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Current dogma dictates that, during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS transcription factors (TFs), ERG and Fli1. Although deletion of either ERG or Fli1 manifests subtle vascular dysfunction, their combined genetic deletion in adult ECs results in acute vasculopathy and multi-organ failure, due to loss of EC fate and integrity, hyperinflammation and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency causes rapid transcriptional silencing of pan and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality, enabling in vivo engraftment of a perfusable vascular network. Genome-wide association study analysis identified vascular diseases that are associated with FLI1/ERG mutations. Constitutive expression of ERG and Fli1 upholds EC fate, physiological function and resilience in adult vasculature, whereas their functional loss can contribute to systemic human diseases.

In December 2019 Malaysia submitted information on the outer limits of its continental shelf beyond 200 miles (OL) in the South China Sea (SCS) to the Commission on the Limits of the Continental Shelf (CLCS). According to Article 76(8) of the UN Convention on the Law of the Sea, Malaysia shall seek CLCS recommendations as the basis for establishing its OL. If notified of a land or maritime dispute, the CLCS shall not consider the submission unless consent is given by all disputants. As of 16 March 2022, the CLCS has received 28 note verbales (NVs) concerning Malaysia’s submission. Apart from those challenging the submission, there are 12 NVs invoking the 2016 SCS Arbitration award to oppose territorial and maritime claims by China in its NVs initially objecting the submission. This article reviews relevant CLCS rules and practice, analyses all 28 NVs, and examines the disputes reflected in the NVs.

As already happens, and will continue to happen ever more, most height coordinates are going to be obtained from geodetic satellite observations (GNSS) instead of levelling, due to the operational simplicity, lower cost, and sufficient accuracy. Levelling will be used for restricted areas and niche applications. Geodetic satellite observations yield geodetic heights referred to the (geocentric) geodetic reference ellipsoid. Their metric is Euclidean, geometric in nature. But geodetic heights have no practical applications because the zero height surface, i,e., reference ellipsoid, has no relation to the real world. To be practical, heights must refer to the geoid, the vertical geodetic reference surface. Geodetic heights must be transformed to practical heights by subtracting geoidal heights from them. The resulting practical heights, orthometric heights, have also Euclidean metric. Interestingly, no gravity needs be observed by the user of this approach. If other than orthometric heights are needed, then the metric must be changed. For dynamic heights and normal heights, the corresponding point metric is just a multiplication factor close to 1 that requires the knowledge of gravity. Practical heights obtained in this way are fully congruent with the terrestrial practical heights (from levelling) if the terrestrial heights are derived from levelled height differences in the rigorous way. The oral presentation will go over their characteristics and how they relate to the latest theoretical advancements and will focus on the future, leaving the quasigeoid alone, explicitly defining all practical heights, with respect to the geoid., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

We estimate the uncertainty of the modelled geoid heights based on the standard deviations of the topographic mass density variation. We model the geoid using the one-step integration method considering mass density variations along with their associated error estimates to calculate the direct and indirect topographic density effects on the geoid heights in the Helmert space. We employ the UNB_TopoDensT_2v01 global lateral density model and its standard deviations and test our algorithms in the Auvergne test area, in central France. Our results show that the topographic mass density variations are currently known well enough to model the geoid with sub-centimetre internal error in topographically mild regions such as Auvergne.

In 2014 Japan’s Cabinet Order No. 302 declared the outer limits of its continental shelf beyond 200 nautical miles (OL) to the west and north of Oki-no-Tori Shima (Area 302). Oki-no-Tori Shima consists of two small, barren, and uninhabitable rocks in the West Pacific. The northern part of Area 302 is broader than what the 2012 recommendations of the Commission on the Limits of the Continental Shelf (CLCS) specify. A question arises whether Order No. 302 violates Article 76(8) of the United Nations Convention on the Law of the Sea (UNCLOS), which provides that the OL established by a coastal state ‘on the basis of’ the CLCS recommendations shall be final and binding. Another question is the role played by the CLCS in ‘assisting’ the coastal states to delimit their national jurisdiction so as to know where the Area (i.e., the Common Heritage of Mankind under UNCLOS Articles 1(1)(1) and 136) begins. The essential questions arising from Area 302 concern how well the UNCLOS mechanism can perform to safeguard the Common Heritage of Mankind through preventing encroachment thereupon by individual coastal states. This article looks at the context and explores the obligations implied by Article 76(8) for coastal states to ‘follow’ the recommendations in establishing the OL, with special reference to the northern part of Area 302. The article also examines legal consequences arising from a breach of these obligations.

The United Nations Convention on the Law of the Sea (LOSC) regulates the establishment of the outer limits of its continental shelf beyond 200 miles by a coastal State. Such limits are legitimised when based on the recommendations of the Commission on the Limits of the Continental Shelf (CLCS) under LOSC Article 76(8). The coastal State must first submit the information for delineating the limits to the CLCS, which will evaluate the information before providing recommendations. The CLCS shall not consider the submission made by any State concerned in a land or maritime dispute unless consent from all disputing parties is given under paragraph 5(a) of Annex I to the CLCS Rules of Procedure. This article interprets paragraph 5(a) and examines the subsequent practice of States sending submissions and/or notifying the CLCS of disputes, and the CLCS in handling various submissions involved in these disputes.

Manuscript submitted to Transactions on Intelligent Transportation Systems for review.

A reliable recognition of human activities using IoT devices (e.g., on-body wearable sensors) enables various applications, such as fitness tracking, bad habit detecting, healthcare support, and eldercare support. However, inaccurate results may cause an adverse effect on users or even an unpredictable accident. In order to improve the accuracy in the daily life activities classification, in this article, we propose countable and uncountable activities to better facilitate the understanding of the nature of daily life activities. We design global and local features and their integrated feature set for classifying countable and uncountable activities. The key idea is to examine human daily life activities from different perspectives and attempt to give a comprehensive description of the characteristics of each activity through leveraging the global and local features. By using only one simple accelerometer, our approach is evaluated to be able to recognize daily life activities with higher accuracy than the state of the art, based on one self-collected and another public available data set.

Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation.We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies.We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products.Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.

The next generation of the Internet of Things (IoT) facilitates the integration of the notion of social networking into smart objects (i.e., things) in a bid to establish the social network of interconnected objects. This integration has led to the evolution of a promising and emerging paradigm of Social Internet of Things (SIoT), wherein the smart objects act as social objects and intelligently impersonate the social behaviour similar to that of humans. These social objects are capable of establishing social relationships with the other objects in the network and can utilize these relationships for service discovery. Trust plays a significant role to achieve the common goal of trustworthy collaboration and cooperation among the objects and provide systems' credibility and reliability. In SIoT, an untrustworthy object can disrupt the basic functionality of a service by delivering malicious messages and adversely affect the quality and reliability of the service. In this survey, we present a holistic view of trustworthiness management for SIoT. The essence of trust in various disciplines has been discussed along with the Trust in SIoT followed by a detailed study on trust management components in SIoT. Furthermore, we analyzed and compared the trust management schemes by primarily categorizing them into four groups in terms of their strengths, limitations, trust management components employed in each of the referred trust management schemes, and the performance of these studies vis-a-vis numerous trust evaluation dimensions. Finally, we have discussed the future research directions of the emerging paradigm of SIoT, particularly for trustworthiness management in SIoT.

Fasteners are represented with varying degrees of fidelity in finite element models in order to meet solver constraints and accuracy requirements. Three reduced-order models are evaluated to quantify how well they perform in terms of calibration effort and accuracy. To baseline their performance, a new series of test data are developed by pulling NAS1351-3-20P screws at angles between pure tension (0°) and pure shear (90°) in 15° increments. First, a nonlinear elastic spring element joins two portions of the fastener shank. Unique load-displacement curves for tension and shear are taken directly from the test data, making it easy to calibrate yet fairly accurate. Second, the fastener is modeled with a solid cylindrical shank. The material properties are only calibrated to the tensile test results; consequently, this model is less accurate for predicting the ultimate shear load, though it comes reasonably close to the ultimate displacement in shear and combined loading. Third, a solid cylinder is divided into tensile and shear regions, and the material properties in each region are calibrated to the corresponding test data. This model deviates further from the ultimate displacement but effectively predicts the ultimate load in combined tension and shear. Each model has advantages, but the first is easiest to implement and most accurate overall.

The interpretation of Article 121(3) of the 1982 U.N. Convention on the Law of the Sea (UNCLOS) was a key part of the Sino-Philippine Arbitration on the South China Sea Award issued in July 2016. T...