Intervalle eines fortschreitenden Schreibgespräches (2016-2023): Implizit mitschwingende Oktave: Der Wert der […] Leerzeichen und/oder der WERT des (Zu)-Erzählenden

In Worte zu fassen, was schwer in Worte zu hüllen geht, sind Wörter das Skelett, von dem, was Menschen anreichert und berührt. Ziel der folgenden gedanklichen Darstellung aus bereits publizierten Artikel ist es, den Raum zu erspüren, der im unausgesprochenen mitschwingt. Doch dafür bedarf es die Unterstützung weiterer Menschen. Die angedeuteten Skizzen explizierter Gedanken, die mit einer Achterbahnfahrt (2016) beginnen, sich über die Gesundheitskompetenz entfalten, die durch eine gezielte Patientenedukation, anhand von Informationen gefördert werden soll. Darauf baut der Death-Literacy Ansatz mit der Frage: „Lernt ihr in einem Sterbeseminar zu sterben?“ (2020), münden in einer Krise, die damit einher geht, dass die Kunst darin besteht zu lesen (2022), woraufhin die formelle Einladung zum Expert:innenaustausch folgt und / oder eine informelle Begegnung zwischen Menschen (2022). Das Jahr 2023 startet mit einem Dialog im Hospiz, indem die Sterbenden äußern, dass sie sich nicht als lehrende Person sehen. Im Raum steht der Tod als Reflexionsgegenstand oder Teil des Lebens, von Sterbenden als Lehrende im Hospiz, mit einer Theorie, die sich nicht explizieren lässt, gilt es diese zu (er)spüren. In der Kontemplation stellt sich eine weitere Frage: Behindert die Dramaturgie des Lebens die Epik der Gegenwart? (2023). Abschließend öffnet sich der Erfahrungsraum einer Pflegenden, die davon berichtet, dass der Tod Handlungen im Raum verändert, die kaum in Worte zu fassen sind (2023). Gerade, dass Unausgesprochene – das schweigende Sprechen des „Körpers“ erklingt so laut, dass es schwer auszuhalten gilt, im Raum des unbeschreibbar Ausgesprochenen/Auszusprechenden. (DIPF/Orig.

Langzeitverhalten von weichballistischen Materialien

Dieser Aufsatz befasst sich mit dem Langzeitverhalten ballistischer Materialien. Vorrangig soll die Frage geklärt werden, ob ballistisches Material qualitätsmindernde Erscheinungen im Schutzverhalten aufweist, die mit dem fortschreitenden Alter des Materials einhergehen. Um diese Frage zu klären, wurden anhand zahlreicher Beschussversuche an polizeilichen Schutzwesten statistisch verlässliche Daten gesammelt und anschließend unter verschiedenen Blickwinkeln ausgewertet. Zusätzlich wurden verschiedene Laborversuche am Aramid-Gewebe durchgeführt.This publication deals with the long-term behavior of ballistic material. It aims to answer the question, whether ballistic material shows significant signs of a deterioration that comes with preceding age. To answer that question numerous shooting tests with bulletproof vests were made to collect statistically reliable Data. The data was then evaluated under different point of views. Additionally various laboratory experiments were performed with Aramid fibre

Ship to Shore: Inuit, Early Europeans, and Maritime Landscapes in the Northern Gulf of St. Lawrence

Recent research at Hare Harbor on the Quebec Lower North Shore in the northeastern Gulf of St. Lawrence reveals great potential for archaeological and historical research on Basque and other early European activities in the northwestern North Atlantic. Although considerable data have been retrieved from Red Bay, Labrador, and a few other sixteenth-century sites in the Strait of Belle Isle and Gulf of St. Lawrence, archaeological knowledge of the early European phase of North American history in this region is limited, and information about post-sixteenth-century Basque occupations is nearly nonexistent. This chapter reports on a multicomponent site with late sixteenth-century Basque and late seventeenth/ early eighteenth–century European (possibly Basque) and Inuit occupations at Hare Harbor, Petit Mécatina Island, 200 km west of the Strait of Belle Isle. The later historic occupation includes hearths, middens, and ballast piles from adjacent land and underwater sites. In addition to domestic cooking hearths and ballast piles associated with the sixteenth-century Basque occupation, the site’s later component contains two structures with paved stone floors, one interpreted as a cookhouse and the other as a blacksmith shop. The ethnic/national origin of these structures, which in earlier reports was designated as Basque on the basis of coarse earthenwares and large amounts of roof tiles, is now equivocal. Excavations in 2009 revealed a sixteenth-century Basque component adjacent to and deeper than the cookhouse (Structure 1) paved floor, raising the possibility that the cookhouse and blacksmith deposits may have a north Biscayan or Channel origin. Excavation also revealed a Labrador Inuit settlement that may be contemporary with the later European occupation. Information recovered from the European and Inuit contexts documents changing economic, social, and political conditions, including the appearance of Inuit in the Gulf of St. Lawrence and their participation in a European cod fishery at Hare Harbor. Given the breadth of activity, changes in technology and economy, and complex international and ethnic relations, a maritime landscape approach that links shore deposits with those from the underwater site over a period of more than 100 years provides a useful framework for interpreting the many strands of evidence from this small but fascinating site situated at the interface of European and Native nations, cultures, and traditions. Utilization of the landscape concept for interpreting maritime anthropology and archaeological sites is relatively novel. Landscape archaeology has traditionally been applied at terrestrial sites to link archaeological components with their broader ecological and social settings, including subsistence resource zones, site hierarchies, settlement patterns, and regional economic networks. Recently, this concept has been extended to maritime anthropological studies in circumpolar and subantarctic settings, but it has rarely been a component of underwater archaeological inquiry. The fortuitous adjacency of both land and marine components at a Basque/European/Inuit site makes Hare Harbor an ideal case study for exploring the utility of the landscape approach in a maritime archaeology context

Magnetic resonance imaging for quantitative assessment of lung aeration: A pilot translational study

Background: Computed tomography is the gold standard for lung aeration assessment, but exposure to ionizing radiation limits its application. We assessed the ability of magnetic resonance imaging (MRI) to detect changes in lung aeration in ex vivo isolated swine lung and the potential of translation of the findings to human MRI scans. Methods: We performed MRI scans in 11 isolated non-injured and injured swine lungs, as well as 6 patients both pre- and post-operatively. Images were obtained using a 1.5 T MRI scanner, with T1 - weighted volumetric interpolated breath-hold examination (VIBE) and T2 - weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences. We scanned swine lungs, with reference samples of water and muscle, at different airway pressure levels: 0, 40, 10, 2 cmH2O. We investigated the relations between MRI signal intensity and both lung density and gas content fraction. We analyzed patients' images according to the findings of the ex vivo model. Results: In the ex vivo samples, the lung T1 - VIBE signal intensity normalized to water or muscle reference signal correlated with lung density (r2 = 0.98). Thresholds for poorly and non-aerated lung tissue, expressed as MRI intensity attenuation factor compared to the deflated lung, were estimated as 0.70 [95% CI: 0.65-0.74] and 0.28 [95% CI: 0.27-0.30], respectively. In patients, dorsal versus ventral regions had a higher MRI signal intensity both pre- and post-operatively (p = 0.031). Comparing post- versus pre-operative scans, lung volume decreased (p = 0.028), while the following increased: MRI signal intensity in ventral (p = 0.043) and dorsal (p < 0.0001) regions, and percentages of non-aerated (p = 0.028) and poorly aerated tissue volumes (p = 0.028). Conclusion: Magnetic resonance imaging signal intensity is a function of lung density, decreasing linearly with increasing gas content. Lung MRI might be useful for estimating lung aeration. Compared to CT, this technique is radiation-free but requires a longer acquisition time and has a lower spatial resolution

The Peritoneal Surface Proteome in a Model of Chronic Peritoneal Dialysis Reveals Mechanisms of Membrane Damage and Preservation

Peritoneal dialysis (PD) fluids are cytotoxic to the peritoneum. Recent studies have shown that alanyl-glutamine (AlaGln) modulates the cellular stress response, improves mesothelial cell survival, reduces submesothelial thickening in experimental models of PD, and in clinical studies improves PD effluent cell stress and immune responses. However, the mechanisms of AlaGln-mediated membrane protection are not yet fully understood. Here, we explore those mechanisms through application of a novel proteomics approach in a clinically relevant in vivo model in rats. Experimental PD was performed for 5 weeks using conventional single-chamber bag (SCB) or neutral dual-chamber bag (DCB), PD fluid (PDF), with or without AlaGln supplementation, via a surgically implanted catheter. Rats subjected to a single dwell without catheter implantation served as controls. The peritoneal surface proteome was directly harvested by detergent extraction and subjected to proteomic analysis by two-dimensional difference gel electrophoresis (2D-DiGE) with protein identification by mass spectrometry. An integrated bioinformatic approach was applied to identify proteins significantly affected by the treatments despite biological variation and interfering high abundance proteins. From 505 of 744 common spots on 59 gels, 222 unique proteins were identified. Using UniProt database information, proteins were assigned either as high abundance plasma proteins, or as cellular proteins. Statistical analysis employed an adapted workflow from RNA-sequencing, the trimmed mean of M-values (TMM) for normalization, and a mixed model for computational identification of significantly differentially abundant proteins. The most prominently enriched pathways after 5 weeks chronic treatment with SCB or DCB, PDFs belonged to clusters reflecting tissue damage and cell differentiation by cytoskeletal reorganization, immune responses, altered metabolism, and oxidative stress and redox homeostasis. Although the AlaGln effect was not as prominent, associated enriched pathways showed mostly regression to control or patterns opposite that of the PDF effect. Our study describes the novel peritoneal surface proteome through combined proteomic and bioinformatic analyses, and assesses changes elicited by chronic experimental PD. The biological processes so identified promise to link molecular mechanisms of membrane damage and protection in the in vivo rat model to pathomechanisms and cytoprotective effects observed in vitro and in clinical PD

Targeted Metabolomic Profiling of Peritoneal Dialysis Effluents Shows Anti-oxidative Capacity of Alanyl-Glutamine

Readily available peritoneal dialysis (PD) effluents from PD patients in the course of renal replacement therapy are a potentially rich source for molecular markers for predicting clinical outcome, monitoring the therapy, and therapeutic interventions. The complex clinical phenotype of PD patients might be reflected in the PD effluent metabolome. Metabolomic analysis of PD effluent might allow quantitative detection and assessment of candidate PD biomarkers for prognostication and therapeutic monitoring. We therefore subjected peritoneal equilibration test effluents from 20 stable PD patients, obtained in a randomized controlled trial (RCT) to evaluate cytoprotective effects of standard PD solution (3.86% glucose) supplemented with 8 mM alanyl-glutamine (AlaGln) to targeted metabolomics analysis. One hundred eighty eight pre-defined metabolites, including free amino acids, acylcarnitines, and glycerophospholipids, as well as custom metabolic indicators calculated from these metabolites were surveyed in a high-throughput assay requiring only 10 μl of PD effluent. Metabolite profiles of effluents from the cross-over trial were analyzed with respect to AlaGln status and clinical parameters such as duration of PD therapy and history of previous episodes of peritonitis. This targeted approach detected and quantified 184 small molecules in PD effluent, a larger number of detected metabolites than in all previous metabolomic studies in PD effluent combined. Metabolites were clustered within substance classes regarding concentrations after a 4-h dwell. PD effluent metabolic profiles were differentiated according to PD patient sub-populations, revealing novel changes in small molecule abundance during PD therapy. AlaGln supplementation of PD fluid altered levels of specific metabolites, including increases in alanine and glutamine but not glutamate, and reduced levels of small molecule indicators of oxidative stress, such as methionine sulfoxide. Our study represents the first application of targeted metabolomics to PD effluents. The observed metabolomic changes in PD effluent associated with AlaGln-supplementation during therapy suggested an anti-oxidant effect, and were consistent with the restoration of important stress and immune processes previously noted in the RCT. High-throughput detection of PD effluent metabolomic signatures and their alterations by therapeutic interventions offers new opportunities for metabolome-clinical correlation in PD and for prescription of personalized PD therapy

The Structural Basis of Gas-Responsive Transcription by the Human Nuclear Hormone Receptor REV-ERBβ

Heme is a ligand for the human nuclear receptors (NR) REV-ERBα and REV-ERBβ, which are transcriptional repressors that play important roles in circadian rhythm, lipid and glucose metabolism, and diseases such as diabetes, atherosclerosis, inflammation, and cancer. Here we show that transcription repression mediated by heme-bound REV-ERBs is reversed by the addition of nitric oxide (NO), and that the heme and NO effects are mediated by the C-terminal ligand-binding domain (LBD). A 1.9 Å crystal structure of the REV-ERBβ LBD, in complex with the oxidized Fe(III) form of heme, shows that heme binds in a prototypical NR ligand-binding pocket, where the heme iron is coordinately bound by histidine 568 and cysteine 384. Under reducing conditions, spectroscopic studies of the heme-REV-ERBβ complex reveal that the Fe(II) form of the LBD transitions between penta-coordinated and hexa-coordinated structural states, neither of which possess the Cys384 bond observed in the oxidized state. In addition, the Fe(II) LBD is also able to bind either NO or CO, revealing a total of at least six structural states of the protein. The binding of known co-repressors is shown to be highly dependent upon these various liganded states. REV-ERBs are thus highly dynamic receptors that are responsive not only to heme, but also to redox and gas. Taken together, these findings suggest new mechanisms for the systemic coordination of molecular clocks and metabolism. They also raise the possibility for gas-based therapies for the many disorders associated with REV-ERB biological functions

Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo.

In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction of Th1 cells resulted in a significant amelioration of colitis. The effect of antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th cells that were generated by an acute immune reaction to nitrophenylacetyl-coupled chicken gamma globulin (NP-CGG) were not affected by treatment with antagomir-148a, both during the effector and the memory phase. In addition, antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic inflammation without affecting the protective immunological memory