Solving the discretised multiphase flow equations with interface capturing on structured grids using machine learning libraries

The authors would like to acknowledge the following EPSRC grants: the PREMIERE programme grant, “AI to enhance manufacturing, energy, and healthcare” (EP/T000414/1); ECO-AI, “Enabling CO capture and storage using AI” (EP/Y005732/1); MUFFINS, “MUltiphase Flow-induced Fluid-flexible structure InteractioN in Subsea” (EP/P033180/1); WavE-Suite, “New Generation Modelling Suite for the Survivability of Wave Energy Convertors in Marine Environments” (EP/V040235/1); INHALE, “Health assessment across biological length scales” (EP/T003189/1); AI-Respire, “AI for personalised respiratory health and pollution” (EP/Y018680/1); RELIANT, “Risk EvaLuatIon fAst iNtelligent Tool for COVID19” (EP/V036777/1); and CO-TRACE, “COvid-19 Transmission Risk Assessment Case Studies — education Establishments” (EP/W001411/1). Also, the authors acknowledge the Innovate UK grant D-XPERT, “AI-Powered Total Building Management System“ (TS/Y020324/1). Support from Imperial-X’s Eric and Wendy Schmidt Centre for AI in Science (a Schmidt Futures program) is gratefully acknowledged. The authors state that, for the purpose of open access, a Creative Commons Attribution (CC BY) license will be applied to any Author Accepted Manuscript version relating to this article.Peer reviewe

Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells

Chemically induced solidification : a new way to produce thin solid-near- net shapes

In-situ observation of the solidification of high carbon steel (4 wt% C) through decarburization has been carried out as a feasibility study into reducing high power usage and high CO2 production involved in steel making. Decarburization has been carried out under both air and pure N2 atmospheres at temperature of 1573K (1300 °C) and 1673K (1400 °C). A solidified shell of around 500μm was formed with carbon concentrations reduced down to 1% in as short as 18s

KinImmerse: Macromolecular VR for NMR ensembles

<p>Abstract</p> <p>Background</p> <p>In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.</p> <p>Methods</p> <p>The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment) or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE.</p> <p>Results</p> <p>In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR) models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs).</p> <p>Conclusion</p> <p>The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis.</p

Clinical application of CSF biomarkers for Alzheimer's disease:From rationale to ratios

Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations of cognitive impairment to facilitate timely and differential diagnosis, improving diagnostic accuracy, providing prognostic information, and guiding personalized management in diverse scenarios. Evidence shows that (1) CSF ratios are superior to amyloid beta (Aβ)1‐42 alone; (2) concordance of CSF ratios to amyloid positron emission tomography (PET) is better than Aβ1‐42 alone; and (3) phosphorylated tau (p‐tau)/Aβ1‐42 ratio is superior to p‐tau alone. CSF biomarkers are recommended for the exclusion of AD as the underlying cause of cognitive impairment, diagnosis of AD at an early stage, differential diagnosis of AD in individuals presenting with other neuropsychiatric symptoms, accurate diagnosis of AD in an atypical presentation, and for clinical trial enrichment. HIGHLIGHTS:  : Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker testing may be underused outside specialist centers. CSF biomarkers improve diagnostic accuracy, guiding personalized management of AD. CSF ratios (amyloid beta [Aβ]1‐42/Aβ1‐40 and phosphorylated tau/Aβ1‐42) perform better than single markers. CSF ratios produce fewer false‐negative and false‐positive results than individual markers. CSF biomarkers should be included in diagnostic work‐up of AD and mild cognitive impairment due to AD

Structural insights into Clostridium perfringens delta toxin pore formation

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins

Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.

In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance

Census 2010 Demographic Profile: Jefferson County

This demographic profile describes characteristics of the local and state population based on results from the 2010 Census. The decennial census is an official enumeration, or count, of all residents on April 1st of the census year. The results of the census provide us with information about basic demographic characteristics of the population, including age, race, ethnicity, household composition, housing occupancy, and housing tenure