3D tomography of cells in micro-channels

We combine confocal imaging, microfluidics and image analysis to record 3D-images of cells in flow. This enables us to recover the full 3D representation of several hundred living cells per minute. Whereas 3D confocal imaging has thus far been limited to steady specimen, we overcome this restriction and present a method to access the 3D shape of moving objects. The key of our principle is a tilted arrangement of the micro-channel with respect to the focal plane of the microscope. This forces cells to traverse the focal plane in an inclined manner. As a consequence, individual layers of passing cells are recorded which can then be assembled to obtain the volumetric representation. The full 3D information allows for a detailed comparisons with theoretical and numerical predictions unfeasible with e.g.\ 2D imaging. Our technique is exemplified by studying flowing red blood cells in a micro-channel reflecting the conditions prevailing in the microvasculature. We observe two very different types of shapes: `croissants' and `slippers'. Additionally, we perform 3D numerical simulations of our experiment to confirm the observations. Since 3D confocal imaging of cells in flow has not yet been realized, we see high potential in the field of flow cytometry where cell classification thus far mostly relies on 1D scattering and fluorescence signals

Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis

Summary Axial mesendoderm is comprised of prechordal plate and notochord. Lack of a suitable Cre driver has hampered the ability to genetically dissect the requirement for each of these components, or genes expressed within them, to anterior patterning. Here, we have utilized Isl1-Cre to investigate roles of the winged helix transcription factor Foxa2 specifically in prechordal plate and ventral endoderm. Foxa2loxP/loxP; Isl1-Cre mutants died at 13.5 dpc, exhibiting aberrations in anterior neural tube and forebrain patterning, and in ventral foregut morphogenesis and cardiac fusion. Molecular analysis of Foxa2loxP/loxP; Isl1-Cre mutants indicated that Foxa2 is required in Isl1 lineages for expression of notochord and dorsal foregut endoderm markers, Shh. Brachyury, and Hlxb9. Our results support a requirement for Foxa2 in prechordal plate for notochord morphogenesis, axial patterning, and patterning of dorsal foregut endoderm. Loss of Foxa2 in ventral endoderm resulted in reduced expression of Sox17, Gata4, and ZO proteins, accounting at least in part for observed lack of foregut fusion, cardia bifida, and increased apoptosis of ventral endoderm

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Aging constitutes the key risk factor for age-related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which protective genes are carried by long-lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin-like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed

Artificial neural networks for 3D cell shape recognition from confocal images

We present a dual-stage neural network architecture for analyzing fine shape details from microscopy recordings in 3D. The system, tested on red blood cells, uses training data from both healthy donors and patients with a congenital blood disease. Characteristic shape features are revealed from the spherical harmonics spectrum of each cell and are automatically processed to create a reproducible and unbiased shape recognition and classification for diagnostic and theragnostic use.Comment: 17 pages, 8 figure

The study of bronze statuettes with the help of neutron-imaging techniques

Until recently fabrication techniques of Renaissance bronzes have been studied only with the naked eye, microscopically, videoscopically and with X-radiography. These techniques provide information on production techniques, yet much important detail remains unclear. As part of an interdisciplinary study of Renaissance bronzes undertaken by the Rijksmuseum Amsterdam, neutron-imaging techniques have been applied with the aim of obtaining a better understanding of bronze workmanship during the Renaissance period. Therefore, an explanation of the fabrication techniques is given to better understand the data collected by these neutron-imaging techniques. The data was used for tomography studies, which reveal hidden aspects that could not at all or scarcely be seen using X-radiography. For this specific study, the representative bronze ‘Hercules Pomarius’ of Willem van Tetrode (ca 1520–1588) has been examined, along with 20 other Renaissance bronzes from the Rijksmuseum collection

Edge spin accumulation in semiconductor two-dimensional hole gases

The controlled generation of localized spin densities is a key enabler of semiconductor spintronics In this work, we study spin Hall effect induced edge spin accumulation in a two-dimensional hole gas with strong spin orbit interactions. We argue that it is an intrinsic property, in the sense that it is independent of the strength of disorder scattering. We show numerically that the spin polarization near the edge induced by this mechanism can be large, and that it becomes larger and more strongly localized as the spin-orbit coupling strength increases, and is independent of the width of the conducting strip once this exceeds the elastic scattering mean-free-path. Our experiments in two-dimensional hole gas microdevices confirm this remarkable spin Hall effect phenomenology. Achieving comparable levels of spin polarization by external magnetic fields would require laboratory equipment whose physical dimensions and operating electrical currents are million times larger than those of our spin Hall effect devices.Comment: 6 pages, 5 figure

Athletes’ Beliefs About and Attitudes Towards Taking Banned Performance-Enhancing Substances: A Qualitative Study

Elite athletes’ beliefs about, and attitudes toward, taking banned performance enhancing substances were explored in 8 focus-group discussions with 57 athletes from 7 different sports. Discussion was initiated by 3 broad open-ended questions pertaining to 3 important themes likely to affect beliefs and attitudes toward banned performance enhancing substances. Thematic content analysis of interview transcripts revealed 9 lower-order themes emerging under the 3 global themes: personal attitudes (reputation and getting caught, health effects, and financial incentives and rewards), social influences (coaches, parents, and medical staff and sport scientists), and control beliefs (i.e., insufficiency of doping testing, resource availability, and sport level and type). Findings provide insight into the beliefs and attitudes that likely underpin motives and intentions to take banned performance-enhancing substances. Results are generally consistent with, and complement, research adopting quantitative approaches based on social– cognitive models examining the beliefs and attitudes linked to taking banned performance-enhancing substances

Operando neutron imaging study of a commercial Li-ion battery at variable charge-discharge current densities

publishedVersio

Single-parameter non-adiabatic quantized charge pumping

Controlled charge pumping in an AlGaAs/GaAs gated nanowire by single-parameter modulation is studied experimentally and theoretically. Transfer of integral multiples of the elementary charge per modulation cycle is clearly demonstrated. A simple theoretical model shows that such a quantized current can be generated via loading and unloading of a dynamic quasi-bound state. It demonstrates that non-adiabatic blockade of unwanted tunnel events can obliterate the requirement of having at least two phase-shifted periodic signals to realize quantized pumping. The simple configuration without multiple pumping signals might find wide application in metrological experiments and quantum electronics.Comment: 4 pages, 4 figure