Viruses in nondisinfected drinking water from municipal wells and community incidence of acute gastrointestinal illness.

BackgroundGroundwater supplies for drinking water are frequently contaminated with low levels of human enteric virus genomes, yet evidence for waterborne disease transmission is lacking.ObjectivesWe related quantitative polymerase chain reaction (qPCR)-measured enteric viruses in the tap water of 14 Wisconsin communities supplied by nondisinfected groundwater to acute gastrointestinal illness (AGI) incidence.MethodsAGI incidence was estimated from health diaries completed weekly by households within each study community during four 12-week periods. Water samples were collected monthly from five to eight households per community. Viruses were measured by qPCR, and infectivity assessed by cell culture. AGI incidence was related to virus measures using Poisson regression with random effects.ResultsCommunities and time periods with the highest virus measures had correspondingly high AGI incidence. This association was particularly strong for norovirus genogroup I (NoV-GI) and between adult AGI and enteroviruses when echovirus serotypes predominated. At mean concentrations of 1 and 0.8 genomic copies/L of NoV-GI and enteroviruses, respectively, the AGI incidence rate ratios (i.e., relative risk) increased by 30%. Adenoviruses were common, but tap-water concentrations were low and not positively associated with AGI. The estimated fraction of AGI attributable to tap-water-borne viruses was between 6% and 22%, depending on the virus exposure-AGI incidence model selected, and could have been as high as 63% among children < 5 years of age during the period when NoV-GI was abundant in drinking water.ConclusionsThe majority of groundwater-source public water systems in the United States produce water without disinfection, and our findings suggest that populations served by such systems may be exposed to waterborne viruses and consequent health risks

Toner ink particle morphology in air-sparged hydrocyclone flotation deinking

Journal ArticleA series of pulping and flotation deinking tests were performed using a pilot-scale air-sparged hydrocyclone (ASH) flotation cell and a toner ink printed furnish. Microscopy studies indicate ink particles in both the flotation accepts and rejects are relatively flat. Many of the ink particles appear to be brittle and easily broken into smaller fragments. In some cases, toner ink particle softening had occurred as indicated by partial fusion of ink particles. Despite this softening, environmental scanning electron microscope (ESEM) images suggest toner ink particles were not elongated by the high shear conditions associated with the airsparged cyclone flotation cell

Impact of titanium doping on Al self-diffusion in alumina

α-Al2O3 is an important refractory material which has numerous technical applications: as an in situ growing self-healing oxide scale, as a massive material and as reinforcement fibres in composites. For modelling diffusion controlled processes (creep, sintering, alpha-alumina scale growth on aluminium bearing Fe or Ni base alloys) it is necessary to study self-diffusion of the constituent elements

Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Neoadjuvant treatment plays a crucial role in the therapy of advanced esophageal cancer. However, response to radiochemotherapy varies widely. Proton pump inhibitors (PPIs) have been demonstrated to impact on chemotherapy in a variety of other cancers. We analyzed the impact of PPI treatment on esophageal cancer cell lines, and investigated mechanisms that mediate the effect of PPI treatment in this tumour. Methods We investigated the effect of esomeprazole treatment on cancer cell survival, adhesion, migration and chemotherapy in human adeno-(OE19) and squamous-cell-carcinoma (KYSE410) cell lines. Furthermore, we investigated the effect of PPI treatment on intra-/extracellular pH and on expression of resistance-relevant miRNAs. Results Esomeprazole significantly inhibited tumour cell survival (in a dose-dependent manner), adhesion and migration in both tumour subtypes. Furthermore, esomeprazole augmented the cytotoxic effect of cisplatin and 5-FU in both tumour subtypes. Surprisingly, PPI treatment led to a significant increase of intracellular pH and a decrease of the extracellular pH. Finally, we found esomeprazole affected expression of resistance-relevant miRNAs. Specifically, miR-141 and miR-200b were upregulated, whereas miR-376a was downregulated after PPI treatment in both tumour types. Conclusion Our study demonstrates for the first time that PPIs impact on tumour cell survival, metastatic potential and sensitivity towards chemotherapy in esophageal cancer cell lines. Furthermore, we observed that in this tumour entity, PPIs do not lead to intracellular acidification, but affect the expression of resistance-relevant miRNAs. Keywords: Proton pump inhibitor; PPI; Esophageal cancer; Metastasis; Chemotherapy; Resistance; microRN

Evolution of porosity in carbide-derived carbon aerogels

Carbide-derived carbon (CDC) aerogel monoliths with very high porosity are synthesized starting from polymeric precursors. Cross-linking by platinum-catalyzed hydrosilylation of polycarbosilanes followed by supercritical drying yields preceramic aerogels. After ceramic conversion and silicon extraction in hot chlorine gas, hierarchically porous carbon materials with specific surface areas as high as 2122 m² g⁻¹ and outstanding total pore volumes close to 9 cm³ g⁻¹ are obtained. Their pore structure is controllable by the applied synthesis temperature as shown by combined nitrogen (-196 °C) and carbon dioxide (0 °C) measurements coupled with electron microscopic methods. The combination of large micropore volumes and the aerogel-type pore system leads to advanced adsorption properties due to a combination of large storage capacities and effective materials transport in comparison with purely microporous reference materials as shown by thermal response measurements

Synthetic Mirnov diagnostic for the validation of experimental observations

A synthetic Mirnov diagnostic has been developed to investigate the capabilities and limitations of an arrangement of Mirnov coils in terms of a mode analysis. Eight test cases have been developed, with different coil arrangements and magnetic field configurations. Three of those cases are experimental configurations of the stellarator Wendelstein 7-X. It is observed that, for a high triangularity of the flux surfaces, the arrangement of the coils plays a significant role in the exact determination of the poloidal mode number. For the mode analysis, torus and magnetic coordinates have been used. In most cases, the reconstruction of the poloidal mode number of a prescribed mode was found to be more accurate in magnetic coordinates. As an application, the signal of an Alfvén eigenmode, which has been calculated with a three-dimensional magnetohydrodynamics code, is compared to experimental observations at Wendelstein 7-X. For the chosen example, the calculated and measured mode spectra agree very well and additional information on the toroidal mode number and localization of the mode has been inferred

The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of sigD

The Gram-positive obligate anaerobe Clostridium difficile causes potentially fatal intestinal diseases. How this organism regulates virulence gene expression is poorly understood. In many bacterial species, the second messenger cyclic di-GMP (c-di-GMP) negatively regulates flagellar motility and, in some cases, virulence. c-di-GMP was previously shown to repress motility of C. difficile. Recent evidence indicates that flagellar gene expression is tightly linked with expression of the genes encoding the two C. difficile toxins TcdA and TcdB, which are key virulence factors for this pathogen. Here, the effect of c-di-GMP on expression of the toxin genes tcdA and tcdB was determined, and the mechanism connecting flagellar and toxin gene expressions was examined. In C. difficile, increasing c-di-GMP levels reduced the expression levels of tcdA and tcdB, as well as that of tcdR, which encodes an alternative sigma factor that activates tcdA and tcdB expression. We hypothesized that the C. difficile orthologue of the flagellar alternative sigma factor SigD (FliA; σ28) mediates regulation of toxin gene expression in response to c-di-GMP. Indeed, ectopic expression of sigD in C. difficile resulted in increased expression levels of tcdR, tcdA, and tcdB. Furthermore, sigD expression enhanced toxin production and increased the cytopathic effect of C. difficile on cultured fibroblasts. Finally, evidence is provided that SigD directly activates tcdR expression and that SigD cannot activate tcdA or tcdB expression independent of TcdR. Taken together, these data suggest that SigD positively regulates toxin genes in C. difficile and that c-di-GMP can inhibit both motility and toxin production via SigD, making this signaling molecule a key virulence gene regulator in C. difficile

Broadband Alfvénic excitation correlated to turbulence level in the Wendelstein 7-X stellarator plasmas

During the first operational phase (OP1) of the Wendelstein 7-X (W7-X) stellarator, poloidal magnetic field fluctuations, $\dot{B}_{\theta}$, were measured in several different plasma scenarios with a system of Mirnov coils. In the spectrograms, multiple frequency bands close together in frequency are observed below f = 600 kHz. Furthermore, a dominant feature is the appearance of a frequency band with the highest spectral amplitude centred between $f = 180-220$ kHz. The fluctuations are observed from the beginning of most W7-X plasmas of OP1, which were often operated solely with electron cyclotron resonance heating. The fluctuations show characteristics known from Alfvén waves and possibly Alfvén eigenmodes (AEs). However, the fast particle drive from heating sources, which is generally a driver necessary for the appearance of AEs in magnetic confinement plasmas, is absent in most of the analysed experiments. A characterization of the Alfvénic fluctuations measured during OP1 plasmas is possible using a newly developed tracking algorithm. In this paper, we extensively survey the different spectral properties of the fluctuations in correlation with plasma parameters and discuss possible driving mechanisms. The correlation studies of the dynamics of the possible ellipticity induced AEs indicate that Alfvén activity in the frequency interval between $f = 100-450$ kHz could be excited due to an interaction with turbulence, or profile effects also affecting the turbulence amplitude

Controlling mRNA stability and translation with the CRISPR endoribonuclease Csy4

The bacterial CRISPR endoribonuclease Csy4 has recently been described as a potential RNA processing tool. Csy4 recognizes substrate RNA through a specific 28-nt hairpin sequence and cleaves at the 3′ end of the stem. To further explore applicability in mammalian cells, we introduced this hairpin at various locations in mRNAs derived from reporter transgenes and systematically evaluated the effects of Csy4-mediated processing on transgene expression. Placing the hairpin in the 5′ UTR or immediately after the start codon resulted in efficient degradation of target mRNA by Csy4 and knockdown of transgene expression by 20- to 40-fold. When the hairpin was incorporated in the 3′ UTR prior to the poly(A) signal, the mRNA was cleaved, but only a modest decrease in transgene expression (∼2.5-fold) was observed. In the absence of a poly(A) tail, Csy4 rescued the target mRNA substrate from degradation, resulting in protein expression, which suggests that the cleaved mRNA was successfully translated. In contrast, neither catalytically inactive (H29A) nor binding-deficient (R115A/R119A) Csy4 mutants were able to exert any of the effects described above. Generation of a similar 3′ end by RNase P-mediated cleavage was unable to rescue transgene expression independent of Csy4. These results support the idea that the selective generation of the Csy4/hairpin complex resulting from cleavage of target mRNA might serve as a functional poly(A)/poly(A) binding protein (PABP) surrogate, stabilizing the mRNA and supporting translation. Although the exact mechanism(s) remain to be determined, our studies expand the potential utility of CRISPR nucleases as tools for controlling mRNA stability and translation

Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region

Methane (CH_4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH_4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit ∼2 kg/h to 5 kg/h through ∼5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. With the observed confirmation of a lognormal emission distribution, this airborne observing strategy and its ability to locate previously unknown point sources in real time provides an efficient and effective method to identify and mitigate major emissions contributors over a wide geographic area. With improved instrumentation, this capability scales to spaceborne applications [Thompson DR, et al. (2016) Geophys Res Lett 43(12):6571–6578]. Further illustration of this potential is demonstrated with two detected, confirmed, and repaired pipeline leaks during the campaign