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The use of water quality indices (WQIs) as a tool to evaluate the status of water quality in rivers has been introduced since the 1960s. The WQI transforms selected water quality parameters into a dimensionless number so that changes in river water quality at any particular location and time could be presented in a simple and easily understandable manner. Although many WQIs have been developed, there is no worldwide accepted method for implementing the steps used for developing a WQI. Thus, there is a continuing interest to develop accurate WQIs that suit a local or regional area. This paper aimed to provide significant contribution to the development of future river WQIs through a review of 30 existing WQIs based on the four steps needed to develop a WQI. These steps are the selection of parameters, the generation of sub-indices, the generation of parameter weights and the aggregation process to compute the final index value. From the 30 reviewed WQIs, 7 were identified as most important based on their wider use and they were discussed in detail. It was observed that a major factor that influences wider use of a WQI is the support provided by the government and authorities to implement a WQI as the main tool to evaluate the status of rivers. Since there is a lot of subjectivity and uncertainty involved in the steps for developing and applying a WQI, it is recommended that the opinion of local water quality experts is taken, especially in the first three steps (through techniques like Delphi method). It was also observed that uncertainty and sensitivity analysis was rarely undertaken to reduce uncertainty, and hence such an analysis is recommended for future studies.

This paper presents a novel approach to incorporate the non-stationarities characterised in the GCM outputs, into the Predictor-Predictand Relationships (PPRs) in statistical downscaling models. In this approach, a series of 42 PPRs based on multi-linear regression (MLR) technique were determined for each calendar month using a 20-year moving window moved at a 1-year time step on the predictor data obtained from the NCEP/NCAR reanalysis data archive and observations of precipitation at 3 stations located in Victoria, Australia, for the period 1950-2010. Then the relationships between the constants and coefficients in the PPRs and the statistics of reanalysis data of predictors were determined for the period 1950-2010, for each calendar month. Thereafter, using these relationships with the statistics of the past data of HadCM3 GCM pertaining to the predictors, new PPRs were derived for the periods 1950-69, 1970-89 and 1990-99 for each station. This process yielded a non-stationary downscaling model consisting of a PPR per calendar month for each of the above three periods for each station. The non-stationarities in the climate are characterised by the long-term changes in the statistics of the climate variables and above process enabled relating the non-stationarities in the climate to the PPRs. These new PPRs were then used with the past data of HadCM3, to reproduce the observed precipitation. It was found that the non-stationary MLR based downscaling model was able to produce more accurate simulations of observed precipitation more often than conventional stationary downscaling models developed with MLR and Genetic Programming (GP).

Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than 1200 B.C. for Schistosoma spp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.

Numerous studies have been conducted to prove the calming and stress-reducing effects on humans of visiting aquatic environments. As a result, many institutions have utilized fish to provide entertainment and treat patients. The most common issue in this approach is controlling the movement of fish to facilitate human interaction. This study proposed an interactive robot, a robotic fish, to alter fish swarm behaviors by performing an effective, unobstructed, yet necessary, defined set of actions to enhance human interaction. The approach incorporated a minimalistic but futuristic physical design of the robotic fish with cameras and infrared (IR) sensors, and developed a fish-detecting and swarm pattern-recognizing algorithm. The fish-detecting algorithm was implemented using background subtraction and moving average algorithms with an accuracy of 78%, while the swarm pattern detection implemented with a Convolutional Neural Network (CNN) resulted in a 77.32% accuracy rate. By effectively controlling the behavior and swimming patterns of fish through the smooth movements of the robotic fish, we evaluated the success through repeated trials. Feedback from a randomly selected unbiased group of subjects revealed that the robotic fish improved human interaction with fish by using the proposed set of maneuvers and behavior.

The increased frequency and magnitude of extreme rainfall events due to anthropogenic climate change, and decadal and multi-decadal climate variability question the stationary climate assumption. The possible violation of stationarity in climate can cause erroneous estimation of design rainfalls derived from extreme rainfall frequency analysis. This may result in significant consequences for infrastructure and flood protection projects since design rainfalls are essential input for design of these projects. Therefore, there is a need to conduct frequency analysis of extreme rainfall events in the context of non-stationarity, when non-stationarity is present in extreme rainfall events. A methodology consisting of threshold selection, extreme rainfall data (peaks over threshold data) construction, trend and non-stationarity analysis, and stationary and non-stationary generalised Pareto distribution (GPD) models was developed in this paper to investigate trends and non-stationarity in extreme rainfall events, and potential impacts of climate change and variability on intensity–frequency–duration (IFD) relationships. The methodology developed was successfully implemented using rainfall data from an observation station in Melbourne (Australia) for storm durations ranging from 6 min to 72 h. Although statistically significant trends were detected in extreme rainfall data for storm durations of 30 min, 3 h and 48 h, statistical non-stationarity tests and non-stationary GPD models did not indicate non-stationarity for these storm durations and other storm durations. It was also found that the stationary GPD models were capable of fitting extreme rainfall data for all storm durations. Furthermore, the IFD analysis showed that urban flash flood producing hourly rainfall intensities have increased over time.

Circular RNAs ( circRNAs ) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We identify and validate a collection of circRNAs in Drosophila , and show that depletion of the brain-enriched circRNA Edis ( circ_Ect4 ) causes hyperactivation of antibacterial innate immunity both in cultured cells and in vivo . Notably, Edis depleted flies display heightened resistance to bacterial infection and enhanced pathogen clearance. Conversely, ectopic Edis expression blocks innate immunity signaling. In addition, inactivation of Edis in vivo leads to impaired locomotor activity and shortened lifespan. Remarkably, these phenotypes can be recapitulated with neuron-specific depletion of Edis , accompanied by defective neurodevelopment. Furthermore, inactivation of Relish suppresses the innate immunity hyperactivation phenotype in the fly brain. Moreover, we provide evidence that Edis encodes a functional protein that associates with and compromises the processing and activation of the immune transcription factor Relish. Importantly, restoring Edis expression or ectopic expression of Edis -encoded protein suppresses both innate immunity and neurodevelopment phenotypes elicited by Edis depletion. Thus, our study establishes Edis as a key regulator of neurodevelopment and innate immunity.

Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia. In the periphery, PTX and OXA significantly increased circulating CD4+ and CD8+ T-cell populations. OXA caused a significant increase in the percentage of interleukin-4+ lymphocytes in the spleen and significant down-regulation of regulatory T (T-reg) cells in the inguinal lymph nodes. However, conditional depletion of T-reg cells in OXA-treated transgenic DEREG mice had no additional effect on pain sensitivity. Furthermore, there was no leukocyte infiltration into the nervous system of OXA- or PTX-treated mice. In the peripheral nervous system, PTX induced expression of the neuronal injury marker activating transcription factor-3 in IB4+ and NF200+ sensory neurons as well as an increase in the chemokines CCL2 and CCL3 in the lumbar dorsal root ganglion. In the central nervous system, PTX induced significant astrocyte activation in the spinal cord dorsal horn, and both PTX and OXA caused reduction of P2ry12+ homeostatic microglia, with no measurable changes in IBA-1+ microglia/macrophages in the dorsal and ventral horns. We also found that PTX induced up-regulation of several inflammatory cytokines and chemokines (TNF-α, IFN-γ, CCL11, CCL4, CCL3, IL-12p70 and GM-CSF) in the spinal cord. Overall, these findings suggest that PTX and OXA cause distinct pathological changes in the periphery and nervous system, which may contribute to chemotherapy-induced neuropathic pain.

The immediate molecular mechanisms behind invasive melanoma are poorly understood. Recent studies implicate microRNAs (miRNAs) as important agents in melanoma and other cancers. To investigate the role of miRNAs in melanoma, we subjected human melanoma cell lines to miRNA expression profiling, and report a range of variations in several miRNAs. Specifically, compared with expression levels in melanocytes, levels of miR-211 were consistently reduced in all eight non-pigmented melanoma cell lines we examined; they were also reduced in 21 out of 30 distinct melanoma samples from patients, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic. The levels of several predicted target mRNAs of miR-211 were reduced in melanoma cell lines that ectopically expressed miR-211. In vivo target cleavage assays confirmed one such target mRNA encoded by KCNMA1. Mutating the miR-211 binding site seed sequences at the KCNMA1 3'-UTR abolished target cleavage. KCNMA1 mRNA and protein expression levels varied inversely with miR-211 levels. Two different melanoma cell lines ectopically expressing miR-211 exhibited significant growth inhibition and reduced invasiveness compared with the respective parental melanoma cell lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate suppressor of melanoma metastasis. The transcription factor MITF, important for melanocyte development and function, is needed for high TRPM1 expression. MITF is also needed for miR-211 expression, suggesting that the tumor-suppressor activities of MITF and/or TRPM1 may at least partially be due to miR-211's negative post transcriptional effects on the KCNMA1 transcript. Given previous reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and glioma, our findings that miR-211 is a direct posttranscriptional regulator of KCNMA1 expression as well as the dependence of this miRNA's expression on MITF activity, establishes miR-211 as an important regulatory agent in human melanoma.

Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases.

Aromatic compounds constitute the second most abundant class of organic substrates and environmental pollutants, a substantial part of which (e.g., phenylalanine or styrene) is metabolized by bacteria via phenylacetate. Surprisingly, the bacterial catabolism of phenylalanine and phenylacetate remained an unsolved problem. Although a phenylacetate metabolic gene cluster had been identified, the underlying biochemistry remained largely unknown. Here we elucidate the catabolic pathway functioning in 16% of all bacteria whose genome has been sequenced, including Escherichia coli and Pseudomonas putida. This strategy is exceptional in several aspects. Intermediates are processed as CoA thioesters, and the aromatic ring of phenylacetyl-CoA becomes activated to a ring 1,2-epoxide by a distinct multicomponent oxygenase. The reactive nonaromatic epoxide is isomerized to a seven-member O-heterocyclic enol ether, an oxepin. This isomerization is followed by hydrolytic ring cleavage and β-oxidation steps, leading to acetyl-CoA and succinyl-CoA. This widespread paradigm differs significantly from the established chemistry of aerobic aromatic catabolism, thus widening our view of how organisms exploit such inert substrates. It provides insight into the natural remediation of man-made environmental contaminants such as styrene. Furthermore, this pathway occurs in various pathogens, where its reactive early intermediates may contribute to virulence.