920 research outputs found

    Design of Cationic Multi-Walled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication

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    Polo-Like Kinase (PLK1) has been identified as a potential target in cancer gene therapy via chemical or genetic inhibitory approaches. The biomedical applications of chemically functionalized carbon nanotubes (f-CNTs) in cancer therapy have been studied due to their ability to efficiently deliver siRNA intracellularly. In this study, we established the capacity of cationic MWNT-NH3+ to deliver the apoptotic siRNA against PLK1 (siPLK1) in Calu6 tumor xenografts by direct intratumoural injections. A direct comparison with cationic liposomes was made. This study validates the PLK1 gene as a potential target in cancer gene therapy including lung cancer, as demonstrated by the therapeutic efficacy of siPLK1:MWNT-NH3+ complexes and their ability to significantly improve animal survival. Biological analysis of the siPLK1:MWNT-NH3+ treated tumors by RT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumourally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labelled, non-coding siRNA sequence complexed with MWNT-NH3+, we established for the first time that the improved therapeutic efficacy observed in f-CNT-based siRNA delivery is directly proportional to the enhanced siRNA retention in the solid tumor and subsequent uptake by tumor cells after local administration in vivo

    Low-cost electronic sensors for environmental research: pitfalls and opportunities

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    Repeat observations underpin our understanding of environmental processes, but financial constraints often limit scientists’ ability to deploy dense networks of conventional commercial instrumentation. Rapid growth in the Internet-Of-Things (IoT) and the maker movement is paving the way for low-cost electronic sensors to transform global environmental monitoring. Accessible and inexpensive sensor construction is also fostering exciting opportunities for citizen science and participatory research. Drawing on 6 years of developmental work with Arduino-based open-source hardware and software, extensive laboratory and field testing, and incor- poration of such technology into active research programmes, we outline a series of successes, failures and lessons learned in designing and deploying environmental sensors. Six case studies are presented: a water table depth probe, air and water quality sensors, multi-parameter weather stations, a time-sequencing lake sediment trap, and a sonic anemometer for monitoring sand transport. Schematics, code and purchasing guidance to reproduce our sensors are described in the paper, with detailed build instructions hosted on our King’s College London Geography Environmental Sensors Github repository and the FreeStation project website. We show in each case study that manual design and construction can produce research-grade scientific instrumentation (mean bias error for calibrated sensors –0.04 to 23%) for a fraction of the conventional cost, provided rigorous, sensor-specific calibration and field testing is conducted. In sharing our collective experiences with build-it- yourself environmental monitoring, we intend for this paper to act as a catalyst for physical geographers and the wider environmental science community to begin incorporating low-cost sensor development into their research activities. The capacity to deploy denser sensor networks should ultimately lead to superior envi- ronmental monitoring at the local to global scales

    Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

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    Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

    Osmotic Dehydration of New Zealand Chestnuts with and without Shell and Pellicle

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    Osmotic dehydration offers an alternative to air-drying for reducing moisture content at ambient temperature. Of four different solutes investigated, 22% (mass basis) sodium chloride (NaCl) and 60% (mass basis) sucrose solutions were the most successful, with each achieving approximately a 10% reduction in wet basis moisture content after 8 h without significant detrimental side effects, although NaCl solutions cause noticeable darkening in the pits on the surface of the chestnuts. The presence of the shell and pellicle did not significantly affect the dehydration rate. Osmotic dehydration by NaCl or sucrose prior to mechanical shell removal produced a small increase in efficiency of the shell removal process

    Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

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    Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

    Observation of the geology and geomorphology of the 1999 Marsokhod test site

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    The Marsokhod rover returned data from six stations that were used to decipher the geomorphology and geology of a region not previously visited by members of the geomorphology field team. Satellite images and simulated descent images provided information about the regional setting. The landing zone was on an alluvial apron flanking a mountain block to the west and a playa surface to the east. Rover color images, infrared spectra analysis of the mountains, and the apron surface provided insight into the rock composition of the nearby mountains. From the return data the geomorphology team interpreted the region to consist of compressionally deformed, ancient marine sediments and igneous rocks exposed by more recent extensional tectonics. Unconsolidated alluvial materials blanket the lower flanks of the mountains. Bn ancient shoreline cut into alluvial material marks a high stand of water during a past, wetter climate period. Playa sediments floor a present-day, seasonally, dry lake. Observations made by the rover using panoramic and close-up (hand specimens-scale) image data and color scene data confirmed the presence of boulders, cobbles, and fines of various provinces. Rover traverses to sites identified as geologically distinct, such as fan, channel, shoreline, and playa, provided useful clues to the geologic interpretations. Analysis of local rocks was given concert only through comparison with distant geologic features. These results demonstrated the importance of a multifaceted approach to site interpretation through comparison of interpretations derived by differing geologic techniques

    Tropical Herbivorous Phasmids, but Not Litter Snails, Alter Decomposition Rates By Modifying Litter Bacteria

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    Consumers can alter decomposition rates through both feces and selective feeding in many ecosystems, but these combined effects have seldom been examined in tropical ecosystems. Members of the detrital food web (litter-feeders or microbivores) should presumably have greater effects on decomposition than herbivores, members of the green food web. Using litterbag experiments within a field enclosure experiment, we determined the relative effects of common litter snails (Megalomastoma croceum) and herbivorous walking sticks (Lamponius portoricensis) on litter composition, decomposition rates, and microbes in a Puerto Rican rainforest, and whether consumer effects were altered by canopy cover presence. Although canopy presence did not alter consumers’ effects, focal organisms had unexpected influences on decomposition. Decomposition was not altered by litter snails, but herbivorous walking sticks reduced leaf decomposition by about 50% through reductions in high quality litter abundance and, consequently, lower bacterial richness and abundance. This relatively unexplored but potentially important link between tropical herbivores, detritus, and litter microbes in this forest demonstrates the need to consider autotrophic influences when examining rainforest ecosystem processes

    Observations of the geology and geomorphology of the 1999 Marsokhod test site

    Get PDF
    The Marsokhod rover returned data from six stations that were used to decipher the geomorphology and geology of a region not previously visited by members of the geomorphology field team. Satellite images and simulated descent images provided information about the regional setting. The landing zone was on an alluvial apron flanking a mountain block to the west and playa surface to the east. Rover color images, infrared spectra analysis of the mountains, and the apron surface provided insight into the rock composition of the nearby mountains. From the return data the geomorphology team interpreted the region to consist of compressionally deformed, ancient marine sediments and igneous rocks exposed by more recent extensional tectonics. Unconsolidated alluvial materials blanket the lower flanks of the mountains. An ancient shoreline cut into alluvial material marks a high stand of water during a past, wetter climate period. Playa sediments floor a present-day, seasonally, dry lake. Observations made by the rover using panoramic and close-up (hand specimens—scale) image data and color scene data confirmed the presence of boulders, cobbles, and fines of various provinces. Rover traverses to sites identified as geologically distinct, such as a fan, channel, shoreline, and playa, provided useful clues to the geologic interpretations. Analysis of local rocks was given context only through comparison with distant geologic features. These results demonstrated the importance of a multifaceted approach to site interpretation through comparison of interpretations derived by differing geologic techniques
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