Ultrasound cavitation and exfoliation dynamics of 2D materials re-vealed in operando by X-ray free electron laser megahertz imaging

Ultrasonic liquid phase exfoliation is a promising method for the production of two-dimensional (2D) layered materials. A large number of studies have been made in investigating the underlying ultrasound exfoliation mechanisms. However, due to the experimental challenges for capturing the highly transient and dynamic phenomena in real-time at sub-microsecond time and micrometer length scales simultaneously, most theories reported to date still remain elusive. Here, using the ultra-short X-ray Free Electron Laser pulses (~25ps) with a unique pulse train structure, we applied MHz X-ray Microscopy and machine-learning technique to reveal unambiguously the full cycles of the ultrasound cavitation and graphite layer exfoliation dynamics with sub-microsecond and micrometer resolution. Cyclic fatigue shock wave impacts produced by ultrasound cloud implosion were identified as the dominant mechanism to deflect and exfoliate graphite layers mechanically. For the graphite flakes, exfoliation rate as high as ~5 angstroms per shock wave impact was observed. For the HOPG graphite, the highest exfoliation rate was ~0.15 angstroms per impact. These new findings are scientifically and technologically important for developing industrial upscaling strategies for ultrasonic exfoliation of 2D materials

Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance

A new genetic mouse model demonstrates the necessity of Foxp3+ T reg cells for infectious tolerance

STRAW-b (STRings for Absorption length in Water-b): the second pathfinder mission for the Pacific Ocean Neutrino Experiment

Since 2018, the potential for a high-energy neutrino telescope, named the Pacific Ocean Neutrino Experiment (P-ONE), has been thoroughly examined by two pathfinder missions, STRAW and STRAW-b, short for short for Strings for Absorption Length in Water. The P-ONE project seeks to install a neutrino detector with a one cubic kilometer volume in the Cascadia Basin's deep marine surroundings, situated near the western shores of Vancouver Island, Canada. To assess the environmental conditions and feasibility of constructing a neutrino detector of that scale, the pathfinder missions, STRAW and STRAW-b, have been deployed at a depth of 2.7 km within the designated site for P-ONE and were connected to the NEPTUNE observatory, operated by Ocean Networks Canada (ONC). While STRAW focused on analyzing the optical properties of water in the Cascadia Basin, \ac{strawb} employed cameras and spectrometers to investigate the characteristics of bioluminescence in the deep-sea environment. This report introduces the STRAW-b concept, covering its scientific objectives and the instrumentation used. Furthermore, it discusses the design considerations implemented to guarantee a secure and dependable deployment process of STRAW-b. Additionally, it showcases the data collected by battery-powered loggers, which monitored the mechanical stress on the equipment throughout the deployment. The report also offers an overview of STRAW-b's operation, with a specific emphasis on the notable advancements achieved in the data acquisition (DAQ) system and its successful integration with the server infrastructure of ONC.Comment: 20 pages, 11 figures, 2 table

Segmented flow generator for serial crystallography at the European X-ray free electron laser

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Revisiting ‘place’ in a realist novel: ‘Thinking space’ in Galdós’s Torquemada en la hoguera (1889)

Departing from the premise that Galdós’s close engagement with space and place deserves to be at the forefront of scholarly attention, this article provides an in-depth study of their significance in Torquemada en la hoguera. It begins by analysing the relationship between the novel’s locations and the real world, demonstrating that the author codes the city of Madrid to express social concerns and promote reader engagement. It then proceeds to examine the public and private spheres, before highlighting the “place of the imagination” in the novel. It reveals that, as in Galdós’s press articles, reality is used as a springboard in Torquemada en la hoguera and, drawing upon recent theories, it posits that places serve as a framework for engaging readers with contemporary concerns and as an imaginative springboard for Galdós. They trigger what is effectively a “thinking space” for the author and it is through unravelling their significance that we can fully appreciate Galdós’s psychological sensitivity, the novel’s modernity, its symbolic value, and imaginative depth. The article concludes by proposing that Galdós’s works deserve to be re-examined as “Novels of the Geographical Imagination” and urges readers to revisit the significance of space and place therein

Design and Operation of a Multi Node Cabled Observatory

Abstract-Over the last three years, the University of Victoria and OceanWorks have designed built and installed the world's first multi node advanced cabled observatory. Located in Saanich Inlet and in the Strait of Georgia on the West Coast of Canada, the Victoria Experimental Network Under the Sea (VENUS) cabled observatory provides power and communications to numerous under water oceanographic instruments and has been continuously delivering near real time data to scientist since February 2006. This paper describes the VENUS Project life from concept to delivery of science data. Details of the architecture, design, capabilities, deployment and commissioning of both observatories will be provided along with lessons learnt. An overview of some of the data management and usage issues is provided

Rehabilitation in advanced, progressive, recurrent cancer: a randomized controlled trial.

CONTEXT: Two million people across the U.K. are living with cancer, often experienced as a long-term condition. They may have unmet needs after active treatment. Rehabilitation aims to address these needs, maximize psychological and physical function, and enable minimum dependency regardless of life expectancy. OBJECTIVES: We aimed to test, in a randomized controlled trial, the clinical and cost effectiveness of a rehabilitation intervention for patients with advanced, recurrent cancer. METHODS: We conducted a two-arm, wait-list control, randomized trial of a complex rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for active, progressive, recurrent hematological and breast malignancies, with a follow-up at three months. The primary outcome was the psychological subscale of the Supportive Care Needs Survey (SCNS). Secondary outcomes were other domains of the SCNS, psychological status, continuity of care, quality of life, and resource use. RESULTS: Forty-one participants were enrolled and 36 completed the trial. The primary outcome was significantly lower in the intervention arm (adjusted difference -16.8, 95% CI -28.34 to -5.3; P = 0.006). The SCNS physical and patient care subscales (-14.2, 95% CI -26.2 to -2.2; P = 0.02 and -7.4, 95% CI -13.7 to -1.1; P = 0.02, respectively) and self-reported health state (12.8, 95% CI 3.2 to 22.4; P = 0.01) also differed significantly. The incremental cost-effectiveness ratio was £19,390 per quality-adjusted life year. CONCLUSION: This intervention significantly reduced the unmet needs of cancer survivors and it is likely that it is cost-effective. Despite small numbers, the main effect size was robust. We recommend implementation alongside evaluation in wider clinical settings and patient populations