Engineering antimicrobial supramolecular polymer assemblies

Antibacterial resistance against conventional antibiotics has emerged as a global health problem. To address this problem, antimicrobial peptides (AMPs) have been recognized as alternatives due to their fast-killing activity and less propensity to induce resistance. Here, the AMPs are engineered via a supramolecular fashion to control and increase their biological performance. The AMPs are modified with ureido-pyrimidinone (UPy) to obtain UPy-AMP monomers, followed by modular self-assembling to realize antibacterial UPy-AMP supramolecular polymers. These positively charged assemblies are illustrated as stable, short fibrous or rod-like UPy-AMP nanostructures with enhanced antibacterial activity and modulable cytotoxicity. Moreover, these antibacterial UPy-AMP assemblies can be internalized by both THP-1 derived macrophages and human kidney cells, which would be an effective potential therapy to deliver the AMPs into mammalian cells to address intracellular infections. Overall, the results present here demonstrate that supramolecular engineering of AMPs provides a powerful tool to enhance the antibacterial activity, modulate cytotoxicity and accelerate the clinical application of AMPs.</p

Engineering antimicrobial supramolecular polymer assemblies

Antibacterial resistance against conventional antibiotics has emerged as a global health problem. To address this problem, antimicrobial peptides (AMPs) have been recognized as alternatives due to their fast-killing activity and less propensity to induce resistance. Here, the AMPs are engineered via a supramolecular fashion to control and increase their biological performance. The AMPs are modified with ureido-pyrimidinone (UPy) to obtain UPy-AMP monomers, followed by modular self-assembling to realize antibacterial UPy-AMP supramolecular polymers. These positively charged assemblies are illustrated as stable, short fibrous or rod-like UPy-AMP nanostructures with enhanced antibacterial activity and modulable cytotoxicity. Moreover, these antibacterial UPy-AMP assemblies can be internalized by both THP-1 derived macrophages and human kidney cells, which would be an effective potential therapy to deliver the AMPs into mammalian cells to address intracellular infections. Overall, the results present here demonstrate that supramolecular engineering of AMPs provides a powerful tool to enhance the antibacterial activity, modulate cytotoxicity and accelerate the clinical application of AMPs.</p

Integrated Management of Industrial and Municipal Wastewater in China. - Demonstration Project in Jiaxing, Zhejiang Province

Årsliste 2000The city of Jiaxing in Zhejiang Province is a medium-size, rapidly expanding Chinese city located in a flat landscape with numerous canals. These are used for navigation, fishing, aquaculture and as drinking and industrial water source, but also as recipients for domestic and industrial wastewater and runoff from agriculture, paved roads and solid waste landfills in the area. The canals are severely polluted. NIVA has been assisting Jiaxing Environmental Protection Bureau (JEPB) in finding solutions to the local wastewater problems. The industry in the area discharges substantial quantities of potentially toxic wastewater to the sewer systems. There are, however, good possibilities for cleaner production routines in various factories. Several measures facilitate the transport of sewage to the nearby Hangzhou Bay, and sewage treatment processes before final disposal have been identified. The project has identified current and future wastewater production and recipient status. Based on pilot-plant operation and computer models a complete system for sewage collection and treatment has been suggested. This is based on transport of untreated sewage to Hanfzhou Bay where the construction of a sewage treatment plant is planned. The treatment methodology is based on a flexible chemically enhanced primary treatment (CEPT), followed by a biological step at a later stage. The project findings put emphasis on knowledge transfer and strengthening of JEPB resources to find solutions to the water-related problems in the city. In addition a detailed abatement plan should be developed, taking existing water quality, user interests and future water quality objectives into account.Direktoratet for Utviklingshjelp (NORAD

Evaluating EDGARv4.tox2 speciated mercury emissions ex-post scenarios and their impacts on modelled global and regional wet deposition patterns

Speciated mercury gridded emissions inventories together with chemical transport models and concentration measurements are essential when investigating both the effectiveness of mitigation measures and the mercury cycle in the environment. Since different mercury species have contrasting behaviour in the atmosphere, their proportion in anthropogenic emissions could determine the spatial impacts. In this study, the time series from 1970 to 2012 of the EDGARv4.tox2 global mercury emissions inventory are described; the total global mercury emission in 2010 is 1772 tonnes. Global grid-maps with geospatial distribution of mercury emissions at a 0.1° × 0.1° resolution are provided for each year. Compared to the previous tox1 version, tox2 provides updates for more recent years and improved emissions in particular for agricultural waste burning, power generation and artisanal and small-scale gold mining (ASGM) sectors. We have also developed three retrospective emissions scenarios based on different hypotheses related to the proportion of mercury species in the total mercury emissions for each activity sector; improvements in emissions speciation are seen when using information primarily from field measurements. We evaluated them using the GEOS-Chem 3-D mercury model in order to explore the influence of speciation shifts, to reactive mercury forms in particular, on regional wet deposition patterns. The reference scenario S1 (EDGARv4.tox2_S1) uses speciation factors from the Arctic Monitoring and Assessment Programme (AMAP); scenario S2 (“EPA_power”) uses factors from EPA's Information Collection Request (ICR); and scenario S3 (“Asia_filedM”) factors from recent scientific publications. In the reference scenario, the sum of reactive mercury emissions (Hg-P and Hg 2+ ) accounted for 25.3% of the total global emissions; the regions/countries that have shares of reactive mercury emissions higher than 6% in total global reactive mercury are China+ (30.9%), India+ (12.5%) and the United States (9.9%). In 2010, the variations of reactive mercury emissions amongst the different scenarios are in the range of −19.3 t/yr (China+) to 4.4 t/yr (OECD_Europe). However, at the sector level, the variation could be different, e.g., for the iron and steel industry in China reaches 15.4 t/yr. Model evaluation at the global level shows a variation of approximately ±10% in wet deposition for the three emissions scenarios. An evaluation of the impact of mercury speciation within nested grid sensitivity simulations is performed for the United States and modelled wet deposition fluxes are compared with measurements. These studies show that using the S2 and S3 emissions of reactive mercury, can improve wet deposition estimates near sources

RSPO3 expands intestinal stem cell and niche compartments and drives tumorigenesis

Objective The gross majority of colorectal cancer cases results from aberrant Wnt/ß-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1 mutations. However, a subset of human colon tumours harbour, mutually exclusive with APC and CTNNB1 mutations, gene fusions in RSPO2 or RSPO3, leading to enhanced expression of these R-spondin genes. This suggested that RSPO activation can substitute for the most common mutations as an alternative driver for intestinal cancer. Involvement of RSPO3 in tumour growth was recently shown in RSPO3-fusion-positive xenograft models. The current study determines the extent into which solely a gain in RSPO3 actually functions as a driver of intestinal cancer in a direct, causal fashion, and addresses the in vivo activities of RSPO3 in parallel. Design We generated a conditional Rspo3 transgenic mouse model in which the Rspo3 transgene is expressed upon Cre activity. Cre is provided by cross-breeding with Lgr5-GFP-CreERT2 mice. Results Upon in vivo Rspo3 expression, mice rapidly developed extensive hyperplastic, adenomatous and adenocarcinomatous lesions throughout the intestine. RSPO3 induced the expansion of Lgr5+ stem cells, Paneth cells, non-Paneth cell label-retaining cells and Lgr4+ cells, thus promoting both intestinal stem cell and niche compartments. Wnt/ß-catenin signalling was modestly increased upon Rspo3 expression and mutant Kras synergised with Rspo3 in hyperplastic growth. Conclusions We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis. This establishes RSPO3 as a potent driver of intestinal cancer and proposes RSPO3 as a candidate target for therapy in patients with colorectal cancer harbouring RSPO3 fusions

f(R)f(R) gravity constrained by PPN parameters and stochastic background of gravitational waves

We analyze seven different viable $f(R)$-gravities towards the Solar System tests and stochastic gravitational waves background. The aim is to achieve experimental bounds for the theory at local and cosmological scales in order to select models capable of addressing the accelerating cosmological expansion without cosmological constant but evading the weak field constraints. Beside large scale structure and galactic dynamics, these bounds can be considered complimentary in order to select self-consistent theories of gravity working at the infrared limit. It is demonstrated that seven viable $f(R)$-gravities under consideration not only satisfy the local tests, but additionally, pass the above PPN-and stochastic gravitational waves bounds for large classes of parameters.Comment: 23 pages, 8 figure

In-plane fluxon in layered superconductors with arbitrary number of layers

I derive an approximate analytic solution for the in-plane vortex (fluxon) in layered superconductors and stacked Josephson junctions (SJJ's) with arbitrary number of layers. The validity of the solution is verified by numerical simulation. It is shown that in SJJ's with large number of thin layers, phase/current and magnetic field of the fluxon are decoupled from each other. The variation of phase/current is confined within the Josephson penetration depth, $\lambda_J$, along the layers, while magnetic field decays at the effective London penetration depth, $\lambda_c \gg \lambda_J$. For comparison with real high-$T_c$ superconducting samples, large scale numerical simulations with up to 600 SJJ's and with in-plane length up to 4000 $\lambda_J$%, are presented. It is shown, that the most striking feature of the fluxon is a Josephson core, manifesting itself as a sharp peak in magnetic induction at the fluxon center.Comment: 4 pages, 4 figures. Was presented in part at the First Euroconference on Vortex Matter in Superconductors (Crete, September 1999

Who makes the decision regarding the treatment of clinically localized prostate cancer-the patient or physician?: Results from a population-based study

Background: The current study examined how patients' sociodemographic, cancer-related, and subjective affective factors impacted their role in treatment decision-making. Methods: The patient sample (N = 788) was taken from a prospective follow-up study of a population-based cohort. Participants included 343 African American and 445 Caucasian-American patients with clinically localized prostate cancer. Multinomial logistic regression was used to investigate relations between the explanatory variables and the nominal 3-level decision-making variable: patient-only, patient-physician shared, and physician-only. Results: Approximately 41% of patients reported patient-only decision-making, 45% reported shared decision-making, and 13% reported physician-only decision-making. The odds of patient-only over physician-only decision-making were greater for younger men (vs those aged ≥ 65 years) (odds ratio [OR], 1.68; 95% confidence interval [95% CI], 1.03-2.74), and were less for men with high (vs low) cancer aggressiveness (OR,0.29; 95% CI, 0.15-0.55). The odds of shared over physician-only decision-making were less for men with high (vs low) cancer aggressiveness (OR, 0.40; 95% CI, 0.22-0.73). Greater odds of patient-only and shared decision-making also were found to be associated with greater concerns about the physical impact of treatment and having enough time for decision-making and lower scores of receiving advice from others. Conclusions: The findings of the current study indicate that, to facilitate a more patient-oriented decision-making process regarding treatment in those with clinically localized prostate cancer, clinicians need to tailor their interventions according to patient age and cancer aggressiveness, help reduce patient concerns and misconceptions regarding the physical impact of treatments, allow sufficient time for patients to consider treatment options, and assist patients in balancing advice and information received from different sources

Influence of spark ignition in the determination of Markstein lengths using spherically expanding flames

Constant pressure outwardly propagating flame experiments in a spherical bomb are performed to examine the duration and radius over which spark ignition effects persist. This is motivated by the need to properly account for such effects in the measurement of laminar burning velocity and Markstein length using the spark ignited expanding flame technique. Ignition energy was varied and its effects on flame propagation in methane-air and isooctane-air mixtures were studied. The Markstein length of the mixture proved critical in the ignition energy dependency of flame propagation. For relatively high values, an underlying common variation of self-sustaining flame speed with radius can be identified by the rapid convergence of curves for different ignition energies. As the Markstein length decreases, low energy spark ignition is found to give rise to a distorted and wrinkled flame kernel. For such mixtures, due to the weak effect of stretch, the kernel subsequently develops into a non-spherically propagating flame. In these cases the spark ignition effect persists up to large radius. It is shown that using low ignition energy leads to a flame speed, during the development phase, which is higher than that of a self-sustaining spherical flame. It is further shown that if this effect is not accounted for, measurements of Markstein length using standard fitting techniques results in a large error. This problem is found to worsen as the Markstein length decreases, such that its apparent measured value becomes increasingly influenced by any distortions of the flame kernel produced by the spark

Charged-Particle Multiplicities in Charged-Current Neutrino-- and Anti-Neutrino--Nucleus Interactions

The CHORUS experiment, designed to search for $\nu_{\mu}\to\nu_{\tau}$ oscillations, consists of a nuclear emulsion target and electronic detectors. In this paper, results on the production of charged particles in a small sample of charged-current neutrino-- and anti-neutrino--nucleus interactions at high energy are presented. For each event, the emission angle and the ionization features of the charged particles produced in the interaction are recorded, while the standard kinematic variables are reconstructed using the electronic detectors. The average multiplicities for charged tracks, the pseudo-rapidity distributions, the dispersion in the multiplicity of charged particles and the KNO scaling are studied in different kinematical regions. A study of quasi-elastic topologies performed for the first time in nuclear emulsions is also reported. The results are presented in a form suitable for use in the validation of Monte Carlo generators of neutrino--nucleus interactions.Comment: 17 pages, 5 figure