887 research outputs found

    Random laser action in ZnO nanorod arrays embedded in ZnO epilayers

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    Random laser action with coherent feedback has been observed in ZnO nanorod arrays embedded in ZnO epilayers. The sample was fabricated by depositing a MgO buffer layer and followed by a layer of ZnO thin film onto a vertically well-aligned ZnO nanorod arrays grown on sapphire substrate. Under 355 nm optical excitation at room temperature, sharp lasing peaks emit at around 390 nm with a linewidth less than 0.4 nm has been observed in all directions. In addition, the dependence of the lasing threshold intensity on the excitation area is shown in good agreement with the random laser theory. Hence, it is demonstrated that random laser action can also be supported in ZnO nanorod arrays. (C) 2004 American Institute of Physics.open11173186sciescopu

    Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

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    Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

    Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

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    BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

    A hybrid discrete bubble-lattice Boltzmann–discrete element model for gas-charged sediments

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    This paper presents a hybrid discrete bubble-lattice Boltzmann–discrete element modelling framework for simulating gas-charged sediments, especially in the seabed. A discrete bubble model proposed in chemical engineering is adapted in the coupled discrete element/lattice Boltzmann method to model the migration of gas bubbles in saturated sediments involving interactions between gas bubbles and fluid/solid phases. Surface tension is introduced into the discrete bubble model in this work, so that it can handle the complex gas–fluid–solid interface. The lattice Boltzmann and discrete element methods are, respectively, employed to simulate fluid flows and mechanical behaviours of sediments. A velocity interpolation-based immerse boundary method is utilised to resolve the coupling between the fluid flow and the solid/gas phase. The proposed technique is preliminarily validated using simulations of bubble migration in fluids, which is followed by high-resolution investigations of the transport of a gas bubble in seabed sediments. It is demonstrated that this hybrid method can reproduce, to a certain degree, the characters of bubbles moving in seabed sediment tests

    Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

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    In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

    Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake.

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    Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcgammaRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcgammaRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcgammaRIIIb. Reduced FcgammaRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility

    Knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal: a cross sectional study

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    <p>Abstract</p> <p>Background</p> <p>Avian influenza is a considerable threat to global public health. Prevention and control depend on awareness and protective behaviours of the general population as well as high risk-groups. This study aims to explore the knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal.</p> <p>Methods</p> <p>The study was based on a cross-sectional study design, using a structured questionnaire administered in face-to-face interviews with 96 poultry workers age 15 and above from the Rupandehi district in Nepal.</p> <p>Results</p> <p>The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly everybody was aware that AI cases had been detected in Nepal and that poultry workers were at risk for infection. The major sources of AI information were radio, TV and newspapers. Knowledge about preventive measures was high with regard to some behaviours (hand washing), but medium to low with regard to others (using cleaning and disinfecting procedures or protective clothing). Poultry workers who got their information from TV and newspapers and those who were more afraid of contracting AI had higher knowledge than those who did not. Being employed as compared to being an owner of a poultry farm as well as having a high level of knowledge was associated with practising more preventive behaviours. While on one hand many specific government control measures found a high degree of acceptance, a majority of study participants also thought that government control and compensation measures as a whole were insufficient.</p> <p>Conclusions</p> <p>The study provides information about knowledge and practices regarding avian influenza among poultry workers in Nepal. It highlights the importance of targeting lack of knowledge as well as structural-material barriers to successfully build preparedness for a major outbreak situation.</p

    A Comparison Between Chinese Children Infected with Coronavirus Disease-2019 and with Severe Acute Respiratory Syndrome 2003

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    OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in two Chinese pediatric cohorts, given that the causative pathogens and are biologically similar. , STUDY DESIGN: This is a cross-sectional study reviewing paediatric patients with SARS (n = 43) and COVID-19 (n=244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, clinical and laboratory features were compared RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiological associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients COVID-19. No SARS patients were asymptomatic at the time of admission. 29.1% and 20.9% COVID-19 patients were asymptomatic on admission and throughout their hospital stay, respectively. More SARS patients required oxygen supplementation than COVID-19 patients (18.6 vs. 4.7%, P = 004). Only 1.6% COVID-19 and 2.3% SARS patients required mechanical ventilation. Leukopenia (37.2% vs. 18.6%, p=0.008), lymphopenia (95.4% versus 32.6%, p<0.01), and thrombocytopenia (41.9% vs 3.8%, p<0.001) were significantly more common in SARS than COVID-19 patients. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in COVID-19 patients regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematological findings than children with SARS

    Physiotherapy and Physical Activity: A cross-sectional survey exploring physical activity promotion, knowledge of physical activity guidelines and the physical activity habits of UK physiotherapists.

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    Objective: Physical inactivity is a public health priority and embedding promotion of physical activity (PA) within healthcare systems is an important lever for change. Many factors influence PA promotion in routine healthcare practice, these include the PA habits of healthcare professionals and also their knowledge of the PA guidelines. Little is known about the extent to which PA is currently promoted in physiotherapy practice or the factors that influence it. Methods: Following ethical approval a cross-sectional survey of UK physiotherapists was conducted. Findings were analysed and reported in accordance with STROBE guidelines. Results: There were 522 respondents, 514 of whom were physiotherapists. Seventy seven percent of respondents routinely discussed PA with patients and 68% routinely delivered Brief Interventions. Assessment of PA status was not routine practice neither was signposting to further sources of PA support. Only 16% of respondents correctly answered questions about the content of the PA guidelines. Only 38% of respondents met current PA recommendations. Clinicians' PA levels were not associated with PA promotion activity. Conclusion: Despite the promising finding that some form of PA promotion is integrated into most respondents' practice, we report a poor understanding of Brief Interventions and poor knowledge of the PA guidelines. Additionally, the majority of respondents were not sufficiently active to meet current PA recommendations
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