Quantification of vaporized targeted nanodroplets using high-frame-rate ultrasound and optics

Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles,are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. Particularly,the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largelyunexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, we show that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalisation of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae-and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies

Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2

BACKGROUND: Circular chromosome conformation capture (4C) has provided important insights into three dimensional (3D) genome organization and its critical impact on the regulation of gene expression. We developed a new quantitative framework based on polymer physics for the analysis of paired-end sequencing 4C (PE-4Cseq) data. We applied this strategy to the study of chromatin interaction changes upon a 4.3 Mb DNA deletion in mouse region 4E2. RESULTS: A significant number of differentially interacting regions (DIRs) and chromatin compaction changes were detected in the deletion chromosome compared to a wild-type (WT) control. Selected DIRs were validated by 3D DNA FISH experiments, demonstrating the robustness of our pipeline. Interestingly, significant overlaps of DIRs with CTCF/Smc1 binding sites and differentially expressed genes were observed. CONCLUSIONS: Altogether, our PE-4Cseq analysis pipeline provides a comprehensive characterization of DNA deletion effects on chromatin structure and function

Lifeworld-led care: Is it relevant for well-being and the fifth wave of public health action?

A recent paper has made the case for a “fifth wave” of public health action. The paper articulated the first four waves as focusing on civil engineering, the germ theory of disease, welfare reforms and lifestyle issues. This article will focus on well-being and will expand on the authors’ articulation of a current need to “discover a new image of what it is to be human” to begin to address the challenges of promoting well-being. This article will consider an alternative way of viewing human beings within a “caring” context and how this alternative view may aid this potential fifth wave of public health action. This alternative view has emerged from the work of Husserl who suggested that any human view of the world without subjectivity has excluded its basic foundation. The phenomenological understanding of “lifeworld” is articulated through five elements, temporality, spaciality, intersubjectivity, embodiment and mood that are all discussed here in detail. A world of colours, sparkling stars, memories, happiness, joy, anger and sadness. It is this “lifeworld’ that when health care or as argued in this article as public health becomes overly focused on decontextualized goals, and measuring quality superficially can be neglected

Dialectics and difference: against Harvey's dialectical post-Marxism

David Harvey`s recent book, Justice, nature and the geography of difference (JNGD), engages with a central philosophical debate that continues to dominate human geography: the tension between the radical Marxist project of recent decades and the apparently disempowering relativism and `play of difference' of postmodern thought. In this book, Harvey continues to argue for a revised `post-Marxist' approach in human geography which remains based on Hegelian-Marxian principles of dialectical thought. This article develops a critique of that stance, drawing on the work of Jacques Derrida, Gilles Deleuze and Felix Guattari. I argue that dialectical thinking, as well as Harvey's version of `post-Marxism', has been undermined by the wide-ranging `post-' critique. I suggest that Harvey has failed to appreciate the full force of this critique and the implications it has for `post-Marxist' ontology and epistemology. I argue that `post-Marxism', along with much contemporary human geography, is constrained by an inflexible ontology which excessively prioritizes space in the theory produced, and which implements inflexible concepts. Instead, using the insights of several `post-' writers, I contend there is a need to develop an ontology of `context' leading to the production of `contextual theories'. Such theories utilize flexible concepts in a multilayered understanding of ontology and epistemology. I compare how an approach which produces a `contextual theory' might lead to more politically empowering theory than `post-Marxism' with reference to one of Harvey's case studies in JNGD

Instrumente und Maßnahmen der kommunalen Klimaanpassung: Empirische Befunde für einen erfolgreichen Transfer

Der vorliegende Bericht untersucht Lern- und Transferprozesse zwischen sowie innerhalb von Städten sowie das Transferpotenzial konkreter Wissenstransfer-Medien, Instrumente und Maßnahmen. Damit wird das Ziel verfolgt, ein besseres Verständnis dieser Prozesse zu entwickeln und einen Beitrag zur Verbesserung des Transfers von kommunalen Klimaanpassungsaktivitäten zu leisten. Er baut dabei auf einer vorangegangenen Analyse des Forschungsstands zum Transfer von Policies durch Haupt et al. (2021) auf und versucht, den bereits generierten Wissensstand auf der Ebene von Policies nun um die Ebene konkreter Instrumente und Maßnahmen zu ergänzen sowie durch empirische Befunde zu ausgewählten Maßnahmen zu untermauern. Die Wissens- und Datengrundlage dieses Berichts umfasst einen Mix aus verschiedenen (Online)-Befragungen und Interviews mit Vertreter:innen relevanter Akteursgruppen, vor allem Vertreter:innen von Stadtverwaltungen, sowie den Erfahrungswerten der drei Projekt-Fallstudienstädte Potsdam, Remscheid und Würzburg

Fragments of equality in representative politics

Deploying a broadly interpretive approach, the article explores the extent to which, and the ways in which, equality is enacted in non-elective as well as elective representation. It argues that the fleeting and fragmentary equalities evident in non-elective representation are democratically significant, and that examining them can enhance understanding of the democratic promise and limits of different modes of representation

Open Database of Epileptic EEG with MRI and Postoperational Assessment of Foci—a Real World Verification for the EEG Inverse Solutions

This paper introduces a freely accessible database http://eeg.pl/epi, containing 23 datasets from patients diagnosed with and operated on for drug-resistant epilepsy. This was collected as part of the clinical routine at the Warsaw Memorial Child Hospital. Each record contains (1) pre-surgical electroencephalography (EEG) recording (10–20 system) with inter-ictal discharges marked separately by an expert, (2) a full set of magnetic resonance imaging (MRI) scans for calculations of the realistic forward models, (3) structural placement of the epileptogenic zone, recognized by electrocorticography (ECoG) and post-surgical results, plotted on pre-surgical MRI scans in transverse, sagittal and coronal projections, (4) brief clinical description of each case. The main goal of this project is evaluation of possible improvements of localization of epileptic foci from the surface EEG recordings. These datasets offer a unique possibility for evaluating different EEG inverse solutions. We present preliminary results from a subset of these cases, including comparison of different schemes for the EEG inverse solution and preprocessing. We report also a finding which relates to the selective parametrization of single waveforms by multivariate matching pursuit, which is used in the preprocessing for the inverse solutions. It seems to offer a possibility of tracing the spatial evolution of seizures in time