Effect of floating treatment wetland coverage ratio and operating parameters on nitrogen removal: toward design optimization.

Floating treatment wetlands (FTWs) have the potential to improve the quality of wastewater discharges, yet design basics are unavailable to size these systems. This study investigates the effect of FTWs' coverage ratio and hydraulic retention time on agri-food wastewater treatment. This was studied in a pilot-scale experiment comprising four lagoons (6.5 m3 each) fed with real effluent from an existing tertiary treatment lagoon. An evaluation of FTW of different sizes (L24, L48, and L72 representing 24, 48, and 72% of pilot lagoons surface areas) and a control, L0 (without FTW), was performed over 16 months. Overall, L72 and L48 moderately improved total nitrogen (TN) mass removal compared to L0 (p < 0.05), while L24 exhibited similar TN mass removal (p = 0.196). The highest improvement was observed for L72, exhibiting up to 55% (mean of 13%) greater N mass removal than the control. The net increase in TN removal by FTWs was mainly related to denitrification, promoted by decreasing dissolved oxygen for increasing FTW coverage ratio. Residence time, temperature, and dissolved oxygen were the main parameters driving TN removal by FTWs. Retrofitting existing lagoons with FTW can facilitate N retrieval through plant harvesting, thereby reducing N remobilization from sediment (common in conventional lagoons).

Anaerobic digestion of urban wastes: integration and benefits of a small-scale system.

This work presents an integrated approach of anaerobic digestion (AD) at the urban scale, based on on-site collected wastes, experimentation in a pilot reactor, and model approach. To cope with urban waste limitations (season inflow, organic matter decrease, limited area), it was proposed a settlement of wastewater (WW), a drying of food waste (FW), and silage of green waste (GW). The results obtained highlight the performance of these pretreatments to concentrate and/or preserve the organic matter over time. Co-digestion in a 30-liter reactor was then successfully carried out, resulting in an 83% of volatile solids reduction and stable methane production of 321 ml CH4/g VSadd, in 35 days. Finally, we developed a standard neighbourhood model with AD based on these experimental results. It appears that 66% of the primary sludge (PS) and 28% of the FWs produced daily could be treated by the proposal process. 14% of the annual production of GW could thus be processed daily. From an energetic point of view, the process generates a surplus of respectively, 2500 MJ/year and 38,000 MJ/year in terms of electricity and heat. The generation of 15 times more heat energy than electricity, supports an installation of anaerobic digestion, close to homes. Moreover, if these results are encouraging, we suggest different scenarios of co-digestion ratios and operational parameters for their optimization.

Phenotype-Based Screens with Conformation-Specific Inhibitors Reveal p38 Gamma and Delta as Targets for HCC Polypharmacology.

The approved kinase inhibitors for hepatocellular carcinoma (HCC) are not matched to specific mutations within tumors. This has presented a daunting challenge; without a clear target or mechanism, no straightforward path has existed to guide the development of improved therapies for HCC. Here, we combine phenotypic screens with a class of conformation-specific kinase inhibitors termed type II to identify a multikinase inhibitor, AD80, with antitumoral activity across a variety of HCC preclinical models, including mouse xenografts. Mass spectrometry profiling found a number of kinases as putative targets for AD80, including several receptor and cytoplasmic protein kinases. Among these, we found p38 gamma and delta as direct targets of AD80. Notably, a closely related analog of AD80 lacking p38δ/γ activity, but retaining several other off-target kinases, lost significant activity in several HCC models. Moreover, forced and sustained MKK6 → p38→ATF2 signaling led to a significant reduction of AD80 activity within HCC cell lines. Together with HCC survival data in The Cancer Genome Atlas and RNA-seq analysis, we suggest p38 delta and gamma as therapeutic targets in HCC and an "AD80 inhibition signature" as identifying those patients with best clinical outcomes.

A whole-animal platform to advance a clinical kinase inhibitor into new disease space.

Synthetic tailoring of approved drugs for new indications is often difficult, as the most appropriate targets may not be readily apparent, and therefore few roadmaps exist to guide chemistry. Here, we report a multidisciplinary approach for accessing novel target and chemical space starting from an FDA-approved kinase inhibitor. By combining chemical and genetic modifier screening with computational modeling, we identify distinct kinases that strongly enhance ('pro-targets') or limit ('anti-targets') whole-animal activity of the clinical kinase inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We demonstrate that RAF-the original intended sorafenib target-and MKNK kinases function as pharmacological liabilities because of inhibitor-induced transactivation and negative feedback, respectively. Through progressive synthetic refinement, we report a new class of 'tumor calibrated inhibitors' with unique polypharmacology and strongly improved therapeutic index in fly and human MTC xenograft models. This platform provides a rational approach to creating new high-efficacy and low-toxicity drugs.

Dickkopf 1 protein circulating levels as a possible biomarker of functional disability and chronic damage in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status. Three hundred seventy-nine patients with RA were evaluated between March 2015 and November 2016. Disease activity was evaluated by disease activity score 28 with C-reactive protein (DAS28CPR), simplified and clinical disease activity scores (SDAI, CDAI), routine assessment of patient index data 3 (RAPID3), functional status using Multidimensional Health Assessment Questionnaire (MD-HAQ), and the Steinbrocker functional classification. DKK1 levels were measured by ELISA. The mean age was 60.7 ± 13.9 years. Disease duration was 13.2 ± 10.9 years. Higher levels of DKK1 were not associated with disease activity by CDAI (p = 0.70), SDAI (p = 0.84), DAS28CRP (p = 0.80), or RAPID3 (p = 0.70). Interestingly higher levels of DKK1 were significantly associated to lower functional status evaluating by the Steinbrocker classification (p = 0,013), severe disability by MD-HAQ (p = 0,004), and variables associated with joint destruction like osteoporosis, higher titles of rheumatoid factor, smoking, and increased hospital admissions related to RA. Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity by CDAI, SDAI, DAS28, and RAPID3. This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA.

Interobserver Agreement in Magnetic Resonance of the Sacroiliac Joints in Patients with Spondyloarthritis.

Background. Clinical, laboratory, and radiologic parameters are used for diagnosis and classification of spondyloarthritis (SpA). Magnetic resonance imaging (MRI) of sacroiliac (SI) joints is being increasingly used to detect early sacroiliitis. We decided to evaluate the interobserver agreement in MRI findings of SI joints of SpA patients between a local radiologist, a rheumatologist, and an expert radiologist in musculoskeletal diseases. Methods. 66 MRI images of the SI joints of patients with established diagnosis of SpA were evaluated. Agreement was expressed in Cohen's kappa. Results. Interobserver agreement between a local radiologist and an expert radiologist was fair (κ = 0.37). Only acute findings showed a moderate agreement (κ = 0.45), while chronic findings revealed 76.5% of disagreement (κ = 0.31). A fair agreement was observed in acute findings (κ = 0.38) as well as chronic findings (κ = 0.38) between a local radiologist and a rheumatologist. There was a substantial agreement between an expert radiologist and a rheumatologist (κ = 0.73). In acute findings, a 100% agreement was achieved. Also chronic and acute plus chronic findings showed high levels of agreement (κ = 0.73 and 0.62, resp.). Conclusions. Our study shows that rheumatologists may have similar MRI interpretations of SI joints in SpA patients as an expert radiologist.

Correlation between rapid-3, DAS28, CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis.

The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5-21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1-1.2), DAS 28 3.8 (IQR 2.7-5.1), and RAPID-3 12.3 (IQR 6-19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p < 0.001), CDAI (r 0.752, p < 0.001), and SDAI (r 0.758, p < 0.001). RAPID-3 had a high correlation with tools regularly used for disease activity assessment of RA patients in daily practice. The ease of its application favors routine use as it does not require laboratory results and joint counts.

Quantification of the fungal fraction released from various preloaded fibrous filters during a simulated ventilation restart.

This study aimed to demonstrate that particles, especially those associated with fungi, could be released from fibrous filters used in the air-handling unit (AHU) of heating, ventilation and air-conditioning (HVAC) systems during ventilation restarts. Quantification of the water retention capacity and SEM pictures of the filters was used to show the potential for fungal proliferation in unused or preloaded filters. Five fibrous filters with various particle collection efficiencies were studied: classes G4, M5, M6, F7, and combined F7 according to European standard EN779:2012. Filters were clogged with micronized rice particles containing the fungus Penicillium chrysogenum and then incubated for three weeks at 25°C and 90% relative humidity. The results indicated that the five clogged tested filters had various fungal growth capacities depending on their water retention capacity. Preloaded filters were subjected to a simulated ventilation restart in a controlled filtration device to quantify that the fraction of particles released was around 1% for the G4, 0.1% for the M5 and the M6, and 0.001% for the F7 and the combined F7 filter. The results indicate that the likelihood of fungal particle release by low efficiency filters is significantly higher than by high efficiency filters.

Sustainable conversion of agriculture wastes into activated carbons: energy balance and arsenic removal from water.

The aims of this study are to investigate the production of activated carbons (AC) from Senegal agricultural wastes such as cashew shells, millet stalks and rice husks and to implement them in adsorption processes devoted to arsenic (V) removal. AC were produced by a direct physical activation with water steam without other chemicals. This production of AC has also led to co-products (gas and bio-oil) which have been characterized in terms of physical, chemical and thermodynamical properties for energy recovery. Considering the arsenic adsorption results and the energy balance for the three studied biomasses, the first results have shown that the millet stalks seem to be more interesting for arsenate removal from natural water and an energy recovery with a GEEelec of 18.9%. Cashew shells, which have shown the best energy recovery (34.3%), are not suitable for arsenate removal. This global approach is original and contributes to a recycling of biowastes with a joint recovery of energy and material.

Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors.

Hepatitis C virus (HCV) replication is dependent on a liver-specific microRNA (miRNA), miR-122. A recent clinical trial reported that transient inhibition of miR-122 reduced viral titres in HCV-infected patients. Here we set out to better understand how miR-122 inhibition influences HCV replication over time. Unexpectedly, we observed the emergence of an HCV variant that is resistant to miR-122 knockdown. Next-generation sequencing revealed that this was due to a single nucleotide change at position 28 (G28A) of the HCV genome, which falls between the two miR-122 seed-binding sites. Naturally occurring HCV isolates encoding G28A are similarly resistant to miR-122 inhibition, indicating that subtle differences in viral sequence, even outside the seed-binding site, greatly influence HCV's miR-122 concentration requirement. In addition, we found that HCV itself reduces miR-122's activity in the cell, possibly through binding and sequestering miR-122. Our study provides insight into the interaction between miR-122 and HCV, including viral adaptation to reduced miR-122 bioavailability, and has implications for the development of anti-miR-122-based HCV drugs.

NH3 biofiltration of piggery air.

An aboveground pilot-scale biofilter filled with wood chips was tested to treat ammonia emissions from a piggery located in Brittany (France). Two long-term tests ("summer" and "autumn" experiments) were carried out to improve biofilter applications for agriculture. The influence of climatic conditions on biofilter performance was taken into account. During summer 2012, the biofilter was operated for 74 days at different empty bed residence times (EBRTs) from 6 to 15 s. Inlet NH3 concentrations were relatively constant (around 15 mg m(-3)). Significant NH3 reductions were achieved at EBRT = 12 s (removal efficiencies, RE, ranged between 90 and 100% for loading rates, LR, of around 4 g m(-3) h(-1)). At a lower EBRT (6 s), RE dropped to roughly 30-50%. This was due to the dramatic increase in the loading rate (LR up to 12 g m(-3) h(-1)) but the results showed that the change in atmospheric conditions (temperature and relative humidity) also had a significant influence on biofilter performance. It was evidenced that the use of a humidifier upstream of the biofilter must be taken into account for large-scale biofilter design, but only for specific conditions (the spraying of the biofilter having to be carried out exceptionally). During autumn 2012, the biofilter was operated for 116 days at EBRT = 12 s. RE were around 80% for LR of around 3 g m(-3) h(-1). In such autumnal atmospheric conditions, a demister system should be installed upstream of the biofilter in order to avoid water accumulation in the bed material. Although biofiltration was suitable for NH3 treatment of piggery air, the need to control accurately the medium moisture content implies that biofilters would not be easily managed by a pig farmer.

Effects of a saturated layer and recirculation on nitrogen treatment performances of a single stage Vertical Flow Constructed Wetland (VFCW).

Upgrades to enhance nitrogen removal were tested in a 2 year old pilot vertical flow constructed wetland in spring and summer periods. The effects of a saturated layer and of recirculation were tested in particular. Two pilots (L = 2 m, W = 1.25 m, H = 1.2 m), filled with expanded schist (Mayennite(®)), were designed with hydraulic saturated layers of 20 and 40 cm at the bottom. Each pilot was fed with raw domestic wastewater under field conditions according to a hydraulic load of 15-38 cm d(-1) (i.e. 158-401 g COD (chemical oxygen demand) m(-2) d(-1)) and to recirculation rates ranging from 0% up to 150%. The initial load during the first 2 years of operation resulted in an incomplete mineralized accumulated sludge leading to total suspended solids (TSS), COD and biochemical oxygen demand (BOD5) release. A 40 cm hydraulic saturated layer enabled an increase of 5-10% total nitrogen (TN) removal compared to a 20 cm saturated layer. Recirculation allowed the dilution of raw wastewater and enhanced nitrification in a single stage. A design of 1.8 m² pe(-1) (48 cm d(-1), 191 g COD m(-2) d(-1)) with a 40 cm saturated layer and 100% recirculation enabled the French standard D4 (35 mg TSS L(-1), 125 mg COD L(-1), 25 mg BOD5 L(-1)), nitrogen concentrations below 20 mg TKN (total Kjeldahl nitrogen) L(-1) and 50 mg TN L(-1), to be met.

Fate of pup inside the Mycobacterium proteasome studied by in-cell NMR.

The Mycobacterium tuberculosis proteasome is required for maximum virulence and to resist killing by the host immune system. The prokaryotic ubiquitin-like protein, Pup-GGE, targets proteins for proteasome-mediated degradation. We demonstrate that Pup-GGQ, a precursor of Pup-GGE, is not a substrate for proteasomal degradation. Using STINT-NMR, an in-cell NMR technique, we studied the interactions between Pup-GGQ, mycobacterial proteasomal ATPase, Mpa, and Mtb proteasome core particle (CP) inside a living cell at amino acid residue resolution. We showed that under in-cell conditions, in the absence of the proteasome CP, Pup-GGQ interacts with Mpa only weakly, primarily through its C-terminal region. When Mpa and non-stoichiometric amounts of proteasome CP are present, both the N-terminal and C-terminal regions of Pup-GGQ bind strongly to Mpa. This suggests a mechanism by which transient binding of Mpa to the proteasome CP controls the fate of Pup.

Evolution of microbial aerosol behaviour in heating, ventilating and air-conditioning systems--quantification of Staphylococcus epidermidis and Penicillium oxalicum viability.

The aim of this study was to develop an experimental set-up and a methodology to uniformly contaminate several filter samples with high concentrations of cultivable bacteria and fungi. An experimental set-up allows contaminating simultaneously up to four filters for range of velocities representative of heating, ventilating and air-conditioning systems. The test aerosol was composed of a microbial consortium of one bacterium (Staphylococcus epidermidis) and one fungus (Penicillium oxalicum) and aerosol generation was performed in wet conditions. Firstly, the experimental set-up was validated in regards to homogeneity of the air flows. The bioaerosol was also characterized in terms of number and particle size distribution using two particle counters: optical particle counter Grimm 1.109 (optical diameters) and TSI APS 3321 (aerodynamic diameters). Moreover, stabilities of the number of particles generated were measured. Finally, concentrations of cultivable microorganisms were measured with BioSamplers (SKC) downstream of the four filters.

Steady- and transient-state H2S biofiltration using expanded schist as packing material.

The performances of three laboratory-scale biofilters (BF1, BF2, BF3) packed with expanded schist for H(2)S removal were studied at different empty bed residence times (EBRT=35, 24 and 16s) in terms of elimination capacity (EC) and removal efficiency (RE). BF1 and BF2 were filled with expanded schist while BF3 was filled with both expanded schist and a nutritional material (UP20; 12% vol). BF1 and BF3 were inoculated with activated sludge, whereas BF2 was not inoculated. A maximum EC of 42 g m(-3) h(-1) was recorded for BF3 at EBRT=35 s demonstrating the ability of schist to treat high H(2)S loading rates, and the ability of UP20 to improve H(2)S removal. Michaelis-Menten and Haldane models were fitted to the experimental elimination capacities while biofilter responses to transient-state conditions in terms of removal efficiency during shock load events were also evaluated for BF1 and BF3.

Assessment of the efficiency of photocatalysis on tetracycline biodegradation.

The use of photocatalysis to improve the biodegradability of an antibiotic compound, tetracycline (TC) was investigated. The toxicity of TC and its degradation products were also examined. The Sturm test was conducted to assess the biodegradability of by-products formed in the photocatalytic process. The toxicity of tetracycline and its by-products was evaluated using a dehydrogenase inhibition test, which showed a decrease in toxicity during photocatalysis. However, the Sturm test results indicated that, like tetracycline, the by-products are not biodegradable. Possible structures of these by-products were determined using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). It was found that, during the photocatalytic process, the TC aromatic ring is not opened and the structure of the identified by-products is quite similar to that of tetracycline. A reaction pathway is proposed.

Signal transduction in receptor for advanced glycation end products (RAGE): solution structure of C-terminal rage (ctRAGE) and its binding to mDia1.

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule that plays a central role in the etiology of diabetes complications, inflammation, and neurodegeneration. The cytoplasmic domain of RAGE (C-terminal RAGE; ctRAGE) is critical for RAGE-dependent signal transduction. As the most membrane-proximal event, mDia1 binds to ctRAGE, and it is essential for RAGE ligand-stimulated phosphorylation of AKT and cell proliferation/migration. We show that ctRAGE contains an unusual α-turn that mediates the mDia1-ctRAGE interaction and is required for RAGE-dependent signaling. The results establish a novel mechanism through which an extracellular signal initiated by RAGE ligands regulates RAGE signaling in a manner requiring mDia1.

Evolution of microbial aerosol behaviour in heating, ventilating and air-conditioning systems--quantification of Staphylococcus epidermidis and Penicillium oxalicum viability.

The aim of this study was to develop an experimental set-up and a methodology to uniformly contaminate several filter samples with high concentrations of cultivable bacteria and fungi. An experimental set-up allows contaminating simultaneously up to four filters for range of velocities representative of heating, ventilating and air-conditioning systems. The test aerosol was composed of a microbial consortium of one bacterium (Staphylococcus epidermidis) and one fungus (Penicillium oxalicum) and aerosol generation was performed in wet conditions. Firstly, the experimental set-up was validated in regards to homogeneity of the air flows. The bioaerosol was also characterized in terms of the number and particle size distribution using two particle counters: optical particle counter Grimm 1.109 (optical diameters) and TSI APS 3321 (aerodynamic diameters). Moreover, stabilities of the number of particles generated were measured. Finally, concentrations of cultivable microorganisms were measured with BioSamplers SKC downstream of the four filters.