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"Williams, O."
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A Data–Driven Approximation of the Koopman Operator: Extending Dynamic Mode Decomposition
The Koopman operator is a
linear
but infinite-dimensional operator that governs the evolution of scalar observables defined on the state space of an autonomous dynamical system and is a powerful tool for the analysis and decomposition of nonlinear dynamical systems. In this manuscript, we present a data-driven method for approximating the leading
eigenvalues, eigenfunctions, and modes
of the Koopman operator. The method requires a data set of snapshot pairs and a dictionary of scalar observables, but does not require explicit governing equations or interaction with a “black box” integrator. We will show that this approach is, in effect, an extension of dynamic mode decomposition (DMD), which has been used to approximate the Koopman eigenvalues and modes. Furthermore, if the data provided to the method are generated by a Markov process instead of a deterministic dynamical system, the algorithm approximates the eigenfunctions of the Kolmogorov backward equation, which could be considered as the “stochastic Koopman operator” (Mezic in Nonlinear Dynamics 41(1–3): 309–325,
2005
). Finally, four illustrative examples are presented: two that highlight the quantitative performance of the method when presented with either deterministic or stochastic data and two that show potential applications of the Koopman eigenfunctions.
Journal Article
The Hermitage
For nearly 250 years the State Hermitage has been one of Europe's most palatial museums. It encompasses more than three million works of art and artifacts displayed within a spectacular architectural ensemble, the heart of which is the famed Winter Palace. The two volumes of The Hermitage Collections capture the masterpieces and discuss the history that make this world-famous institution a cultural destination and a global treasure. Many of its rarely reproduced works are included in these two volumes, such as The Raphael Loggias (as copied from the Vatican), Michelangelo's Crouching Boy, The Gonzaga Cameo, Leonardo da Vinci's Madonna with a Flower (The Benois Madonna), and Titian's St. Sebastian. The Hermitage collections were developed beginning in 1764 by Catherine the Great, Empress of Russia. Today, the Hermitage collections constitute one of the great art museums of the world.\"--Publisher's description.
Book
Serotype Distribution and Disease Severity in Adults Hospitalized with Streptococcus pneumoniae Infection, Bristol and Bath, UK, 2006‒2022
Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.
Journal Article
Positioning higher education institutions : from here to there
Higher education is of growing public and political importance for society and the economy. Globalisation is transforming it from a local and national concern into one of international significance. In order to fulfil societal, governmental and business sector needs, many universities are aiming to (re-)position themselves. The book initially considers their \"compass\". They aspire to transformational planning, mission and strategy in which social justice is important, people are not treated as mere means to an end, and traditional moral positions are respected. This transformational urge is sometimes vitiated by blunt demands of new public management that overlook universities? potential for serving the public good. The volume then addresses universities? success in meeting their targets. Often the challenge in evaluation is the need to reconcile tensions, for example between structure and pastoral care of students; institutional competition and collaboration; roles of academics and administrators; performance-based funding versus increased differentiation. Measurement is supposed to provide discipline, align institutional and state policy, and provide a vital impetus for change. Yet many of these measurement instruments are not fully fit for purpose. They do not take sufficient account of institutional missions, either of \"old\" or of specialist universities; and sophisticated measurement of the student experience requires massive resources. Change and positioning have become increasingly key elements of a complex but heterogeneous sector requiring new services and upgraded instruments.
Book
The Development of Thin-Film Freezing and Its Application to Improve Delivery of Biologics as Dry Powder Aerosols
While the formulation of pharmaceuticals as liquids is common practice, powders are associated with enhanced stability, avoidance of the cold chain, lower dosing requirements, and more convenient administration. These are particularly critical for proteins, as they are expensive and complicated to manufacture. Powders also have improved aerosol properties for pulmonary delivery. Conventional techniques for formulating powders include spray-drying, shelf freeze-drying, spray freeze-drying, and spray freezing into liquid, but they produce powders with poor aerosol performance and/or activity due to suboptimal powder properties. Thin-film freezing (TFF) is a new cryogenic technique that can engineer highly porous, brittle, powder matrices with excellent aerosol performance properties and stability. Herein, we describe TFF in comparison to other cryogenic techniques. Physical properties of TFF powders such as morphology, moisture sorption, stability, solubility, and dissolution, as well as aerosol properties are discussed. In addition, factors that significantly affect the physical and aerosol properties of dry powders prepared by TFF, such as solids content, drug loading, solvent system, excipient, and dry powder delivery device, are analyzed. Finally, we provide evidence supporting the applicability of using TFF to prepare dry powder formulations of protein-based pharmaceuticals, enabling their cold chain-free storage as well as efficient pulmonary delivery.
Journal Article
Full spectrum fluorescence lifetime imaging with 0.5 nm spectral and 50 ps temporal resolution
The use of optical techniques to interrogate wide ranging samples from semiconductors to biological tissue for rapid analysis and diagnostics has gained wide adoption over the past decades. The desire to collect ever more spatially, spectrally and temporally detailed optical signatures for sample characterization has specifically driven a sharp rise in new optical microscopy technologies. Here we present a high-speed optical scanning microscope capable of capturing time resolved images across 512 spectral and 32 time channels in a single acquisition with the potential for ~0.2 frames per second (256 × 256 image pixels). Each pixel in the resulting images contains a detailed data cube for the study of diverse time resolved light driven phenomena. This is enabled by integration of system control electronics and on-chip processing which overcomes the challenges presented by high data volume and low imaging speed, often bottlenecks in previous systems.
High data volumes from multidimensional imaging techniques can lead to slow collection and processing times. Here, the authors implement multispectral fluorescence lifetime imaging microscopy (FLIM) that uses time-correlated photon counting technology to reach simultaneously high imaging rates combined with high spectral and temporal resolution.
Journal Article
Pseudomonas guariconensis Necrotizing Fasciitis, United Kingdom
We describe a case of necrotizing fasciitis in the United Kingdom in which Pseudomonas guariconensis was isolated from multiple blood culture and tissue samples. The organism carried a Verona integron-encoded metallo-β-lactamase gene and evidence of decreased susceptibility to β-lactam antimicrobial agents. Clinicians should use caution when treating infection caused by this rare pathogen.
Journal Article
Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now?
Hot-melt extrusion (HME) is a globally recognized, robust, effective technology that enhances the bioavailability of poorly soluble active pharmaceutical ingredients and offers an efficient continuous manufacturing process. The twin-screw extruder (TSE) offers an extremely resourceful customizable mixer that is used for continuous compounding and granulation by using different combinations of conveying elements, kneading elements (forward and reverse configuration), and distributive mixing elements. TSE is thus efficiently utilized for dry, wet, or melt granulation not only to manufacture dosage forms such as tablets, capsules, or granule-filled sachets, but also for designing novel formulations such as dry powder inhalers, drying units for granules, nanoextrusion, 3D printing, complexation, and amorphous solid dispersions. Over the past decades, combined academic and pharmaceutical industry collaborations have driven novel innovations for HME technology, which has resulted in a substantial increase in published articles and patents. This article summarizes the challenges and models for executing HME scale-up. Additionally, it covers the benefits of continuous manufacturing, process analytical technology (PAT) considerations, and regulatory requirements. In summary, this well-designed review builds upon our earlier publication, probing deeper into the potential of twin-screw extruders (TSE) for various new applications.
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Journal Article