DNA nanotechnology has proven to be a powerful strategy for the bottom-up preparation of colloidal nanoparticle (NP) superstructures, enabling the coordination of multiple NPs with orientation and ...separation approaching nanometer precision. To do this, NPs are often conjugated with chemically modified, single-stranded (ss) DNA that can recognize complementary ssDNA on the DNA nanostructure. The limitation is that many NPs cannot be easily conjugated with ssDNA, and other conjugation strategies are expensive, inefficient, or reduce the specificity and/or precision with which NPs can be placed. As an alternative, the conjugation of nanoparticle-binding peptides and peptide nucleic acids (PNA) can produce peptide-PNA with distinct NP-binding and DNA-binding domains. Here, we demonstrate a simple application of this method to conjugate semiconductor quantum dots (QDs) directly to DNA nanostructures by means of a peptide-PNA with a six-histidine peptide motif that binds to the QD surface. With this method, we achieved greater than 90% capture efficiency for multiple QDs on a single DNA nanostructure while preserving both site specificity and precise spatial control of QD placement. Additionally, we investigated the effects of peptide-PNA charge on the efficacy of QD immobilization in suboptimal conditions. The results validate peptide-PNA as a viable alternative to ssDNA conjugation of NPs and warrant studies of other NP-binding peptides for peptide-PNA conjugation.
The physical and chemical properties of synthetic DNA have transformed this prototypical biopolymer into a versatile nanoscale building block material in the form of DNA nanotechnology. DNA ...nanotechnology is, in turn, providing unprecedented precision bioengineering for numerous biomedical applications at the nanoscale including next generation immune-modulatory materials, vectors for targeted delivery of nucleic acids, drugs, and contrast agents, intelligent sensors for diagnostics, and theranostics, which combines several of these functionalities into a single construct. Assembling a DNA nanostructure to be programmed with a specific number of targeting moieties on its surface to imbue it with concomitant cellular uptake and retention capabilities along with carrying a specific therapeutic dose is now eminently feasible due to the extraordinary self-assembling properties and high formation efficiency of these materials. However, what remains still only partially addressed is how exactly this class of materials is taken up into cells in both the native state and as targeted or chemically facilitated, along with how stable they are inside the cellular cytosol and other cellular organelles. In this minireview, we summarize what is currently reported in the literature about how (i) DNA nanostructures are taken up into cells along with (ii) what is understood about their subsequent stability in the complex multi-organelle environment of the cellular milieu along with biological fluids in general. This allows us to highlight the many challenges that still remain to overcome in understanding DNA nanostructure-cellular interactions in order to fully translate these exciting new materials.
Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19.
To measure air and surface environmental ...contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients.
30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus.
Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive.
The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen.
The foot domain in Bambara Green, Christopher Ryan
Language (Baltimore),
03/2015, Letnik:
91, Številka:
1
Journal Article
Recenzirano
Recent research has shed new light on the role and characteristics of prosodic domains, including segmental and tonal feet, in an array of languages. This research extends to African languages, but ...much work remains to be done. Tonal African languages are particularly problematic, as correlates of stress or metrical prominence are often not well defined or are absent altogether. In addition, descriptive work may omit details of the structure and function of prosodic domains. An exception to this is Bambara, where research implicates a pivotal role for foot structure in segmental and tonal processes. These processes reference a foot domain; however, there are conflicting accounts of certain defining characteristics of its structure. This article aims to challenge two long-held claims about Bambara prosodic structure. The data presented support a claim that all Bambara feet are uniformly trochaic and parsed from left to right in all instances. I intend to illustrate that Bambara segmental and tonal feet are a single, structurally unified prosodic entity.
Non‐alcoholic steatohepatitis (NASH) results from the accumulation of excessive liver lipids leading to hepatocellular injury, inflammation, and fibrosis that greatly increase the risk for ...hepatocellular carcinoma (HCC). Despite the well‐characterized clinical and histological pathology for NASH‐driven HCC in humans, its etiology remains unclear and there is a deficiency in pre‐clinical models that recapitulate the progression of the human disease. Therefore, we developed a new mouse model amenable to genetic manipulations and gene targeting that mimics the gradual NASH to HCC progression observed in humans. C57BL/6NJ mice were fed a Western high‐fat diet and sugar water (HFD/SW) and monitored for effects on metabolism, liver histology, tumor development, and liver transcriptome for up to 54 weeks. Chronic HFD/SW feeding led to significantly increased weight gain, serum and liver lipid levels, liver injury, and glucose intolerance. Hepatic pathology progressed and mice developed hepatocellular ballooning, inflammation, and worse fibrosis was apparent at 16 weeks, greatly increased through 32 weeks, and remained elevated at 54 weeks. Importantly, hepatocellular cancer spontaneously developed in 75% of mice on HFD/SW, half of which were HCC, whereas none of the mice on the chow diet developed HCC. Chronic HFD/SW induced molecular markers of de novo lipogenesis, endoplasmic reticulum stress, inflammation, and accumulation of p62, all of which also participate in the human pathology. Moreover, transcriptome analysis revealed activation of HCC‐related genes and signatures associated with poor prognosis of human HCC. Overall, we have identified a new preclinical model that recapitulates known hallmarks of NASH‐driven HCC that can be utilized for future molecular mechanistic studies of this disease.
Aquifer flow systems near seawater interfaces can be complicated by density-driven flows and the formation of stagnation zones, which inevitably introduces uncertainty into groundwater age-dating. ...While age-dating has proved effective to understand the seawater intrusion and aquifer salinization process in coastal aquifers, further efforts are needed to propagate model and data uncertainty to the uncertainty associated with the inferred age distributions. This study was performed in a coastal aquifer located close to the Yellow Sea, South Korea, where there is a decreasing trend of groundwater levels due to recent heavy exploitation, raising a warning of induced seawater intrusion. We inferred the groundwater age distributions in wells around the intrusion zone and estimated the uncertainty associated with the inference based on multiple age tracers including 3H, tritiogenic 3He, radiogenic 4He, CFC-11, CFC-12 and CFC-113 using Bayesian inference. We examined various models representing the age distributions including traditional parametric Lumped Parameter Models (LPMs) and two non-parametric “shape-free” models. The results showed that the mean ages at the study site ranged from 10.9 to 522.5 y. Complex, multimodal distributions of ages occurred near a seawater intrusion area and upland recharge zones, implying converging paths of a wide range of different ages in those regions. In particular, the age distributions estimated near the seawater intrusion interface were characterized by heavy-tailed mixing structures with elevated concentrations of 4He. This likely indicates density-driven upward flow at the seawater intrusion interface, forcing old groundwater rich in 4He into the shallow aquifer. The Bayesian inference estimated large uncertainties particularly for the old age distributions, which was attributed partly to the gradual accumulation of 4He in groundwater. The Bayesian inference improved understanding of flow dynamics at a complex seawater interface and identified opportunities to further reduce uncertainty of old water age estimates that characterize upwelling groundwater near the interface.
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•Aquifer salinization was accelerated by over-exploitation of coastal groundwater.•Irregular water mixing along the intrusion area was explained by age mixing models.•Multiple age tracers revealed age structure of upward flow at the seawater interface.•Age-dating uncertainty was demonstrated by the Bayesian inference and DIC measure.•Uncertainty analysis points to ways to improve the age-dating of the mixing zone.
Gradients in contaminant concentrations and isotopic compositions commonly are used to derive reaction parameters for natural attenuation in aquifers. Differences between field‐scale (apparent) ...estimated reaction rates and isotopic fractionations and local‐scale (intrinsic) effects are poorly understood for complex natural systems. For a heterogeneous alluvial fan aquifer, numerical models and field observations were used to study the effects of physical heterogeneity on reaction parameter estimates. Field measurements included major ions, age tracers, stable isotopes, and dissolved gases. Parameters were estimated for the O2 reduction rate, denitrification rate, O2 threshold for denitrification, and stable N isotope fractionation during denitrification. For multiple geostatistical realizations of the aquifer, inverse modeling was used to establish reactive transport simulations that were consistent with field observations and served as a basis for numerical experiments to compare sample‐based estimates of “apparent” parameters with “true“ (intrinsic) values. For this aquifer, non‐Gaussian dispersion reduced the magnitudes of apparent reaction rates and isotope fractionations to a greater extent than Gaussian mixing alone. Apparent and true rate constants and fractionation parameters can differ by an order of magnitude or more, especially for samples subject to slow transport, long travel times, or rapid reactions. The effect of mixing on apparent N isotope fractionation potentially explains differences between previous laboratory and field estimates. Similarly, predicted effects on apparent O2 threshold values for denitrification are consistent with previous reports of higher values in aquifers than in the laboratory. These results show that hydrogeological complexity substantially influences the interpretation and prediction of reactive transport.
This paper explores people's knowledge and understandings of microplastics; the role of media in framing perceptions and socio-cultural dimensions to popular solutions to reduce single-use plastics. ...We conducted 6 focus groups (2016–17) involving participants with no obvious knowledge of microplastics and some with special interest. Most people were unaware of microplastics though environmentally conscious participants had heard of microbeads due to media reporting concerning regulation. Few made connections between their personal use of plastics and ocean pollution. Plastic pollution was associated with macro-plastic ‘islands’ in the Great Pacific Garbage Patch and powerful media images of charismatic wildlife entanglement remote from participants lives. The scale of microplastics (not easily detected), poor understanding of the science behind microplastics and cultural ideas about healthy and appropriate behaviour presents barriers to change. Science communicators, NGOs, industry and policy makers must take account of media representations and the culturally embedded nature of plastics in society.
We study the topology characteristics of the Kenyan overnight interbank market and their impacts on bank stability. Our intraday transaction dataset covers 2003 to 2012, including six major liquidity ...shocks. We uncover new results that the Kenyan interbank network is an incomplete network with higher interconnectedness and exposure during liquidity shocks, such that the shocks tend to spread quickly throughout the network. The main implication of our finding is that in such tiered networks, core banks could pose risks to the whole system. Consistently, our further empirical results suggest that the high interbank network interconnectedness can smoothen liquidity flow during quiet times, but may lead to over-exposure to borrowing banks directly or indirectly, especially during disturbances.
•Kenyan interbank network has different features to those in industrial countries.•Kenya has a highly interconnected incomplete network especially during shocks.•Local and global shocks have significant impacts on Kenya network structure.•In the core-periphery structure, the core consists large, local and listed banks.•Interconnectedness over exposes banks to borrowers (in)directly during shocks.
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