Ratiometric Fluorescent Sensors Illuminate Cellular Magnesium Imbalance in a Model of Acetaminophen-Induced Liver Injury.

Magnesium(II) plays catalytic, structural, regulatory, and signaling roles in living organisms. Abnormal levels of this metal have been associated with numerous pathologies, including cardiovascular disease, diabetes, metabolic syndrome, immunodeficiency, cancer, and, most recently, liver pathologies affecting humans. The role of Mg2+ in the pathophysiology of liver disease, however, has been occluded by concomitant changes in concentration of interfering divalent cations, such as Ca2+, which complicates the interpretation of experiments conducted with existing molecular Mg2+ indicators. Herein, we introduce a new quinoline-based fluorescent sensor, MagZet1, that displays a shift in its excitation and emission wavelengths, affording ratiometric detection of cellular Mg2+ by both fluorescence microscopy and flow cytometry. The new sensor binds the target metal with a submillimolar dissociation constant─well suited for detection of changes in free Mg2+ in cells─and displays a 10-fold selectivity against Ca2+. Furthermore, the fluorescence ratio is insensitive to changes in pH in the physiological range, providing an overall superior performance over existing indicators. We provide insights into the metal selectivity profile of the new sensor based on computational modeling, and we apply it to shed light on a decrease in cytosolic free Mg2+ and altered expression of metal transporters in cellular models of drug-induced liver injury caused by acetaminophen overdose.

Water Vapor Induced Superionic Conductivity in ZnPS3.

Next-generation batteries based on sustainable multivalent working ions, such as Mg2+, Ca2+, or Zn2+, have the potential to improve the performance, safety, and capacity of current battery systems. Development of such multivalent ion batteries is hindered by a lack of understanding of multivalent ionics in solids, which is crucial for many aspects of battery operation. For instance, multivalent ionic transport was assumed to be correlated with electronic transport; however, we have previously shown that Zn2+ can conduct in electronically insulating ZnPS3 with a low activation energy of 350 meV, albeit with low ionic conductivity. Here, we show that exposure of ZnPS3 to environments with water vapor at different relative humidities results in room-temperature conductivity increases of several orders of magnitude, reaching as high as 1.44 mS cm-1 without decomposition or structural changes. We utilize impedance spectroscopy with ion selective electrodes, ionic transference number measurements, and deposition and stripping of Zn metal, to confirm that both Zn2+ and H+ act as mobile ions. The contribution from Zn2+ to the ionic conductivity in water vapor exposed ZnPS3 is high, representing superionic Zn2+ conduction. The present study demonstrates that it is possible to enhance multivalent ion conduction of electronically insulating solids as a result of water adsorption and highlights the importance of ensuring that increased conductivity in water vapor exposed multivalent ion systems is in fact due to mobile multivalent ions and not solely H+.

Pancreas MRI Segmentation Into Head, Body, and Tail Enables Regional Quantitative Analysis of Heterogeneous Disease.

BACKGROUND: Quantitative imaging studies of the pancreas have often targeted the three main anatomical segments, head, body, and tail, using manual region of interest strategies to assess geographic heterogeneity. Existing automated analyses have implemented whole-organ segmentation, providing overall quantification but failing to address spatial heterogeneity. PURPOSE: To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI. STUDY TYPE: Retrospective. SUBJECTS: One hundred and fifty nominally healthy subjects from UK Biobank (100 subjects for method development and 50 subjects for validation). A separate 390 UK Biobank triples of subjects including type 2 diabetes mellitus (T2DM) subjects and matched nondiabetics. FIELD STRENGTH/SEQUENCE: A 1.5 T, three-dimensional two-point Dixon sequence (for segmentation and volume assessment) and a two-dimensional axial multiecho gradient-recalled echo sequence. ASSESSMENT: Pancreas segments were annotated by four raters on the validation cohort. Intrarater agreement and interrater agreement were reported using Dice overlap (Dice similarity coefficient [DSC]). A segmentation method based on template registration was developed and evaluated against annotations. Results on regional pancreatic fat assessment are also presented, by intersecting the three-dimensional parts segmentation with one available proton density fat fraction (PDFF) image. STATISTICAL TEST: Wilcoxon signed rank test and Mann-Whitney U-test for comparisons. DSC and volume differences for evaluation. A P value < 0.05 was considered statistically significant. RESULTS: Good intrarater (DSC mean, head: 0.982, body: 0.940, tail: 0.961) agreement and interrater (DSC mean, head: 0.968, body: 0.905, tail: 0.943) agreement were observed. No differences (DSC, head: P = 0.4358, body: P = 0.0992, tail: P = 0.1080) were observed between the manual annotations and our method's segmentations (DSC mean, head: 0.965, body: 0.893, tail: 0.934). Pancreatic body PDFF was different between T2DM and nondiabetics matched by body mass index. DATA CONCLUSION: The developed segmentation's performance was no different from manual annotations. Application on type 2 diabetes subjects showed potential for assessing pancreatic disease heterogeneity. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Fair shares: building and benefiting from healthcare AI with mutually beneficial structures and development partnerships.

Artificial intelligence (AI) algorithms are used in an increasing range of aspects of our lives. In particular, medical applications of AI are being developed and deployed, including many in image analysis. Deep learning methods, which have recently proved successful in image classification, rely on large volumes of clinical data generated by healthcare institutions. Such data is collected from their served populations. In this opinion article, using digital mammographic screening as an example, we briefly consider the background to AI development and some issues around its deployment. We highlight the importance of high quality clinical data as fundamental to these technologies, and question how the ownership of resultant tools should be defined. Though many of the ethical issues concerning the development and use of medical AI technologies continue to be discussed, the value of the data on which they rely remains a subject that is seldom considered. This potentially controversial issue can and should be addressed in a way which is beneficial to all parties, particularly the population in general and the patients we serve.

Impacts of irrigation efficiency on water-dependent sectors are heavily controlled by region-specific institutions and infrastructures.

Farmers' investment in more efficient irrigation systems represents a primary adaptation strategy when confronting climate change. However, the regional benefits of these investments and their influence on the conflicting demands among different water dependent stakeholders for intensely irrigated regions remains an open question. Using the Pacific Northwest of the United States as an illustrative region of focus, we show that higher irrigation efficiency has diverse effects across stakeholders that are contingent on many local climatic, institutional and infrastructural factors such as the availability of water storage, the location of hydropower generators, and water rights. These complexities limit simple abstractions of irrigation efficiency as broader policy challenge and are central to its inclusion within the class of "wicked problems". Additionally, we argue that the widely used rebound effect concept, which implicitly discourages irrigation efficiency supporting policies, should not be assumed to fully capture the nuances of the complex suite of regional impacts that emerge from irrigation efficiency investments. Consequently, the evaluation of irrigation efficiency investments requires a broader framing across a diversity of perspectives. policies and actions that are pluralistic, context-specific, and closely engage various groups of stakeholders in the policymaking process.

Separation of quadrupolar and paramagnetic shift interactions with TOP-STMAS/MQMAS in solid-state lighting phosphors.

A new approach for processing satellite-transition magic-angle spinning (STMAS) and multiple-quantum magic-angle spinning (MQMAS) data, based on the two-dimensional one-pulse (TOP) method, which separates the second-rank quadrupolar anisotropy and paramagnetic shift interactions via a double shearing transformation, is described. This method is particularly relevant in paramagnetic systems, where substantial inhomogeneous broadening may broaden the lineshapes. Furthermore, it possesses an advantage over the conventional processing of MQMAS and STMAS spectra because it overcomes the limitation on the spectral width in the indirect dimension imposed by rotor synchronization of the sampling interval. This method was applied experimentally to the 27 Al solid-state nuclear magnetic resonance of a series of yttrium aluminum garnets (YAGs) doped with different lanthanide ions, from which the quadrupolar parameters of paramagnetically shifted and bulk unshifted sites were extracted. These parameters were then compared with density functional theory calculations, which permitted a better understanding of the local structure of Ln substituent ions in the YAG lattice.

Magnitude-intrinsic water-fat ambiguity can be resolved with multipeak fat modeling and a multipoint search method.

PURPOSE: To develop a postprocessing algorithm for multiecho chemical-shift encoded water-fat separation that estimates proton density fat fraction (PDFF) maps over the full dynamic range (0-100%) using multipeak fat modeling and multipoint search optimization. To assess its accuracy, reproducibility, and agreement with state-of-the-art complex-based methods, and to evaluate its robustness to artefacts in abdominal PDFF maps. METHODS: We introduce MAGO (MAGnitude-Only), a magnitude-based reconstruction that embodies multipeak liver fat spectral modeling and multipoint optimization, and which is compatible with asymmetric echo acquisitions. MAGO is assessed first for accuracy and reproducibility on publicly available phantom data. Then, MAGO is applied to N = 178 UK Biobank cases, in which its liver PDFF measures are compared using Bland-Altman analysis with those from a version of the hybrid iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL) algorithm, LiverMultiScan IDEAL (LMS IDEAL, Perspectum Diagnostics Ltd, Oxford, UK). Finally, MAGO is tested on a succession of high field challenging cases for which LMS IDEAL generated artefacts in the PDFF maps. RESULTS: Phantom data showed accurate, reproducible MAGO PDFF values across manufacturers, field strengths, and acquisition protocols. Moreover, we report excellent agreement between MAGO and LMS IDEAL for 6-echo, 1.5 tesla human acquisitions (bias = -0.02% PDFF, 95% confidence interval = ±0.13% PDFF). When tested on 12-echo, 3 tesla cases from different manufacturers, MAGO was shown to be more robust to artefacts compared to LMS IDEAL. CONCLUSION: MAGO resolves the water-fat ambiguity over the entire fat fraction dynamic range without compromising accuracy, therefore enabling robust PDFF estimation where phase data is inaccessible or unreliable and complex-based and hybrid methods fail.

Tarnishing Silver Metal into Mithrene.

Silver metal exposed to the atmosphere corrodes and becomes tarnished as a result of oxidation and precipitation of the metal as an insoluble salt. Tarnish has so poor a reputation that the word itself connotes corruption and disrespectability; however, tarnishing is a facile synthetic approach for preparing thin metal-sulfide films on silver or copper metal that might be exploited to prepare more elaborate materials with desirable optoelectronic properties. In this work, we prepare luminescent semiconducting thin films of mithrene, a metal-organic chalcogenolate assembly, by replacing the tarnish-causing atmospheric sulfur source with diphenyl diselenide. Mithrene, or silver benzeneselenolate [AgSePh]∞, is a crystalline solid that contains both an organic supramolecular phase and a two-dimensional inorganic coordination polymer phase. This compound gradually accumulates as the sole product of silver metal corrosion. The chemical reaction is carried out on metallic silver thin films and yields crystalline films with thicknesses ranging from 5 to 100 nm. We use the large-area films (>6 cm2) afforded by this method to measure the optical properties of this compound. The mild-temperature, wafer-scale processing of hybrid chalcogenolate thin films may prove useful in the application of hybrid organic-inorganic materials in semiconductor devices and hierarchical architectures.

Study protocol: HepaT1ca - an observational clinical cohort study to quantify liver health in surgical candidates for liver malignancies.

BACKGROUND: Accurate assessment of liver health prior to undertaking resectional liver surgery or chemoembolisation for primary and secondary cancers is essential for patient safety and optimal outcomes. LiverMultiScan™, an MRI-based technology, non-invasively quantifies hepatic fibroinflammatory disease, steatosis and iron content. We hypothesise that LiverMultiScan™can quantify liver health prior to surgery and inform the risk assessment for patients considering liver surgery or chemoembolization and seek to evaluate this technology in an operational environment. METHODS/DESIGN: HepaT1ca is an observational cohort study in two tertiary-referral liver surgery centres in the United Kingdom. The primary outcome is correlation between the pre-operative liver health assessment score (Hepatica score - calculated by weighting future remnant liver volume by liver inflammation and fibrosis (LIF) score) and the post-operative liver function composite integer-based risk (Hyder-Pawlik) score. With ethical approval and fully-informed consent, individuals considering liver surgery for primary or secondary cancer will undergo clinical assessment, blood sampling, and LiverMultiScan™multiparametric MRI before and after surgical liver resection or TACE. In nested cohorts of individuals undergoing chemotherapy prior to surgery, or those undergoing portal vein embolization (PVE) as an adjunct to surgery, an additional testing session prior to commencement of treatment will occur. Tissue will be examined histologically and by immunohistochemistry. Pre-operative liver health assessment scores and the post-operative risk scores will be correlated to define the ability of LiverMultiScan™to predict the risk of post-operative morbidity and mortality. Because technology performance in this setting is unknown, a pragmatic sample size will be used. For the primary outcome, n = 200 for the main cohort will allow detection of a minimum correlation coefficient of 0.2 with 5% significance and power of 80%. DISCUSSION: This study will refine the technology and clinical application of multiparametric MRI (including LiverMultiScan™), to quantify pre-existing liver health and predict post-intervention outcomes following liver resection. If successful, this study will advance the technology and support the use of multiparametric MRI as part of an enhanced pre-operative assessment to improve patient safety and to personalise operative risk assessment of liver surgery/non-surgical intervention. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier: NCT03213314 .

Web-Based Activity Within a Sexual Health Economy: Observational Study.

BACKGROUND: Regular testing for sexually transmitted infections (STIs) is important to maintain sexual health. Self-sampling kits ordered online and delivered in the post may increase access, convenience, and cost-effectiveness. Sexual health economies may target limited resources more effectively by signposting users toward Web-based or face-to-face services according to clinical need. OBJECTIVE: The aim of this paper was to investigate the impact of two interventions on testing activity across a whole sexual health economy: (1) the introduction of open access Web-based STI testing services and (2) a clinic policy of triage and signpost online where users without symptoms who attended clinics for STI testing were supported to access the Web-based service instead. METHODS: Data on attendances at all specialist public sexual health providers in an inner-London area were collated into a single database. Each record included information on user demographics, service type accessed, and clinical activity provided, including test results. Clinical activity was categorized as a simple STI test (could be done in a clinic or online), a complex visit (requiring face-to-face consultation), or other. RESULTS: Introduction of Web-based services increased total testing activity across the whole sexual health economy by 18.47% (from 36,373 to 43,091 in the same 6-month period-2014-2015 and 2015-2016), suggesting unmet need for testing in the area. Triage and signposting shifted activity out of the clinic onto the Web-based service, with simple STI testing in the clinic decreasing from 16.90% (920/5443) to 12.25% (511/4172) of total activity, P<.001, and complex activity in the clinic increasing from 69.15% (3764/5443) to 74.86% (3123/4172) of total activity, P<.001. This intervention created a new population of online users with different demographic and clinical profiles from those who use Web-based services spontaneously. Some triage and signposted users (29.62%, 375/1266) did not complete the Web-based testing process, suggesting the potential for missed diagnoses. CONCLUSIONS: This evaluation shows that users can effectively be transitioned from face-to-face to Web-based services and that this introduces a new population to Web-based service use and changes the focus of clinic-based activity. Further development is underway to optimize the triage and signposting process to support test completion.

Dual-Channel, Molecular-Sieving Core/Shell ZIF@MOF Architectures as Engineered Fillers in Hybrid Membranes for Highly Selective CO2 Separation.

A novel core/shell porous crystalline structure was prepared using a large pore metal organic framework (MOF, UiO-66-NH2, pore size, ∼ 0.6 nm) as core surrounded by a small pore zeolitic imidazolate framework (ZIF, ZIF-8, pore size, ∼ 0.4 nm) through a layer-by-layer deposition method and subsequently used as an engineered filler to construct hybrid polysulfone (PSF) membranes for CO2 capture. Compared to traditional fillers utilizing only one type of porous material with rigid channels (either large or small), our custom designed core/shell fillers possess clear advantages via pore engineering: the large internal channels of the UiO-66-NH2 MOFs create molecular highways to accelerate molecular transport through the membrane, while the thin shells with small pores (ZIF-8) or even smaller pores generated at the interface by the imperfect registry between the overlapping pores of ZIF and MOF enhance molecular sieving thus serving to distinguish slightly larger N2 molecules (kinetic diameter, 0.364 nm) from smaller CO2 molecules (kinetic diameter, 0.33 nm). The resultant core/shell ZIF@MOF and as-prepared hybrid PSF membranes were characterized by transmission electron microscopy, X-ray diffraction, wide-angle X-ray scattering, scanning electron microscopy, Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, and contact angle tests. The dependence of the separation performance of the membranes on the MOF/ZIF ratio was also studied by varying the number of layers of ZIF coatings. The integrated PSF-ZIF@MOF hybrid membrane (40 wt % loading) with optimized ZIF coating cycles showed improved hydrophobicity and excellent CO2 separation performance by simultaneously increasing CO2 permeability (CO2 permeability of 45.2 barrer, 710% higher than PSF membrane) and CO2/N2 selectivity (CO2/N2 selectivity of 39, 50% higher than PSF membrane), which is superior to most reported hybrid PSF membranes. The strategy of using dual-channel molecular sieving core/shell porous crystals in hybrid membranes thus provides a promising means for CO2 capture from flue gas.

Tunable Anisotropic Photon Emission from Self-Organized CsPbBr3 Perovskite Nanocrystals.

We report controllable anisotropic light emission of photons originating from vertically aligned transition dipole moments in spun-cast films of CsPbBr3 nanocubes. By depositing films of nanocrystals on precoated substrates we can control the packing density and resultant radiation pattern of the emitted photons. We develop a technical framework to calculate the average orientation of light emitters, i.e., the angle between the transition dipole moment vector (TDM) and the substrate. This model is applicable to any emissive material with a known refractive index. Theoretical modeling indicates that oriented emission originates from an anisotropic alignment of the valence band and conduction band edge states on the ionic crystal lattice and demonstrates a general path to model the experimentally less accessible internal electric field of a nanosystem from the photoluminescent anisotropy. The uniquely accessible surface of the perovskite nanoparticles allows for perturbation of the normally isotropic emissive transition. The reported sensitive and tunable TDM orientation and control of emitted light will allow for applications of perovskite nanocrystals in a wide range of photonic technologies inaccessible to traditional light emitters.

Design Rules for Self-Assembly of 2D Nanocrystal/Metal-Organic Framework Superstructures.

We demonstrate the guiding principles behind simple two dimensional self-assembly of MOF nanoparticles (NPs) and oleic acid capped iron oxide (Fe3 O4 ) NCs into a uniform two-dimensional bi-layered superstructure. This self-assembly process can be controlled by the energy of ligand-ligand interactions between surface ligands on Fe3 O4 NCs and Zr6 O4 (OH)4 (fumarate)6 MOF NPs. Scanning transmission electron microscopy (TEM)/energy-dispersive X-ray spectroscopy and TEM tomography confirm the hierarchical co-assembly of Fe3 O4 NCs with MOF NPs as ligand energies are manipulated to promote facile diffusion of the smaller NCs. First-principles calculations and event-driven molecular dynamics simulations indicate that the observed patterns are dictated by combination of ligand-surface and ligand-ligand interactions. This study opens a new avenue for design and self-assembly of MOFs and NCs into high surface area assemblies, mimicking the structure of supported catalyst architectures, and provides a thorough fundamental understanding of the self-assembly process, which could be a guide for designing functional materials with desired structure.

para-Azaquinodimethane: A Compact Quinodimethane Variant as an Ambient Stable Building Block for High-Performance Low Band Gap Polymers.

Quinoidal structures incorporating expanded para-quinodimethane (p-QM) units have garnered great interest as functional organic electronic, optical, and magnetic materials. The direct use of the compact p-QM unit as an electronic building block, however, has been inhibited by the high reactivity conveyed by its biradical character. Herein, we introduce a stable p-QM variant, namely p-azaquinodimethane (p-AQM), that incorporates nitrogen atoms in the central ring and alkoxy substituents on the periphery to increase the stability of the quinoidal structure. The succinct synthesis from readily available precursors leads to regio- and stereospecific p-AQMs that can be readily integrated into the backbone of conjugated polymers. The quinoidal character of the p-AQM unit endows the resulting polymers with narrow band gaps and high carrier transport mobilities. The study of a series of copolymers employing different numbers of thiophene units revealed an unconventional trend in band gaps, which is distinct from the widely adopted donor-acceptor approach to tuning the band gaps of conjugated polymers. Theoretical calculations have shed light on the nature of this trend, which may provide a unique class of conjugated polymers with promising optical and electronic properties.

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Quadrites and crossed-chain crystal structures in polymer semiconductors.

Many high-performance conjugated polymers for organic photovoltaics and transistors crystallize such that chains are parallel, resulting in significant anisotropy of the nanoscale charge transport properties. Here we demonstrate an unusual intercrystallite relationship where thin lamellae adopt a preferred epitaxial relationship with crossed-chains at the interface. The crossed-chains may allow either crystal to use the other as an "electronic shunt", creating efficient quasi-three-dimensional transport pathways that reduce the severity of grain boundaries and defects in limiting transport.

Actin pedestal formation by enterohemorrhagic Escherichia coli enhances bacterial host cell attachment and concomitant type III translocation.

Attachment of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells is critical for colonization and is associated with localized actin assembly beneath bound bacteria. The formation of these actin "pedestals" is dependent on the translocation of effectors into mammalian cells via a type III secretion system (T3SS). Tir, an effector required for pedestal formation, localizes in the host cell plasma membrane and promotes attachment of bacteria to mammalian cells by binding to the EHEC outer surface protein Intimin. Actin pedestal formation has been shown to foster intestinal colonization by EHEC in some animal models, but the mechanisms responsible for this remain undefined. Investigation of the role of Tir-mediated actin assembly promoting host cell binding is complicated by other, potentially redundant EHEC-encoded binding pathways, so we utilized cell binding assays that specifically detect binding mediated by Tir-Intimin interaction. We also assessed the role of Tir-mediated actin assembly in two-step assays that temporally segregated initial translocation of Tir from subsequent Tir-Intimin interaction, thereby permitting the distinction of effects on translocation from effects on cell attachment. In these experimental systems, we compromised Tir-mediated actin assembly by chemically inhibiting actin assembly or by infecting mammalian cells with EHEC mutants that translocate Tir but are specifically defective in Tir-mediated pedestal formation. We found that an inability of Tir to promote actin assembly resulted in a significant and striking decrease in bacterial binding mediated by Tir and Intimin. Bacterial mutants defective for pedestal formation translocated type III effectors to mammalian cells with reduced efficiency, but the decrease in translocation could be entirely accounted for by the decrease in host cell attachment.

Enhancing fullerene-based solar cell lifetimes by addition of a fullerene dumbbell.

Cost-effective, solution-processable organic photovoltaics (OPV) present an interesting alternative to inorganic silicon-based solar cells. However, one of the major remaining challenges of OPV devices is their lack of long-term operational stability, especially at elevated temperatures. The synthesis of a fullerene dumbbell and its use as an additive in the active layer of a PCDTBT:PCBM-based OPV device is reported. The addition of only 20 % of this novel fullerene not only leads to improved device efficiencies, but more importantly also to a dramatic increase in morphological stability under simulated operating conditions. Dynamic secondary ion mass spectrometry (DSIMS) and TEM are used, amongst other techniques, to elucidate the origins of the improved morphological stability.