Effects of anisotropy on the geometry of tracer particle trajectories in turbulent flows

Using curvature and torsion to describe Lagrangian trajectories gives a full description of these as well as an insight into small and large time scales as temporal derivatives up to order 3 are involved. One might expect that the statistics of these properties depend on the geometry of the flow. Therefore, we calculated curvature and torsion probability density functions (PDFs) of experimental Lagrangian trajectories processed using the Shake-the-Box algorithm of turbulent von Kármán flow, Rayleigh-Bénard convection and a zero-pressuregradient boundary layer over a flat plate. The results for the von-Kármán flow compare well with experimental results for the curvature PDF and numerical simulation of homogeneous and isotropic turbulence for the torsion PDF. For the experimental Rayleigh-Bénard convection, the power law tails found agree with those measured for von-Kármán flow. Results for the logarithmic layer within the boundary layer differ slightly, we give some potential explanation below. To detect and quantify the effect of anisotropy either resulting from a mean flow or large-scale coherent motions on the geometry or tracer particle trajectories, we introduce the curvature vector. We connect its statistics with those of velocity fluctuations and demonstrate that strong large-scale motion in a given spatial direction results in meandering rather than helical trajectories

Delta1 Expression, Cell Cycle Exit, and Commitment to a Specific Secretory Fate Coincide within a Few Hours in the Mouse Intestinal Stem Cell System

The stem cells of the small intestine are multipotent: they give rise, via transit-amplifying cell divisions, to large numbers of columnar absorptive cells mixed with much smaller numbers of three different classes of secretory cells - mucus-secreting goblet cells, hormone-secreting enteroendocrine cells, and bactericide-secreting Paneth cells. Notch signaling is known to control commitment to a secretory fate, but why are the secretory cells such a small fraction of the population, and how does the diversity of secretory cell types arise? Using the mouse as our model organism, we find that secretory cells, and only secretory cells, pass through a phase of strong expression of the Notch ligand Delta1 (Dll1). Onset of this Dll1 expression coincides with a block to further cell division and is followed in much less than a cell cycle time by expression of Neurog3 – a marker of enteroendocrine fate – or Gfi1 – a marker of goblet or Paneth cell fate. By conditional knock-out of Dll1, we confirm that Delta-Notch signaling controls secretory commitment through lateral inhibition. We infer that cells stop dividing as they become committed to a secretory fate, while their neighbors continue dividing, explaining the final excess of absorptive over secretory cells. Our data rule out schemes in which cells first become committed to be secretory, and then diversify through subsequent cell divisions. A simple mathematical model shows how, instead, Notch signaling may simultaneously govern the commitment to be secretory and the choice between alternative modes of secretory differentiation

Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile

In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE2 we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Iab and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens

SRM・CRMの観点から考察する商社営業のコンピテンシー

Stem cells have captured the imagination of the general public by their potential as new therapeutic tools in the fight against degenerative diseases. This potential is based on their capability for self-renewal and at the same time for producing progenitor cells that will eventually provide the building blocks for tissue and organ regeneration. These processes are carefully orchestrated in the organism by means of a series of molecular cues. An emerging molecule which is responsible for some of these physiological responses is adrenomedullin, a 52-amino acid regulatory peptide which increases proliferation and regulates cell fate of stem cells of different origins. Adrenomedullin binds to specific membrane receptors in stem cells and induces several intracellular pathways such as those involving cAMP, Akt, or MAPK. Regulation of adrenomedullin levels may help in directing the growth and differentiation of stem cells for applications (e.g., cell therapy) both in vitro and in vivo. © 2012 Elsevier Inc.Peer Reviewe

Insufficiency fractures of the spine in relation to cancellous bone density : An in vitro study

Schroder G, Flachsmeyer D, Kullen CM, et al. Insuffizienzfrakturen der Wirbelsäule in Abhängigkeit von der spongiösen Knochendichte. Orthopädie. 2022;51(7):547-555.BACKGROUND: The risk of osteoporotic insufficiency fractures (Fx) at the axial skeleton increases with decreasing bone density, with an accumulation in the thoracic and thoracolumbar regions. To better understand the differential distribution of Fx along the spine, morphological and osteodensitometric studies were performed by computed tomography (CT) in the various spine sections. In addition, we aimed to clarify whether Hounsfield units (HU) found on CT examinations from other indications correlate with bone density and could be grounds for osteologic diagnosis.; MATERIAL AND METHODS: The entire spines of 26body donors were fixed in aPlexiglas water phantom and analyzed by high-resolution spiral CT. In addition, CT morphological cancellous bone density was measured in HU from C3 to S2 (624 vertebral bodies). Bone mineral density (BMD, mg/ml) was calculated and used to estimate osteoporosis (OPO).; RESULTS: OPO was present in all spines. Significantly increased sintering fractures were found in the thoracic and thoracolumbar regions when BMD was below 60 mg/ml. Fx in the cervical spine area were not found overall. Cancellous bone density was significantly higher in the cervical (median 188.6 HU) than in the lumbar (median 63.6 HU) and sacral (median 25.5 HU) spine.; DISCUSSION: BMD loss of vertebral body cancellous bone leads to an increased risk of Fx, which is also found in the cadaver spines. However, an apparent threshold for the occurrence of sintering fractures is not undercut in the cervical region. Finding athreshold for HU would be relevant to clinical practice. © 2022. The Author(s).Hintergrund Das Risiko für osteoporotische Insuffizienzfrakturen (Fx) am Achsenskelett steigt mit zunehmender Abnahme der Knochendichte, wobei sich thorakal und thorakolumbal eine Häufung findet. Um die unterschiedliche Verteilung von Fx entlang der Wirbelsäule (WS) besser zu verstehen, wurden morphologische und osteodensitometrische Untersuchungen mittels Computertomographie (CT) in den verschiedenen WS-Abschnitten durchgeführt. Zudem war zu klären, ob die bei CT-Untersuchungen aus anderen Indikationen gefunden Hounsfield-Einheiten (HE) mit der Knochendichte korrelieren und Anlass für eine osteologische Diagnostik sein könnten. Material und Methoden Von 26 Körperspenden wurden die gesamten WS in einem Plexiglas-Wasser-Phantom fixiert und mittels hochauflösende Spiral-CT analysiert. Zusätzlich erfolgte die Messung der CT-morphologischen Spongiosadichte in HE von C3 bis S2 (624 Wirbelkörper). Der Knochenmineralgehalt (KMG, mg/ml) wurde ermittelt und zur Abschätzung einer Osteoporose (OPO) herangezogen. Ergebnisse Bei allen WS lag eine OPO vor. Bei einem KMG unterhalb von 60 mg/ml fanden sich signifikant vermehrte Sinterungsfrakturen im thorakalen und thorakolumbalen Bereich. Osteoporotische Insuffizienzfrakturen im HWS-Bereich fanden sich insgesamt nicht. Die Spongiosadichte war signifikant höher in den zervikalen (Median 188,6 HE) als in den lumbalen (Median 63,6 HE) und sakralen (Median 25,5 HE) Wirbelkörpern aller untersuchten WS. Schlussfolgerung Ein KMG-Verlust der Wirbelkörperspongiosa führt zu einem erhöhten Fx-Risiko, welches sich auch bei den verwendeten WS findet. Jedoch wird im zervikalen Bereich ein scheinbarer Schwellenwert für das Auftreten von Sinterungsfrakturen nicht unterschritten. Einen Schwellenwert für HE zu finden, wäre für die klinische Praxis relevant

Chemogenetic Silencing of Differentiating Cortical Neurons Impairs Dendritic and Axonal Growth

Gasterstadt I, Schroder M, Cronin L, et al. Chemogenetic Silencing of Differentiating Cortical Neurons Impairs Dendritic and Axonal Growth. Frontiers in Cellular Neuroscience . 2022;16: 941620.Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are tools for controlling neuronal activity at the single cell level by triggering specific G protein signaling. Our objective was to investigate if prolonged silencing of differentiating cortical neurons can influence dendritic and axonal maturation. The DREADD hM4Di couples to G(i/o) signaling and evokes hyperpolarization via GIRK channels. HM4Di was biolistically transfected into neurons in organotypic slice cultures of rat visual cortex, and activated by clozapine-N-oxide (CNO) dissolved in H2O; controls expressed hM4Di, but were mock-stimulated with H2O. Neurons were analyzed after treatment for two postnatal time periods, DIV 5-10 and 10-20. We found that CNO treatment delays the maturation of apical dendrites of L2/3 pyramidal cells. Further, the number of collaterals arising from the main axon was significantly lower, as was the number of bouton terminaux along pyramidal cell and basket cell axons. The dendritic maturation of L5/6 pyramidal cells and of multipolar interneurons (basket cells and bitufted cells) was not altered by CNO treatment. Returning CNO-treated cultures to CNO-free medium for 7 days was sufficient to recover dendritic and axonal complexity. Our findings add to the view that activity is a key driver in particular of postnatal L2/3 pyramidal cell maturation. Our results further suggest that inhibitory G protein signaling may represent a factor balancing the strong driving force of neurotrophic factors, electrical activity and calcium signaling

All behavioural data for 'Conscious access in the near absence of attention: Critical extensions on the dual-task paradigm'

Matlab structure containing all behavioural data supporting our research article 'Conscious access in the near absence of attention: Critical extensions on the dual-task paradigm'<br><br>Includes data for 24 subjects across 3 experiments.<div>- Exp1: Face gender discrimination</div><div>- Exp2: Disk colour discrimination</div><div>- Exp3: Blended face/disk discrimination<br><br>Data is organised by experimental conditions for type 1 and type 2 signal detection analysis. For each trial subjects' 8AFC decision + 4-level confidence rating is supplied along with the signal truth on that trial and, for sanity checking, the correctness of the trial response.<br><br>For instance, <b>dualtask_data.Exp1.confidence.SP(1,6,2)</b> prints to screen the 1st 8AFC selection made by subject 2 in the 6th block of the Single Peripheral condition in Experiment 1: <b><u>-2</u></b> (indicating a confidence rating of '2' on the left side of the response screen).</div

Breaking strength and bone microarchitecture in osteoporosis: a biomechanical approximation based on load tests in 104 human vertebrae from the cervical, thoracic, and lumbar spines of 13 body donors

Schroder G, Reichel M, Spiegel S, et al. Breaking strength and bone microarchitecture in osteoporosis: a biomechanical approximation based on load tests in 104 human vertebrae from the cervical, thoracic, and lumbar spines of 13 body donors. Journal of Orthopaedic Surgery and Research . 2022;17(1): 228.Background The purpose of the study was to investigate associations between biomechanical resilience (failure load, failure strength) and the microarchitecture of cancellous bone in the vertebrae of human cadavers with low bone density with or without vertebral fractures (VFx). Methods Spines were removed from 13 body donors (approval no. A 2017-0072) and analyzed in regard to bone mineral density (BMD), Hounsfield units (HU), and fracture count (Fx) with the aid of high-resolution CT images. This was followed by the puncture of cancellous bone in the vertebral bodies of C2 to L5 using a Jamshidi (TM) needle. The following parameters were determined on the micro-CT images: bone volume fraction (BVF), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), degree of anisotropy (DA), trabecular number (Tb.N), trabecular pattern factor (Tb.Pf), and connectivity density (Conn.D). The axial load behavior of 104 vertebral specimens (C5, C6, T7, T8, T9, T12, L1, L3) was investigated with a servohydraulic testing machine. Results Individuals with more than 2 fractures had a significantly lower trabecular pattern factor (Tb.Pf), which also proved to be an important factor for a reduced failure load in the regression analysis with differences between the parts of the spine. The failure load (FL) and endplate sizes of normal vertebrae increased with progression in the craniocaudal direction, while the HU was reduced. Failure strength (FS) was significantly greater in the cervical spine than in the thoracic or lumbar spine (p < 0.001), independent of sex. BVF, Tb.Th, Tb.N, and Conn.D were significantly higher in the cervical spine than in the other spinal segments. In contrast, Tb.Sp and Tb.Pf were lowest in the cervical spine. BVF was correlated with FL (r = 0.600, p = 0.030) and FS (r = 0.763, p = 0.002). Microarchitectural changes were also detectable in the cervical spine at lower densities. Conclusions Due to the unique microarchitecture of the cervical vertebrae, fractures occur much later in this region than they do in the thoracic or lumbar spine. Trial registration Approval no. A 2017-0072