Plasma Lens Prototype Progress: Plasma Diagnostics And Particle Tracking For ILC e+ Source

In recent years, the concept of high-gradient, symmetric focusing using active plasma lenses has regained notable attention owing to its potential benefits in terms of compactness and beam dynamics when juxtaposed with traditional focusing elements. An enticing application lies in the optical matching of extensively divergent positrons originating from the undulator-based ILC positron source, thereby enhancing the positron yield in subsequent accelerating structures. Through a collaboration between the University of Hamburg and DESY Hamburg, a scaled-down prototype for this purpose has been conceptualized and fabricated. In this presentation, we provide an overview of the ongoing progress in the development of this prototype. Furthermore, first insights into the development of a particle tracking code especially designed for plasma lenses with implemented Bayes optimization, are given.Comment: TALK PRESENTED AT THE INTERNATIONAL WORKSHOP ON FUTURE LINEAR COLLIDERS (LCWS2023), 15-19 MAY 2023. C23-05-15.3., LCWS23, SLAC, Plasma lens, ILC, 3 page

Effective removal of the rotifer Brachionus calyciflorus from a Chlorella vulgaris microalgal culture by homogeneous solar photo-Fenton at neutral pH

In this study, a citrate-modified photo-Fenton process was successfully applied to decontaminate a Chlorella vulgaris microalgae culture spiked with the rotifer Brachionus calyciflorus (5 individuals mL−1). The applied treatment (1 mg L−1 Fe2+, 20 mg L−1 H2O2, 17.5 mg L−1 citric acid) had only moderate effects on viability and regrowth of the microalgae since, after a short post-treatment delay of a few days, they reached final cell densities similar to that obtained for microalgae cultures that were not spiked. The decontamination was effective as no regrowth of rotifers was observed in the microalgae cultures after treatment. The efficacy of the citrate-modified photo-Fenton treatment was also studied with a higher starting concentration of 20 rotifers mL−1 and was compared with a solar light/H2O2 treatment. Results show that both treatments had similar efficacies on the rotifer elimination, but that the citrate-modified photo-Fenton treatment had a lower negative impact on the regrowth of microalgae than the solar light/H2O2 treatment. However, when microalgae cultures were spiked with 20 rotifers mL−1, rotifers were only partially inactivated and post-treatment regrowth occurred, which highlights the importance to apply the photo-Fenton process at an early stage of a contamination to achieve full rotifer elimination. In any case, a contamination with 5 rotifers mL−1 is already a significant threat as numbers above 1000 rotifers mL−1 were reached after 14 days and caused the microalgae culture to fail. Overall, our treatment suggests that the citrate-modified solar photo-Fenton process is an environmentally friendly solution to support the maintenance of contaminant-free microalgal cultures

Valuations on lattice polytopes

This survey is on classification results for valuations defined on lattice polytopes that intertwine the special linear group over the integers. The basic real valued valuations, the coefficients of the Ehrhart polynomial, are introduced and their characterization by Betke and Kneser is discussed. More recent results include classification theorems for vector and convex body valued valuations. © Springer International Publishing AG 2017

Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor-related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation

A systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system

Specificity data for groups of transcription factors (TFs) in a common regulatory network can be used to computationally identify the location of cis-regulatory modules in a genome. The primary limitation for this type of analysis is the paucity of specificity data that is available for the majority of TFs. We describe an omega-based bacterial one-hybrid system that provides a rapid method for characterizing DNA-binding specificities on a genome-wide scale. Using this system, 35 members of the Drosophila melanogaster segmentation network have been characterized, including representative members of all of the major classes of DNA-binding domains. A suite of web-based tools was created that uses this binding site dataset and phylogenetic comparisons to identify cis-regulatory modules throughout the fly genome. These tools allow specificities for any combination of factors to be used to perform rapid local or genome-wide searches for cis-regulatory modules. The utility of these factor specificities and tools is demonstrated on the well-characterized segmentation network. By incorporating specificity data on an additional 66 factors that we have characterized, our tools utilize ∼14% of the predicted factors within the fly genome and provide an important new community resource for the identification of cis-regulatory modules

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

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Vascular surveillance by haptotactic blood platelets in inflammation and infection

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets

Structural alterations in functional neurological disorder and related conditions: A software and hardware problem?

Functional neurological (conversion) disorder (FND) is a condition at the interface of neurology and psychiatry. A “software” vs. “hardware” analogy describes abnormal neurobiological mechanisms occurring in the context of intact macroscopic brain structure. While useful for explanatory and treatment models, this framework may require more nuanced considerations in the context of quantitative structural neuroimaging findings in FND. Moreover, high co-occurrence of FND and somatic symptom disorders (SSD) as defined in DSM-IV (somatization disorder, somatoform pain disorder, and undifferentiated somatoform disorder; referred to as SSD for brevity in this article) raises the possibility of a partially overlapping pathophysiology. In this systematic review, we use a transdiagnostic approach to review and appraise the structural neuroimaging literature in FND and SSD. While larger sample size studies are needed for definitive characterization, this article highlights that individuals with FND and SSD may exhibit sensorimotor, prefrontal, striatal-thalamic, paralimbic, and limbic structural alterations. The structural neuroimaging literature is contextualized within the neurobiology of stress-related neuroplasticity, gender differences, psychiatric comorbidities, and the greater spectrum of functional somatic disorders. Future directions that could accelerate the characterization of the pathophysiology of FND and DSM-5 SSD are outlined, including “disease staging” discussions to contextualize subgroups with or without structural changes. Emerging neuroimaging evidence suggests that some individuals with FND and SSD may have a “software” and “hardware” problem, although if structural alterations are present the neural mechanisms of functional disorders remain distinct from lesional neurological conditions. Furthermore, it remains unclear whether structural alterations relate to predisposing vulnerabilities or consequences of the disorder. Keywords: Conversion disorder, Psychogenic, Neuroimaging, MRI, Functional neurological disorder, Somatic symptom disorde

A Defined, Feeder-Free, Serum-Free System to Generate In Vitro Hematopoietic Progenitors and Differentiated Blood Cells from hESCs and hiPSCs

Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimentional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells