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Design thinking, an approach traditionally used to develop or improve products, services, or processes within design and engineering sectors, has emerged as a novel pedagogical approach. As design thinking becomes more widely established within education contexts, it is important to gain deeper insight as to how such learning environments operate. The aim of this study was to explore online design thinking through the lens of psychological safety. We used a qualitative single-case study design to investigate nine students' experiences across a nine-week design-thinking project. Data were collected via semi-structured interviews and reflective journal entries, and analysed through reflexive thematic analysis. Our findings suggested that psychological safety is a valuable consideration in the design and implementation of online design-thinking learning environments. Facilitators of psychological safety included having collaborative environments, encouraging leadership, and a focus on team formation. Barriers to psychological safety included difficulties connecting, fear of speaking, and cultural considerations. Our findings also highlighted several outcomes of psychologically safe team climates, including creativity, collaboration, and the development of approaches to working with uncertainty.

Abstract Most COVID-19 vaccines elicit immunity against the SARS-CoV-2 Spike protein. However, Spike protein mutations in emerging strains and immune evasion by the SARS-CoV-2 virus demonstrates the need to develop more broadly targeting vaccines. To facilitate this, we use mass spectrometry to identify immunopeptides derived from seven relatively conserved structural and non-structural SARS-CoV-2 proteins (N, E, Nsp1/4/5/8/9). We use two different B-lymphoblastoid cell lines to map Human Leukocyte Antigen (HLA) class I and class II immunopeptidomes covering some of the prevalent HLA types across the global human population. We employ DNA plasmid transfection and direct antigen delivery approaches to sample different antigens and find 248 unique HLA class I and HLA class II bound peptides with 71 derived from N, 12 from E, 28 from Nsp1, 19 from Nsp4, 73 from Nsp8 and 45 peptides derived from Nsp9. Over half of the viral peptides are unpublished. T cell reactivity tested against 56 of the detected peptides shows CD8+ and CD4+ T cell responses against several peptides from the N, E, and Nsp9 proteins. Results from this study will aid the development of next-generation COVID vaccines targeting epitopes from across a number of SARS-CoV-2 proteins.

BackgroundMajor histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, was until recently considered to be monomorphic. MR1 presents metabolites in the context of host responses to bacterial infection. MR1-restricted TCRs specific to tumor cells have been described, raising interest in their potential therapeutic application for cancer treatment. The diversity of MR1-ligand biology has broadened with the observation that single nucleotide variants (SNVs) exist within MR1 and that allelic variants can impact host immunity.MethodsThe TCR from a MR1-restricted T-cell clone, MC.7.G5, with reported cancer specificity and pan-cancer activity, was cloned and expressed in Jurkat E6.1 TCRαβ− β2M− CD8+ NF-κB:CFP NFAT:eGFP AP-1:mCherry cells or in human donor T cells. Functional activity of 7G5.TCR-T was demonstrated using cytotoxicity assays and by measuring cytokine release after co-culture with cancer cell lines with or without loading of previously described MR1 ligands. MR1 allele sequencing was undertaken after the amplification of the MR1 gene region by PCR. In vivo studies were undertaken at Labcorp Drug Development (Ann Arbor, MI, USA) or Epistem Ltd (Manchester, UK).ResultsThe TCR cloned from MC.7.G5 retained MR1-restricted functional cytotoxicity as 7G5.TCR-T. However, activity was not pan-cancer, as initially reported with the clone MC.7.G5. Recognition was restricted to cells expressing a SNV of MR1 (MR1*04) and was not cancer-specific. 7G5.TCR-T and 7G5-like TCR-T cells reacted to both cancer and healthy cells endogenously expressing MR1*04 SNVs, which encode R9H and H17R substitutions. This allelic specificity could be overcome by expressing supraphysiological levels of the wild-type MR1 (MR1*01) in cell lines.ConclusionsHealthy individuals harbor T cells reactive to MR1 variants displaying self-ligands expressed in cancer and benign tissues. Described “cancer-specific” MR1-restricted TCRs need further validation, covering conserved allomorphs of MR1. Ligands require identification to ensure targeting MR1 is restricted to those specific to cancer and not normal tissues. For the wider field of immunology and transplant biology, the observation that MR1*04 may behave as an alloantigen warrants further study.

Abstract Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer+CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02-restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age.

Abstract Interprofessional education (IPE) during undergraduate education and training has been found to improve collaboration between health care students. This supports interprofessional working in clinical practice to enhance patient safety and care delivery. Undergraduate students from pharmacy and medical programmes worked online in pairs to review notes of hospital patients due to be discharged. Students were tasked to complete a discharge letter and undertake an online consultation with a simulated patient prior to discharge. Online interactions were recorded and assessed using a validated tool to measure interprofessional professionalism. Students undertook this intervention in different pairings with different patient cases for three iterations after receiving feedback and undertaking a reflective exercise. The aim was to investigate the student learning and development that could be used to inform intervention optimisation and scale-up. Qualitative data were collected from different sources. Method triangulation was employed to develop a comprehensive understanding of the student learning and development. Data was collected from written feedback provided by the assessment team, student reflections on their performance, and from semi-structured interviews conducted with the student pairs and one to one with the assessment team. Content and thematic analysis was used to analyse these data and the Kirkpatrick/Barr evaluation model provided a framework to organise the themes. Eighteen students (nine from each professional programme) completed the study and a total of 27 IPE sessions were conducted. The assessment team completed 54 assessment tools and 31 student reflections were received (from a maximum of 36). Students were interviewed in their interprofessional pairs to yield nine interview transcripts and one interview was conducted with the assessment team. Students reported and were observed to improve in interprofessional collaboration over the three iterations following feedback and rehearsal opportunities. Longitudinal observation and assessment of student interprofessional working in changing teams provided the opportunity to capture the influence of interdependence on student performance and assessment of competence.

Abstract Communication distances of wireless sensor networks (WSNs) are greatly limited in settings where vegetation coverage is moderate or dense, and power consumption can be an issue in remote environmental settings. A newer innovative technology called “Low Power Wide Area Sensor Networks” (LPWAN) is capable of greater communication distances while consuming less power than traditional WSNs. This research evaluates the design and in-field performance of a LPWAN configuration in headwater catchments to measure environmental variables. The performance of the Beta LPWAN deployment indicate reduced signal strength in topographic valleys, but better actual than modelled data transmission performance. System performance during extreme cold temperatures (below – 15 ºC) resulted in increased sensor down time. The configuration of antennae combinations provides the greatest improvement in signal strength and system performance. This technology facilitates remote collection of physically-based, spatially-distributed information within regions with limited accessibility, ultimately advancing data collection capabilities into areas that are not feasible to visit regularly.

Genes involved in distinct diabetes types suggest shared disease mechanisms. Here we show that One Cut Homeobox 1 (ONECUT1) mutations cause monogenic recessive syndromic diabetes in two unrelated patients, characterized by intrauterine growth retardation, pancreas hypoplasia and gallbladder agenesis/hypoplasia, and early-onset diabetes in heterozygous relatives. Heterozygous carriers of rare coding variants of ONECUT1 define a distinctive subgroup of diabetic patients with early-onset, nonautoimmune diabetes, who respond well to diabetes treatment. In addition, common regulatory ONECUT1 variants are associated with multifactorial type 2 diabetes. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. Loss of ONECUT1 altered transcription factor binding and enhancer activity and NKX2.2/NKX6.1 expression in pancreatic progenitor cells. Collectively, we demonstrate that ONECUT1 controls a transcriptional and epigenetic machinery regulating endocrine development, involved in a spectrum of diabetes, encompassing monogenic (recessive and dominant) as well as multifactorial inheritance. Our findings highlight the broad contribution of ONECUT1 in diabetes pathogenesis, marking an important step toward precision diabetes medicine.

Abstract Background Interprofessional education (IPE) has been identified as a strategy towards improving competence at interprofessional working and collaboration within teams. Entrustable professional activities (EPAs) provide a framework for translating competencies into elements of clinical practice, some of which in healthcare are inherently interprofessional. However, it is challenging to reconcile that entrustment decisions about student competence in an interprofessional activity are made about an individual without considering the dynamics and tensions between interprofessional team members and the task itself. This can influence students’ development and demonstration of competence at interprofessional collaboration. Methods In this study, undergraduate medical and pharmacy students worked in pairs online (Zoom) to undertake the hospital discharge process (a professional activity reliant on interprofessional collaboration) for a simulated patient, producing a hospital discharge letter and completing a consultation with the simulated patient. The online sessions were recorded and interprofessional behaviours were assessed using a validated scale completed by an interprofessional assessment team. Students undertook this IPE intervention three times after receiving feedback and a period of reflection each time. Results Eighteen students participated across the entire intervention and 27 one-hour online IPE sessions were completed and recorded. Students demonstrated statistically significant improvements in interprofessional behaviours across the three iterations (p

Objectives In an increasingly global society, there is a need to develop culturally competent doctors who can work effectively across diverse populations. International learning opportunities in undergraduate healthcare programmes show various benefits. In medical education, these occur predominantly towards the end of degree programmes as electives, with scant examples of programmes for preclinical students. This study set out to identify the multicultural learning experiences following an early year international medical student exchange programme between the UK and Malaysian campuses of one UK medical school.Setting Two cohorts of international exchange programme for second year medical students in the UK and Malaysia.Design Interpretivist qualitative design using semistructured interviews/focus groups with students and faculty.Methods Participants were asked about their learning experiences during and after the exchange. Data were recorded with consent and transcribed verbatim. Thematic analysis was used to analyse the data.Results Four themes were identified: (1) overall benefits of the exchange programme, (2) personal growth and development, (3) understanding and observing a different educational environment and (4) experiencing different healthcare systems.Conclusion The international exchange programme highlighted differences in learning approaches, students from both campuses gained valuable learning experiences which increased their personal growth, confidence, cultural competence, giving them an appreciation of a better work–life balance and effective time management skills. It is often a challenge to prepare healthcare professionals for work in a global multicultural workplace and we would suggest that exchange programmes early on in a medical curriculum would go some way to addressing this challenge.

Aquatic environments are polluted with a multitude of organic micropollutants, which challenges risk assessment due the complexity and diversity of pollutant mixtures. The recognition that certain source-specific background pollution occurs ubiquitously in the aquatic environment might be one way forward to approach mixture risk assessment. To investigate this hypothesis, we prepared one typical and representative WWTP effluent mixture of organic micropollutants (EWERBmix) comprised of 81 compounds selected according to their high frequency of occurrence and toxic potential. Toxicological relevant effects of this reference mixture were measured in eight organism- and cell-based bioassays and compared with predicted mixture effects, which were calculated based on effect data of single chemicals retrieved from literature or different databases, and via quantitative structure-activity relationships (QSARs). The results show that the EWERBmix supports the identification of substances which should be considered in future monitoring efforts. It provides measures to estimate wastewater background concentrations in rivers under consideration of respective dilution factors, and to assess the extent of mixture risks to be expected from European WWTP effluents. The EWERBmix presents a reasonable proxy for regulatory authorities to develop and implement assessment approaches and regulatory measures to address mixture risks. The highlighted data gaps should be considered for prioritization of effect testing of most prevalent and relevant individual organic micropollutants of WWTP effluent background pollution. The here provided approach and EWERBmix are available for authorities and scientists for further investigations. The approach presented can furthermore serve as a roadmap guiding the development of archetypic background mixtures for other sources, geographical settings and chemical compounds, e.g. inorganic pollutants.

T cells expressing either alpha-beta or gamma-delta T cell receptors (TCR) are critical sentinels of the adaptive immune system, with receptor diversity being essential for protective immunity against a broad array of pathogens and agents. Programs available to profile TCR clonotypic signatures can be limiting for users with no coding expertise. Current analytical pipelines can be inefficient due to manual processing steps, open to data entry errors and have multiple analytical tools with unique inputs that require coding expertise. Here we present a bespoke webtool designed for users irrespective of coding expertise, coined ‘TCR_Explore’, enabling analysis either derived via Sanger sequencing or next generation sequencing (NGS) platforms. Further, TCR_Explore incorporates automated quality control steps for Sanger sequencing. The creation of flexible and publication ready figures are enabled for different sequencing platforms following universal conversion to the TCR_Explore file format. TCR_Explore will enhance a user’s capacity to undertake in-depth TCR repertoire analysis of both new and pre-existing datasets for identification of T cell clonotypes associated with health and disease. The web application is located at https://tcr-explore.erc.monash.edu for users to interactively explore TCR repertoire datasets.

Flexible magnetic sensors with high sensitivity have a wide variety of medical and industrial uses, however, making such sensors robust and flexible at the same time can be challenging. Here, the authors demonstrate a high sensitivity flexible magnetic sensor that exhibits self-healing under an applied alternative magnetic field, with complete performance recovery.

Koh, Papanikolaou et al. discuss the application of artificial intelligence in cancer imaging. The authors highlight opportunities for exploiting machine learning algorithms in this field, and outline barriers in their implementation and how these might be addressed.

Various surface modification strategies are being developed to endow dental titanium implant surfaces with micro- and nano-structures to improve their biocompatibility, and first of all their osseointegration. These modifications have the potential to address clinical concerns by stimulating different biological processes. This study aims to evaluate the biological responses of ananatase-modified blasted/etched titanium (SLA-anatase) surfaces compared to blasted/acid etched (SLA) and machined titanium surfaces. Using unipolar pulsed direct current (DC) sputtering, a nanocrystalline anatase layer was fabricated. In vitro experiments have shown that SLA-anatase discs can effectively promote osteoblast adhesion and proliferation, which are regarded as important features of a successful dental implant with bone contact. Furthermore, anatase surface modification has been shown to partially enhance osteoblast mineralization in vitro, while not significantly affecting bacterial colonization. Consequently, the recently created anatase coating holds significant potential as a promising candidate for future advancements in dental implant surface modification for improving the initial stages of osseointegration.

Abstract Whereas strong demand is a key factor driving high inflation in the US, inflation in the Euro Area is mainly due to adverse external supply shocks (in Europe, energy prices are much higher due to the war in Ukraine). Standard monetary policy response to such shocks is to accommodate first-round effects, to fight spiralling inflationary expectations in order to prevent second-round effects. Long run inflation expectations — as measured by the survey of professional forecasters — still seem to be well anchored. The ECB’s announced tightening intends to dampen rising household’s inflation expectations. Given the current high uncertainty about the economic outlook, a soft landing calls for modest, data-dependent steps, allowing for a reversal in case the outlook worsens.

Using a season-long field manipulation with an established model fish system on the Great Barrier Reef, this study demonstrates that limiting motorboat activity on reefs leads to faster growth and survival of more fish offspring compared to reefs experiencing busy motorboat traffic. Noise mitigation and abatement could therefore present a valuable opportunity for enhancing ecosystem resilience.

The micro- and nanostructures, chemical composition, and wettability of titanium surfaces are essential for dental implants’ osseointegration. Combining hydrophilicity and nanostructure has been shown to improve the cell response and to shorten the healing time. This study aimed to investigate the biological response to different wettability levels and nanotopographical modifications in aged and non-aged titanium surfaces. By plasma etching titanium surfaces with the fluorine gas 2,3,3,3-tetrafluoropropene (R1234yF), additional nanostructures were created on the sample surfaces. Furthermore, this treatment resulted in sustained superhydrophilicity and fluoride accumulation. We examined the effect of various nanostructuring processes and aging using scanning electron microscopy, roughness analyses, and wettability measurement. In addition, all the surface modifications were tested for their effects on fibroblast adhesion, proliferation, and viability as well as osteoblast differentiation. Our study indicates that the plasma etching, with 2,3,3,3-tetrafluoropropene, of the machined and SLA surface neither favored nor had an adverse effect on the biological response of the SAOS-2 osteoblast cell line. Although the fluorine-plasma-etched surfaces demonstrated improved fibroblast cell viability, they did not lead to improved early osseointegration. It is still unclear which surface properties mainly influence fibroblast and osteoblast adhesion. Further physiochemical aspects, such as electrostatic interaction and surface tension, are crucial to be analyzed along with wettability and roughness.

Program PKM ini bertujuan untuk menyelesaikan permasalahan yang dihadapi oleh mitra, di mana siswa belum memiliki pengetahuan mengenai potensi bencana di daerahnya. Siswa belum pernah dibekali pengetahuan dalam bentuk pelatihan dalam menghadapi bencana. Sekolah juga belum memiliki sarana dan prasarana mitigasi bencana seperti rambu-rambu dan peta jalur evakuasi. Solusi yang ditawarkan berupa Kegiatan Sekolah Siaga Bencana (SSB). Metode pelaksanaan dibagi ke dalam tiga tahapan yaitu tahapan persiapan, pelaksanaan kegiatan, dan monitoring dan evaluasi program. Tahapan persiapan meliputi observasi awal, studi awal, menyiapan dan pemasangan rambu-rambu mitigasi serta penyusunan modul kegiatan. Untuk tahapan pelaksanaan kegiatan meliputi pemberian materi, simulasi bencana dan evaluasi. Tahapan selanjutnya adalah evaluasi program. Melalui kegiatan ini diketahui bahwa indeks kesiapsiagaan siswa SMA Negeri 11 Luwu menghadapi bencana dalam kategori Tinggi sebesar 34,5%, kategori Sedang sebesar 62,1% dan kategori Rendah sebesar 3,4%.

Mass coral bleaching events coupled with local stressors have caused regional-scale loss of corals on reefs globally. Following the loss of corals, the structural complexity of these habitats is often reduced. By providing shelter, obscuring visual information, or physically impeding predators, habitat complexity can influence predation risk and the perception of risk by prey. Yet little is known on how habitat complexity and risk assessment interact to influence predator-prey interactions. To better understand how prey's perception of threats may shift in degraded ecosystems, we reared juvenile Pomacentrus chrysurus in environments of various habitat complexity levels and then exposed them to olfactory risk odours before simulating a predator strike. We found that the fast-start escape responses were enhanced when forewarned with olfactory cues of a predator and in environments of increasing complexity. However, no interaction between complexity and olfactory cues was observed in escape responses. To ascertain if the mechanisms used to modify these escape responses were facilitated through hormonal pathways, we conducted whole-body cortisol analysis. Cortisol concentrations interacted with habitat complexity and risk odours, such that P. chrysurus exhibited elevated cortisol levels when forewarned with predator odours, but only when complexity levels were low. Our study suggests that as complexity is lost, prey may more appropriately assess predation risk, likely as a result of receiving additional visual information. Prey's ability to modify their responses depending on the environmental context suggests that they may be able to partly alleviate the risk of increased predator-prey interactions as structural complexity is reduced.

We assess relationships among 192 species in all 12 monocot orders and 72 of 77 families, using 602 conserved single-copy (CSC) genes and 1375 benchmarking single-copy ortholog (BUSCO) genes extracted from genomic and transcriptomic datasets. Phylogenomic inferences based on these data, using both coalescent-based and supermatrix analyses, are largely congruent with the most comprehensive plastome-based analysis, and nuclear-gene phylogenomic analyses with less comprehensive taxon sampling. The strongest discordance between the plastome and nuclear gene analyses is the monophyly of a clade comprising Asparagales and Liliales in our nuclear gene analyses, versus the placement of Asparagales and Liliales as successive sister clades to the commelinids in the plastome tree. Within orders, around six of 72 families shifted positions relative to the recent plastome analysis, but four of these involve poorly supported inferred relationships in the plastome-based tree. In Poales, the nuclear data place a clade comprising Ecdeiocoleaceae+Joinvilleaceae as sister to the grasses (Poaceae); Typhaceae, (rather than Bromeliaceae) are resolved as sister to all other Poales. In Commelinales, nuclear data place Philydraceae sister to all other families rather than to a clade comprising Haemodoraceae+Pontederiaceae as seen in the plastome tree. In Liliales, nuclear data place Liliaceae sister to Smilacaceae, and Melanthiaceae are placed sister to all other Liliales except Campynemataceae. Finally, in Alismatales, nuclear data strongly place Tofieldiaceae, rather than Araceae, as sister to all the other families, providing an alternative resolution of what has been the most problematic node to resolve using plastid data, outside of those involving achlorophyllous mycoheterotrophs. As seen in numerous prior studies, the placement of orders Acorales and Alismatales as successive sister lineages to all other extant monocots. Only 21.2% of BUSCO genes were demonstrably single-copy, yet phylogenomic inferences based on BUSCO and CSC genes did not differ, and overall functional annotations of the two sets were very similar. Our analyses also reveal significant gene tree-species tree discordance despite high support values, as expected given incomplete lineage sorting (ILS) related to rapid diversification. Our study advances understanding of monocot relationships and the robustness of phylogenetic inferences based on large numbers of nuclear single-copy genes that can be obtained from transcriptomes and genomes.

CD8+ T cells are a pivotal part of the immune response to viruses, playing a key role in disease outcome and providing long-lasting immunity to conserved pathogen epitopes. Understanding CD8+ T cell immunity in humans is complex due to CD8+ T cell restriction by highly polymorphic Human Leukocyte Antigen (HLA) proteins, requiring T cell epitopes to be defined for different HLA allotypes across different ethnicities. Here we evaluate strategies that have been developed to facilitate epitope identification and study immunogenic T cell responses. We describe an immunopeptidomics approach to sequence HLA-bound peptides presented on virus-infected cells by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using antigen presenting cell lines that stably express the HLA alleles characteristic of Indigenous Australians, this approach has been successfully used to comprehensively identify influenza-specific CD8+ T cell epitopes restricted by HLA allotypes predominant in Indigenous Australians, including HLA-A*24:02 and HLA-A*11:01. This is an essential step in ensuring high vaccine coverage and efficacy in Indigenous populations globally, known to be at high risk from influenza disease and other respiratory infections.

Background Surgery is often avoided in the setting of pediatric orbital complications from acute sinusitis unless necessitated by alarming ophthalmological signs. Criteria for surgical intervention are not well-defined. Objective We aim to review our experiences, management practices and patient outcomes over a ten-year period for Chandler III patients. Methods A retrospective review was performed from January 1, 2007 through December 31, 2016 of patients treated for orbital symptoms secondary to acute sinusitis at a free-standing tertiary-care pediatric hospital. Results Of the 186 patients reviewed, 42 Chandler III patients were included. Average age was 82.6 months (SD 50.6) with a slight male predominance (M to F, 1.8 to 1). 27 patients (64.3%) underwent intervention including endoscopic sinus surgery (ESS) with or without orbitotomy. Late surgical intervention (>48hrs from admission) demonstrated significant increase in overall length of stay (LOS) when compared with early surgical intervention and/or medical management (median, 6.9 vs 3.6 vs 3.7 days; p

HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A*11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A*11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A*11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A*11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A*11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A*11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A*11:01-expressing individuals.

Surface engineering of chromium-oxide-passivated alloys (e.g., stainless steels) by low-temperature infusion of interstitial solutes (carbon, nitrogen) from a gas phase requires “surface activation” by removing or perforating the passivating oxide film. We demonstrate a new approach for surface activation based on pyrolysis of a reagent powder, introduce advanced methodology to study its microstructure, and compare it to an established activation method. Rather than a bare alloy surface, stripped of its oxide, we find that an “activated” surface involves a reaction layer containing high concentrations of Cl, carbon, or nitrogen. We propose a model for the microscopic mechanism of surface activation that will enable future systematic development toward more effective process schemes.

Anadromous European smelt (Osmerus eperlanus) is a keystone species in lake and river ecosystems. In the past and present, stock declines in several of its habitats have been reported. The reasons for this are unclear. Experimental research on the early life stages could help to reveal the potential causes. For this purpose, knowledge on artificial propagation and rearing of early life stages is needed. Following from previous work, we show how to scale up and mass rear European smelt using conventional hatchery equipment and present a simplified protocol for first feeding. Smelt eggs, after egg adhesiveness is removed, can be incubated in standard hatchery equipment commonly used in aquaculture. Incubation in McDonald-type jars shows even improved results when settling of floating eggs is prevented. Next to avoiding egg loss this simultaneously reduces labor for daily care. First feeding of larval smelt can be achieved with decapsulated artemia cysts, eliminating the need for the labor-intensive green water production. Using the protocol presented, larvae of different stages can be produced in large quantities allowing further experimental studies.

The corrosion resistance of Cr-containing alloy parts made by additive manufacturing can be significantly improved by a post-treatment of gas-phase-based infusion of concentrated interstitial solute (carbon and nitrogen). We demonstrate this universal approach for the example of low-temperature nitrocarburization by solid-reagent pyrolysis applied to Alloy 22 (UNS N06022) parts made by laser powderbed fusion. We show that the post-treatment improves the crevice-corrosion resistance of these parts, as well as the corrosion resistance of corresponding parts made from wrought Alloy 22 to surpass the maximum crevice corrosion test temperature specified in ASTM G48-D, whereas non-treated samples typically fail well below. Similarly, cyclic potentiodynamic polarization testing (ASTM G61-86) demonstrates that the post-treatment makes the additively manufactured alloy and the wrought alloy more corrosion-resistant than the non-treated wrought alloy.

Influenza A virus is a respiratory pathogen that is responsible for regular epidemics and occasional pandemics that result in substantial damage to life and the economy. The yearly reformulation of trivalent or quadrivalent flu vaccines encompassing surface glycoproteins derived from the current circulating strains of the virus does not provide sufficient cross-protection against mismatched strains. Unlike the current vaccines that elicit a predominant humoral response, vaccines that induce CD8+ T cells have demonstrated a capacity to provide cross-protection against different influenza strains, including novel influenza viruses. Immunopeptidomics, the mass spectrometric identification of human-leukocyte-antigen (HLA)-bound peptides isolated from infected cells, has recently provided key insights into viral peptides that can serve as potential T cell epitopes. The critical elements required for a strong and long-living CD8+ T cell response are related to both HLA restriction and the immunogenicity of the viral peptide. This review examines the importance of HLA and the viral immunopeptidome for the design of a universal influenza T-cell-based vaccine.