Effects of flow-bed interactions on barrier impact

Debris flow mobility is governed by complex interactions at the flow-bed interface. These interactions may cause flow bulking and increase in momentum. Both factors need to be considered for the design of barriers installed along the flow path. In this study, channelized debris flow over a wet erodible bed impacting a terminal flexible barrier is modelled in a 28-m-long and 2-m-wide flume facility with 20o slope inclination in Hong Kong. Tests with flow volumes of 6 m3 and 9 m3 overriding both erodible and non-erodible beds are conducted. The change in normalised flow energy over the erodible bed section, the change in flow momentum and the impact dynamics on the terminal barrier is assessed

Effects of plant roots on soil-water retention and induced suction in vegetated soil

Plant evapotranspiration (ET) is considered to be a hydrological effect that would induce soil suction and hence influence the stability of geotechnical infrastructure. However, other hydrological effect, such as the change of soil water retention curve (SWRC) induced by roots, is generally ignored. This study aims to investigate and compare the effects of root-induced changes in SWRC with the effects of ET on suction responses in clayey sand. Two series of laboratory tests together with 21 numerical transient seepage analyses were conducted. A tree species, Schefflera heptaphylla, which is commonly used for ecological restoration in many subtropical regions, was selected for investigation. In order to consider any effects of tree variability on induced suction, six tree individuals with similar age were tested with and without the supply of light. It is revealed that under dark condition when ET was minimal, vegetated soil could induce higher suction than bare soil by 100% after subjecting to a wetting event with a return period of 100 years. This may be explained by the increases in the air-entry value and the size of hysteresis loop induced by roots. Water balance calculation from the numerical analyses shows that even under the supply of light, the amount of ET was only 1.7% of the total volume of water infiltrated. This means that during the wetting event, the contribution of root-water uptake to induced suction in vegetated soil was relatively little, as compared with the effects of root-induced change in SWRC. (C) 2015 Elsevier B.V. All rights reserved

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio

Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Effects of the construction sequence of twin tunnels at different depths on an existing pile

Any tunnelling process inevitably induces changes in stress in the ground and may adversely affect nearby pile foundations. The interaction between tunnelling and an existing pile has been investigated by researchers and a certain amount of fundamental understanding has been gained. However, the effects of different tunnel excavation sequences on an adjacent pile remain to be understood. In this paper, a series of three-dimensional centrifuge model tests and numerical back-analyses were carried out to investigate the effects of construction sequence of twin tunnels on an existing pile in dry sand. Two tunnelling sequences were investigated: (i) a sequence involving tunnelling near the pile toe followed by tunnelling near the mid-depth of the pile shaft (i.e., test TS); (ii) sequence involving tunnelling near the mid-depth of the pile shaft followed by tunnelling near the pile toe (i.e., test ST). The measured cumulative pile settlement was about 33% larger for tunnelling sequence ST than for tunnelling sequence TS. Due to different tunnelling sequences, the apparent losses of pile capacity were 40% and 29% for sequences ST and TS, respectively. Although the computed reductions in normal stress acting on the pile induced by twin tunnelling were almost the same in tests TS and ST, tunnelling near the pile toe induced a larger decrease in the end-bearing and shaft resistances at the lower part of the pile in test ST than in test TS. In contrast to the measured pile head settlements, different tunnelling sequences had a limited effect on measured ground surface settlements and additional bending moments in the pile

Gas production behaviour of gas hydrate–bearing clayey-sand during depressurization: novel in-flight centrifuge modelling

Gas hydrate-bearing sediments (GHBS) are vastly distributed around the globe. While gas production attempts are made through GHBS, long-term production remains a challenge due to complex inter-related mechanisms involved. Better understating of long-term responses requires sound physical modelling conducted under controlled conditions. A novel centrifuge energy harvesting chamber (CEHC) at the HKUST centrifuge facility is used in this study. This is the first chamber that can operate at elevated gravities with the capability of sustaining the thermodynamically favourable conditions for gas hydrate formation, sustaining a continuous inflow of high-pressure water at the boundaries during dissociation, and an in-flight control of wellbore pressure and surcharge loading. Centrifuge modelling can recreate the insitu stress gradient in a relatively small model and expedite conduction and convection processes involved during dissociation. Consequently, long-term in-situ mechanisms can be evaluated with a small model and short time. A test was conducted at 40g to evaluate the temperature-pressure response as well as gas production behaviour of hydrate-bearing clayey-sand during depressurization. The results suggests that the gas flow rate is governed by the initial available latent heat as well as the conduction and convection heat through the surrounding sediments. However, as the depressurization progresses, the gas production rate is governed by the competing effects of hydrate dissociation and re-formation which both evolves the permeability of the sediment. Details of the experiment and test results are reported in this paper

Base stability of multi-propped excavations in soft clay subjected to hydraulic uplift

Excavations in soft clay underlain with an aquifer may be destabilized by hydraulic uplift. Previous studies on this subject are based mainly on field observations. Dewatering from the aquifer is a common method to improve base stability where ground settlement is not a major concern. Alternatively, piles readily installed as part of the top-down construction method for multi-propped excavation may be considered to provide base stability and minimize ground settlement outside the excavation. This paper presents results from two centrifuge tests that were conducted to simulate multi-propped excavations in-flight (with and without piles) in soft clay destabilized by hydraulic pressure from an underlying sand aquifer. Moreover, coupled three-dimensional finite element analyses were carried out to back-analyse the centrifuge tests. Numerical parametric studies were also conducted to study the influence of pile length on the effectiveness of base stabilization. It is revealed that both for excavations with and without piles, the artesian pressure required to initiate uplift inside the excavation is about 1.2 times the overburden pressure of the clay. By using "anti-uplift" piles inside the excavation, the ultimate hydraulic uplift resistance increases by 16%, while the uplift movement can be reduced by 80%. The presence of piles also increases the passive resistance in front of the wall by 70%, but reduces the mobilized undrained shear strength, cu, of clay by 53%