Universal approximation properties of feedforward artificial neural networks.

In this thesis we summarise several results in the literature which show the approximation capabilities of multilayer feedforward artificial neural networks. We show that multilayer feedforward artificial neural networks are capable of approximating continuous and measurable functions from Rn to R to any degree of accuracy under certain conditions. In particular making use of the Stone-Weierstrass and Hahn-Banach theorems, we show that a multilayer feedforward artificial neural network can approximate any continuous function to any degree of accuracy, by using either an arbitrary squashing function or any continuous sigmoidal function for activation. Making use of the Stone-Weirstrass Theorem again, we extend these approximation capabilities of multilayer feedforward artificial neural networks to the space of measurable functions under any probability measure

CMAS challenges to CMC-T/EBC systems

Gas turbine technology is undergoing a major transition with the recent implementation of SiC based ceramic composites (CMCs) in aircraft engines. While the potential improvement in temperature capability (≥1500°C) is unprecedented, there are a number of issues that limit the full exploitation of such potential. In addition to the longstanding concern for low temperature oxidative embrittlement and the limited temperature capability of current bond coats and matrices, the susceptibility of the protective SiO2 to volatilization in the combustion environment requires the use of environmental barrier coatings (EBCs) to achieve durability targets. Most EBC concepts, however, are based on silicates and are thus susceptible to degradation by molten silicate deposits generically known as CMAS originating from mineral debris ingested into engines with the intake air. This presentation will discuss the thermodynamic and mechanistic foundation of the degradation of EBCs by CMAS, recent progress in establishing the relevant phase equilibria for these systems, and the role of the CMAS composition on the extent of degradation, as well as perspective on mitigation. (Research supported by ONR, AFOSR and the P&W Center of Excellence in Composites at UCSB.

Realistic description of electron-energy loss spectroscopy for One-Dimensional Sr2_2CuO3_3

We investigate the electron-energy loss spectrum of one-dimensional undoped CuO$_{3}$ chains within an extended multi-band Hubbard model and an extended one-band Hubbard model, using the standard Lanczos algorithm. Short-range intersite Coulomb interactions are explicitly included in these models, and long-range interactions are treated in random-phase approximation. The results for the multi-band model with standard parameter values agree very well with experimental spectra of Sr$_{2}$CuO$_{3}$. In particular, the width of the main structure is correctly reproduced for all values of momentum transfer. It is shown for both models that intersite Coulomb interactions mainly lead to an energy shift of the spectra. We find no evidence for enhanced intersite interactions in Sr$_{2}$CuO$_{3}$.Comment: 4 pages, 4 figure

A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes : role of dosing and glycaemic control

Background The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis. Methods A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period. Results Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time. Conclusions Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications. Trial registration EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

CDMS, Supersymmetry and Extra Dimensions

The CDMS experiment aims to directly detect massive, cold dark matter particles originating from the Milky Way halo. Charge and lattice excitations are detected after a particle scatters in a Ge or Si crystal kept at ~30 mK, allowing to separate nuclear recoils from the dominating electromagnetic background. The operation of 12 detectors in the Soudan mine for 75 live days in 2004 delivered no evidence for a signal, yielding stringent limits on dark matter candidates from supersymmetry and universal extra dimensions. Thirty Ge and Si detectors are presently installed in the Soudan cryostat, and operating at base temperature. The run scheduled to start in 2006 is expected to yield a one order of magnitude increase in dark matter sensitivity.Comment: To be published in the proceedings of the 7th UCLA symposium on sources and detection of dark matter and dark energy in the universe, Marina del Rey, Feb 22-24, 200

Potential for critical raw material prospectivity in the UK

The UK Critical Minerals Strategy (BEIS, 2022) includes a commitment to “begin a nationalscale assessment of the critical minerals within the UK. By March 2023, we will collate geoscientific data and identify target areas of potential”. This report provides that national-scale assessment of the geological potential for critical raw materials in the UK. It represents the published output of a study, jointly funded by the British Geological Survey and the Department for Business and Trade, which reviewed available geoscientific data in order to identify areas of potential geological prospectivity for critical raw materials in the UK. Critical raw materials (CRMs) are those mineral commodities that are both economically important and at risk of supply disruption. The commodities addressed in this report are those identified as critical to the UK by the Critical Minerals Intelligence Centre (CMIC) (Lusty et al., 2021). These CRMs are currently obtained from mining across the world, but at the time of writing none are produced in the UK, although tungsten has been mined in recent years. Some CRMs such as lithium, tin and graphite are typically the primary products of mines, whereas others are produced as co- or by-products of major commodities such as gold, copper or zinc. Current understanding of the UK’s mineral resource endowment rests largely on evidence from historic mining and exploration, together with targeted academic research. The UK has an extensive history of mining that dates to prehistoric times. Gold, barite, fluorite, gypsum, potash and polyhalite are among the commodities that are currently mined, and exploration for many raw materials is occurring across the whole of the UK. The work presented in this report follows a methodology known as a mineral systems approach, which relies on the concept that all mineral deposits of a certain type were formed by a combination of particular geological processes (McCuaig et al., 2010). The processes that must operate for a mineral deposit to form are identified and translated into mappable target criteria derived from available datasets. Key datasets to be used would typically include geological maps, geochemical soil and stream sediment maps, geophysical maps, and mineral occurrence databases. The UK has full geological map coverage, but other datasets are incomplete, with high-resolution geophysical data only being available for limited areas. New stream sediment geochemistry maps were created as part of this work and are available on the CMIC interactive map portal1 , but the whole country is not covered for all elements. These data limitations mean that this report only provides a knowledge-driven assessment of geological potential for CRM prospectivity across the UK. It provides maps for CRMs (grouped or singly as geologically appropriate) indicating the areas where the geological criteria have been met and thus there is potential for deposits of these CRMs to occur. It is important to note that the maps represent areas of potential prospectivity, not where deposits of critical minerals are guaranteed to be found, and also that mineral deposits could be found beyond the identified prospective areas, where localised geological conditions are suitable. The areas identified in the maps can be considered as targets for more detailed research and exploration. This report focuses solely on the geological potential and does not consider other aspects such as environmental designations and planning considerations that may affect the development of a mineral deposit. Combining all the individual maps highlights areas that are prospective for several CRMs and are thus priority for further geological investigations. From north to south, these areas include: areas of prospective geology around Loch Maree near Gairloch; parts of the central Highlands and Aberdeenshire; areas of prospective geology in mid-County Tyrone in Northern Ireland; parts of Cumbria; parts of the North Pennine Orefield; areas in north-west Wales and Pembrokeshire; and south-west England. These areas should now be the focus for collection of new geological, geochemical and geophysical data, in order to identify new CRM prospects for detailed investigation

Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding

Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that disrupts all exposed histone surfaces to comprehensively assess how proteins recognize nucleosomes. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk interactions, whereas nearly half of the nucleosome disk participates only minimally in protein binding. Our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly engages the acidic patch, and we elucidate a redundant mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub and establishes universal principles of nucleosome recognition

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed