and phase of different monsoon climate variables. A wide range of theoretical, observational, and modeling findings on the Asian monsoon, aerosols, and their interactions are synthesized. A new paradigm is proposed on investigating aerosol‐monsoon interactions, in which natural aerosols such as desert dust, black carbon from biomass burning, and biogenic aerosols from vegetation are considered integral components of an intrinsic aerosol‐monsoon climate system, subject to external forcing of global warming, anthropogenic aerosols, and land use and change. Future research on aerosol‐monsoon interactions calls for an integrated approach and international collaborations based on long‐term sustained observations, process measurements, and improved models, as well as using observations to constrain model simulations and projections.
Key Points
The fast‐developing Asia has suffered severe air pollution problem
Aerosol affects the Asian monsoon
Aerosol‐monsoon interactions dictate the climate change in the region
Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but ...not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection ...in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.
Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially ...useful in early diagnosis.
We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients’ outcomes.
Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016).
Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.
In the past 10 years, ZnO as a semiconductor has attracted considerable attention due to its unique properties, such as high electron mobility, wide and direct band gap and large exciton binding ...energy. ZnO has been considered a promising material for optoelectronic device applications, and the fabrications of high quality p-type ZnO and p-n junction are the key steps to realize these applications. However, the reliable p-type doping of the material remains a major challenge because of the self-compensation from native donor defects (VO and Zni) and/or hydrogen incorporation. Considerable efforts have been made to obtain p-type ZnO by doping different elements with various techniques. Remarkable progresses have been achieved, both theoretically and experimentally. In this paper, we discuss p-type ZnO materials: theory, growth, properties and devices, comprehensively. We first discuss the native defects in ZnO. Among the native defects in ZnO, VZn and O i act as acceptors. We then present the theory of p-type doping in ZnO, and summarize the growth techniques for p-type ZnO and the properties of p-type ZnO materials. Theoretically, the principles of selection of p-type dopant, codoping method and XZn-2VZn acceptor model are introduced. Experimentally, besides the intrinsic p-type ZnO grown at O-rich ambient, p-type ZnO (MgZnO) materials have been prepared by various techniques using Group-I, IV and V elements. We pay a special attention to the band gap of p-type ZnO by band-gap engineering and room temperature ferromagnetism observed in p-type ZnO. Finally, we summarize the devices based on p-type ZnO materials.
The novel coronavirus disease 2019 (COVID-19) epidemic that emerged in December 2019 has rapidly evolved in recent months to become a worldwide and ongoing pandemic. Shortage of medical masks remains ...an unresolved problem. This study aims to investigate the filtration efficiency (FE) of home-made masks that could be used as alternatives for community mitigation of COVID-19.
Experimental observational analytic study.
The FE of home-made masks and medical masks (as the control) were tested under laminar flow within a scaled air duct system using nebulised NaCl aerosols sized 6–220 nm. The size-resolved NaCl aerosol count was measured using a scanning mobility particle-sizer spectrometer. Home-made masks with an external plastic face shield also underwent a splash test. In addition, the fibre structures of medical masks were studied under an electron microscope after treatment with either 75% alcohol or soap and water at 60 °C.
The FE of the home-made masks at 6–200 nm were non-inferior to that of medical masks (84.54% vs 86.94%, P = 0.102). Both types of masks achieved an FE of 90% at 6–89 nm. A significantly higher FE was achieved when one piece of tissue paper was added adjacent to the inner surface of the medical mask than medical mask alone (6–200 nm: 91.64% vs 86.94%, P < 0.0001; 6–89 nm: 94.27% vs 90.54%, P < 0.0001; 90–200 nm: 82.69% vs 73.81%, P < 0.0001). The plastic face shield prevented the home-made mask from fluid splash. The fibre structures of the external surface of medical masks were damaged after treatment with either 75% alcohol or soap and water at 60 °C.
The home-made masks in this study, which were made of one piece of tissue paper and two pieces of kitchen towels, layered from face to external, had an FE at 6–200 nm non-inferior to that of medical mask materials, which had a certified FE of ≥95% at 3 μm. In the current COVID-19 pandemic with the shortage of medical masks, these home-made masks combined with an external plastic shield could be used as an alternative to medical masks for community mitigation. In addition, one piece of tissue paper could be placed adjacent to the inner surface of a medical mask to prolong effective lifespan of the medical mask. These demand reduction strategies could be used to reserve medical masks for use in healthcare and certain high-risk community settings, such as symptomatic persons, caregivers and attendees to healthcare institutions.
•Our home-made masks have filtration efficiency comparable to medical masks.•They may be used as alternatives in low-risk community settings.•Plastic face shields may be used in situations when social distancing and/or face masks are not feasible.•Decontamination of medical masks with 75% alcohol or soap and water damages the fibres and is not recommended.•Community mitigation measures are an important part of the global efforts in combating COVID-19.
The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology. In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first ...orally bioavailable CGRP receptor antagonist.
Adults with migraine with or without aura (International Headache Society criteria) treated a moderate or severe attack with oral telcagepant 50 mg (n = 177), 150 mg (n = 381), 300 mg (n = 371), or placebo (n = 365) in a randomized, double-blind trial. The 5 co-primary endpoints were pain freedom, pain relief, and absence of photophobia, absence of phonophobia, and absence of nausea, all at 2 hours postdose. The key secondary endpoint was 2-24 hour sustained pain freedom. The prespecified primary efficacy analyses evaluated the 150 mg and 300 mg groups; the 50-mg group was included on an exploratory basis to further characterize the dose response but was not prespecified for analysis. Tolerability was assessed by adverse experience reports.
Telcagepant 300 mg was more effective (p <or= 0.001) than placebo on all primary endpoints and the key secondary endpoint, as was telcagepant 150 mg (p <or= 0.05). Telcagepant 300 mg showed a slight numeric advantage over telcagepant 150 mg on most measures. Telcagepant 50 mg values were numerically intermediate between placebo and telcagepant 150 mg and 300 mg. The percentages of patients with adverse experiences were 32.2% for telcagepant 50 mg, 32.0% for telcagepant 150 mg, 36.2% for telcagepant 300 mg, and 32.2% for placebo.
This study confirmed previous findings that telcagepant 300 mg was effective at relieving pain and other migraine symptoms at 2 hours and providing sustained pain freedom up to 24 hours. In this study, telcagepant 150 mg was also effective. Telcagepant was generally well tolerated.
Importantly, occupational exposure to ironcontaining particulates and genetic susceptibility loci involving ironassociated genes are associated with manifestations of COPD (5). ...because the airways ...are constantly exposed to atmospheric iron sources, with cigarette smoking further impacting these processes (10), there is a need for a regulatory network to sequester, detoxify, and excrete this prooxidant species and thereby maintain homeostasis. Regulating extracellular free iron levels in the lung, numerous soluble iron-related proteins or carriers are found in BAL fluid, including transferrin (one of the most abundant BAL proteins 44.5%) (34), ferritin (35), lactoferrin (a glycoprotein belonging to the transferrin family that sequesters iron) (36), ceruloplasmin (a ferroxidase that oxidizes iron to the Fe31 state) (37), and lipocalin 2 (a siderophore that sequesters iron) (38), all of which are thought to be produced by secretory leukocytes, epithelial cells (EPIs), and/or ECs. (Received in original form February 8, 2017; accepted in final form April 12, 2017) Supported by the National Institutes of Health (NIH) under NHLBI grants K99 HL125899 (S.M.C.), P01 HL114501, R01 HL055330, R01 HL079904, and P01 HL105339 (A.M.K.C.) and American Lung Association grant RG-348928 (S.M.C.); British Heart Foundation grants PG/14/27/30679 (S.M. and I.M.A.) and PG/15/56/31573 (G.J.Q.); the Medical Research Council/Association of British Pharmaceutical Industries COPDMAP (I.M.A.); the Wellcome Trust (093080/Z/10/Z I.M.A.); the National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London (G.J.Q.); the Commission of European Communities grants 115010 and 643607 (K.F.C.); NIHR Senior Investigator Award NF-SI-0515-10016 (K.F.C.); National Institute of Environmental Health Sciences grant H50669 (K.F.C.); National Environmental Research Council grant NE/H012893 (K.F.C.); and Medical Research Council grant G1001367 (K.F.C.). Cohen RT, Strunk RC, Field JJ, Rosen CL, Kirkham FJ, Redline S, Stocks J, Rodeghier MJ, DeBaun MR. Environmental tobacco smoke and airway obstruction in children with sickle cell anemia.
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