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Many processes in living cells involve interaction and cooperation of multiple proteins to fulfill a specific function. To understand biological processes in their full complexity, it is not sufficient to only identify the molecules being involved but also to understand the kinetic aspects of a reaction. Mass spectrometry (MS) is a very powerful tool which allows to precisely identify the molecules of a reaction. Usually this is done with tandem-MS experiments for purpose of de-novo peptide sequencing. However, since this involves protein digestion, a statement of the in-vivo constitution of non-covalently bound protein complexes is not possible. In order to detect an intact protein complex it is necessary to analyze the biological system softly and in a near-native environment with native MS. Native MS allows the non-destructive analysis of these non-covalent protein complexes as well as to detect their components. However, up to now native MS does not offer a possibility to resolve the timing of the constitution of protein complexes on a fast time-scale. Therefore, the progress of reactions on fast time-scales is invisible. However, a method which delivers both types of information - identification of the components of a protein complex, as well as time-resolving their interaction - would be of high interest.
A suitable ionization technique for native MS is laser-induced liquid-bead ion desorption (LILBID). LILBID employs well-defined droplets which are irradiated by IR laser pulses to generate gas phase ions. The not-continuous, repetitive nature of ion generation offers itself to the development of a time-resolved (TR) native MS system which is able to investigate protein complexes on a fast time scale. The LILBID-droplets can serve as reaction vessels if they are levitated in an electrodynamic Paul-trap. This new setup would allow sample manipulation and MS analysis on precise and fast reaction time-scales. The first part of this dissertation presents the construction and characterization of a setup for TR-LILBID-MS.
An example for a complex biological system is the self-assembly of beta-amyloid (Aβ). This small peptide is the major component in plaques related to Alzheimer’s disease. Clinically relevant is especially the 42 amino acid peptide Aβ42 which aggregates from monomers to oligomers through to fibrils. The oligomers are the neurotoxic species in this process and thus of high interest. Nevertheless, standard analytical techniques are unable to detect those oligomers which makes MS an optimal tool to study the oligomerization process of Aβ with the focus on disease relevant oligomers. TR-LILBID-MS allows to follow the oligomerization of Aβ enabling to study molecules which influence this kinetic. Combining MS with ion-mobility spectrometry adds an additional dimension - the collision cross section - to the mass-to-charge ratio obtained from MS. Therewith structural alterations induced by ligands can be correlated to differences in the aggregation kinetic. This allows to draw a picture of the aggregation process of Aβ for the development of disease-relevant small oligomers on a molecular level.
Die in der vorliegenden Arbeit gewonnenen Erkenntnisse zur Reaktivität zweifach reduzierter 9,10-Dihydro-9,10-diboraanthracene [A]2– erweitern das Einsatzspektrum von Hauptgruppenverbindungen im Hinblick auf die Aktivierung kleiner Moleküle. Komplementär zu Übergangsmetallkomplexen und FLPs ermöglichen die Salze M2[A] (M+ = Li+, Na+, K+) die Entwicklung neuartiger Synthesestrategien. Als besondere Herausforderung gilt die Aktivierung des stabilen H2-Moleküls, dessen Bindung die Dianionen [A]2– homolytisch in einer konzertierten Reaktion spalten.
Untersuchungen zur Kinetik der H2-Addition an M2[A] stellten die Abhängigkeit dieses Reaktionsschritts vom borgebundenen Substituenten und vom Kation heraus. Eine geringe sterische Abschirmung der Boratome durch kleine borgebundene Substituenten (C≡CtBu, Me, H) begünstigt die H2-Aufnahme gegenüber großen Substituenten (pTol, Xyl, Et). Die maximale Ausbeute an M2[A-H2] wird für M+ = Li+ erst nach mehreren Tagen bei 100 °C erhalten, während einige Stunden bei nur 50 °C für die quantitative Bildung von K2[A-H2] ausreichen.
Unter den Salzen M2[A] eignet sich Li2[68] mit borgebundenen Me-Substituenten besonders gut für den Einsatz als Hydrierungskatalysator. Mit Li2[68] konnten das Imin Ph(H)C=NtBu, das terminale Alken Ph2C=CH2 und Anthracen erfolgreich im NMR-Maßstab hydriert werden (Katalysatorladung 37 mol%, THF-d8, 1 atm H2-Initialdruck, 100 °C, 16 h). Im Reaktionsautoklaven war für die Hydrierung von Ph(H)C=NtBu eine Verringerung der Katalysatorladung auf 10 mol% Li2[68] möglich (THF, 7 atm H2-Initialdruck, 100 °C, 18 h). Konkurrenzreaktionen begründen Einschränkungen in Bezug auf die Substratpalette, da M2[68] (M+ = Li+, Na+) mit elektronenarmen ungesättigten Verbindungen, die C=C-, C≡C-, C=O- oder C=N-Bindungen enthalten, [4+2]-Cycloadditionsprodukte bilden können. Die Reversibilität dieser Reaktion entscheidet, ob Li2[68] als Katalysator fungiert oder irreversibel in den Strukturen gebunden bleibt.
Vielseitiger sind die H2-Aktivierungsprodukte M2[A-H2] als H–-Donoren geeignet: Na2[68-H2] ersetzt Halogenid- durch H–-Substituenten in Bromethan, sowie in Chlorsilanen und PCl3; CO2 wird in Natriumformiat überführt. Unabhängig von der Anzahl der Chlorliganden werden die Produkte immer vollständig hydriert. Eine erneute Reduktion von 68 kann wieder Na2[68] bereitstellen, das H2 aufnimmt und Na2[68-H2] regeneriert, welches für neue H–-Abgaben zur Verfügung steht. Bei der experimentellen Umsetzung des Kreislaufs ist es wichtig, die beschriebenen Reaktionsschritte nacheinander auszuführen und jeweils nur stöchiometrische Mengen des Elektrophils zuzugeben. Bei Abweichungen vom schrittweisen Syntheseprotokoll finden formale nukleophile Substitutionen mit M2[68] statt und monoanionische Spezies entstehen, z. B. wenn Et3SiBr als Elektrophil anwesend ist.
Gegenüber CO2 zeigt Li2[68] eine hohe Reaktivität, durch die selektiv CO und [CO3]2– gebildet werden. Wie zuvor bei den H–-Transferreaktionen ermöglicht die Reduktion der Neutralverbindung 68 die Regeneration von Li2[68].
Die Dianionen [A]2– stechen unter anderen cyclischen Borverbindungen in niedrigen Oxidationsstufen heraus, da mit [A]2– nicht nur die Aktivierung von H2 oder CO2 gelang, sondern erstmalig über die Einbindung der Additionsprodukte in zum Teil katalytische Folgereaktionen berichtet werden konnte.
Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
Purpose: Bacterial biofilms are a major problem in the treatment of infected dental and orthopedic implants. The purpose of this study is to investigate the cleaning effect of an electrolytic approach (EC) compared to a powder-spray system (PSS) on titanium surfaces. Materials and Methods: The tested implants (different surfaces and alloys) were collated into six groups and treated ether with EC or PSS. After a mature biofilm was established, the implants were treated, immersed in a nutritional solution, and streaked on Columbia agar. Colony-forming units (CFUs) were counted after breeding and testing (EC), and control (PSS) groups were compared using a paired sample t-test. Results: No bacterial growth was observed in the EC groups. After thinning to 1:1,000,000, 258.1 ± 19.9 (group 2), 264.4 ± 36.5 (group 4), and 245.3 ± 40.7 (group 6) CFUs could be counted in the PSS groups. The difference between the electrolytic approach (test groups 1, 3, and 5) and PSS (control groups 2, 4, and 6) was statistically extremely significant (p-value < 2.2 × 10−16). Conclusion: Only EC inactivated the bacterial biofilm, and PSS left reproducible bacteria behind. Within the limits of this in vitro test, clinical relevance could be demonstrated.
Formation of the anteroposterior and dorsoventral body axis in Caenorhabditis elegans depends on cortical flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar asymmetries are established during left-right symmetry breaking: Centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) from contacts to the medial cortex, resulting in their unmixing from apical myosin. Contact localization and advection of PAR-6 requires balanced CDC-42 activation, while asymmetric retention and advection of PAR-3 can occur independently of PAR-6. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1 and opposing retention of antagonistic CDC-42 and Wnt pathway components leads to planar asymmetries. The most obvious mark of planar asymmetry, retention of PAR-3 at a single cell-cell contact, is required for proper cytokinetic cell intercalation. Hence, our data uncover how planar polarity is established in a system without the canonical planar cell polarity pathway through planar asymmetric retention of aPARs.
Die Dissertation (Universität Eichstätt-Ingolstadt) beginnt mit dem Satz "Am Ende stritt man um Akten" und endet auf Seite 483 mit eben dem gleichen Satz. Zwischen Anfang und Ende dieser akribisch gearbeiteten Publikation, die Denzler bescheiden eine "Studie" nennt, werden die massenweise in den Archiven vorhandenen Akten, die während der letzten Visitation des Reichskammergerichts von 1767–1776 produziert wurden, nach ihrer Entstehung und Funktion untersucht. Als Leitbild der Untersuchung dient der "Reformhorizont" der Aufklärung, vor dessen Hintergrund das Visitationsgeschehen in Gestalt seiner Hand- und Druckschriften analysiert wird. "Reform"-zeiten, -räume, -akteure, -verfahren sowie -inhalte geben dem engagiert geschriebenen Buch eine klare Gliederung für die Untersuchung aller Schriftgattungen von den Protokollen, Schreiben, Diktaten, Abschriften, Diarien, Korrespondenzen, Instruktionen, Berichten bis zu Gutachten und Notizen, die alle das Visitationsgeschehen in und als "Akten" repräsentieren: 562 Aktenbündel; von 1056 Sitzungen sind 13 Bände Beratungsprotokolle überliefert, die 15732 Folioseiten umfassen; 50 Visitationsbeschlüsse liegen vor; die schriftlichen Befragungen von 92 Gerichtsmitgliedern ergaben 25000 Antworten (355, 478); hinzu kommen noch die Produktion aus der visitationseigenen Druckerei sowie 200 Einzelpublikationen zur Visitation und eine visitationseigene Zeitschrift als schriftliches Untersuchungsmaterial. Daraus entsteht ein höchst umfassendes und anschauliches Bild über Medientechnik, Schriftkultur, Justizkontrolle und Dienstaufsicht im Rahmen der Visitation. Aus dem quantitativen Befund in diesem "tintenklecksenden Saeculum", wie es Schiller genannt hat, leitet Denzler die These ab, dass die Visitation von 1767 eine enorme Vermehrung und Aufwertung von Schriftlichkeit schlechthin dokumentiert (16). Vor diesem Hintergrund soll die alltägliche Bedeutung der Schriftlichkeit für die Visitation analysiert und der "Entstehungs- und Überlieferungskontext" möglichst genau im "Schriftalltag" rekonstruiert werden. Dieser "Schriftalltag" reflektiert auch den Justizalltag in seiner rechtshistorischen Bedeutung. Diesen zu beschreiben ist zwar nicht Denzlers vorrangiges Ziel, aber die Kulturgeschichte des Geschriebenen beleuchtet und ergänzt die Geschichte der Rechtspraxis am Beispiel der Visitation von 1767 in vielfältiger Weise. Das belegen auch das reiche Quellen- und Literaturverzeichnis (489–562) und die Statistiken über Personalia, Visitationskosten, Examina, Gesandtschaftsquartiere, Verfahren usw. (565–604). ...
A twentieth century-long coupled atmosphere-ocean regional climate simulation with COSMO-CLM (Consortium for Small-Scale Modeling, Climate Limited-area Model) and NEMO (Nucleus for European Modelling of the Ocean) is studied here to evaluate the added value of coupled marginal seas over continental regions. The interactive coupling of the marginal seas, namely the Mediterranean, the North and the Baltic Seas, to the atmosphere in the European region gives a comprehensive modelling system. It is expected to be able to describe the climatological features of this geographically complex area even more precisely than an atmosphere-only climate model. The investigated variables are precipitation and 2 m temperature. Sensitivity studies are used to assess the impact of SST (sea surface temperature) changes over land areas. The different SST values affect the continental precipitation more than the 2 m temperature. The simulated variables are compared to the CRU (Climatic Research Unit) observational data, and also to the HOAPS/GPCC (Hamburg Ocean Atmosphere Parameters and Fluxes from Satellite Data, Global Precipitation Climatology Centre) data. In the coupled simulation, added skill is found primarily during winter over the eastern part of Europe. Our analysis shows that, over this region, the coupled system is dryer than the uncoupled system, both in terms of precipitation and soil moisture, which means a decrease in the bias of the system. Thus, the coupling improves the simulation of precipitation over the eastern part of Europe, due to cooler SST values and in consequence, drier soil.
Libra – a global virtual currency project initiated by Facebook – has been the subject of many controversial discussions since its announcement in June 2019. This paper provides a differentiated view on Libra, recognising that different development scenarios of Libra are conceivable.
Libra could serve purely as an alternative payment system in combination with a dedicated payment token, the Libra coin. Alternatively, the Libra project could develop into a broader financial infrastructure for advanced financial services such as savings and loan products operating on the Libra blockchain. Based on a comparison of the Libra architecture with other cryptocurrencies, the opportunities and challenges for the development of the respective Libra ecosystems are investigated form a commercial, regulatory and monetary policy perspective.
Wir lassen die überwältigende Fülle an Werken im Arsenale hinter uns. Das Ziel sind die Giardini, der ursprüngliche und neben dem Arsenale zweite große Ausstellungsort der Kunstschau. Dort befindet sich einer der Hauptanziehungspunkte der Biennale: Im Zentralpavillon steht die in den Medien bereits oft erwähnte und gezeigte sogenannte "Blutmaschine". Ein riesiger Roboterarm mit überdimensionaler Wischschaufel, wirkt sie in ihrer Motorik dennoch ausgesprochen menschlich. Die 32 Bewegungen, die das chinesische Künstlerduo Sun Yuan und Peng Yu dem Industrieroboter "in den Leib" programmiert haben, erinnern an Winken, Tanzen, Po-Wackeln, Innehalten und Überlegen. ...
Local crowding out in China
(2019)
In China, between 2006 and 2013, local public debt crowded out the investment of private firms by tightening their funding constraints, while leaving state-owned firms’ investment unaffected. We establish this result using a purpose-built dataset for Chinese local public debt. Private firms invest less in cities with more public debt, the reduction in investment being larger for firms located farther from banks in other cities or more dependent on external funding. Moreover, in cities where public debt is high, private firms’ investment is more sensitive to internal cash flow, also when cash-flow sensitivity is estimated jointly with the probability of being credit-constrained.
Of the hepatic cell lines developed for in vitro studies of hepatic functions as alternatives to primary human hepatocytes, many have lost major liver-like functions, but not HepaRG cells. The increasing use of the latter worldwide raises the need for establishing the reference functional status of early biobanked HepaRG cells. Using deep proteome and secretome analyses, the levels of master regulators of the hepatic phenotype and of the structural elements ensuring biliary polarity were found to be close to those in primary hepatocytes. HepaRG cells proved to be highly differentiated, with functional mitochondria, hepatokine secretion abilities, and an adequate response to insulin. Among differences between primary human hepatocytes and HepaRG cells, the factors that possibly support HepaRG transdifferentiation properties are discussed. The HepaRG cell system thus appears as a robust surrogate for primary hepatocytes, which is versatile enough to study not only xenobiotic detoxification, but also the control of hepatic energy metabolism, secretory function and disease-related mechanisms.
We analyze debt and debt management of Americans nearing retirement age. We show that older people have numerous financial obligations that can lead to financial distress. Using data from the 2015 National Financial Capability Study and an extensive literature review, we show that lack of financial literacy, lack of information, and behavioral biases help explain the prevalence of debt later in life. Our evidence indicates that debt at older ages can negatively influence retirement well-being.
Den Visitationen am Reichskammergericht (RKG) wurden in letzter Zeit zwei unterschiedliche wissenschaftliche Untersuchungen gewidmet. Während Alexander Denzler den Aussagewert medialer Schriftkultur im "Schriftalltag" am Beispiel der letzten Visitation des RKGs (1767–1776) untersucht hat,1 widmet sich Anette Baumann als quellenversierte langjährige Leiterin der "Forschungsstelle der Gesellschaft für Reichskammergerichtsforschung" in Wetzlar den Visitationen von 1529–1588.2 Sie werden von ihr als "Expertentreffen" von Juristen interpretiert, die auch für das Verfassungsverständnis im Alten Reich bedeutsam sind. Das tragende Quellenmaterial bildet – neben einschlägiger Sekundärliteratur – vor allem der reiche Korrespondenz- und Aktenbestand im Wiener Haus-, Hof- und Staatsarchiv in Gestalt von Visitationsabschieden, Protokollen, Korrespondenzen, Vollmachten, Gutachten, Voten, Ladungen, Instruktionen, Gravamina, Fragebögen, persönlichen Notizen, Schreiben, Berichten und Augenscheinkarten,3 die das analysierte Schriftgut der Visitationen repräsentieren. Mit Hilfe einer erstellten Datenbank, die übrigens verschiedenen Forschungsinstitutionen – darunter auch dem MPI für europäische Rechtsgeschichte – zur Verfügung steht, ist es Baumann möglich, in den Beständen gezielt "nach Visitationsbelangen zu suchen" (17). Ziel ihrer gründlichen Untersuchung ist es, die Arbeit der Visitationskommission (VK) in dem "komplexen Kommunikationsprozess" (5) aufzuhellen, in dessen Mittelpunkt die VK stand – eingebettet in das Beziehungsgeflecht zwischen Kaiser, Reichsständen, Reichstag und Reichskammergericht (RKG). Durch die Reichskammergerichtsordnung von 1521 war die Kommission erstmals als "Visitation" reichsgesetzlich eingesetzt worden, um als Kontrollorgan einerseits das RKG finanziell zu sichern und andererseits die Abstellung von "Gebrechen" zu garantieren, d.h. das Gericht arbeitsfähig zu machen und zu erhalten. Die VK war somit eine Institution des Alten Reiches, die ursprünglich zur jährlichen Kontrolle bestimmt war. Eingesetzt von Kaiser und Reichsständen stand sie im Spannungsverhältnis politischer und konfessioneller Konstellationen auf dem Reichstag. Folgerichtig legt Baumann ihre Untersuchung auch weniger als Institutionengeschichte an, sondern als eine Darstellung von Reichsverfassungspraxis am Beispiel der VK. Aus dem reichen Archivmaterial werden die "Kommunikationsprozesse" herausdestilliert, um auf verfassungsmäßige Regelhaftigkeiten als Ordnungskategorien der Visitationsverfahren schließen zu können. Dabei stellt sich immer die Frage, ob die beobachteten Verfahren zu rechtlicher "Verfassung" geronnen sind oder sich noch im vorrechtlichen Raum ritualisierter Verfasstheit bewegen. So gesehen bietet das geschilderte Geschehen um die und in der VK einen Blick in das Laboratorium über die Entwicklung rechtlicher und politischer Regelungs- und Verfassungsprozesse. ...
Over the life-cycle, wealth holdings tend to be highest in the early part of retirement. The quality of financial decisions among older adults is therefore an important determinant of their financial security during the asset drawdown phase. This paper assesses how financial literacy shapes financial decision-making at older ages. We devised a special module in the Singapore Life Panel survey to measure financial literacy to study its relationship with three aspects of household financial and investment behaviors: credit card debt repayment, stock market participation, and adherence to age-based investment glide paths. We found that the majority of respondents age 50+ has some grasp of concepts such as interest compounding and inflation, but fewer know about risk diversification. We provide evidence of a statistically significant positive association between financial literacy and each of the three aspects of suboptimal financial decision-making, controlling for many other factors, including education. A one-unit increase in the financial literacy score was associated with an 8.3 percentage point greater propensity to hold stocks, and a 1.7 percentage point higher likelihood of following an age-appropriate investment glide path. The financial literacy score is only weakly positively linked with timely credit card balance repayment, both in terms of statistical significance and estimate size.
This collection edited by Dave De ruysscher, Albrecht Cordes, Serge Dauchy and Heikki Pihlajamäki considers what size or varieties of business were considered to be the best. The answer to this question depends on the time period under examination, and it also differs between jurisdictions. The chapters in the collection take a broad approach as they collectively cover a long time span and have a wide geographical spread. They consider examples from the Middle Ages, the early modern period and the 19th century. The places examined here are now in the jurisdictions of Germany, Italy, Belgium, Spain and England. As a whole, the chapters address some of the tension between the perceived advantages and disadvantages of big business against the small and medium enterprises (SMEs) and also the limited liability corporation in comparison to the unlimited liability partnership form. The edited collection takes a deliberately integrative approach, as it combines concepts and ideas from legal studies with those of economic history, business studies and comparative political analysis. ...
Many Americans claim Social Security benefits early, though this leaves them with lower benefits throughout retirement. We build a lifecycle model that closely tracks claiming patterns under current rules, and we use it to predict claiming delays if, by delaying benefits, people received a lump sum instead of an annuity. We predict that current early claimers would defer claiming by a year given actuarially fair lump sums, and the predictions conform with respondents’ answers to a strategic survey about the lump sum. In other words, such a reform could provide an avenue for encouraging delayed retirement without benefit cuts or tax increases. Moreover, many people would still defer claiming even for smaller lump sums.
We show that firm liability structure and associated cash flow matter for firm behavior, and that financial market participants price stocks accordingly. Looking at firm level stock price changes around monetary policy announcements, we find that firms that have more cash flow exposure see their stock prices affected more. The stock price reaction depends on the maturity and type of debt issued by the firm, and the forward guidance provided by the Fed. This effect has remained intact during the ZLB period. Importantly, we show that the effect is not a rule of thumb behavior outcome and that the marginal stock market participant actually studies and reacts to the liability structure of firm balance sheets. The cash flow exposure at the time of monetary policy actions predicts future net worth, investment, and assets, verifying the stock pricing decision and also providing evidence of cash flow effects on firms' real behavior. The results hold for S&P500 firms that are usually thought of not being subject to tight financial constraints.
A common prediction of macroeconomic models of credit market frictions is that the tightness of financial constraints is countercyclical. As a result, theory implies a negative collateralizability premium; that is, capital that can be used as collateral to relax financial constraints provides insurance against aggregate shocks and commands a lower risk compensation compared with non-collateralizable assets. We show that a longshort portfolio constructed using a novel measure of asset collateralizability generates an average excess return of around 8% per year. We develop a general equilibrium model with heterogeneous firms and financial constraints to quantitatively account for the collateralizability premium.
Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis
(2019)
Background: Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated.
Methods: Therefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein.
Results: While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001).
Conclusions: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis.
Trial registration: ClinicalTrials.gov identifier: NCT03584204.
Aims: The examination of histological sections is still the gold standard in diagnostic pathology. Important histopathological diagnostic criteria are nuclear shapes and chromatin distribution as well as nucleus-cytoplasm relation and immunohistochemical properties of surface and intracellular proteins. The aim of this investigation was to evaluate the benefits and drawbacks of three-dimensional imaging of CD30+ cells in classical Hodgkin Lymphoma (cHL) in comparison to CD30+ lymphoid cells in reactive lymphoid tissues.
Materials and results: Using immunoflourescence confocal microscopy and computer-based analysis, we compared CD30+ neoplastic cells in Nodular Sclerosis cHL (NScCHL), Mixed Cellularity cHL (MCcHL), with reactive CD30+ cells in Adenoids (AD) and Lymphadenitis (LAD). We confirmed that the percentage of CD30+ cell volume can be calculated. The amount in lymphadenitis was approx. 1.5%, in adenoids around 2%, in MCcHL up to 4,5% whereas the values for NScHL rose to more than 8% of the total cell cytoplasm. In addition, CD30+ tumour cells (HRS-cells) in cHL had larger volumes, and more protrusions compared to CD30+ reactive cells. Furthermore, the formation of large cell networks turned out to be a typical characteristic of NScHL.
Conclusion: In contrast to 2D histology, 3D laser scanning offers a visualisation of complete cells, their network interaction and spatial distribution in the tissue. The possibility to differentiate cells in regards to volume, surface, shape, and cluster formation enables a new view on further diagnostic and biological questions. 3D includes an increased amount of information as a basis of bioinformatical calculations.