Knowledge, documentation and a London location

Purpose – As documents, and the whole information and communication environment, become increasingly digital, it is natural to assume that physical location becomes of less importance. The aim of this paper is to highlight two newly published books, which remind us that this idea should be examined with a critical eye. Design/methodology/approach – This editorial takes the form of a literature review and a viewpoint. Findings – The paper finds books of this kind remind us that a physical place, a locality, has sometimes been a very powerful stimulus to the development of collections, of memory institutions, and of the advances in education and dissemination of knowledge which are associated with them. This is worth remembering as we move into a digital information world. Originality/value – The paper offers the author's viewpoint as well as highlighting these two books which join a small number which have analysed and celebrated the history of intellectual advances in London

Quantitative electron energy-loss spectroscopy (EELS) analyses of lead zirconate titanate

Electron energy-loss spectroscopy (EELS) analyses have been performed on a sol–gel deposited lead zirconate titanate film, showing that EELS can be used for heavy as well as light element analysis. The elemental distributions within the sol–gel layers are profiled using the Pb N<sub>6,7</sub>-edges, Zr M-edges, Ti L-edges and O K-edge. A multiple linear least squares fitting procedure was used to extract the Zr signal which overlaps with the Pb signal. Excellent qualitative information has been obtained on the distribution of the four elements. The non-uniform and complementary distributions of Ti and Zr within each sol–gel deposited layer are observed. The metal:oxygen elemental ratios are quantified using experimental standards of PbTiO<sub>3</sub>, PbZrO<sub>3</sub>, ZrO<sub>2</sub> and TiO<sub>2</sub> to provide relevant cross-section ratios. The quantitative results obtained for Ti/O and Pb/O are very good but the Zr/O results are less accurate. Methods of further improving the results are discussed

COVID-19 Misinformation and Social Network Crowdfunding: Cross-sectional Study of Alternative Treatments and Antivaccine Mandates

BackgroundCrowdfunding is increasingly used to offset the financial burdens of illness and health care. In the era of the COVID-19 pandemic and associated infodemic, the role of crowdfunding to support controversial COVID-19 stances is unknown.ObjectiveWe sought to examine COVID-19-related crowdfunding focusing on the funding of alternative treatments not endorsed by major medical entities, including campaigns with an explicit antivaccine, antimask, or antihealth care stances.MethodsWe performed a cross-sectional analysis of GoFundMe campaigns for individuals requesting donations for COVID-19 relief. Campaigns were identified by key word and manual review to categorize campaigns into "Traditional treatments," "Alternative treatments," "Business-related," "Mandate," "First Response," and "General." For each campaign, we extracted basic narrative, engagement, and financial variables. Among those that were manually reviewed, the additional variables of "mandate type," "mandate stance," and presence of COVID-19 misinformation within the campaign narrative were also included. COVID-19 misinformation was defined as "false or misleading statements," where cited evidence could be provided to refute the claim. Descriptive statistics were used to characterize the study cohort.ResultsA total of 30,368 campaigns met the criteria for final analysis. After manual review, we identified 53 campaigns (0.17%) seeking funding for alternative medical treatment for COVID-19, including popularized treatments such as ivermectin (n=14, 26%), hydroxychloroquine (n=6, 11%), and vitamin D (n=4, 7.5%). Moreover, 23 (43%) of the 53 campaigns seeking support for alternative treatments contained COVID-19 misinformation. There were 80 campaigns that opposed mandating masks or vaccination, 48 (60%) of which contained COVID-19 misinformation. Alternative treatment campaigns had a lower median amount raised (US $1135) compared to traditional (US$2828) treatments (P<.001) and a lower median percentile of target achieved (11.9% vs 31.1%; P=.003). Campaigns for alternative treatments raised substantially lower amounts (US $115,000 vs US$52,715,000, respectively) and lower proportions of fundraising goals (2.1% vs 12.5%) for alternative versus conventional campaigns. The median goal for campaigns was significantly higher (US $25,000 vs US$10,000) for campaigns opposing mask or vaccine mandates relative to those in support of upholding mandates (P=.04). Campaigns seeking funding to lift mandates on health care workers reached US $622 (0.15$410,000 goal.ConclusionsA small minority of web-based crowdfunding campaigns for COVID-19 were directed at unproven COVID-19 treatments and support for campaigns aimed against masking or vaccine mandates. Approximately half (71/133, 53%) of these campaigns contained verifiably false or misleading information and had limited fundraising success.International registered report identifier (irrid)RR2-10.1001/jamainternmed.2019.3330

Synthesis, Characterization, and Direct Intracellular Imaging of Ultrasmall and Uniform Glutathione‐Coated Gold Nanoparticles

Gold nanoparticles (AuNPs) with core sizes below 2 nm and compact ligand shells constitute versatile platforms for the development of novel reagents in nanomedicine. Due to their ultrasmall size, these AuNPs are especially attractive in applications requiring delivery to crowded intracellular spaces in the cytosol and nucleus. For eventual use in vivo, ultrasmall AuNPs should ideally be monodisperse, since small variations in size may affect how they interact with cells and how they behave in the body. Here we report the synthesis of ultrasmall, uniform 144‐atom AuNPs protected by p ‐mercaptobenzoic acid followed by ligand exchange with glutathione (GSH). Quantitative scanning transmission electron microscopy (STEM) reveals that the resulting GSH‐coated nanoparticles (Au(GSH)) have a uniform mass distribution with cores that contain 134 gold atoms on average. Particle size dispersity is analyzed by analytical ultracentrifugation, giving a narrow distribution of apparent hydrodynamic diameter of 4.0 ± 0.6 nm. To evaluate the nanoparticles’ intracellular fate, the cell‐penetrating peptide TAT is attached noncovalently to Au(GSH), which is confirmed by fluorescence quenching and isothermal titration calorimetry. HeLa cells are then incubated with both Au(GSH) and the Au(GSH)‐TAT complex, and imaged without silver enhancement of the AuNPs in unstained thin sections by STEM. This imaging approach enables unbiased detection and quantification of individual ultrasmall nanoparticles and aggregates in the cytoplasm and nucleus of the cells. The synthesis and characterization of an ultrasmall and uniform glutathione‐coated gold nanoparticle is reported. It is also shown that scanning transmission electron microscopy (STEM) enables the visualization and quantification of individual gold nanoparticles as well as small aggregates in the cytoplasm and nucleus of HeLa cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92372/1/2277_ftp.pd

Who and when should we screen for prostate cancer? Interviews with key opinion leaders

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening

Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM

Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid β-peptide, Aβ(1-40)(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild type Alzheimer's amyloid peptide, wt-Aβ(1-40), using both in situ atomic force and electron microscopy, circular dichroism and thioflavin T fluorescence assays. For arc-Aβ(1-40) at the end of the 'lag'-period of fibrillization an abrupt appearance of ∼3nm size 'spherical aggregates' with a homogeneous morphology, was identified. Then, the aggregation proceeds with a rapid growth of amyloid fibrils with a variety of morphologies, while the spherical aggregates eventually disappeared during in situ measurements. Arc-Aβ(1-40) was also shown to form fibrils at much lower concentrations than wt-Aβ(1-40): ≤2.5μM and 12.5μM, respectively. Moreover, at the same concentration, 50μM, the aggregation process proceeds more rapidly for arc-Aβ(1-40): the first amyloid fibrils were observed after c.a. 72h from the onset of incubation as compared to approximately 7days for wt-Aβ(1-40). Amyloid fibrils of arc-Aβ(1-40) exhibit a large variety of polymorphs, at least five, both coiled and non-coiled distinct fibril structures were recognized by AFM, while at least four types of arc-Aβ(1-40) fibrils were identified by TEM and STEM and their mass-per-length statistics were collected suggesting supramolecular structures with two, four and six β-sheet laminae. Our results suggest a pathway of fibrillogenesis for full-length Alzheimer's peptides with small and structurally ordered transient spherical aggregates as on-pathway immediate precursors of amyloid fibrils. © 2012 Elsevier Inc

X-ray absorption spectroscopy systematics at the tungsten L-edge

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W<sup>0</sup>(PMe<sub>3</sub>)<sub>6</sub>], [W<sup>II</sup>Cl<sub>2</sub>(PMePh<sub>2</sub>)<sub>4</sub>], [W<sup>III</sup>Cl<sub>2</sub>(dppe)<sub>2</sub>][PF<sub>6</sub>] (dppe = 1,2-bis(diphenylphosphino)ethane), [W<sup>IV</sup>Cl<sub>4</sub>(PMePh<sub>2</sub>)<sub>2</sub>], [W<sup>V</sup>(NPh)Cl<sub>3</sub>(PMe<sub>3</sub>)<sub>2</sub>], and [W<sup>VI</sup>Cl<sub>6</sub>] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L<sub>3,2</sub>-edges and the L<sub>1</sub> rising-edge energy with metal Z<sub>eff</sub>, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>] and [W<sup>IV</sup>(mdt)<sub>2</sub>(CN)<sub>2</sub>]<sup>2–</sup> (mdt<sup>2–</sup> = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W<sup>IV</sup> species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z<sub>eff</sub> in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z<sub>eff</sub> or, as in the case of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>], add other subtlety by modulating the redox level of other ligands in the coordination sphere

Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1

Most animal species operate according to a 24-h period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN modulates hippocampal-dependent memory, but the molecular and cellular mechanisms that account for this effect remain largely unknown. Here, we identify cell-type-specific structural and functional changes that occur with circadian rhythmicity in neurons and astrocytes in hippocampal area CA1. Pyramidal neurons change the surface expression of NMDA receptors. Astrocytes change their proximity to synapses. Together, these phenomena alter glutamate clearance, receptor activation, and integration of temporally clustered excitatory synaptic inputs, ultimately shaping hippocampal-dependent learning in vivo. We identify corticosterone as a key contributor to changes in synaptic strength. These findings highlight important mechanisms through which neurons and astrocytes modify the molecular composition and structure of the synaptic environment, contribute to the local storage of information in the hippocampus, and alter the temporal dynamics of cognitive processing