Search

Background: In biomedical imaging research, experimental biologists generate vast amounts of data that require advanced computational analysis. Breakthroughs in experimental techniques, such as multiplex immunofluorescence tissue imaging, enable detailed proteomic analysis, but most biomedical researchers lack the programming and Artificial Intelligence (AI) expertise to leverage these innovations effectively. Methods: Cinco de Bio (CdB) is a web-based, collaborative low-code/no-code modelling and execution platform designed to address this challenge. It is designed along Model-Driven Development (MDD) and Service-Orientated Architecture (SOA) to enable modularity and scalability, and it is underpinned by formal methods to ensure correctness. The pre-processing of immunofluorescence images illustrates the ease of use and ease of modelling with CdB in comparison with the current, mostly manual, approaches. Results: CdB simplifies the deployment of data processing services that may use heterogeneous technologies. User-designed models support both a collaborative and user-centred design for biologists. Domain-Specific Languages for the Application domain (A-DSLs) are supported through data and process ontologies/taxonomies. They allow biologists to effectively model workflows in the terminology of their field. Conclusions: Comparative analysis of similar platforms in the literature illustrates the superiority of CdB along a number of comparison dimensions. We are expanding the platform’s capabilities and applying it to other domains of biomedical research.

Abstract The resonant excitation of electronic transitions with coherent laser sources creates quantum coherent superpositions of the involved electronic states. Most time-resolved studies have focused on gases or isolated subsystems embedded in insulating solids, aiming for applications in quantum information. Here, we focus on the coherent control of orbital wavefunctions in the correlated quantum material Tb2Ti2O7, which forms an interacting spin liquid ground state. We show that resonant excitation with a strong THz pulse creates a coherent superposition of the lowest energy Tb 4f states. The coherence manifests itself as a macroscopic oscillating magnetic dipole, which is detected by ultrafast resonant x-ray diffraction. We envision the coherent control of orbital wavefunctions demonstrated here to become a new tool for the ultrafast manipulation and investigation of quantum materials.

Abstract Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

Abstract Background Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program. The main objectives were to identify the causal mutation for a variety of diseases of individuals and families enrolled, and to discover novel disease genes. Methods Unsolved patients in whom standard genomic diagnostic techniques such as targeted gene panel, exome-wide next generation sequencing, and/or chromosomal microarray, had already been performed were recruited. Genome sequencing and enhanced genomic analysis from the research setting were applied to aid novel gene discovery. Results In total, 16/50 (32%) families/cases were solved. One or more candidate variants of uncertain significance were detected in 18/50 (36%) families. No candidate variants were identified in 16/50 (32%) families. Two novel disease genes (TOP3B, PRKACB) and two novel genotype–phenotype correlations (NARS, and KMT2C genes) were identified. Three out of eight patients with suspected mosaic tuberous sclerosis complex had their diagnosis confirmed which provided reproductive options for two patients. The utility of confirming diagnoses for patients with mosaic conditions (using high read depth sequencing and ddPCR) was not specifically envisaged at the onset of the project, but the flexibility to offer recruitment and analyses on an as-needed basis proved to be a strength of the AHA-UDP. Conclusion AHA-UDP demonstrates the utility of a UDP approach applying genome sequencing approaches in diagnosing adults with rare diseases who have had uninformative conventional genetic analysis, informing clinical management, recurrence risk, and recommendations for relatives.

Abstract Accurate screening of COVID-19 infection status for symptomatic patients is a critical public health task. Although molecular and antigen tests now exist for COVID-19, in resource-limited settings, screening tests are often not available. Furthermore, during the early stages of the pandemic tests were not available in any capacity. We utilized an automated machine learning (ML) approach to train and evaluate thousands of models on a clinical dataset consisting of commonly available clinical and laboratory data, along with cytokine profiles for patients (n = 150). These models were then further tested for generalizability on an out-of-sample secondary dataset (n = 120). We were able to develop a ML model for rapid and reliable screening of patients as COVID-19 positive or negative using three approaches: commonly available clinical and laboratory data, a cytokine profile, and a combination of the common data and cytokine profile. Of the tens of thousands of models automatically tested for the three approaches, all three approaches demonstrated > 92% sensitivity and > 88 specificity while our highest performing model achieved 95.6% sensitivity and 98.1% specificity. These models represent a potential effective deployable solution for COVID-19 status classification for symptomatic patients in resource-limited settings and provide proof-of-concept for rapid development of screening tools for novel emerging infectious diseases.

Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash features. Some of these systems are constrained by their long setup time, positioning requirements and considerable hardware costs. As such, there is a need for an autonomous low-cost system (~EUR 500), such as Timex cameras, that can be rapidly deployed in the field, while still producing the outcomes required for coastal monitoring. This research presents an assessment of the effect of the sampling strategy (time-lapse intervals) on the precision of shoreline detection for two low-cost cameras located in a remote coastal area in western Ireland, overlooking a dissipative beach–dune system. The analysis shows that RMSD in the detected shoreline is similar to other studies for sampling intervals ranging between 1 s and 30 s (i.e., RMSDmean for Camera 1 = 1.4 m and Camera 2 = 0.9 m), and an increase in the sampling interval from 1 s to 30 s had no significant adverse effect on the precision of shoreline detection. The research shows that depending on the intended use of the detected shorelines, the current standard of 1 s image sampling interval when using Timex cameras can be increased up to 30 s without any significant loss of accuracy. This positively impacts battery life and memory storage, making the systems more autonomous; for example, the battery life increased from ~10 days to ~100 days when the sampling interval was increased from 1 to 5 s.

Rootstocks are gaining importance in viticulture as a strategy to combat abiotic challenges, as well as enhancing scion physiology. Photosynthetic parameters such as maximum rate of carboxylation of RuBP (Vcmax) and the maximum rate of electron transport driving RuBP regeneration (Jmax) have been identified as ideal targets for potential influence by rootstock and breeding. However, leaf specific direct measurement of these photosynthetic parameters is time consuming, limiting the information scope and the number of individuals that can be screened. This study aims to overcome these limitations by employing hyperspectral imaging combined with artificial intelligence (AI) to predict these key photosynthetic traits at the canopy level. Hyperspectral imaging captures detailed optical properties across a broad range of wavelengths (400 to 1000 nm), enabling use of all wavelengths in a comprehensive analysis of the entire vine’s photosynthetic performance (Vcmax and Jmax). Artificial intelligence-based prediction models that blend the strength of deep learning and machine learning were developed using two growing seasons data measured post-solstice at 15 h, 14 h, 13 h and 12 h daylengths for Vitis hybrid ‘Marquette’ grafted to five commercial rootstocks and ‘Marquette’ grafted to ‘Marquette’. Significant differences in photosynthetic efficiency (Vcmax and Jmax) were noted for both direct and indirect measurements for the six rootstocks, indicating that rootstock genotype and daylength have a significant influence on scion photosynthesis. Evaluation of multiple feature-extraction algorithms indicated the proposed Vitis base model incorporating a 1D-Convolutional neural Network (CNN) had the best prediction performance with a R2 of 0.60 for Vcmax and Jmax. Inclusion of weather and chlorophyll parameters slightly improved model performance for both photosynthetic parameters. Integrating AI with hyperspectral remote phenotyping provides potential for high-throughput whole vine assessment of photosynthetic performance and selection of rootstock genotypes that confer improved photosynthetic performance potential in the scion.

Summary: Direct air capture (DAC) is a promising carbon dioxide removal technology, but its effectiveness hinges on access to cheap, low-carbon energy. Here, we present a spatial techno-economic and environmental assessment of the coupling of solid sorbent DAC with different energy sources. We found that the most cost- and energy-efficient option is to couple DAC with thermal power plants, e.g., nuclear and natural gas combined cycle with carbon capture. These two options have a gross levelized cost of DAC (LCODgross) starting at $246–$503 and $314–$557 per tCO2, respectively, for different regions. For renewable energy and energy storage options, regions with good solar irradiation can achieve low LCODgross, at $319 per tCO2 when utilizing concentrated solar power, whereas regions with low solar irradiation are unsuitable for this option due to the high cost and large land requirement. Achieving an LCODgross of ≤$200 per tCO2 would require significant improvements in the current technology. Science for society: Cost-effective transition pathways to keep global temperature rise below 2°C require billions of tons of CO2 removal from the atmosphere annually. Direct air capture (DAC) offers advantages like permanent storage of CO2 with low land use but it is energy-intensive. Thus, sustainable and cost-effective large-scale DAC deployment needs optimal site identification for cheap, low-carbon energy and regional co-benefit maximization. This study presents a global assessment of DAC energy supply options, including conventional and renewable energy sources, considering region-specific factors. Our analysis identifies the most suitable energy supply options for different regions, assessed based on techno-economic and environmental performance and potential co-benefits. The results help provide a foundation of evidence that will be essential for developing business models, strategies, and policies for the sustainable and cost-effective large-scale deployment of DAC systems.

Not available.

Dating back to when the inventor of the game, James Naismith, developed a mentoring relationship with John McClendon one of the African American pioneers in basketball (founder of the “fast-break”), there are countless examples of these intersections. Entering the college basketball culture as the most decorated recruiting class in National Collegiate Athletic Association basketball history, the University of Michigan Fab Five's legacy catalyzes a new era of American basketball culture. Gracefully talented, the Fab Five abruptly disrupted the institution of basketball, the National Collegiate Athletic Association, and the identity of basketball athletes globally. This paper presents a sociocultural exploration of the residual impact of the Fab Five's legacy. As authentic, confident, and culturally competent, the five young men intentionally resisted and acknowledged the intersections of race, culture, and class within the college basketball culture. We critically assess the evolution of basketball culture, grounded by the sociocultural experiences of the Fab Five, imprinting upon contemporary generations of college basketball programs and their player. Through these experiences, the Fab Five's success through conflict, during their short stint in college basketball and beyond their professional careers trailblazed a path for the modern-day basketball athlete. Known for their style of play, their expression of fashion on and off the court, and eagerness to talk smack, the Fab Five backed up their talk with performance. Their performance on and off the court, revolutionized the culture of basketball; Even more, American society. The Fab Five's legacy is the cultural catalyst for basketball culture on all levels.

BACKGROUND: One characteristic of alcohol use disorder is compulsive drinking or drinking despite negative consequences. When quinine is used to model such aversion-resistant drinking, female rodents typically are more resistant to punishment than males. Using an operant response task where C57BL/6J responded for ethanol mixed with quinine, we previously demonstrated that female mice tolerate higher concentrations of quinine in ethanol than males. Here, we aimed to determine whether this female vulnerability to aversion-resistant drinking behavior is similarly observed with footshock punishment. METHODS: Male and female C57BL/6J mice were trained to respond for 10% ethanol in an operant task on a fixed-ratio three schedule. After consistent responding, mice were tested in a punishment session using either a 0.25 mA or 0.35 milliamp (mA) footshock. To assess footshock sensitivity, a subset of mice underwent a flinch, jump, and vocalize test in which behavioral responses to increasing amplitudes of footshock (0.05 to 0.95 mA) were assessed. In a separate cohort of mice, males and females were trained to respond for 2.5% sucrose and responses were punished using a 0.25 mA footshock. RESULTS: Males and females continued to respond for 10% ethanol when paired with a 0.25 mA footshock. Females alone continued to respond for ethanol when a 0.35 mA footshock was delivered. Both males and females reduced responding for 2.5% sucrose when punished with a 0.25 mA footshock. Footshock sensitivity in the flinch, jump, and vocalize test did not differ by sex. CONCLUSIONS: Females continue to respond for 10% ethanol despite a 0.35 mA footshock, and this behavior is not due to differences in footshock sensitivity between males and females. These results show that female C57BL/6J mice are generally more resistant to punishment in an operant self-administration paradigm. The findings add to the literature characterizing aversion-resistant alcohol-drinking behaviors in females.

Zoos consistently implement codes of conduct in efforts to manage visitor behaviour. However, few studies have examined the use of the codes of conduct in zoos, even though they carry significant ethical implications regarding the relationship between humans and animals in society. This study provides an explorative investigation into the use of codes of conduct at the Chengdu Research Base of Giant Panda Breeding (Panda Base). Positioning the Panda Base as a place to negotiate the boundaries between humans and animals, this study surveyed visitors’ initial engagement with the Base’s code of conduct, their compliance with the code, and their assessment of the code. The findings point to a significant disparity between how visitors engage with and perceive the value of the code, which failed to prevent visitors from having close contact with animals at the Panda Base. We argue that Foucault’s philosophy on taboos in modern society can help us understand the ineffectiveness of the codes of conduct in zoos. However, Kant’s philosophy can orient human-animal interactions more ethically and provide an opportunity to consider the significance of codes of conduct in zoos. Suggestions for improving the effectiveness of codes of conduct at zoos are provided.

Wildlife-human relations in the United States are predominantly influenced by Euro-American sociocultural dynamics and (neo)colonial legacies. Humans dominate nonhuman animals through violence, suffering, and death. Wildlife management as a practice is becoming increasingly criticized. Disagreement emerges from epistemological and ontological foundations and remains contentious in theory and practice. Environmental education reinforces the subjugation of nonhumans and particular individuals that are governed by human decision-making, and power assemblages. However, public values have shifted to a mutualism orientation where management practices are challenged by shifting moral standards of society that value the intrinsic rights, welfare, and agency of individual beings. We present two related case studies that showcase posthuman pedagogy and illustrate how 'real-world' field experiences can shape students' ontologies and cosmologies. This work draws from the first author's fieldwork on salmon-sea lion-human relations in the Columbia River Basin of the Pacific Northwest US. This includes over 120 semi-structured interviews, two deployments of the Vertically Integrated Project (VIP) model, participant observation, and archival data. We focus on four specific fieldwork moments captured by student reflection. Posthuman pedagogy allows educators and scholars to rest with the material relations that dictate the lives of nonhuman participants and provides pragmatic openings for more-than-human worlds.

Grapevine leaves have diverse shapes and sizes which are influenced by many factors including genetics, vine phytosanitary status, environment, leaf and vine age, and node position on the shoot. To determine the relationship between grapevine leaf shape or size and leaf canopy temperature, we examined five seedling populations grown in a vineyard in California, USA. The populations had one parent with compound leaves of the Vitis piasezkii type and a different second parent with non-compound leaves. In previous work, we had measured the shape and size of the leaves collected from these populations using 21 homologous landmarks. Here, we paired these morphological data with canopy temperature measurements made using a handheld infrared thermometer. After recording time of sampling and canopy temperature, we used a linear model between time of sampling and canopy temperature to estimate temperature residuals. Based on these residuals, we determined if the canopy temperature of each vine was cooler or warmer than expected, based on the time of sampling. We established a relationship between leaf size and canopy temperature: vines with larger leaves were cooler than expected. By contrast, leaf shape was not strongly correlated with variation in canopy temperature. Ultimately, these findings indicate that vines with larger leaves may contribute to the reduction of overall canopy temperature; however, further work is needed to determine whether this is due to variation in leaf size, differences in the openness of the canopy or other related traits.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied ribonucleic acid (RNA)-seq and genome-scale loss-offunction clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations. Atm-/-nu-/-lymphomas, which phenotypically resemble either activated B-cell-like or germinal center Bcell-like DLBCL, harbor a complex karyotype, and are characterized by MYC pathway activation. In Atm-/-nu-/-lymphomas, we discovered nucleotide biosynthesis as a MYCdependent cellular vulnerability that can be targeted through the synergistic nucleotidedepleting actions of mycophenolate mofetil (MMF) and the WEE1 inhibitor, adavosertib (AZD1775). The latter is mediated through a synthetically lethal interaction between RRM2 suppression and MYC dysregulation that results in replication stress overload in Atm-/-nu-/-lymphoma cells. Validation in cell line models of human DLBCL confirmed the broad applicability of nucleotide depletion as a therapeutic strategy for MYC-driven DLBCL independent of ATM mutation status. Our findings extend current understanding of lymphomagenic mechanisms underpinning ATM loss and highlight nucleotide metabolism as a targetable therapeutic vulnerability in MYC-driven DLBCL.

Wildlife tourism is one of the strongest-performing sectors in the global tourism market. While tourists’ preferences for and affection towards animals are a cornerstone of the industry, a better understanding of how experiences, including animal–tourist encounters and visitation frequency, influence visitors’ animal preferences is required. Through a comparison of preferences among first-time and repeat visitors of four species (giant panda “Ailuropoda melanoleuca”, red panda “Ailurus fulgens”, peafowl “Pavo cristatus”, and swan “Cygnus”), both before and after animal encounters at the Chengdu Research Base of Giant Panda Breeding (Panda Base), the results show that different species elicit varied and, at times, contrasting tourist preferences. As a result, animal preferences in wildlife tourism can vary based on different stages of visitation. Highlighting this dynamic relationship between animal preferences and visitation experiences is further elucidated through consumer learning theory and lively capital. The outcomes of this study contribute to a deeper grasp of human–animal interactions and have broader implications for the development of conservation programs in captive wildlife venues.