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Midlatitude waterbodies are experiencing increased cyanobacteria blooms that necessitate health advisories to protect waterbody users. Although surface waters may contain cyanotoxins such as microcystin (MC), at concentrations that pose potential public health risks, little is known about MC contamination of shoreline sediments. Based on growing evidence that lake and reservoir sediments can accumulate MCs, we hypothesized that shoreline sediments (i.e., recreational beaches) may accumulate MCs and thereby pose a potential health risk to recreational users even if people stay out of contaminated water. We sampled nearshore surface water, shoreline sediment, and porewater from seven Washington State, USA, lakes/reservoirs recreational beaches to determine MC presence/absence during or immediately following cyanobacteria blooms. We found MCs in shoreline sediments at all waterbodies using ELISA and LC-MS/MS. MC concentrations in shoreline sediments and porewaters persisted for 20 days following dissipation of cyanobacteria blooms when MC concentrations were near analytical reporting limits in corresponding surface waters. A human health risk assessment based on potential MC exposure through incidental ingestion of porewaters and sediments found, even when very high MC concentrations occur in surface waters (i.e., >11,000 μg/L), estimated ingestion doses are below MC World Health Organization tolerable daily intake and U.S. Environmental Protection Agency’s risk reference dose. While our findings suggest MCs in Washington State recreational beaches in 2018 did not present a significant human health risk, future blooms with higher MC concentrations could pose human health risks via the shoreline sediment/porewater exposure pathway.

The amyloid-β peptide (Aβ)-in particular, the 42-amino acid form, Aβ1-42-is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Thus, several therapeutic modalities aiming to inhibit Aβ synthesis or increase the clearance of Aβ have entered clinical trials, including γ-secretase inhibitors, anti-Aβ antibodies, and amyloid-β precursor protein cleaving enzyme inhibitors. A unique class of small molecules, γ-secretase modulators (GSMs), selectively reduce Aβ1-42 production, and may also decrease Aβ1-40 while simultaneously increasing one or more shorter Aβ peptides, such as Aβ1-38 and Aβ1-37. GSMs are particularly attractive because they do not alter the total amount of Aβ peptides produced by γ-secretase activity; they spare the processing of other γ-secretase substrates, such as Notch; and they do not cause accumulation of the potentially toxic processing intermediate, β-C-terminal fragment. This report describes the translation of pharmacological activity across species for two novel GSMs, (S)-7-(4-fluorophenyl)-N2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (BMS-932481) and (S,Z)-17-(4-chloro-2-fluorophenyl)-34-(3-methyl-1H-1,2,4-triazol-1-yl)-16,17-dihydro-15H-4-oxa-2,9-diaza-1(2,4)-cyclopenta[d]pyrimidina-3(1,3)-benzenacyclononaphan-6-ene (BMS-986133). These GSMs are highly potent in vitro, exhibit dose- and time-dependent activity in vivo, and have consistent levels of pharmacological effect across rats, dogs, monkeys, and human subjects. In rats, the two GSMs exhibit similar pharmacokinetics/pharmacodynamics between the brain and cerebrospinal fluid. In all species, GSM treatment decreased Aβ1-42 and Aβ1-40 levels while increasing Aβ1-38 and Aβ1-37 by a corresponding amount. Thus, the GSM mechanism and central activity translate across preclinical species and humans, thereby validating this therapeutic modality for potential utility in AD.

Hydrogen embrittlement is a complex phenomenon, involving several length- and timescales, that affects a large class of metals. It can significantly reduce the ductility and load-bearing capacity and cause cracking and catastrophic brittle failures at stresses below the yield stress of susceptible materials. Despite a large research effort in attempting to understand the mechanisms of failure and in developing potential mitigating solutions, hydrogen embrittlement mechanisms are still not completely understood. There are controversial opinions in the literature regarding the underlying mechanisms and related experimental evidence supporting each of these theories. The aim of this paper is to provide a detailed review up to the current state of the art on the effect of hydrogen on the degradation of metals, with a particular focus on steels. Here, we describe the effect of hydrogen in steels from the atomistic to the continuum scale by reporting theoretical evidence supported by quantum calculation and modern experimental characterisation methods, macroscopic effects that influence the mechanical properties of steels and established damaging mechanisms for the embrittlement of steels. Furthermore, we give an insight into current approaches and new mitigation strategies used to design new steels resistant to hydrogen embrittlement.

Heavy hydrogen gets frozen in place Hydrogen embrittlement contributes to the failure of steel in a wide variety of everyday applications. Various strategies to mitigate hydrogen embrittlement, such as adding carbides into the steel, are hard to validate because we are unable to map the hydrogen atoms. Chen et al. combined fluxing steel samples with deuterium and a cryogenic transfer protocol to minimize hydrogen diffusion, allowing for detailed structural analysis (see the Perspective by Cairney). Their findings revealed hydrogen trapped in the cores of the carbide precipitates. The technique will be applicable to a wide range of problems, including corrosion, catalysis, and hydrogen storage. Science , this issue p. 1196 ; see also p. 1128

Concord grape juice is associated with many health benefits, and so it can be sold at a premium price. However, there is currently no method to verify the percent composition of Concord grape juice in grape juice blends. In order to guard against potential adulteration, a rapid method for authentication is required. Fourier Transform infrared (FT-IR) spectroscopy was used to develop a model which predicts the percent composition of Concord grape juice. The model was based on a training set of 64 samples with Concord concentrations ranging from 50% to 100%. Data was collected on an external validation set with a standard error of prediction of 5.6% using 7 factors. The results suggest the feasibility of using FT-IR coupled with chemometrics as a production-scale tool for authentication claims of Concord in grape juice blends, protecting consumers and businesses against deceptive labelling.

Graphitic materials and graphite composites experience dimensional change when exposed to\ud radiation-induced atomic displacements. This has major implications for current and future\ud technological ranging from nuclear fission reactors to the processing of graphene-silicon\ud hybrid devices. Dimensional change in nuclear graphites is a complex problem involving the\ud filler, binder, porosity, cracks and atomic-level effects all interacting within the polygranular\ud structure. An improved understanding of the atomistic mechanisms which drive dimensional\ud change within individual graphitic crystals is required to feed into the multiscale modelling of\ud this system.\ud In this study, micromechanically exfoliated samples of highly oriented pyrolytic graphite\ud have been ion irradiated and studied in situ using transmission electron microscopy (TEM) in\ud order to gain insights into the response of single graphitic crystals to displacing radiation.\ud Under continuous ion bombardment, a complex dynamic sequence of deformation evolves\ud featuring several distinct stages from the inducement of strain, the creation of dislocations\ud leading to dislocation arrays, the formation of kink band networks and localised doming of the sample. Observing these ion irradiation-induced processes using in situ TEM reveals\ud previously unknown details of the sequence of microstructural developments and physics\ud driving these phenomena. A mechanistic model consistent with the microstructural changes\ud observed is presented.

Thermoelectric materials are of interest for converting waste heat to electricity and could be useful in applications such as power generation.1 Currently, bulk bismuth telluride (Bi2Te3) is the most commonly used material for thermoelectric coolers and waste heat recovery. However, theoretical calculation2 predicts that the thermoelectric performance of Bi2Te3 can be dramatically improved by confining its dimensions to the nanometre scale. Electrodeposition provides a bottom-up technique compared to conventional coating methods, such as physical vapor deposition (PVD). It is of advantage in the efficient use of the starting material and can be used to plate curved surfaces and even inside of topologically demanding surfaces.3 The use of electrodeposition to fill nano-structures is also achievable, which is exploited in the Damascene process to grow 20 nm diameter Cu wire.4 In electrochemical experiments water is the most commonly used solvent but its limitation includes narrow potential window, which is crucial in electrodeposition as water reduction will be a competing process for metal reduction/deposition and introduces complexity to experiments. Here we employ an electrolyte system based on tetrabutylammonium chlorometallate metal sources with compatible tetraalkyl halide supporting electrolytes in non-aqueous, weakly coordinating solvents,5,6 which provides the ability to deposit alloys with desired structures and properties. In this work we report the deposition of Bi2Te3 films from dichloromethane. Bi2Te3 is a narrow band gap layered semi-conductor and it is demonstrated that the composition and structure of the BiTe films can be controlled by tuning the electrochemical parameters, such as the electrolyte concentration and deposition potential (Figure 1).7 We then investigate Bi2Te3 nucleation and growth using transmission electron microscopy (TEM) with a boron doped diamond electrode, acting as the electron transparent substrate.8 We observe the initial stage of Bi, Te and BiTe nuclei after electrodeposition (from individual atoms to atom arrays and nanocrystals) This work is conducted as part of the ADEPT project funded by EPSRC (EP/N035437/1). [1] Materials 7.4 (2014): 2577-2592. [2] Physical review B 47.24 (1993): 16631. [3] Proceedings of the National Academy of Sciences 106.35 (2009): 14768-14772. [4] IBM Journal of Research and Development 42.5 (1998): 567-574. [5] Chemistry-A European Journal 22.1 (2016): 302-309. [6] RSC Advances 3.36 (2013): 15645-15654. [7] Journal of Electroanalytical Chemistry 839 (2019): 134-140. [8] ACS nano 12.7 (2018), 7388-7396 Figure 1

Flexible Cu (In, Ga) Se2 (CIGS) solar cells are very attractive renewable energy sources because of their high conversion efficiencies, their low cost potential and their many application possibilities. However, they are at present highly susceptible to long term environmental degradation as a result of water vapor ingress through the protective encapsulation layer to the absorber (CIGS) layer. The basic methodology to prevent the water vapor permeation is to combine an oxide layer (e.g. AlOx) coating with suitable polymer substrates. Nevertheless, micro and nano-scale defects can appear at any stage of the coating process thus affecting the module efficiency and lifespan. The main aim of this research paper is to use surface metrology techniques including: White Light Scanning Interferometry (WLSI), Atomic Force Microscopy (AFM) and Environmental Scanning Electron Microscopy (ESEM) to characterise the aluminum oxide (Al2O3) barrier film defects, which appear to be directly responsible for the water vapor permeability. This paper reports on the development of a characterisation method for defect detection based on “Wolf Pruning” method and then correlates this with measured water vapor transmission rates (WVTRs) using standard MOCON® test. The results presented in this paper provided a detailed knowledge of the nature of micro and nano-scale defects on the Al2O3 barrier films which are responsible for water vapor and oxygen ingress. This result can then be used to provide the basis for developing roll-to-roll in process metrology devices for quality control of flexible PV module manufacture.

This paper shows that visible-light ptychography can be used to distinguish quantitatively between healthy and tumorous unstained cells. Advantages of ptychography in comparison to conventional phase-sensitive imaging techniques are highlighted. A novel procedure to automatically refocus ptychographic reconstructions is also presented, which improves quantitative analysis.

This paper discusses ptychography, a coherent diffraction imaging technique. Advantages of ptychography with respect conventional imaging techniques for cell visualisation are highlighted and demonstrated using unstained healthy and tumorous mouse cells as the object under investigation. A novel procedure to automatically refocus a possible slightly out of focus ptychographic data set will be discussed, by which an improved quantitative analysis and discrimination is enabled.

This paper is intended to introduce ptychography, a novel and very promising phase retrieval technique. It is based on the lens-less recording of a series of diffraction patterns caused by coherent object illumination. In the visible region of light, ptychography has successfully been implemented for visible light microscopy and optical metrology. Ptychography has also successfully been applied to X-ray microscopy where it is difficult to manufacture good quality lenses and where, at high X-ray energies, absorption contrast is low but where phase contrast is significant. In the course of this paper theoretical fundamentals of ptychography are explained, advantages in comparison to traditional optical techniques are represented and applications are shown.

There are many different strategies that allow the solving of the well-known phase problem corresponding to the loss of phase information during a physical measurement. In microscopy, and, in particular, in transmission electron microscopy, most of these strategies focus on the retrieval of high-resolution information with the importance of lower resolution data often overlooked. Ptychography offers a means to investigate such data. Ptychography is a robust diffractive imaging technique with fast convergence for phase retrieval but, until now, has not been applied at the nanoscale. In this paper, we use the ptychographical iterative engine to retrieve the phase change at the exit plane of metallic nanoparticles using a conventional transmission electron microscope. Ptychographical reconstructions yielded images with a phase resolution of $\ensuremath{\pi}/10$ and a spatial resolution of 1 nm. These results stand as a first step toward aberration-free lensless imaging. The technique lends itself to be an alternative to off-axis electron holography or focal series reconstruction.

The estuarine mysid, Mysidopsis bahia , is widely used in establishing acute and chronic toxicity of saline aqueous samples. Survival, growth and fecundity are some of the common endpoints analyzed in short-term chronic toxicity tests. The present study proposes use of a new sublethal endpoint, sexual maturity. A mysid is considered to be sexually mature if it shows presence of gonads that can be clearly distinguished as the testis or the brood sac. This endpoint can be measured by a K-factor, defined as the ratio of the total number of mysids achieving sexual maturity to the total number of surviving mysids. Three sets of parallel tests were conducted using cadmium chloride as a toxicant. Both tests in each set were initiated simultaneously using 8-day-old mysids. One of the two tests in each set was terminated after 96 h of exposure with survival, growth and sexual maturity evaluated as endpoints. The second test from each set was conducted over a 7-day period and survival, growth, fecundity and sexual maturity were evaluated as endpoints. Results indicate that sexual maturity is a sensitive endpoint and can be used as an estimator of chronic toxicity.

Transmission electron microscopy applies either parallel or focused electron beams for illuminating the object, and all high resolution methods such as lattice imaging, electron holography or diffractive imaging rely on interference effects which necessitate coherent electrons. In lattice imaging the effects of partial spatial and partial temporal coherence are usually dealt with by applying Gaussian envelopes to the contrast transfer function to describe the dampening of higher spatial frequencies. This means the coherence is only modelled indirectly, for partial spatial coherence by a convergence angle and for temporal coherence by a defocus spread due to chromatic broadening. To measure the coherence function would enable a full quantification of the contrast observed in these interference experiments and can be done by the following methods: 1. Young’s slits experiment: interference of electrons that pass fine holes nanomachined into a thick specimen using e.g. a focused ion beam instrument [1] 2. electron diffraction: interference between Bragg diffracted discs in convergent beam electron diffraction of thin crystalline specimens [2] 3. electron holography: interference of two phase-related electron beams created by splitting the electron beam by an electrostatic bi-prism [3] 4. comparison of the defocused far-field ring pattern formed behind an illuminated aperture with simulations

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.

Surface topography analysis plays a very significant role in determining the functional performance for many engineering surfaces. In this paper, feature characterisation techniques, based on the ‘Wolf pruning’ method are implemented to characterise micro and nano-scale features which have a dominant effect on the functional lifespan of flexible Photovoltaic (PV) modules. The densities and dimensions of the potential significant features are calculated by means of the feature “characterisation toolbox”. The outcome of this study has shown the potential of areal feature segmentation for detecting functionally significant defects present in Atomic Layer Deposition (ALD) barrier coatings of Al2O3 on polymer films. The analysis provides the basis for the development in process metrology for Roll-to-Roll (R2R) production of barrier coatings as applied to flexible PV arrays and is a first step in the demonstration of in-process use of feature parameters.

This paper seeks to establish a correlation between surface topographical defects and water vapour transmission rate (WVTR) measured under laboratory conditions for aluminium–oxide (Al2O3) barrier film employed in flexible photovoltaic (PV) modules. Defects in the barrier layers of PV modules causing high WVTR are not well characterised and understood. A WVTR of ~10−1 g/m2/day is sufficient for the most packaging applications, but ≤10−6 g/m2/day is required for the encapsulation of long–life flexible PV modules (Carcia et al., 2010a, 2010b). In this study, surface metrology techniques along with scanning electron microscopy (SEM) were used for a quantitative characterisation of the barrier film defects. The investigation have provided clear evidence for the correlation of surface defect density and the transmission of water vapour through the barrier coating layer. The outcomes would appear to suggest that small numbers of large defects are the dominant factor in determining WVTR for these barrier layers.

The combination of a Gerchberg-Saxton phase retrieval algorithm with a genetic algorithm is used to retrieve the phase of a TEM or STEM probe and pinpoint its defocus. Results from modelled data and initial experimental work are included.

Ptychographical iterative phase retrieval is a promising new transmission imaging technique which uses a set of measured intensities from the consecutive illumination of overlapping regions of the specimen to form an image of the transmission function in phase and amplitude. Although the technique has been shown to work very effectively in both the light-optical and X-ray domains, electron ptychography poses significant difficulties, not least of which is the uncertainty in probe position due to drift and other instabilities. We demonstrate three methods for deriving the relative positions of the illumination spot on the specimen a-posteriori.

Ambient water toxicity estimations were conducted in Piles Creek as part of an ecological risk assessment study. This creek is part of a highly polluted estuarine system located near Linden, New Jersey. An upstream and a downstream site in the creek were evaluated for effects on survival, growth and sexual maturity of the estuarine mysid, Mysidopsis bahia. Manasquan Inlet, Manasquan, New Jersey, served as the reference site. Seven-day screening toxicity tests were conducted once a month over a three month period. Results indicate that survival of mysids was not affected in any toxicity test. Mysid growth was significantly reduced at both of the test sites, in two out of three trials. Sexual maturity was shown to be adversely affected in mysids exposed to ambient waters from both test sites throughout the duration of the study.

A possible configuration for undertaking diffractive imaging microscopy in the conventional scanning transmission electron microscope (STEM) is to defocus the probe by a large distance in order to minimise the number of diffraction patterns required to reconstruct the ptychographical image. Although the characteristics of STEM probes have been well explored and measured near the beam crossover, they are rarely observed (or calculated) at very large defoci. In this paper we compare probes calculated under a variety of approximations with measured data from a JEOL 2010F in STEM mode. When the illumination aperture is narrow and the defocus is large (near parallel illumination useful for ptychographical imaging) the Ronchigram cannot be used easily to characterize aberration, We develop an alternative method of estimating the effective aperture size and condenser lens spherical aberration.

Transparent barrier films such as Al 2 O 3 used for prevention of oxygen and/or water vapour permeation are the subject of increasing research interest when used for the encapsulation of flexible photovoltaic modules. However, the existence of micro-scale defects in the barrier surface topography has been shown to have the potential to facilitate water vapour ingress, thereby reducing cell efficiency and causing internal electrical shorts. Previous work has shown that small defects (≤ 3 μm lateral dimension) were less significant in determining water vapour ingress. In contrast, larger defects (≥ 3 μm lateral dimension) seem to be more detrimental to the barrier functionality. Experimental results based on surface topography segmentation analysis and a model presented in this paper will be used to test the hypothesis that the major contributing defects to water vapour transmission rate are small numbers of large defects. The model highlighted in this study has the potential to be used for gaining a better understanding of photovoltaic module efficiency and performance.

The compaction behaviour of a commercial granulated clay (magnesium aluminium smectite, gMgSm) was investigated using macroscopic pressure-density measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray microtomography (XμT) and small-angle X-ray scattering (SAXS). This material was studied as a potential compaction excipient for pharmaceutical tabletting, but also as a model system demonstrating the capabilities of SAXS for investigating compaction in other situations.\ud \ud Bulk compaction measurements showed that the gMgSm was more difficult to compact than polymeric pharmaceutical excipients such as spheronised microcrystalline cellulose (sMCC), corresponding to harder granules. Moreover, in spite of using lubrication (magnesium stearate) on the tooling surfaces, rather high ejection forces were observed, which may cause problems during commercial tabletting, requiring further amelioration. Although the compacted gMgSm specimens were more porous, however, they still exhibited acceptable cohesive strengths, comparable to sMCC. Hence, there may be scope for using granular clay as one component of a tabletting formulation.\ud \ud Following principles established in previous work, SAXS revealed information concerning the intragranular structure of the gMgSm and its response to compaction. The results showed that little compression of the intragranular morphology occurred below a relative density of 0 · 6, suggesting that granule rearrangements or fragmentation were the dominant mechanisms during this stage. By contrast, granule deformation became considerably more important at higher relative density, which also coincided with a significant increase in the cohesive strength of compacted specimens.\ud \ud Spatially-resolved SAXS data was also used to investigate local variations in compaction behaviour within specimens of different shape. The results revealed the expected patterns of density variations within flat-faced cylindrical specimens. Significant variations in density, the magnitude of compressive strain and principal strain direction were also revealed in the vicinity of a debossed feature (a diametral notch) and within bi-convex specimens. The variations in compaction around the debossed notch, with a small region of high density below and low density along the flanks, appeared to be responsible for extensive cracking, which could also cause problems in commercial tabletting.