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Supplementary methods, Supplementary Figures S1-S5 with legends

Environmental and ecological concerns related to the use of peat in horticulture and agriculture are pressuring growers and growing medium providers to find sustainable alternatives. Identification and screening of substrates from renewable resources suitable for a circular economy are required. As part of the on-going “BioSubstrate” project, we aimed to test the performance of newly developed materials from different biomasses and residual products and different processing. The suitability of 25 new materials, based on a range of raw materials from extruded willow to degassed digestate fibers, were tested as: 1) standalone substrates and 2) partial peat replacements. Two independent plant bioassays were conducted: a lab germination test using lettuce seeds and a greenhouse pot test using three different leaf vegetable species (chinese cabbage, lettuce and cress). The lab germination test found six growing media (originating from different processing methods of willow, wood chips and miscanthus) to be non-phytotoxic as indicated by a germination index >80% and a germination speed similar to double-distilled water. The direct sowing test found that all growing media tested performed better with partial peat replacement than as standalone. The pH and electrical conductivity (EC) of the 25 substrates measured in the lab assay were significantly correlated (0.576** and 0.761**, respectively) with the extracted solution from the pots in the greenhouse assay. Fresh weight (FW), dry weight (DW), germination percentage at day 2 and at day 5 were positively correlated with each other. The EC, pH and germination percentage on day 2 accounted for 93.43% of variance in principal component analysis. Four mixtures of peat and willow composted with a N-source clustered together with the control when a cluster analysis was performed, showing that some types of processed willow-based substrates have the potential to replace or partially replace peat in the future.

Lygus Hahn (Hemiptera: Miridae) feeding in faba beans (Vicia faba Linnaeus (Fabaceae)) often results in a reduction in seed quality and economic losses. Traditionally, seed damage is assessed subjectively through visual examination by a trained individual, but the use of non-destructive imaging to evaluate seed quality is gaining momentum. The focus of this study was to determine the ability to quantify Lygus species damage in faba bean using shortwave-infrared imaging and two analysis techniques: (1) spectral angle mapper and (2) simple reflectance indices. Seed samples were visually assessed for damage before imaging in 242 wavebands between 980 and 2500 nm. Four spectral intervals, involving 102 wavebands, were identified as optimal for the detection of seed damage using spectral angle mapper. A strong relationship was obtained between the area of seed damage derived using spectral angle mapper and visually (R2 = 0.95). Seed damage derived by thresholding of two normalised faba bean damage indices involving reflectance at 1086 and 1313 nm and 2218 and 2342 nm also showed a strong relationship with the visual assessment (R2 = 0.92). The two image analysis techniques provided similar results. The study suggests that imaging in the shortwave-infrared wavelengths and the derivation of simple indices can effectively quantify faba bean damage by Lygus feeding.

Hot pepper (Capsicum chinense Jacq.) is an economically important commercial crop cultivated in Trinidad for domestic consumption and for export in its fresh and processed forms. Collar rot and wil...

This study examines how microscale differences in skeletal ultrastructure affect the crystallographic and nanomechanical properties of two related bryozoan species: (i) Hornera currieae, which is found at relatively quiescent depths of c. 1000 m, and (ii) Hornera robusta, which lives at depths of 50-400 m where it is exposed to currents and storm waves. Microstructural and Electron Backscatter Diffraction (EBSD) observations show that in both species the secondary walls are composed of low-Mg calcite crystallites that grow with their c-axes perpendicular to the wall. Branches in H. currieae develop a strong preferred orientation of the calcite c-axes, while in H. robusta the c-axes are more scattered. Microstructural observations suggest that the degree of scattering is controlled by the underlying morphology of the skeletons: in H. currieae the laminated branch walls are smooth and relatively uninterrupted, whereas the wall architecture of H. robusta is modified by numerous deflections, forming pustules and ridges associated with microscopic tubules. Modelling of the Young's modulus and measurements of nanoindentation hardness indicate that the observed scattering of the crystallite c-axes affects the elastic modulus and nanohardness of the branches, and therefore controls the mechanical properties of the skeletal walls. At relatively high pressure in deep waters, the anisotropic skeletal architecture of H. currieae is aimed at concentrating elasticity normal to the skeleton wall. In comparison, in the relatively shallow and active hydrographic regime of the continental shelf, the elastically isotropic skeleton of H. robusta is designed to increase protection from external predators and stronger omni-directional currents.

Neem leaves possess antimicrobial, insecticidal and nitrification inhibitory biochemicals that may influence compost stability. However, if neem-based compost achieves stability, it can prove useful by providing fertilizer-cum-pesticide properties. Therefore, conventional (physico-chemical), thermogravimetric (TGA) and spectroscopic analyses (FTIR and 13C SS NMR) were used to evaluate the effects of neem leaf content on stability. Treatments included 0, 10, 20, 30, 40 and 50% neem leaves by volume combined with complimentary amounts of corn stover to form 50% of the substrate formulation (SF). Cow manure constituted the additional 50%. Despite all treatments reaching ambient temperature (32 °C ± 1 °C) by the 40th day, Solvita® results showed high CO2 respiration, thereby classifying the compost treatments as active, whereas decreased C:N ratio, NH4+: NO3− ratio and NH4+ values among treatments indicated stability. Furthermore, TGA, FTIR and 13C NMR revealed degradation of labile organic matter and showed that complex aromatic and lignin compounds were also degraded, particularly when neem leaves were added to the mixture, suggesting that aromatisation does not always indicate stability in compost. Spearman’s rank correlation showed that physico-chemical methods were poorly correlated to respirometric, thermal and spectroscopic methods. It also suggests that these respirometric and advanced methods are important in understanding the mechanisms affecting neem compost stability.

The coast of southeast Africa is dominated by sandy beaches that tend to be confined within log-spiral or headland-bound embayments. Investigations using serendipitous air imagery data set have been previously undertaken and conclusions drawn about the stability of the coast. We show that conclusions drawn from this data, with respect to the high water mark (HWM) position are fraught with errors, which include tidal state, pressure regime, beach slope, high-swell erosion, seasonal and multi-annual changes. We highlight and discuss these sources of error, together with their magnitudes. The most significant of these are the high-swell, seasonal and multi-annual variations. From case studies we show that the seasonal beach rotation and long-term beach width variation are responsible for tens of metres of unaccounted HWM variation, 30 to 50 m is common, with maximums reaching 60 to 100 m. Overall the southeast African coastline appears to be in a state of long-term dynamic equilibrium. There is no evidence of any sea-level rise-forced transgression in the coastal sediment budget, despite sea-level rise (SLR). If such a signal is, in fact present, it is lost within the beach width variation. Some southeast African coastal reaches are suffering chronic erosion, but these are related to anthropogenic impacts. The extreme difficulty of placing a HWM, with any temporal validity on this coast precludes the routine use of the Bruun Rule. Although no transgressive signature is found, there is evidence of a decreasing coastal sand budget as a result of anthropogenic or natural climate change, or both. This decrease in the coastal sand volume is likely to result in increased future erosion. Copyright © 2016 John Wiley & Sons, Ltd.

Microbial mats were the dominant habitat type in shallow marine environments between the Palaeoarchean and Phanerozoic. Many of these (termed ‘microbialites’) calcified as they grew but such lithified mats are rare along modern coasts for reasons such as unsuitable water chemistry, destructive metazoan influences and competition with other reef-builders such as corals or macroalgae. Nonetheless, extant microbialites occur in unique coastal ecosystems such as the Exuma Cays, Bahamas or Lake Clifton and Hamelin Pool, Australia, where limitations such as calcium carbonate availability or destructive bioturbation are diminished. Along the coast of South Africa, extensive distributions of living microbialites (including layered stromatolites) have been discovered and described since the early 2000s. Unlike the Bahamian and Australian ecosystems, the South African microbialites form exclusively in the supratidal coastal zone at the convergence of emergent groundwater seepage. Similar systems were documented subsequently in southwestern Australia, Northern Ireland and the Scottish Hebrides, as recently as 2018, revealing that supratidal microbialites have a global distribution. This review uses the best-studied formations to contextualise formative drivers and processes of these supratidal ecosystems and highlight their geological, ecological and societal relevance. Dynamic interchanges between salinity states both exclude many destructive metazoans and competitors and provides optimal nutrient conditions for benthic microbial and microalgal growth. The outflowing groundwater seeps are alkaline and rich in calcium carbonate, which reflects local catchment geological processes. These habitats support a diverse microbial community dominated by Cyanobacteria as well as some metazoan species previously unknown to science, or unknown for the region. Several taxa (from invertebrates to fish) utilise this environment as refugia. Supratidal microbialites are important coastal features because of the organisms they support and the ecological processes that they facilitate, such as habitat connectivity. Culturally and socially, the value of these habitats is increasingly being appreciated, for example as traditional freshwater supply points or as an unrealised geotourism opportunity. This review also frames new information about threats, opportunities for future research and conservation trajectories for these unique geobiological habitats.

Contemporary shore platform stromatolites (SPS) are becoming well known. We describe the physical environment and macrostructures from contemporary shore platform stromatolites (SPS) on the wave-dominated southeast African coast. This was then compared with Mesoarchaean (2.97 Ga) stromatolites from White Umfolozi (100 km inland). We use the Tinley Manor SPS occurrence as the basis for physical environmental comparison, but where necessary draw on evidence from other SPS environments. SPS and Mesoarchean Umfolozi stromatolites contain similar stromatolitic structures and wave deposits. The SPS environment is wave dominated and the occurrence of similar sedimentary structures associated with the Mesoarchean Umfolozi Stromatolites indicates a paleoenvironment associated with waves. The contemporary Tinley Manor SPS wave climate is robust and from this locality we have identified broad limits in which SPS can develop and be preserved. Applying this knowledge to the Mesoarchaean White Umfolozi stromatolites suggests that they formed in a protected wave climate where wave incursions were less frequent. Both these wave-influenced settings are/were subject to very-low siliciclastic-input. The frequency of marine sediment input appears to be a limiting factor on microbialite growth in both the contemporary SPS and Archaean examples.

Historically, radial immunodiffusion (RID) has been the only method that directly measures IgG; however, recent studies have reported IgG concentrations in colostrum, milk, and plasma as measured using an ELISA. To our knowledge no comparison between RID and ELISA methods has been made for bovine colostrum or plasma. The objective of this study was to compare IgG concentrations measured by both methods in samples of bovine colostrum before and after heat treatment and bovine plasma. Concentration of IgG was quantified using a commercially available RID kit and a modified ELISA. Samples of bovine colostrum and plasma were collected from individual animals and colostrum was tested before and after heat treatment at 60°C for 30 min. All samples were tested using both methods. Pearson correlation coefficients were determined for RID and ELISA values from unheated colostrum, heat-treated colostrum, and plasma samples. Mixed models were used to determine the effect of assay on IgG measurement in colostrum and plasma and effect of heat treatment on IgG concentration in colostrum. A weak correlation was found between ELISA and RID results in plasma and unheated colostrum. Concentration of IgG was significantly lower in all sample types when measured by ELISA compared to RID. Thus, direct comparison of ELISA and RID results is not recommended. Colostrum IgG concentration significantly decreased after heat treatment as measured by ELISA, but means were not different when measured by RID. Correlation plots between colostrum values measured before and after heat treatment indicated changes in the colostrum protein matrix due to heat affected RID and ELISA assays differently. This investigation compared RID and ELISA results, but no conclusions could be drawn as to the accuracy of either assay.

Aims To evaluate clinical outcomes in patients with typical biliary pain, normal ultrasonic findings, and a positive 99m technetium (Tc)-labelled hepatic iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK) provocation indicating gallbladder dyskinesia, as per Rome III criteria, undergoing laparoscopic cholecystectomy (LC). Methods and materials Consecutive patients undergoing LC for gallbladder dyskinesia were identified retrospectively. They were followed up by telephone interview and review of the electronic case records to assess symptom resolution. Results One hundred consecutive patients (median age 44; 80% female) with abnormal gallbladder ejection fraction (GB-EF Conclusion In one of the largest outcome series of gallbladder dyskinesia patients in the UK with a positive provocation HIDA scintigraphy examination and LC, the present study shows that the test is a useful functional diagnostic tool in the management of patients with typical biliary pain and normal ultrasound, with favourable outcomes following surgery.

Extant peritidal, micritic stromatolites and tufa are growing discontinuously along the southeast African Indian Ocean rocky peritidal zone. Microbialites are ubiquitous on this coast but only calcify when carbonate rich groundwater is present; if horizontal surfaces (shore platforms) are present stromatolites develop, if vertical surfaces are present tufa forms. Tufa and stromatolites are end members of a spectrum dictated by coastal topography. Extant shore-platform stromatolites (SPS) occur in very high wave energy settings, often around headlands, boulder beaches and/or beach ridges, storm swash-terraces and coastal dunes. Stromatolite growth is seen on soft coastlines but the preservation potential is very low/ zero. SPS are produced by mineral precipitation, not trapping and binding. SPS are developing in a mildly transgressive siliciclastic setting. Laminar and colloform stromatolite morphologies could be preserved in the geological record as micritic lenses on a palaeo-shore platform surface. SPS share many features with Precambrian stromatolites. Terraces associated with oceanic or lacustrine flooding surfaces should not be ignored when searching for potential stromatolite deposits on Mars.

Coastal erosion on the southeast African coastline shows an apparent 18 year cycle which last peaked in 2006. It is in phase with the longshore sediment transport cycle. Both these cycles appear to be in phase with the Lunar Nodal Cycle (LNC). However, the dominant tidal erosion driver on this coast appears to be the 4.4 year Lunar Perigean Subharmonic (LPS). We suggest that the apparent 18 year coastal erosion and longshore sediment budget cycle is a response to the 18 year Mean Annual Precipitation Cycle. This cycle is 180° out of phase with the apparent coastal erosion- and longshore sediment transport- cycles. The summer rainfall areas, of southeastern Africa show an 18 year MAP cyclicity, which drives river runoff and hence controls sediment input to the coast and nearshore environment. The MAP cycle dominates the coastal sediment budget during the LNC trough and suppresses the LPS coastal erosion cycle during this time. This explains why LPS coastal erosion occurs close to the LNC peak. Thus although the LPS cycle dominates the coastline, it is masked during the wet portion of the 18 year MAP cycle. It seems very likely that the LNC drives the MAP cycle in some way but this process is not known. Nevertheless, these relationships can be used to predict, in a general way, both cyclic coastal erosion and the longshore sediment volume fluctuation. This can be translated into a vital coastal planning tool which has the potential to forecast cyclic coastal erosion and hence significantly reduce the sea-defense expenditure bill. Based on this, severe cyclic coastal erosion is anticipated in 2023 and 2024.

Webcams have become popular means of showcasing beach conditions for a wide variety of beach users. However, webcams can also be a useful tool in assessing changes in coastal morphology and coastal processes. This information can be used by managers to assist in planning. A number of fixed-position beach webcams are freely available to the South African public via various tourism, surfing, weather and aviation websites, individual clubs and a cell-phone network provider. The advantages of these public networks are that the information is free and as the webcams are fixed, afford a consistent and comparable view of the beach. The disadvantage is that you are at the mercy of the provider: resolution is generally poor, downtime and communication are out of your control, and you have no influence over the positioning of the webcam or the discontinuity of service. Notwithstanding the above, the existing webcams can still provide valuable information. From the network of beach webcams available in South Africa we analyse imagery from three beach webcams located in the province of KwaZulu-Natal, at Umhlanga, Margate beach and lagoon, and Amanzimtoti beach and lagoon to examine the coastal dynamics. From these case studies we illustrate seasonal beach rotation and lagoon mouth dynamics, specifically why outlets migrate southwards in opposition to regional longshore drift.

Smith, A.M, Green, A.N, Cooper, J.A.G. et al., 2014. Cliff-top storm deposits (55-63m amsl) from Morgan Bay, South Africa. In: Green, A.N. and Cooper, J.A.G. (eds.), Proceedings 13th International Coastal Symposium (Durban, South Africa), Journal of Coastal Research, Special Issue No. 70, pp. 349–353, ISSN 0749-0208. Cliff-top storm deposits (CTSDs) occur south of Morgan Bay, South Africa at elevations varying from ±55- to 63m. These occur as a ±10m-wide horizontal fringe of shell breccia mixed into a very thin (>15cm) sandy soil on the cliff top platform. Visually it is evident that the shell breccia is of various ages. Comparisons with proven wave breccia from this area indicate the same source. We suggest that this breccia was deposited as fall-out from wave and wind-borne plumes produced by wave bores striking the cliff base. These bores would likely have been produced by waves at least ~40m in height. Alternative interpretations, such as a perched marine desposit or tsunamiite are rejected i...

Smith, A.M., Guastella, L.A., Goble, B.J., 2014. Forecasting lagoon outlet erosion: KwaZulu-Natal, southeast Africa. In: Green, A.N. and Cooper, J.A.G. (eds.), Proceedings 13th International Coastal Symposium (Durban, South Africa), Journal of Coastal Research, Special Issue No. 70, pp. 151–156, ISSN 0749-0208. The Amanzimtoti Lagoon is at the mouth of the Amanzimtoti River. The lagoon outlet changes systematically in response to the 18 year long Dyer-Tyson summer rainfall cycle (DTC). During the dry part of the DTC the lagoon is generally closed, opening only during heavy rainstorms. When closed the lagoon is separated from the sea by a baymouth bar, varying from 30 to 60 m wide. The open-days per year have increased dramatically as the DTC has entered the wet phase. Early in the DTC the lagoon rarely opened, and when this occurred it breached near the centre of the headland bound bay, but as the DTC-driven runoff cycle has progressed the outlet has remained open. However, during this open phase...

Guastella, L.A., Smith, A, M., Breetzke T., 2014. Coastal management and mis-management: comparing successes and failures at two lagoon outlets in KwaZulu-Natal, South Africa. In: Green, A.N. and Cooper, J.A.G. (eds.), Proceedings 13th International Coastal Symposium (Durban, South Africa), Journal of Coastal Research, Special Issue No. 70, pp. 513–520, ISSN 0749-0208. KwaZulu-Natal (KZN) has a high energy, dynamic coastline. The coast is a significant asset, utilised for residential, industrial, transport, nature conservation and recreational purposes. It is also the discharge point for many steep gradient, short-headed rivers. These rivers have highly variable discharges and, together with variable coastal erosion and deposition cycles, place stress on coastal resources and infrastructure. Many of the rivers, particularly those with smaller catchments, discharge into back-beach lagoons before discharging into the ocean. Lagoon outlet dynamics are variable and, when combined with ocean swells an...

Aberrantly activated PI3K/mTOR signaling is frequently implicated as an oncogenic driver in human cancer. In response to nutrient and growth factor stimuli, mTOR complex 1 (mTORC1) regulates cell growth and cap-dependent protein translation through phosphorylation and activation of S6K, and through phosphorylation and inactivation of the translational repressor 4EBP1. While suppression of mTORC1 activity causes rapid dephosphorylation of its substrates S6K and 4EBP1, it has also been reported that the translational repressor 4EBP3 is transcriptionally induced during prolonged mTORC1 inhibition.1 We have designed a series of complete and selective bi-steric inhibitors of mTORC1 by covalently linking rapamycin, a selective yet incomplete mTORC1 inhibitor, with mTOR kinase active-site inhibitors. These compounds potently and durably suppress phosphorylation of S6K and 4EBP1, induce growth suppression and apoptosis in multiple cancer cell lines, and cause tumor growth inhibition in xenograft models. In the present study we evaluated the utility of 4EBP3 mRNA expression as a pharmacodynamic (PD) biomarker of mTORC1 inhibition by our bi-steric inhibitors. We further interrogated whether tumor mTORC1 inhibition and anti-tumor efficacy could be predicted by monitoring this PD marker in surrogate tissue. First, we demonstrated that 4EBP3 mRNA and protein levels increased in response to mTORC1 inhibition in a concentration- and time-dependent manner in MDA-MB-468, MCF-7, and HCC1954 breast carcinoma cells. Kinetic studies in which we compared the response of bi-steric inhibitors to that of short duration-of-action active-site inhibitors revealed that 4EBP3 induction requires sustained mTORC1 inhibition, as loss of mTORC1 inhibition correlated with a rapid return to baseline 4EBP3 expression. Treatment with inhibitors of varying potency against mTORC1 also demonstrated a strong correlation between magnitude of cell growth inhibition and 4EBP3 mRNA induction. Additionally, suppression of tumor 4EBP1 phosphorylation and induction of 4EBP3 mRNA was observed in MCF-7 and HCC9154 tumor xenografts following in vivo administration of bi-steric inhibitors with a concomitant induction of murine 4ebp3 in peripheral blood mononuclear cells (PBMCs). Initial studies indicate that ex vivo exposure of human PBMCs to a mTORC1 inhibitor also promotes 4EBP3 mRNA expression. Together, these data suggest that 4EBP3 could provide a sensitive mRNA-based in vivo biomarker of prolonged mTORC1 inhibition, as is the case following administration of a single dose of a bi-steric mTORC1 inhibitor. The concordance between the responses in tumor and PBMC suggests it may be possible to monitor tumor mTORC1 inhibition by monitoring 4EBP3 in surrogate tissue. In summary, 4EBP3 mRNA represents a potential PD biomarker of mTORC1 inhibitor response as an alternative to measurement of the phosphorylation status of mTORC1 substrates. 1. Tsukumo, T., et al. Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3. Nat Commun 7:11776. doi: 10.1038/ncomms11776 (2016). Citation Format: Bianca J. Lee, Nuntana Dinglasan, Tram Nguyen, Ed Lorenzana, Stacy Wilson, G. Leslie Burnett, James B. Aggen, Robert J. Nichols, Mallika Singh, David Wildes, Jaqueline A.M. Smith. 4EBP3 mRNA as a biomarker of therapeutic response to treatment with mTORC1 inhibitors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B108. doi:10.1158/1535-7163.TARG-19-B108

Activation of phosphatidylinositol 3-kinase (PI3K)/PTEN pathway and oncogenic signaling via the mechanistic target of rapamycin (mTOR) occur in a majority of high-grade glial brain tumors. Allosteric mTOR inhibitors, such as rapamycin and other rapalogs, incompletely block mTORC1 by reducing phosphorylation of some substrates, including S6K1, but not 4EBP1. In contrast, ATP-competitive inhibitors, such as sapanisertib, fully inhibit mTORC1. However these inhibitors are also active against mTORC2 and lipid kinases, likely enhancing toxicity. A new class of selective mTORC1 inhibitor that interacts with both the ATP- and FKBP12/FRB-binding sites has been developed, which we term ‘bi-steric’. The prototype bi-steric inhibitor, RapaLink-1, blocks phosphorylation of many mTORC1 substrates, including 4EBP1. Importantly, RapaLink-1 showed improved efficacy in glioblastoma models in vivo as compared to rapamycin or sapanisertib (Fan et al., Cancer Cell 2017). Revolution Medicines has developed novel next-generation bi-steric mTORC1-selective inhibitors that exhibit potent and selective (>10-fold) inhibition of mTORC1 over mTORC2 in vitro in cell line models. Two of these compounds, RM-001 and RM-006, showed sustained blockade of mTORC1 signaling, including dephosphorylation of 4EBP1, following weekly ip dosing in an orthotopic U87MG-Luc model of glioblastoma. Repeated weekly administration of these agents resulted in significantly greater anti-tumor efficacy, as assessed via tumor burden (bioluminescence imaging) and overall survival in comparison to daily sapanisertib and the rapalog everolimus, and weekly dosing of the first generation bi-steric RapaLink-1, all at maximally tolerated doses. In summary, our data demonstrate that bi-steric mTORC1 selective inhibitors elict marked anti-tumor efficacy at doses that are well tolerated in a preclinical model of glioblastoma. Our study emphasizes the importance of mTOR as a central target in glioblastoma, and showcases the therapeutic potential of novel and selective clinical bi-steric mTORC1 inhibitors under development as investigational new drugs.

Laser induced fluorescence spectra of two electronic transitions, [17.6]2.5–X2.5 and [23.3]2.5–X2.5, of IrO have been obtained at high resolution by using a single mode ring dye laser to excite IrO molecules in a laser-ablation molecular beam source. The 191 IrO– 193 IrO isotope shifts in the rotational lines, observed at a linewidth of ∼0.006 cm −1 FWHM, established the vibrational assignment of the [23.3]2.5–X2.5 band as 1–0 and confirmed the previous 0–0 assignment of the [17.6]2.5–X2.5 band. The higher J rotational lines of both transitions are observed to split into closely spaced doublets resulting from quadrupole hyperfine structure caused by the I = 3/2 nuclear spin in 191 Ir and 193 Ir. Analysis of the spectra shows that the hyperfine structure is concentrated in the two excited states with quadrupole coupling constants, eQq 0 , of −0.0463(15) cm −1 and −0.0278(18) cm −1 for the [17.6]2.5 and [23.3]2.5 states respectively.

A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior.

Cooper, J.A.G., Green, A.N. and Smith, A.M. 2013. BARDEX II: Vertical stacking of multiple highstand shoreline deposits from the Cretaceous to the present: facies development and preservation. A sequence of vertically stacked shoreline facies exposed by unprecedented water level lowering in Lake St Lucia, South Africa, records multiple occupation of the same shoreline (5–6m amsl) on at least eight occasions since the late Cretaceous. The sequence involves a basal wave-cut surface that is the outcrop of a regional unconformity cut into Late Cretaceous siltstone with occasional borings, representing a hardground (Facies 1). This is succeeded by a limestone unit indicative of sedimentation in a region of low terrigenous input quite different to today. This commences with a 10cm-thick unit comprising corals and giant clams that colonised the hardground as a shallow reef (Facies 2). The reef has an erosional upper surface that is overlain by a 30–50cm thick coquina (Facies 3) with characteristic sand-...

Cooper, J.A.G., Smith A.M., and Arnscheidt, J. 2013. Contemporary stromatolite formation in high intertidal rock pools, Giant's Causeway, Northern Ireland: preliminary observations. Contemporary stromatolites are known from a variety of settings ranging from Antarctic dry valleys to hypersaline tropical lagoons. Their formation requires a source of calcium carbonate, binding by cyanobacteria and the elimination of other competing organisms by extremes of environmental conditions. In this paper we report the contemporary development of stromatolites in intertidal rock pools at the Giant's Causeway, Northern Ireland. The rock pools are high in the tidal frame and located on the landward margin of wide rock platforms that dissipate all but the most energetic waves. They are only infrequently inundated by marine waters but are fed by groundwater that emerges from surrounding high cliffs. Adjacent storm-swash deposits provide a potential source of calcium carbonate. The stromatolites occur in two dist...

Medium scale clinoforms within sandstones of the Vryheid Formation, northern KwaZulu-Natal, South Africa have in the past been interpreted as the products of Gilbert-type or river-dominated deltaic deposition. Detailed sedimentary logging of these rocks reveals a tempestite association, overlain by a series of moderate to very large scale climbing bedforms. These are intersected at various stratigraphic levels by massive sandstone filled channels, some with subordinate rippled bases, which are orthogonally orientated to the largest scale bedding surfaces (clinoforms) of the climbing bedform association. The sedimentary architecture is dominated by the south-easterly, south-westerly and north-westerly dipping clinoforms, all orientated oblique to the east–west trending palaeo-coastline. Local dip direction reversals are commonplace. This is at odds with Gilbert-type or river-dominated deltaic settings where: (1) sediment progrades normal to the shoreline; (2) distributary channels do not intersect the underlying deltaic foresets orthogonally; and (3) wave action is typically limited. We subsequently interpret the succession as a shelf sand ridge that evolved on a subaqueous delta, fed by sediment exchange from the upper to lower shoreface via a series of rippled scour depressions. To foster such thick (∼30 m) shelf ridge development, it is likely that these remained attached to the shoreface for a significant period of time. In light of these findings, caution should be adopted in applying a blanket deltaic interpretation of shallow marine deposits comprising similar medium scale clinoforms.

The narrow transform margin of southeast Africa and its associated sedimentological and hydrodynamic setting differs to other documented continental margins. The Durban Bluff continental shelf is extremely narrow and steep (8 km wide with a gradient ranging from 2 to 8°) characterised by a wave- and oceanic current-dominated regime. Seismic Sequence Boundary 2, developed during the Last Interglacial regression, spans the entire shelf separating the Holocene sediment wedge (Seismic Unit H) from underlying Pleistocene deposits. A wave ravinement surface marks the Holocene transgression, comprising a pavement lag of well sorted gravels and bioclastics overlain by inshore reef-derived carbonate rich sediments and offshore by quartzose mid-shelf sands. The shelf sands represent the transgressive Holocene to modern sediment wedge forming a seaward thinning unit stacked against the Pleistocene Blood Reef aeolianite/beachrock substrate. The sediment wedge is dynamic and constantly redistributed by currents associated with the Durban Eddy inshore of the Agulhas Current and bottom surge associated with high swells and marine storm events. These have been instrumental in shaping large-scale shoreface attached and detached sand ridges. The presence of mud lenses in the vicinity of Blood Reef represents deposition from turbid flood waters with preservation facilitated by the morphology of the Durban Bluff and Blood Reef. Palynological results, reflecting the local subtropical vegetation and recently introduced neophytes, together with radiocarbon dates, provide a very recent age for this sediment supporting a terrestrial origin and deposition from a single large flood event.

Calcifying tufa stromatolites are forming on a high energy coast of the South African Indian Ocean. The tufa stromatolites form in upper intertidal to supra tidal rock pools, encrust bedrock and are linked both laterally and vertically to physico-chemical properties of their pool water. Calcification only occurs in pools where dissolved carbonate-rich, spring-fed groundwater is routed, and d18O values are consistent with calcification in a mixture of freshwater and seawater. Increasing pH and less negative isotope values away from the spring are consistent with CO2 degassing and in-stream calcification, albeit with some in-mixing of seawater. The rocky shore setting of these active tufa stromatolites is new and invites serious comparison with some Archaean rocky substrate peritidal stromatolites (e.g. the c. 3.45 Ga Strelley Pool sequences, Pilbara Craton). This new association shows that initial encrustation of rocky intertidal substrates can begin with freshwater influence in the intertidal zone, a facies detail that should be sought in ancient peritidal stromatolites.

Recent excavations at Coedmore Quarry, Durban, KwaZulu-Natal, have revealed the presence of tempestites and complex, large-scale deformation features in the Dwyka Group. The striated surface of the underlying Natal Group sandstone, upon which the Dwyka Group rests, is clear evidence of glacial erosion during the advance of a glacial ice sheet. However, the glaciation was interrupted by an interglacial (the Ethekwinian Interglacial) that probably resulted in a significant sea-level rise (±100 m). During the interglacial period, a sedimentary succession, characterized by resedimentation products, tempestites and relatively rare stadials (thin diamictites and varvites), was laid down. Subsequently, during a further glacial period, large-scale soft sediment deformations occurred in the region. We suggest that the deformed sedimentary sequence represents an olistostrome. This feature was most probably initiated by ice-push and/or earthquake activity at the basin margin, but reached its final position (at Coedmore) through gravity sliding into the main Karoo Basin, the Coedmore region may have been a localized palaeodeep (Coedmore Deep) within this part of the main Karoo Basin.

During 2006–2007, the KwaZulu-Natal coast of South Africa was exposed to several large swell events (Ho > 3 m), near the peak of the lunar nodal cycle, causing shoreline recession. The largest swell (Hs = 8.5 m) struck the coast on the March equinox (18th–20th) and generated a strong storm-return flow. Observations made before, during and after record dramatic coastal erosion (shoreline recession of up to 40 m and substantial property damage). This swell event removed the semi-continuous nearshore bar system and ‘conditioned’ the coast such that lesser subsequent swell events accomplished much greater amounts of coastal erosion than expected (up to 100 m at certain erosion hotspots) because waves reached the coast without significant energy dissipation. Subsequent bar generation rebuilt the inshore bars within six months. The styles of erosion during the March ’07 event and other 2007 swells were markedly different. Lesser swells are focused by headlands and result in megarip development and activation of erosion hotspots. The March ’07 event still-water level was raised (equinoctial spring high tide and a storm surge of 0.33–0.45 m) to a level that rendered most headlands (and erosion hotspots) ineffective and resulted in laterally extensive erosion of soft shorelines. Results record cumulative effects of successive swell events on coastal behaviour that proved to be critical in enabling erosion to proceed at rapid rates after the coast had been initially destabilized. Unlike hurricanes and tsunamis, surges associated with swell events are relatively minor and therefore extensive erosion is linked with high lunar tides. There is circumstantial evidence that swell-induced erosion follows the broad 18.6 yr lunar nodal tidal cycle when the chances of large swells coinciding with high water levels are increased.

Background Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. Methods We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Results TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7 ng/mL and 50.8 ng/mL, respectively, consistent with modest selectivity for NET in vivo. Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5 ng/mL and 23.9 ng/mL, respectively. A single-dose, open-label PET study (4-20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [(11)C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [(11)C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30-40 h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21 ng/mL, and at doses of greater than 4 mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35 ng/mL. Conclusions These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.

The tau -> mu nu nu branching ratio has been measured using data collected from 1990 to 1995 by the OPAL detector at the LEP collider. The resulting value of B(tau -> mu nu nu) = 0.1734 +- 0.0009(stat) +- 0.0006(syst) has been used in conjunction with other OPAL measurements to test lepton universality, yielding the coupling constant ratios gmu/ge=1.0005+-0.0044 and gt/ge=1.0031+-0.0048, in good agreement with the Standard Model prediction of unity. A value for the Michel parameter eta = 0.004 +- 0.037 has also been determined and used to find a limit for the mass of the charged Higgs boson mH+- > 1.25 tan beta, in the Minimal Supersymmetric Standard Model.

Three strains of necrotoxigenic Escherichia coli when pretreated with potassium sorbate at pH 7, when sorbate is predominantly in the anionic form, showed an elevated resistance to sodium chloride (27% w/v) compared to a control (no sorbate at pH 7). However, when the strains were subjected to sorbate at pH 5 and 4·75, when a large proportion of sorbate is protonated, the resistance to sodium chloride was reduced. Prior stress with sorbate at pH 7 also induced heat resistance (56°C for 80 min, one strain only tested). By using dialysis, the observed heat resistance was found to be mediated by an extracellular component that was identified tentatively as a protein with a molecular mass greater than 10 kDa. Although this protein was heat resistant at 75°C for 20 min, it was inactivated at 100°C for 20 min. Since necrotoxigenic strains of E. coli have been isolated from cheese and the preservatives sorbate and salt are sometimes used in cheese, this work emphasizes the need for further studies in this area to allow a more accurate risk assessment.

Kv1.3 channels regulate proliferation of normal lymphocytes, but the role of voltage-gated potassium channels in transformed hematopoietic cells is not known. We examined transcripts for Kv1.3, h-erg, h-eag, and BEC1 genes in primary lymphocytes and leukemias and in several hematopoietic cell lines. Surprisingly, BEC1, formerly thought to be brain-specific, was present in all the primary leukemias examined, in resting peripheral blood lymphocytes, and in proliferating activated tonsillar cells, lymphocytes from Sjögren's patients, and Epstein-Barr virus-transformed B-cells. Only h-erg mRNA was up-regulated in the cancer cells, but this was not due to proliferation per se, because it was not elevated in any of the proliferating noncancerous lymphocyte types examined. Nor did h-erg transcript levels correlate with the B-cell subset, because it was elevated in immature neoplastic B-CLL cells (CD5(+)) and in a CD5(-) Burkitt's lymphoma cell line (Raji) but not in Sjögren's syndrome cells (enriched in CD5(+) B-cells) or Epstein-Barr virus-transformed B-cells, which are mature CD5(-) B-cells. The protein and whole cell current levels roughly corresponded with the amount of mRNA expressed in three hematopoietic cell lines: CEM (an acute lymphoblastic leukemic line), K562 (a chronic myelogenous leukemic line), and U937 (an acute promyelocytic leukemic line). The selective HERG channel blocker, E-4031, reduced proliferation of CEM, U937, and K562 cells, and this appears to be the first direct evidence of a functional role for the HERG current in cancer cells. Selective up-regulation of h-erg appears to occur in neoplastic hematopoietic cells, thus providing a marker and potential therapeutic target.

There are few published results in the literature on patello-femoral arthroplasty. The aim of this study was to help to define the place of patello-femoral arthroplasty in the treatment of isolated patello-femoral arthritis. All patients who underwent patello-femoral arthroplasty using the Lubinus prosthesis for patello-femoral arthritis between 1992 and 1998 in two neighbouring district general hospitals were studied. There were 34 patients who underwent 45 arthroplasties. The modified Hungerford and Kenna scoring system and the Insall and Crosby scoring system were used to clinically evaluate the patients. Serial radiographs were assessed for patellar malalignment, mechanical failure and progressive arthritic change. Twenty-three knees (64%) had a good or excellent result, six (17%) had an unsatisfactory result and seven (19%) were revised to either a total knee arthroplasty (5 knees) or patellofemoral arthroplasty (2 knees). Although the results do not compare favourably with those of total knee replacement for generalised arthritis of the knee; we believe that with careful patient selection coupled with careful surgical technique, patello-femoral arthroplasty can be successfully used to treat isolated patello-femoral osteoarthritis.

Searches for first generation scalar and vector leptoquarks, and for squarks in R-parity violating SUSY models with the direct decay of the squark into Standard Model particles, have been performed using e+e- collisions collected with the OPAL detector at LEP at e+e- centre-of-mass energies between 189 and 209 GeV. No excess of events is found over the expectation from Standard Model background processes. Limits are computed on the leptoquark couplings for different values of the branching ratio to electron-quark final states.

RESUMELes sols irrigues dans le bassin de la riviere Columbia dans l'est de l'etat de Washington sont sensibles a l'erosion eolienne et a la percolation des nitrates lorsque laisses nus au cours des mois d'hiver. On encourage les producteurs a incorporer des recoltes de couverture dans leurs rotations ou a laisser les residus de recoltes sur leurs champs durant l'hiver pour minimiser l'erosion. Une couverture composee de vegetation active est necessaire pour fixer les nitrates et empecher la percolation. Quoique certains cultivateurs aient adopte ces pratiques, il est difficile d'estimer la surface totale sous couvert durant les mois d'hiver. Les images satellitales radar constituent un outil utile pour effectuer un suivi quant a l'adoption de telles pratiques. Notre objectif est de determiner la faisabilite de detecter les differents types de couvert a l'aide d'images satellitales radar. Durant l'hiver 1999–2000, trois images RADARSAT-1 de cette region ont ete acquises. Des donnees de terrain ont ete col...

Data on muon pair production obtained by the OPAL collaboration at centre of mass energies near the Z peak are analysed. Small angular mismatches between the directions of the two muons are used to assess the effects of initial state photon radiation and initial-final-state radiation interference on the forward-backward asymmetry of muon pairs. The dependence of the asymmetry on the invariant mass of the pair is measured in a model-independent way. Effective vector and axial-vector couplings of the Z boson are determined and compared to the Standard Model expectations., 31 pages, 8 figures, Accepted by Physics Letters B

Microbial adhesion to the host tissue represents an early, critical step in the pathogenesis of most infectious diseases. BORRELIA: burgdorferi, the causative agent of Lyme disease (LD), expresses two surface-exposed decorin-binding adhesins, DbpA and DbpB. A decorin-deficient (Dcn(-/-)) mouse was recently developed and found to have a relatively mild phenotype. We have now examined the process of experimental LD in Dcn(-/-) mice using both needle inoculation and tick transmission of spirochetes. When exposed to low doses of the infective agent, Dcn(-/-) mice had fewer Borrelia-positive cultures from most tissues analyzed than did Dcn(+/+) or Dcn(+/-) mice. When the infection dose was increased, similar differences were not observed in most tissues but were seen in bacterial colonization of joints and the extent of Borreila-induced arthritis. Quantitative PCR demonstrated that joints harvested from Dcn(-/-) mice had diminished Borrelia numbers compared with issues harvested from Dcn(+/+) controls. Histological examination also revealed a low incidence and severity of arthritis in Dcn(-/-) mice. Conversely, no differences in the numbers of Borreila-positive skin cultures were observed among the different genotypes regardless of the infection dose. These differences, which were observed regardless of genetic background of the mice (BALB/c or C3H/HeN) or method of infection, demonstrate the importance of decorin in the pathogenesis of LD.

The lifetime and oscillation frequency of the B0 meson has been measured using B0->D*+l-v decays recorded on the Z0 peak with the OPAL detector at LEP. The D*+ -> D0pi+ decays were reconstructed using an inclusive technique and the production flavour of the B0 mesons was determined using a combination of tags from the rest of the event. The results t_B0 = 1.541 +- 0.028 +- 0.023 ps, Dm_d = 0.497 +- 0.024 +- 0.025 ps-1 were obtained, where in each case the first error is statistical and the second systematic.

The inclusive production rate of phi mesons from the decay of b hadrons produced in Z0 decays was measured to be Br(b->phi+X) = 0.0282+-0.0013(stat.)+-0.0019(syst.), using data collected by the OPAL detector at LEP.

RESUMEL'amenagement des residus des cultures a des effets sur les ressources du sol qui sont essentielles pour une agriculture soutenable. L'estimation des residus est importante pour l'etude des effets des pratiques de gestion du sol et le developpement des modeles globaux pour comprendre l'impact de l'agriculture sur la dynamique du carbone dans la biosphere. La capacite d'estimer les residus de ble au niveau du champs en utilisant les bandes larges disponibles sur les capteurs satellitaires et autres bandes ou des indices deduits des donnees hyperfrequences est etudie en utilisant un type de sol sujet a differentes pratiques culturelles et sur une variete de sous-groupes de sol dans une meme localite. Des mesures de reflectance ont ete effectuees en juillet, aout et septembre avec un spectro-radiometre base au sol. Les resultats indiquent que quelque soit la pratique culturale ou le type de sol, le residu peut etre estime en utilisant l'indice differentiel normalise (NDITM5 TM7) deduit des bandes large...

The magnitude of the Cabibbo-Kobayashi-Maskawa matrix element Vcb has been measured using B0 to D*l nu decays recorded on the Z0 peak using the OPAL detector at LEP. The D* to D0 pi+ decays were reconstructed both in the particular decay modes D0 to K- pi+ and D0 to K- pi+ pi- and via an inclusive technique. The product of |Vcb| and the decay form factor of the B0 to D* l nu transition at zero recoil F(1) was measured to be F(1)|Vcb| = (37.1+-1.0+-2.0)x10^-3, where the uncertainties are statistical and systematic respectively. By using Heavy Quark Effective Theory calculations for F(1), a value of |Vcb| = (40.7+-1.1+-2.2+-1.6)x 10^-3 was obtained, where the third error is due to theoretical uncertainties in the value of F(1). The branching ratio Br(B0 to D* l nu) was also measured to be (5.26+-0.20+-0.46)%.

Hydrofluorocarbons are alternative refrigerants receiving attention for use in domestic refrigerating systems. New synthetic lubricants are required with these working fluids to ensure lubricant suitability. The objective of this experimental investigation is to compare the tribological performance of the newly developed polyvinylether (PVE) synthetic lubricant to its polyol ester (POE) counter-part. Experimental setups were varied using actual hermetically sealed refrigerating compressors. This investigation included an evaluation of the conforming contact between the small end of the connecting rod and the gudgeon pin. This was done in conjunction with observations of the large end of the connecting rod as well as the compressor valve plates. Observations were carried out using light microscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) micro-analysis and X-ray photoelectron spectroscopy (XPS) analysis. The extent of the surface damage observed varied with the type of lubricant and the operating pressures.