Tidal Range Resource of the Patagonian Shelf

With vast potential for renewable energy conversion, the ocean could help reduce our reliance on fossil fuels. Of the various forms of ocean energy, tidal range power is both mature and predictable, dating back to 1966. However, only a few regions of the world are suited to tidal range power. Here, we examine the tidal range potential of the Patagonian shelf – estimated to contain over 100 GW of tidal dissipation. We use a high resolution global tidal atlas (TPXO9) to examine this resource from theoretical and technical perspectives. The theoretical resource is 913 TWh (104 GW) – considerably exceeding neighbouring Argentina’s electricity demand (∼143 TWh in 2021). We find that due to near-resonance with the semidiurnal tides, the resource is concentrated in two regions – Golfo de San Matías, and Bahía Grande to Río Grande. Three sites are chosen for further analysis after considering practical constraints such as water depth and proximity to the electricity grid. Through 0D modelling with tidal range power plant operation we find that the selected sites offer high energy extraction potential, exceeding 40% of the available resource. Further analysis shows how the combination of the sites can reduce the periods of no-generation to under 20%

Ocean-related options for climate change mitigation and adaptation: A machine learning-based evidence map protocol

BackgroundOcean-related options (OROs) to mitigate and adapt to climate change are receiving increasing attention from practitioners, decision-makers, and researchers. In order to guide future ORO development and implementation, a catalogue of scientific evidence addressing outcomes related to different ORO types is critical. However, until now, such a synthesis has been hindered by the large size of the evidence base. Here, we detail a protocol using a machine learning-based approach to systematically map the extent and distribution of academic evidence relevant to the development, implementation, and outcomes of OROs.MethodTo produce this systematic map, literature searches will be conducted in English across two bibliographic databases using a string of search terms relating to the ocean, climate change, and OROs. A sample of articles from the resulting de-duplicated corpus will be manually screened at the title and abstract level for inclusion or exclusion against a set of predefined eligibility criteria in order to select all relevant literature on marine and coastal socio-ecological systems, the type of ORO and its outcomes. Descriptive metadata on the type and location of intervention, study methodology, and outcomes will be coded from the included articles in the sample. This sample of screening and coding decisions will be used to train a machine learning model that will be used to estimate these labels for all the remaining unseen publications. The results will be reported in a narrative synthesis summarising key trends, knowledge gaps, and knowledge clusters

MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis

Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphoprotein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. We found increased phosphorylation of MP2K1 in MS patients relative to the controls. Moreover, we identified one SNP located in the PHDGH gene and another on IRF8 gene that were associated with MP2K1 phosphorylation levels, providing a first clue on how this MS risk gene may act. The analyses in patients treated with disease-modifying drugs identified the phosphorylation of each receptor’s downstream kinases. Finally, using flow cytometry, we detected in MS patients increased STAT1, STAT3, TF65, and HSPB1 phosphorylation in CD19+ cells. These findings indicate the activation of cell survival and proliferation (MAPK), and proinflammatory (STAT) pathways in the immune cells of MS patients, primarily in B cells. The changes in the activation of these kinases suggest that these pathways may represent therapeutic targets for modulation by kinase inhibitors

Tidal range resource of the Patagonian shelf

With vast potential for renewable energy conversion, the ocean could help reduce our reliance on fossil fuels. Of the various forms of ocean energy, tidal range power is both mature and predictable, dating back to 1966. However, only a few regions of the world are suited to tidal range power. Here, we examine the tidal range potential of the Patagonian shelf - estimated to contain over 100 GW of tidal dissipation. We use a high resolution global tidal atlas (TPXO9) to examine this resource from theoretical and technical perspectives. The theoretical resource is 913 TWh (104 GW) -- considerably exceeding neighbouring Argentina's electricity demand (~143 TWh in 2021). We find that due to near-resonance with the semidiurnal tides, the resource is concentrated in two regions - Golfo de San Matias, and Bahia Grande to Rio Grande. Three sites are chosen for further analysis after considering practical constraints such as water depth and proximity to the electricity grid. Through 0D modelling with tidal range power plant operation we find that the selected sites offer high energy extraction potential, exceeding 40\% of the available resource. Further analysis shows how the combination of the sites can reduce the periods of no-generation to under 20%

A Dynamic Wheelchair Armrest for Promoting Arm Exercise and Mobility After Stroke.

Arm movement recovery after stroke can improve with sufficient exercise. However, rehabilitation therapy sessions are typically not enough. To address the need for effective methods of increasing arm exercise outside therapy sessions we developed a novel armrest, called Boost. It easily attaches to a standard manual wheelchair just like a conventional armrest and enables users to exercise their arm in a linear forward-back motion. This paper provides a detailed design description of Boost, the biomechanical analysis method to evaluate the joint torques required to operate it, and the results of pilot testing with five stroke patients. Biomechanics results show the required shoulder flexion and elbow extension torques range from -25% to +36% of the torques required to propel a standard pushrim wheelchair, depending on the direction of applied force. In pilot testing, all five participants were able to exercise the arm with Boost in stationary mode (with lower physical demand). Three achieved overground ambulation (with higher physical demand) exceeding 2 m/s after 2-5 practice trials; two of these could not propel their wheelchair with the pushrim. This simple to use, dynamic armrest provides people with hemiparesis a way to access repetitive arm exercise outside of therapy sessions, independently right in their wheelchair. Significantly, Boost removes the requirements to reach, grip, and release the pushrim to propel a wheelchair, an action many individuals with stroke cannot complete

Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis

Background: Multiple sclerosis (MS) is a major health problem, leading to a significant disability and patient suffering. Although chronic activation of the immune system is a hallmark of the disease, its pathogenesis is poorly understood, while current treatments only ameliorate the disease and may produce severe side effects. Methods: Here, we applied a network-based modeling approach based on phosphoproteomic data to uncover the differential activation in signaling wiring between healthy donors, untreated patients, and those under different treatments. Based in the patient-specific networks, we aimed to create a new approach to identify drug combinations that revert signaling to a healthy-like state. We performed ex vivo multiplexed phosphoproteomic assays upon perturbations with multiple drugs and ligands in primary immune cells from 169 subjects (MS patients, n=129 and matched healthy controls, n=40). Patients were either untreated or treated with fingolimod, natalizumab, interferon-β, glatiramer acetate, or the experimental therapy epigallocatechin gallate (EGCG). We generated for each donor a dynamic logic model by fitting a bespoke literature-derived network of MS-related pathways to the perturbation data. Last, we developed an approach based on network topology to identify deregulated interactions whose activity could be reverted to a "healthy-like" status by combination therapy. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to validate the prediction of combination therapies. Results: Analysis of the models uncovered features of healthy-, disease-, and drug-specific signaling networks. We predicted several combinations with approved MS drugs that could revert signaling to a healthy-like state. Specifically, TGF-β activated kinase 1 (TAK1) kinase, involved in Transforming growth factor β-1 proprotein (TGF-β), Toll-like receptor, B cell receptor, and response to inflammation pathways, was found to be highly deregulated and co-druggable with all MS drugs studied. One of these predicted combinations, fingolimod with a TAK1 inhibitor, was validated in an animal model of MS. Conclusions: Our approach based on donor-specific signaling networks enables prediction of targets for combination therapy for MS and other complex diseases. Keywords: Combination therapy; Immunotherapy; Kinases; Logic modeling; Multiple sclerosis; Network modeling; Pathways; Personalized medicine; Phosphoproteomics; Signaling networks; Treatment; xMAP assay

Data infrastructures for AI in medical imaging: a report on the experiences of five EU projects

Abstract Artificial intelligence (AI) is transforming the field of medical imaging and has the potential to bring medicine from the era of ‘sick-care’ to the era of healthcare and prevention. The development of AI requires access to large, complete, and harmonized real-world datasets, representative of the population, and disease diversity. However, to date, efforts are fragmented, based on single–institution, size-limited, and annotation-limited datasets. Available public datasets (e.g., The Cancer Imaging Archive, TCIA, USA) are limited in scope, making model generalizability really difficult. In this direction, five European Union projects are currently working on the development of big data infrastructures that will enable European, ethically and General Data Protection Regulation-compliant, quality-controlled, cancer-related, medical imaging platforms, in which both large-scale data and AI algorithms will coexist. The vision is to create sustainable AI cloud-based platforms for the development, implementation, verification, and validation of trustable, usable, and reliable AI models for addressing specific unmet needs regarding cancer care provision. In this paper, we present an overview of the development efforts highlighting challenges and approaches selected providing valuable feedback to future attempts in the area. Key points • Artificial intelligence models for health imaging require access to large amounts of harmonized imaging data and metadata. • Main infrastructures adopted either collect centrally anonymized data or enable access to pseudonymized distributed data. • Developing a common data model for storing all relevant information is a challenge. • Trust of data providers in data sharing initiatives is essential. • An online European Union meta-tool-repository is a necessity minimizing effort duplication for the various projects in the area

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis, The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition. Vegf(165) promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons