Mathematical and physical approaches to infer absolute zenith wet delays from double differential interferometric observations using ERA5 atmospheric reanalysis

Atmospheric water vapor (WV) is one of the driving constituents of the atmosphere. The modelling and forecasting of WV and derived quantities like precipitable water is reliable on regional scales but challenging on small scales because of its high spatial and temporal variation. Interferometric synthetic aperture radar (InSAR) can be exploited to retrieve integrated atmospheric water vapor (IWV) from path delay observations along the radar line of sight. InSAR-derived IWV maps feature a very high spatial resolution but the double-differential interferometric observations only provide changes of IWV between acquisition times and with respect to a certain spatial reference. In this study we present a method to derive the absolute IWV by combining ERA5 numerical weather model data with differential path delay observations from InSAR time series. We propose different functional approaches to merge the regional trend of WV from ERA5 with the high resolution IWV signal from InSAR. We apply this to a Sentinel-1 Persistent Scatterer InSAR time series in the Upper Rhine Graben and validate against IWV observations at GNSS stations of the Upper Rhine Graben Network

Service-based survey of dystonia in Munich

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000. Copyright (C) 2002 S. Karger AG, Base

Control of Perfusable Microvascular Network Morphology Using a Multiculture Microfluidic System

The mechanical and biochemical microenvironment influences the morphological characteristics of microvascular networks (MVNs) formed by endothelial cells (ECs) undergoing the process of vasculogenesis. The objective of this study was to quantify the role of individual factors in determining key network parameters in an effort to construct a set of design principles for engineering vascular networks with prescribed morphologies. To achieve this goal, we developed a multiculture microfluidic platform enabling precise control over paracrine signaling, cell-seeding densities, and hydrogel mechanical properties. Human umbilical vein endothelial cells (HUVECs) were seeded in fibrin gels and cultured alongside human lung fibroblasts (HLFs). The engineered vessels formed in our device contained patent, perfusable lumens. Communication between the two cell types was found to be critical in avoiding network regression and maintaining stable morphology beyond 4 days. The number of branches, average branch length, percent vascularized area, and average vessel diameter were found to depend uniquely on several input parameters. Importantly, multiple inputs were found to control any given output network parameter. For example, the vessel diameter can be decreased either by applying angiogenic growth factors—vascular endothelial growth factor (VEGF) and sphingosine-1-phsophate (S1P)—or by increasing the fibrinogen concentration in the hydrogel. These findings introduce control into the design of MVNs with specified morphological properties for tissue-specific engineering applications.National Science Foundation (U.S.). Science and Technology Center Emergent Behaviors of Interated Cellular Systems (EBICS) (Grant CBET-0939511)National Science Foundation (U.S.) (Fellowship

Are internists in an non-prescriptive setting favourable to guidelines? A survey in a Department of Internal Medicine in Switzerland.

A cross-sectional anonymous postal survey was carried out in a Department of Internal Medicine in order to assess physicians' knowledge about and attitudes towards clinical practice guidelines and to evaluate the role of age in determining their use and opinions. The study took place in a Swiss University Hospital where exposure to guidelines had been limited. The questionnaire was sent to the 174 physicians of the Department. The response rate was 67% (116/174). The spontaneous definitions of guidelines were heterogeneous and referred to information of uncertain validity. Most participants, especially the younger groups of junior and senior residents, reported using guidelines and were favourable to their development. Less favourable attitudes were observed among senior staff physicians and consultants. For instance, the latter more often held the opinion that guidelines are too rigid to apply to individual patients, were likely to decrease physician reimbursement and to hamper research (respectively, 32% vs 24%, 50% vs 31% and 18% vs 7% when compared with the opinions of residents). In conclusion, in a non-prescriptive hospital setting, where the development, dissemination and implementation of guidelines are emerging, the concept of 'guideline' was heterogeneous. Despite generally positive attitudes towards guidelines, the opinion of senior staff physicians constitute a barrier to their dissemination and implementation

Mechanisms of tumor cell extravasation in an in vitro microvascular network platform

A deeper understanding of the mechanisms of tumor cell extravasation is essential in creating therapies that target this crucial step in cancer metastasis. Here, we use a microfluidic platform to study tumor cell extravasation from in vitro microvascular networks formed via vasculogenesis. We demonstrate tight endothelial cell–cell junctions, basement membrane deposition and physiological values of vessel permeability. Employing our assay, we demonstrate impaired endothelial barrier function and increased extravasation efficiency with inflammatory cytokine stimulation, as well as positive correlations between the metastatic potentials of MDA-MB-231, HT-1080, MCF-10A and their extravasation capabilities. High-resolution time-lapse microscopy reveals the highly dynamic nature of extravasation events, beginning with thin tumor cell protrusions across the endothelium followed by extrusion of the remainder of the cell body through the formation of small (~1 μm) openings in the endothelial barrier which grows in size (~8 μm) to allow for nuclear transmigration. No disruption to endothelial cell–cell junctions is discernible at 60×, or by changes in local barrier function after completion of transmigration. Tumor transendothelial migration efficiency is significantly higher in trapped cells compared to non-trapped adhered cells, and in cell clusters versus single tumor cells.National Cancer Institute (U.S.) (R33 CA174550-01)National Science Foundation (U.S.). Graduate Research FellowshipNational Science Foundation (U.S.). Science and Technology Center Emergent Behaviors of Interated Cellular Systems (EBICS) (CBET-0939511

Elucidation of the Roles of Tumor Integrin 1 in the Extravasation Stage of the Metastasis Cascade

Tumor integrin β1 (ITGB1) contributes to primary tumor growth and metastasis, but its specific roles in extravasation have not yet been clearly elucidated. In this study, we engineered a three-dimensional microfluidic model of the human microvasculature to recapitulate the environment wherein extravasation takes place and assess the consequences of β1 depletion in cancer cells. Combined with confocal imaging, these tools allowed us to decipher the detailed morphology of transmigrating tumor cells and associated endothelial cells in vitro at high spatio-temporal resolution not easily achieved in conventional transmigration assays. Dynamic imaging revealed that β1-depleted cells lacked the ability to sustain protrusions into the subendothelial matrix in contrast with control cells. Specifically, adhesion via α3β1 and α6β1 to subendothelial laminin was a critical prerequisite for successful transmigration. β1 was required to invade past the endothelial basement membrane, whereas its attenuation in a syngeneic tumor model resulted in reduced metastatic colonization of the lung, an effect not observed upon depletion of other integrin alpha and beta subunits. Collectively, our findings in this novel model of the extravasation microenvironment revealed a critical requirement for β1 in several steps of extravasation, providing new insights into the mechanisms underlying metastasis.National Cancer Institute (U.S.) (Grant 1U01CA202177-01

High Cell Diversity and Complex Peptidergic Signaling Underlie Placozoan Behavior.

Placozoans, together with sponges, are the only animals devoid of a nervous system and muscles, yet both respond to sensory stimulation in a coordinated manner. How behavioral control in these free-living animals is achieved in the absence of neurons and, more fundamentally, how the first neurons evolved from more primitive cells for communication during the rise of animals are not yet understood [1-5]. The placozoan Trichoplax adhaerens is a millimeter-wide, flat, free-living marine animal composed of six morphologically identified cell types distributed across a simple body plan [6-9]: a thin upper epithelium and a columnar lower epithelium interspersed with a loose layer of fiber cells in between. Its genome contains genes encoding several neuropeptide-precursor-like proteins and orthologs of proteins involved in neurosecretion in animals with a nervous system [10-12]. Here we investigate peptidergic signaling in T. adhaerens. We found specific expression of several neuropeptide-like molecules in non-overlapping cell populations distributed over the three cell layers, revealing an unsuspected cell-type diversity of T. adhaerens. Using live imaging, we discovered that treatments with 11 different peptides elicited striking and consistent effects on the animals' shape, patterns of movement, and velocity that we categorized under three main types: (1) crinkling, (2) turning, and (3) flattening and churning. Together, the data demonstrate a crucial role for peptidergic signaling in nerveless placozoans and suggest that peptidergic volume signaling may have pre-dated synaptic signaling in the evolution of nervous systems

Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation

Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell–cell interactions. LPS-stimulated neutrophils (PMNs) and tumor cells (TCs) form heterotypic aggregates under flow, and arrest due to both mechanical trapping and neutrophil–endothelial adhesions. Surprisingly, PMNs are not static following aggregation, but exhibit a confined migration pattern near TC–PMN clusters. We discover that PMNs are chemotactically confined by self-secreted IL-8 and tumor-derived CXCL-1, which are immobilized by the endothelial glycocalyx. This results in significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, which also contributes to increasing the extravasation potential of adjacent tumor cells through modulation of the endothelial barrier. Strikingly similar migration patterns and extravasation behaviors were also observed in an in vivo zebrafish model upon PMN–tumor cell coinjection into the embryo vasculature. These insights into the temporal dynamics of intravascular tumor–PMN interactions elucidate the mechanisms through which inflamed neutrophils can exert proextravasation effects at the distant metastatic site. Keywords: metastasis; inflammation; neutrophils; extravasation; cell migratio

The Early ANTP Gene Repertoire: Insights from the Placozoan Genome

The evolution of ANTP genes in the Metazoa has been the subject of conflicting hypotheses derived from full or partial gene sequences and genomic organization in higher animals. Whole genome sequences have recently filled in some crucial gaps for the basal metazoan phyla Cnidaria and Porifera. Here we analyze the complete genome of Trichoplax adhaerens, representing the basal metazoan phylum Placozoa, for its set of ANTP class genes. The Trichoplax genome encodes representatives of Hox/ParaHox-like, NKL, and extended Hox genes. This repertoire possibly mirrors the condition of a hypothetical cnidarian-bilaterian ancestor. The evolution of the cnidarian and bilaterian ANTP gene repertoires can be deduced by a limited number of cis-duplications of NKL and “extended Hox” genes and the presence of a single ancestral “ProtoHox” gene