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Improving the utilization of platinum in proton-exchange membrane (PEM) fuel cells is critical to reducing their cost. In the past decade, numerous Pt-based oxygen reduction reaction catalysts with high specific and mass activities have been developed. However, the high activities are mostly achieved in rotating disk electrode (RDE) measurement and have rarely been accomplished at the membrane electrode assembly (MEA) level. The failure of these direct translations from RDE to MEA has been well documented with several key reasons having been previously identified. One of them is the resistance caused by complex mass transport pathways in the MEA. Herein, we improve the proton and oxygen transportations in the MEA by building a thin and uniform distribution of ionomer on the catalyst surface. As a result, a PEM fuel cell design is capable of showing a current density improvement of 38% at the same voltage (0.6 V) under the H

Background The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) is validated for measuring mental wellbeing in populations aged 11 + and has been translated into 30 + languages. The aims of this study were a) to translate and validate WEMWBS for use in Swahili-speaking populations to facilitate measurement and understanding of wellbeing, evaluation of policy and practice, and enable international comparisons; and b) to examine sociodemographic characteristics associated with higher and lower mental wellbeing in participants in the Girls’ Education Challenge (GEC) project in Tanzania. Methods A short questionnaire including WEMWBS and similar scales for comparison, socio-demographic information, and self-reported health was translated into Swahili using gold standard methodology. This questionnaire was used to collect data from secondary school students, learner guides, teacher mentors and teachers taking part in the GEC project in Tanzania. Focus groups were used to assess acceptability and comprehensibility of WEMWBS and conceptual understanding of mental wellbeing. These were audio-taped, transcribed and analysed thematically. Internal consistency of WEMWBS, correlation with comparator scales and confirmatory factor analysis were completed as quantitative validation. Finally, multivariable logistic regression was used to explore associations between individual characteristics and ‘high’ and ‘low’ mental wellbeing, defined as the highest and lowest quartile of WEMWBS scores. Results 3052 students and 574 adults were recruited into the study. Participants reported that WEMWBS was understandable and relevant to their lives. Both WEMWBS and its short form met quantitative standards of reliability and validity, were correlated with comparator scales and met the criteria to determine a single factor structure. For students in the GEC supported government schools: mental wellbeing was higher in students in the final two ‘forms’ of school compared with the first two. In addition: being male, urban residence, the absence of markers of social marginality and better self-reported health were all significantly associated with better mental wellbeing. For adults, urban residence and better self-reported health were associated with better mental wellbeing. Conclusions The Swahili translation of WEMWBS is available for use. Further work to explore how to intervene to increase mental wellbeing in vulnerable GEC participants is needed.

As natural habitats continue to shrink in Kenya's Amboseli Ecosystem, livestock depredation by lions Panthera leo threatens both the livelihoods of pastoralist communities and the lion populations affected by retaliatory killings. Finding ways for people and carnivores to coexist at the landscape scale is crucial to the long-term persistence of many threatened animal populations. The fortification of existing traditional bomas to make them predator-proof reduces night-time depredation of livestock. However, the sustainability and cost-effectiveness of such an initiative rely on boma owners taking responsibility for the upkeep and repair of their bomas. In August 2018 we surveyed 88 predator-proof bomas constructed during 2012–2018 and recorded their characteristics and levels of damage. We examined which variables influence disrepair, using a series of statistical analyses, including generalized linear mixed models. Our results reveal there was more disrepair in bomas constructed with wooden posts, confirming the benefit of using recycled plastic posts; in bomas with lower livestock density, suggesting that fewer animals could cause more damage or that such damage is not repaired; and in bomas located further away from a neighbouring predator-proof boma, suggesting a social element in encouraging or enabling boma owners to carry out maintenance. We recommend the consideration and further investigation of this social influence in guiding and improving the sustainability of conservation programmes that use predator-proof bomas, with a view to reducing negative interactions between pastoralists and lions.

In the past three years, several offshore platforms have commissioned sulfate removal units (SRUs) with a new, Thin-Membrane Technology which allows the highest active membrane area to be packaged into the standard spiral wound, sulfate removal element. These newly installed elements are the first of their kind to utilize the new technology and demonstrate how offshore platforms can benefit from this innovation. The spiral wound element was developed in the 1970s to package RO and NF membranes into a compact, efficient, and modular spiral element. Since that time, incremental improvements in element design and materials of construction have led to enhanced efficiencies and productivity. However, the overall element design and membrane construction have remained largely unchanged. Most notably, in recent years, efforts to fit more material into the present spiral element configuration reached an optimal plateau. Advances in automated manufacturing resulted in either increasing the membrane surface area or increasing the thickness of the feed/brine spacer. Either enhancement could be selected depending on the quality of the feedwater or the efficiency of the pre-treatment. However, it was not possible for the designers of SRUs to capitalize on the benefits associated with both enhancements simultaneously. For this reason, when treating high quality feedwater, SRU designers prefer to use spiral elements that contain higher surface area to reduce capital cost, footprint, and weight. When treating high fouling feedwater with minimal pretreatment, SRU designers use elements with the thicker feed/brine spacer to reduce differential pressure losses, minimize fouling and improve cleaning effectiveness. Designers selecting elements with thicker spacer forfeit the benefits associated with higher area elements while designers who select elements with higher area forfeit the benefits of the thicker spacer. But in recent years, thanks to innovations in material science, a new generation of sulfate removal elements are now being manufactured and deployed in full scale systems on offshore platforms. These new elements offer both a larger surface area and a thicker feed/brine spacer. This paper will detail the innovation in the construction of the new membrane material and compare its effects on element performance with the previous generation membranes. The paper will analyze the operation of these new elements in SRUs running on offshore platforms for as much as one year. Based on the operation of these new elements, the footprint, weight, and capital cost benefits of the new membrane relative to current membranes will be analyzed.

S3. Expression of mcoEltd1 in 4T1 cells does not affect cell growth in vitro but increases tumour growth and metastasis.

S1. Expression of mcoEltd1 in E0771 cells does not affect cell growth or invasion.

Supplementary Figure and Table Legends

S2. E0771 mcoEltd1 tumours have increased vessel and M2 macrophage markers.

Supplementary Table 1. QPCR primer sequences

1: JAG1 antibody characterization. 2: antibody inhibition of JAG1 mediated Notch signalling in tumor cell lines. 3: antibody inhibition of JAG1 signalling in vascular cells. 4: antibody inhibition of JAG1 signalling in HUVEC-HUVSMC co-culture. 5: effect of anti-Notch pathway treatment on MDA-MB231 2D growth and J1-65D titration and effect on 3D growth and gene expression. 6: J1-65D treatment of established OVCAR3 xenograft. 7: JAG1 antibodies cross-reactivity with rat Jag1. 8: anti-JAG1 treatment effect in a rat brain metastasis model.

S6. Eltd1 increases myeloid accumulation in the spleen.

S4. Eltd1 expressing tumour cells proliferate in the presence of endothelial cells and modifies their secretome.

S5. Representative flow cytometry dot plots indicating the gating strategy for identification of myeloid and lymphoid populations and PD-L1.

Supplementary material and methods. Supplementary table 1: cell lines and growth conditions. Supplementary table 2: Notch ligands and control protein for plate coating. Supplementary table 3: qPCR primers. Supplementary table 4: flow cytometry antibodies. Supplementary table 5: ICC/IHC antibodies. Supplementary table 6: titration of Notch1-JAG1 binding inhibition by JAG1 antibodies. Supplementary table 7: amino acid sequence of JAG1 antibodies. Supplementary table 8: blood analysis on antibody-treated tumor-bearing rats.

ELTD1/ADGRL4 expression is increased in the vasculature of a number of tumor types and this correlates with a good prognosis. Expression has also been reported in some tumor cells with high expression correlating with a good prognosis in hepatocellular carcinoma (HCC) and a poor prognosis in glioblastoma. Here we show that 35% of primary human breast tumors stain positively for ELTD1, with 9% having high expression that correlates with improved relapse-free survival. Using immunocompetent, syngeneic mouse breast cancer models we found that tumors expressing recombinant murine Eltd1 grew faster than controls, with an enhanced ability to metastasize and promote systemic immune effects. The Eltd1-expressing tumors had larger and better perfused vessels and tumor–endothelial cell interaction led to the release of proangiogenic and immune-modulating factors. M2-like macrophages increased in the stroma along with expression of programmed death-ligand 1 (PD-L1) on tumor and immune cells, to create an immunosuppressive microenvironment that allowed Eltd1-regulated tumor growth in the presence of an NY-ESO-1–specific immune response. Eltd1-positive tumors also responded better to chemotherapy which could explain the relationship to a good prognosis observed in primary human cases. Thus, ELTD1 expression may enhance delivery of therapeutic antibodies to reverse the immunosuppression and increase response to chemotherapy and radiotherapy in this subset of tumors. ELTD1 may be useful as a selection marker for such therapies.Implications:ELTD1 expression in mouse breast tumors creates an immunosuppressive microenvironment and increases vessel size and perfusion. Its expression may enhance the delivery of therapies targeting the immune system.

The role of Notch signaling and its ligand JAGGED1 (JAG1) in tumor biology has been firmly established, making them appealing therapeutic targets for cancer treatment. Here, we report the development and characterization of human/rat-specific JAG1-neutralizing mAbs. Epitope mapping identified their binding to the Notch receptor interaction site within the JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective binding to the murine Jag1 ortholog. These antibodies were able to specifically inhibit JAG1-Notch binding in vitro, downregulate Notch signaling in cancer cells, and block the heterotypic JAG1-mediated Notch signaling between endothelial and vascular smooth muscle cells. Functionally, in vitro treatment impaired three-dimensional growth of breast cancer cell spheroids, in association with a reduction in cancer stem cell number. In vivo testing showed variable effects on human xenograft growth when only tumor-expressed JAG1 was targeted (mouse models) but a more robust effect when stromal-expressed Jag1 was also targeted (rat MDA-MB-231 xenograft model). Importantly, treatment of established triple receptor-negative breast cancer brain metastasis in rats showed a significant reduction in neoplastic growth. MRI imaging demonstrated that this was associated with a substantial improvement in blood–brain barrier function and tumor perfusion. Lastly, JAG1-targeting antibody treatment did not cause any detectable toxicity, further supporting its clinical potential for cancer therapy.

S7. Mice with Eltd1 expressing tumours have less specific T CD8+ cells raised against the tumour NY-ESO-1 antigen.

The tumor suppressor p53 is widely dysregulated in cancer and represents an attractive target for immunotherapy. Because of its intracellular localization, p53 is inaccessible to classical therapeutic monoclonal antibodies, an increasingly successful class of anticancer drugs. However, peptides derived from intracellular antigens are presented on the cell surface in the context of MHC I and can be bound by T-cell receptors (TCR). Here, we report the development of a novel antibody, T1-116C, that acts as a TCR mimic to recognize an HLA-A*0201–presented wild-type p53 T-cell epitope, p5365–73(RMPEAAPPV). The antibody recognizes a wide range of cancers, does not bind normal peripheral blood mononuclear cells, and can activate immune effector functions to kill cancer cells in vitro. In vivo, the antibody targets p5365–73 peptide–expressing breast cancer xenografts, significantly inhibiting tumor growth. This represents a promising new agent for future cancer immunotherapy. Cancer Res; 77(10); 2699–711. ©2017 AACR.

Supplemental Materials and Methods from Development of a T-cell Receptor Mimic Antibody against Wild-Type p53 for Cancer Immunotherapy

CCR Translation for the Article from A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy

Supplementary Data from Immunomodulation of FOXP3+ Regulatory T Cells by the Aromatase Inhibitor Letrozole in Breast Cancer Patients

Suppl Table 1: Quantitation of T1-116C binding sites per target cell; Suppl Figure 1: Validation of the HLA-A2/p53RMP tetramer; Suppl Figure 2: ELISA screening of HLA-A2/p53RMP tetramer-reactive TCRm hybridoma supernatants; Suppl Figure 3: T1-116C staining of HL-60 cells; Suppl Figure 4: TP53 transcripts levels in cancer cell lines; Suppl Figure 5: The proteasome actively turns over p53 in NCI-H1395 lung cancer cells; Suppl Figure 6: The p53 TCRm T1-116C does not stain normal human peripheral blood mononuclear cells (PBMCs).

Purpose: We have shown previously that tumor infiltration by FOXP3+ regulatory T cells (Treg) is associated with increased relapse and shorter survival of patients with both in situ and invasive breast cancer. Because estrogen regulates Treg numbers in mice and promotes the proliferation of human Tregs, we hypothesized that blocking estrogen receptor-α signaling would abrogate Tregs and be associated with response to hormonal therapy and increased survival.Experimental Design: FOXP3+ Tregs were quantified in tumor samples collected at baseline by incisional biopsy and after 6 months at definitive surgery in 83 elderly breast cancer patients (T2-4 N0-1) enrolled in a randomized phase II trial based on 6 months of primary letrozole (2.5 mg/d) or 6 months of letrozole plus oral “metronomic” cyclophosphamide (50 mg/d).Results: Treg number ranged from 0 to 380 (median, 30) before treatment and from 0 to 300 (median, 8) after treatment. There was a significant reduction in Tregs in letrozole and letrozole-cyclophosphamide patients (P < 0.0001 and P < 0.002, respectively) after treatment. Treg number at residual histology was inversely related with response (P < 0.03 and P = 0.50, respectively) and a greater Treg reduction was observed in responding patients (P < 0.03).Conclusion: This study suggests that aromatase inhibitors may have an indirect antitumor mechanism of action through reducing Tregs in breast tumors and may be of use in estrogen receptor-α-negative tumors in combination with immunotherapy approaches.

Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm.Experimental Design: We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)–treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treated with rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm.Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P < 0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all “GCB”) than the Hans' algorithm (two GCB, five non-GCB).Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials. (Clin Cancer Res 2009;15(17):5494–502)

This thesis explores Tasmanians' experiences of forests. Tasmania has been socially and environmentally shaped by decades of conflict popularly and provocatively termed the 'forestry wars'. In this context, I examine the link between human-forest engagements and 'ontological security' ‚Äö- a sense of familiarity and trust in the world and the self. In critiquing and remodelling Giddens' conceptualisation of ontological security, I argue that forests do important emotional and existential 'work' for people. For most participants, the state's forests symbolised ontological and emotional aspects of ontological security. Environmental sociology literature often adopts macro-level, realist, and/or quantitative frameworks which privilege themes of self-interest, rationality, or 'quantifiable' experiences of the nonhuman environment. The existing literature regarding Tasmanians' experiences with/in forests is dominated by political, discursive, and historical perspectives which heavily emphasise the construction of environmental conflict. Sociological approaches to this Tasmanian case study are absent. In contrast to these bodies of literature, I explore human-forest engagements through under-examined themes of vulnerability, ontology, emotion, and relationship. I conducted semi-structured interviews with 27 Tasmanians across the state. Eleven participants also contributed materials that they felt represented Tasmanian forests, including photographs, lyrics, and written pieces. Almost all participants were critical and distrustful of Tasmanian forestry politics, management, and practices, expressed concerns about local and global environmental issues, and associated forest experiences with processes of wellbeing, immersion, self-identity, and ontology. Yet participants also expressed ambivalent attitudes about Tasmania's forestry industry. These key findings indicate that Tasmanians' engagements with/in forests are complex, emotionally significant, and are bound up in experiences of identity, ontology, and vulnerability. These data illustrate Tasmanian forests as symbolic of six key aspects of ontological security: material constancy; routine and ritual; escape and refuge; self-narrative; the nonhuman; and the future. Through these operationalised points, I argue that participants' understandings and experiences of Tasmanian forests reflect the construction and experience of ontological security. This thesis contributes a unique micro-sociological approach to understanding human-forest engagements in Tasmania, and in doing so, undermines the polarising and alienating rhetoric of 'Tasmania's forestry wars'. This research also contributes a reworked model of ontological security, demonstrating the utility of the concept for qualitative research in environmental sociology.

GSK3358699 is a mononuclear myeloid-targeted bromodomain and extra-terminal domain (BET) family inhibitor which demonstrates immunomodulatory effects in vitro. This phase 1, randomized, first-in-human study evaluated the safety, pharmacokinetics, and pharmacodynamics of GSK3358699 in healthy male participants (NCT03426995).Part A (N = 23) included three dose-escalating periods of 1-40 mg of GSK3358699 or placebo in two cohorts in a single ascending-dose crossover design. Part C (N = 25) was planned as an initial dose of 10 mg of GSK3358699 or placebo daily for 14 days followed by selected doses in four sequential cohorts.In part A, exposure to GSK3358699 and its metabolite GSK3206944 generally increased with increasing doses. The median initial half-life ranged from 0.7 to 1.1 (GSK3358699) and 2.1 to 2.9 (GSK3206944) hours after a single dose of 1-40 mg. GSK3206944 concentrations in monocytes were quantifiable at 1-hour post-dose following 10 mg of GSK3358699 and 1 and 4 hours post-dose following 20-40 mg. Mean predicted percentage inhibition of ex vivo lipopolysaccharide-induced monocyte chemoattractant protein (MCP)-1 reached 75% with 40 mg of GSK3358699. GSK3358699 did not inhibit interleukin (IL)-6 and tumour necrosis factor (TNF). The most common adverse event (AE) was headache. Four AEs of nonsustained ventricular tachycardia were observed across parts A and C. One serious AE of atrial fibrillation (part C) required hospitalization.Single doses of GSK3358699 are generally well tolerated with significant metabolite concentrations detected in target cells. A complete assessment of pharmacodynamics was limited by assay variability. A causal relationship could not be excluded for cardiac-related AEs, resulting in an inability to identify a suitable repeat-dose regimen and study termination.

The 1992 Republican Constitution of Ghana obligates the state to guarantee that all citizens have access to education, good health, housing, water, sanitation, employment and food security. As a consequence, the government implemented the ongoing Livelihood Empowerment Against Poverty (LEAP) programme in 2008 to sustain development in these areas. Although Ghana has achieved pockets of progress in reducing extreme poverty and hunger, there is considerable evidence of poverty and widening inequality across the country. This study draws on the theoretical lens of the human rights-based approach (HRBA) to poverty reduction to examine how the implementation of the LEAP programme aligns with beneficiaries’ human rights entitlements. It argues that the LEAP programme has failed to align with the HRBA and leaves unattended Ghana’s constitutional obligations. This study employed an exploratory sequential mixed design (SMD) strategy using a two-phase, chronological design to explore beneficiaries’ and key stakeholders’ experiences of the LEAP programme. The first phase was grounded on a qualitative research approach using in-depth face-to-face interviews, focus group discussions, participant observation and document analysis. The second phase employed a quantitative research approach, drawing on the themes that emerged from the first phase to develop a standardised questionnaire to conduct a household cross-sectional survey with a sample of 250 respondents. The findings suggest that the LEAP programme has led to some positive outcomes for beneficiaries, including enhanced self-esteem and happiness, household cohesion, social interaction and increased community involvement for beneficiaries. Nevertheless, many of the beneficiaries perceived their deprivation (poverty) as a way of life, making them vulnerable and defenceless. For them, the LEAP programme was an act of charity from the government and not an escape route from poverty. The study also found that the community engagement approach used by the LEAP implementers failed to conform to the active stakeholder engagement approach of community participation, consultation and collaboration. Overall, the evidence suggests that the implementation of the LEAP programme only partially aligns with the HRBA to poverty reduction, which potentially undermines efforts to eradicate poverty and sustain development in Ghana. The findings from this study confirm support for a community-based empowerment model that captures the emerging dynamics and complexities in advancing the social and economic status of the vulnerable and indigent in society. This new model of community based empowerment is underpinned by beneficiaries’ active engagement in economic activities and their economic empowerment. This model of economic empowerment addresses the inadequacies associated with the LEAP programme that directly threaten its sustainability. The new model has the potential to advance and strengthen the human rights of beneficiaries, widen the scope of beneficiaries and support the long-term…

The aim of this study is to present the anthracological results from three archaeological sites located in the North, North West and South East of Sri Lanka. The study is based on the observation and analysis of 1689 charcoal fragments using for support the reference collection of South Indian wood at the Institute of Archaeology ( UCL), Inside Wood (2004-onwards) and several wood anatomy atlases. Mantai (200 BCE-850 CE), an urban site, has yielded 25 taxa with significant presence of cf. Cocos nucifera among other taxa. Kantharodai (400-170- BCE), an urban site, has yielded 19 taxa from arid zones (Fabaceae, Rubiaceae), mangroves (Rhizophoraceae) and dune zones (cf. Cocos nucifera). Kirinda (500–900 CE), a fishing settlement, has yielded 24 taxa including Fabaceae (Dalbergia, Acacia) and Rubiaceae, belonging to dry deciduous forest and open savannas. This collective data set allows for the identification of discernible patterns related to the use of ecological interfaces between the forest and the open plains, used and actively managed by humans, and the possibility to identify if this changed with an increase in maritime trade and/or changes in agriculture over time. This study provides evidence of the differences in the vegetation present as well as use of wood fuel and other specific uses of wood for each site examined. It also sheds new light on tropical anthracology regarding quantification and accuracy in taxa identification.

Alda Balthrop-Lewis, Thoreau’s Religion: Walden Woods, Social Justice, and the Politics of Asceticism. Cambridge: Cambridge University Press, 2021, pp. 308, ISBN: 978-1-108-83510-7 (hbk).

The overview Evidence for water and aqueous processes during the initial infilling phase of Gale crater are abundant. Since 2012, the Mars Science Laboratory (MSL) rover Curiosity has investigated a variety of fluviolacustrine environments represented by the Bradbury and Mount Sharp groups. Both units accumulated as a result of sediment transport as bedload by fluvial processes, or by sediment settling from suspension in a lake. What is unclear is the duration that water persisted within Gale crater after the crater infilling was complete. In this contribution, we present evidence of water present within the base of the aeolian Stimson formation, which is recorded in the stratigraphic record by fluidization structures. We will describe the morphology of these structures, the mechanism of emplacement and implications for the history of aqueous processes in Gale crater. The Background The Stimson formation is the portion of a broader mound skirting unit which has been directly investigated by the MSL rover. This mound skirting unit unconformably drapes the northern flank of the present-day Mount Sharp. Where encountered on the traverse, the Stimson formation represents the preserved expression of an ancient aeolian dune field. Specifically, the stratigraphic record and the sedimentary architecture indicates that it was a dry dune field: water played no role in the accumulation of this sediment body. This fact is betrayed by the absence of fine-grained interdune deposits, microtopography, or other facies which are characteristic of water at or near the depositional surface. At the time the Stimson formation accumulated, Gale was devoid of surface water. The Observations Around Sol 3434, as Curiosity traverse onto the east side of the Greenheugh pediment, it encountered prominent erosion-resistant bedrock ridges which formed a polygonal (boxwork) network. These structures were observed in the basal portion of the Stimson formation, just a few metres above the base Stimson formation unconformity. Internally, these structures consisted of convolute, folded and warped laminations. Laterally, these structures were juxtapose against undeformed Stimson formation: large-scale cross-bedding composed of well-sorted medium-grained sandstones. Figure1: Polygonal (boxwork) ridges observed at Feòrachas Closer inspection of these internally-deformed ridge structures yielded evidence of both ductile displacement and destruction of primary stratification in a vertical orientation. The displacement and destruction are localised to the polygonal, linear ridges. Where stratification was displaced, laminations were folded into upright closed antiforms, with a tight bend radi on the hinge. Often, these are adjacent to open-folded synforms. Folding of laminations become tighter and more prominent with increasing vertical distance through the antiforms. Some original cross-laminations exhibited complex, recumbent folding where the underlying bounding surface exhibited open-folded synforms. In some ridges, such as at the Lamington sandstone target, stratification was destroyed, and was replaced by continuous, vertically-oriented laminations that cross-cut horizontally-orientated laminations adjacent to the ridge (Figure 2). These laminations are oriented parallel to the long axis of the ridges, occasionally displaying vertical fold structures. In some locations these erosion-resistant ridges contained vertically oriented fractures, with a few subordinate horizontal fractures, which were found to cross-cut some of the ductile deformation. Figure 2: Close-up view of deformation structures within the Feorachas structure Figure 3: Lamington Sandstone: example of vertical laminations within a sand dyke The Interpretation These structures are interpreted to represent fluidization of sediment caused by water escaping through unconsolidated sediment, under pressure. The linear ridges such as the Lamington structure are interpreted to represent well-cemented sand dykes. The result is the partial or complete destruction of primary sedimentary structures (e.g. cross-bedding) and replacement with secondary sedimentary structures related with fluidization. The tight antiforms are interpreted to be cusps while the vertical laminations are interpreted as pipes. Synforms, cusps and pipes exhibit pervasive vertical shear. The recumbent folding was also interpreted as evidence of vertical shear due to the displacement of the underlying bounding surfaces into vertical synforms. The vertical shear seen in cusp and synforms, and the vertical laminations observed in the dykes are evidence for the fluidization of sediment caused by upward fluid drag supporting the grain weight as water escapes through an open system under pressure. The source of the fluid may include groundwater upwelling or pore water from liquefaction occurring below the Stimson. As brittle deformation overprinted the soft sediment deformation, the trigger or cause of the fluidization may have been cyclic and caused brittle failure after the sediment regained its strength. The implications Regardless of the origin of the water, these fluidization structures provide evidence of persistent water within Gale crater after the exhumation of Mount Sharp, and the accumulation of the Stimson dune field. Presence of this water indicates: Water percolated into the base of the Stimson formation, either from fractures within the Mount Sharp group, from strata higher up on Mount Sharp, or from Meteoric sources. Water was present at the time which the Stimson formation was unconsolidated: which would be penecontemporaneous with dune field formation. This may represent a secondary habitable environment within the lithosphere.

The geologic origin of the ancient, phyllosilicate-rich bedrock at Oxia Planum, Mars, the landing site of ESA’s ExoMars rover, is unknown. The phyllosilicates record ancient aqueous processes, but the processes that formed the host bedrock remain elusive. Here, we use high-resolution orbital image and topographic datasets (HiRISE, CTX, CaSSIS) to investigate and characterize fluvial sinuous ridges (FSRs), found across the Oxia Planum region. The FSRs form segments up to 70 km long, with sub-horizontal layering commonly exposed in ridge margins. Some FSRs comprise multi-story ridge systems; many are embedded within and are being exhumed from the phyllosilicate-rich bedrock. We interpret the FSRs as deposits of ancient, episodically active, alluvial river systems (channel-belt and overbank deposits) at Oxia Planum. Thus, the phyllosilicate-rich bedrock was formed at least partly by ancient alluvial rivers, active across the wider region. Our alluvial hypothesis does not exclude other sources of sediment playing a role in building the terrain as well. Future exploration by ExoMars can verify this interpretation and provides an opportunity to investigate some of the oldest river deposits in the Solar System.

International audience; Aeolian processes have shaped and contributed to the geological record in Gale crater, Mars, long after the fluviolacustrine system existed ∼3 Ga ago. Understanding these aeolian deposits, particularly those which have been lithified and show evidence for aqueous alteration, can help to constrain the environment at their time of deposition and the role of liquid water later in Mars' history. The NASA Curiosity rover investigated a prominent outcrop of aeolian sandstone within the Stimson formation at the Greenheugh pediment as part of its investigation of the Glen Torridon area. In this study, we use geochemical data from ChemCam to constrain the effects of aeolian sedimentary processes, sediment provenance, and diagenesis of the sandstone at the Greenheugh pediment, comparing the Greenheugh data to the results from previous Stimson localities situated 2.5 km north and >200 m lower in elevation. Our results, supported by mineralogical data from CheMin, show that the Stimson formation at the Greenheugh pediment was predominately sourced from an olivine-rich unit that may be present farther up the slopes of Gale crater's central mound. Our results also suggest that the Greenheugh pediment Stimson formation was cemented by surface water runoff such as that which may have formed Gediz Vallis. The lack of alteration features in the Stimson formation at the Greenheugh pediment relative to those of the Emerson and Naukluft plateaus suggests that groundwater was not as available at this locality compared to the others. However, all sites share diagenesis at the unconformity

This is a stratigraphic-based geologic map of the Glen Torridon region, Gale crater, Mars around the locations studied by the Curiosity rover. This map accompanies Fedo et al. (2022, Journal of Geophysical Research - Planets). Corner coordinates for map area as follows Northwest: 137.3767, -4.7206 Northeast: 137.3919, -4.7206 Southwest: 137.3767, -4.7383 Southeast: 137.3919, -4.7383

This is a registration of the study materials for publication.

This is a registration of the data and codebooks for publication.

This is a registration of Study 3 for publication.

This study utilizes instruments from the Curiosity rover payload to develop an integrated paleoenvironmental and compositional reconstruction for the 65-m thick interval of stratigraphy comprising the Hartmann's Valley and Karasburg members of the Murray formation, Gale crater, Mars. The stratigraphy consists of cross-stratified sandstone (Facies 1), planar-laminated sandstone (Facies 2), and planar-laminated mudstone (Facies 3). Facies 1 is composed of sandstone showing truncated sets of concave-curvilinear laminae stacked into cosets. Sets are estimated to be meter-to sub-meter-scale, consistent with low-height dunes. Thin stratigraphic intervals of Facies 1 and stacking patterns with Facies 2 and 3 support a wet aeolian dune interpretation. Meter-thick packages of planar-laminated sandstone (Facies 2) are interpreted to represent interfingering dune-interdune strata. Facies 3 consists of meter-thick packages of planar-laminated mudstone interpreted to represent lacustrine deposition with persistent standing water. Integration of geochemistry with each facies reveals some compositional control based on the depositional process. Models for source rock composition from Alpha Particle X-Ray Spectrometer measurements show that facies derived from a basaltic source. Alteration indices and geochemical trends provide evidence that moderate chemical weathering occurred before compositional changes due to diagenesis. Differences in wt% FeO(T) and TiO2 between facies are minimal, though trends point to sediment sorting in transport. Comparisons to terrestrial basaltic sedimentary systems indicate that the Hartmann's Valley and Karasburg facies reflect deposition in an environment where diverse subaqueous and subaerial facies persisted adjacent to a long-lived body of water.

The integration process for immigrants is a multi-dimensional concept, influenced by a wide range of structural and individual factors, including social connections that immigrants make in the host society. An important part of this social connection can be developed with other co-nation immigrants within the immigrant community. However, this sometimes can be challenging due to the divisions that might exist within communities. Drawing on data with a mixed-method design, this study focuses on the Afghan community in Western Australia to understand, firstly, the relationship between Afghan immigrants’ social connections within their community and successful integration within Australian society, and secondly the causes of divisions and challenges within the community. To do this, the Immigration Policy Lab (IPL) Integration Index was used to measure the level of integration among 115 Afghan participants in the quantitative phase, with 18 interviews and two focus groups conducted in the qualitative phase, to understand Afghan experiences of divisions within their community. Findings show that there is a correlation between Afghans’ social connections within their community and the four dimensions of economic, social, linguistic, and navigational integration. Qualitative findings also showed the details of the challenges that Afghans face within their community due to ethnic/regional divisions as well as the challenges women face in the community.

Significance IgG antibodies are a key component of adaptive humoral immunity but can cause organ damage if they bind self-antigen, as occurs in the autoimmune disease systemic lupus erythematosus (SLE). Many of the proinflammatory effects of IgG are mediated by ligating Fcγ receptors (FcγRs) expressed by tissue-resident leukocytes such as macrophages. One of the most serious complications of SLE is kidney inflammation: lupus nephritis. Here we show that IgG ligation of FcγRs on macrophages in the kidney leads to a change in their metabolism, resulting in a switch toward glycolysis. Administration of a glycolysis inhibitor attenuated IgG-associated kidney macrophage activation, proinflammatory cytokine secretion, and kidney inflammation. Therefore, manipulating macrophage metabolism may be a useful therapeutic strategy in lupus nephritis., IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis.

Introduction: Hyperbaric oxygen treatment (HBOT) may be complicated by oxygen toxicity seizures, which typically occur with hyperbaric partial pressures of oxygen exceeding 203 kPa (2 atmospheres absolute). All other hyperbaric units in Australia exclusively use a multiplace chamber when treating with United States Navy Treatment Table 6 (USN TT6) due to this perceived risk. The purpose of this study was to determine the safety of a monoplace chamber when treating decompression illness (DCI) with USN TT6. Methods: A retrospective review of the medical records of all patients treated at Fiona Stanley Hospital Hyperbaric Medicine Unit with USN TT6 between November 2014 and June 2020 was undertaken. These data were combined with previous results from studies performed at our hyperbaric unit at Fremantle Hospital from 1989 to 2014, creating a data set covering a 30-year period. Results: One thousand treatments with USN TT6 were performed between 1989 and 2020; 331 in a monoplace chamber and 669 in a multiplace chamber. Four seizures occurred: a rate of 0.59% (1/167) in a multiplace chamber; and none in a monoplace chamber, indicating no statistically significant difference between seizures in a monoplace versus multiplace chamber (P = 0.31). Conclusions: The rate of oxygen toxicity seizures in a monoplace chamber is not significantly higher than for treatment in the multiplace chamber. We conclude that using the monoplace chamber for USN TT6 in selected patients poses an acceptably low seizure risk.

This article examines the role of legal frameworks and everyday interaction in the negotiation of religious diversity in Victoria, Australia. We argue that both formal legal frameworks and everyday interactions are significant in encouraging the respectful negotiation of religious difference. Experiences of historical privilege and visibility impact how religious people and groups experience and understand these processes. Or, put another way, the social position of various faith groups in Australian society shapes how people engage with both legal frameworks such as anti-discrimination legislation, and with other people in everyday interaction. Further, people’s everyday interactions shape their responses towards legal frameworks. Anti-discrimination and anti-vilification laws also shape everyday interactions through an effect that can be described as the ‘shadow of the law’, in which legal decisions communicate information about normative expectations that particular forms of behaviour are acceptable or unacceptable.

This article explores how bushwalking in Tasmania, Australia functions as a performance of ‘everyday resistance’. ‘Everyday resistance’ refers to experiences of relationship with the nonhuman, through which individuals resist alienating and dominating forms of human–nonhuman engagements encouraged by central Western cultural narratives. The work of Tasmanian environmental activists is easily understood as ‘political’, encouraging ‘counter-narratives’ of critical forms of human–nonhuman engagement. Drawing from interviews conducted with 27 Tasmanians, this article contends that participants’ descriptions of their forest experiences reflect these same forms of counter-narrative. As such, I argue that personal experiences perform an important role as critical, resistant, and disruptive representations of human–nonhuman engagement. This radical power is easily overlooked, however, as such everyday activities lack the visibility, intelligibility, and intent of organised environmental activism. I therefore argue that forest experiences should be recognised as a performance of relational, compassionate connection with the nonhuman that is vital, dynamic, and often underestimated in its significance.

Background: Red needle cast caused by Phytophthora pluvialis Reeser, Sutton & E. Hansen, and less frequently P. kernoviae Brasier, Beales & S.A.Kirk, is an important foliar disease of Pinus radiata D.Don (radiata pine) in plantations throughout parts of New Zealand. Significant growth loss occurs following years when severe outbreaks occur. Aerial spraying with a copper-based fungicide has potential for disease control. Research is being carried out to optimise application timing, supported by complementary studies to understand RNC epidemiology. Methods: In order to determine the pathogen infection periods, a field trial was conducted over two years at two forests in the Central North Island of New Zealand. Batches of potted radiata pine seedlings were placed beneath diseased pine stands at fortnightly intervals, before returning them to an open nursery area for assessments of infection every two weeks (based on visual symptoms and qPCR) over a period of three months. A hybrid modelling approach was employed to establish relationships between the proportion of plants showing symptoms and weather conditions during the fortnight of exposure and previous fortnights. Gradient boosting machine learning analyses were used to identify the most important weather variables, followed by analysis of these by generalised mixed effects models, generalised least square models and ordinary least square models. Results: Development of RNC symptoms and detection of Phytophthora pluvialis and P. kernoviae on exchange seedlings was greatest for those exposed between April and September (Southern Hemisphere mid-autumn to early-spring). At this time, temperatures, solar radiation and evapotranspiration were lower, and rainfall and foliage wetness were plentiful. Modelling identified temperature and relative humidity several months before the date of exposure as the most important weather variables explaining infection. Conclusions: Because of autocorrelation, it was not possible to determine those variables that drive sporulation, dispersal, infection and symptom development. This will require more detailed exchange plant studies together with controlled environment inoculation experiments. Nevertheless, results of this and earlier work complement recent research indicating that it may be possible to manage RNC by fungicide applications made in late summer or autumn, early in the annual disease cycle.

IgG antibodies form immune complexes (IC) that propagate inflammation and tissue damage in autoimmune diseases such as systemic lupus erythematosus. IgG IC engage Fcγ receptors (FcγR) on mononuclear phagocytes (MNP), leading to widespread changes in gene expression that mediate antibody effector function. Bromodomain and extra-terminal domain (BET) proteins are involved in governing gene transcription. We investigated the capacity of BET protein inhibitors (iBET) to alter IgG FcγR-mediated MNP activation. We found that iBET dampened IgG IC-induced pro-inflammatory gene expression and decreased activating FcγR expression on MNPs, reducing their ability to respond to IgG IC. Despite FcγR downregulation, iBET-treated macrophages demonstrated increased phagocytosis of protein antigen, IgG IC, and apoptotic cells. iBET also altered cell morphology, generating more amoeboid MNPs with reduced adhesion. iBET treatment impaired chemotaxis towards a CCL19 gradient in IC-stimulated dendritic cells (DC) in vitro, and inhibited IC-induced DC migration to draining lymph nodes in vivo, in a DC-intrinsic manner. Altogether, our data show that iBET modulates FcγR-mediated MNP activation and migration, revealing the therapeutic potential of BET protein inhibition in antibody-mediated diseases.