Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer

Background: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. Methods: Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. Results: Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. Conclusions: This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential

Indikatoren zur Ausbildung im Hochschulbereich : Studie zum Innovationssystem Deutschlands Nr. 10-2003

Dieser Bericht wurde im Rahmen der erweiterten Berichterstattung zur technologischen Leistungsfähigkeit Deutschlands im Auftrag des Bundesministeriums für Bildung und Forschung erstellt

Bildung und Qualifikation als Grundlage der technologischen Leistungsfähigkeit Deutschlands: Bericht des Konsortiums "Bildungsindikatoren und technologische Leistungsfähigkeit"

Der Strukturwandel zur Wissens- und Dienstleistungswirtschaft führt zu einer steigenden Nachfrage nach hoch qualifizierten Erwerbstätigen, die im Innovationswettbewerb eine Schlüsselrolle spielen. Dies betrifft zentral zum einen wissenschaftlich ausgebildetes Personal für Forschung und Entwicklung - hier sind vor allem Naturwissenschaftler/innen und Ingenieur/innen gefordert -, zum anderen aber auch Personal für hochwertige Dienstleistungsfunktionen wie Produkt- und Programmplanung, Marketing, Finanzierung, Konstruktion etc., die wichtig sind, um Innovationen in Gang zu bringen und umzusetzen. Geringe Qualifikationen werden hingegen immer weniger nachgefragt. Die voranschreitende Qualifikationsintensivierung zeigt sich u. a. daran, dass in Deutschland die Zahl der Akademiker/innen in der gewerblichen Wirtschaft von 1998 bis 2007 um gut 355.000 Personen zunahm, während die der übrigen Beschäftigten im gleichen Zeitraum um ca. 770.000 zurückging. Der Akademikeranteil stieg dadurch im genannten Zeitraum von 6,9 % auf 8,6 %. Besonders für die wissensintensiven Branchen sind die akademischen Berufsgruppen, aber auch Meister/innen und Techniker/innen, von außerordentlicher Bedeutung. Während in der verarbeitenden Industrie Naturwissenschaftler/innen und Ingenieure/innen besonders gefragt sind, absorbieren die wissensintensiven Dienstleistungssparten prozentual mehr Hochqualifizierte mit nicht naturwissenschaftlich-technischen Qualifikationen. Weiterhin ist auch der Anteil der Beschäftigten mit abgeschlossener Berufsausbildung in den wissensintensiven Zweigen der gewerblichen Wirtschaft höher (78 %) als in den übrigen Bereichen (62 %)

ASSESSING THE ROLE OF THE SILOVIKI IN SHAPING NATIONAL SECURITY POLICY IN RUSSIA

This thesis examines the influence of the Siloviki, the former and current intelligence and security officials with whom Valdimir Putin surrounds himself, on Russia’s autocratic system and security policy. The relationship between Putin and the Siloviki is deeply rooted in Soviet-era practices and emphasizes loyalty to the Kremlin and centralized control. While not all Siloviki have direct access to or pull with Putin, some prominent Siloviki include Nikolai Patrushev, Sergei Naryshkin and Valery Gerasimov. This thesis shows the influence of the Siloviki in such major military operations as the annexation of Crimea in 2014, as well as the invasions of Georgia (2008) and Ukraine (2022)—although the recent battlefield failures in Ukraine have exposed weaknesses and prompted shifts in the leadership. The dominance of the Siloviki underscores a broader strategy to maintain Russia's great power status, often at the expense of the sovereignty of neighboring states. This entrenched autocratic framework, characterized by militarization and a defensive posture against perceived Western threats, is likely to persist and shape Russia's security policy for decades to come. The Siloviki's role further cements their influence and highlights the complex power dynamics within the Kremlin under Putin's leadership.Distribution Statement A. Approved for public release: Distribution is unlimited.Lt Col, German Air Forc

Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL

Decidual macrophages (DM) are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact

Grazing behavior of two Holstein dairy cow strains under organic farming conditions in Switzerland

The aim of the thesis was to test if concentrate supplementation is required in an organic, pasture-based feeding system and if concentrate supplementation influences grazing behavior. The study consisted of two trials, both with a crossover design performed on an organic farm in Switzerland with 12 Swiss Holstein cows and 12 Holstein cows of New Zealand origin. In the first trial the focus was on the impact of concentrate supplementation on milk yield and composition, grazing and rumination behavior, physical activity, and blood metabolites and the differences between the two cow strains. In the second trial the focus laid on the estimation of plant species selection by dairy cows with plant wax markers and whether differences exist between concentrates supplemented and non-supplemented cows in selection behavior. Concentrate supplementation had an impact on milk yield and composition, the time animals spent grazing, herbage dry matter intake and physical activity, but no on rumination behavior. Supplemented cows had a more stable energy status, but no indices for strong negative energy balance were recorded for non-supplemented cows, for both cow strains. In the second trial the main focus was on the estimation of herbage composition of grazing dairy cows with plant wax markers, namely alkanes, long-chain fatty acids and long-chain alcohols (LCOH). Concentrate samples, feces samples from each cow and samples from each paddock were taken and plant species were manually separated. All plant species, concentrate and feces samples were analyzed for their marker contents. Corrections of fecal recovery were calculated in relation to dosed ytterbium. The estimations of diet composition were performed with the software “EatWhat” based on non-negative least squares. Results were compared to the botanical composition with the Aitchison distance. The most accurate diet composition estimation was achieved with alkanes, LCOH and a correction of fecal recovery. No differences in selected plant composition between cow strains were recorded, but supplemented cows selected more Trifolium repens compared to non-supplemented cows. However, further studies are required to confirm the feasibility of the approach and validate the calculation of fecal recovery. Understanding the grazing behavior and the consequences of concentrate supplementation may lead to management measures that increase production efficiency and ensure animal welfare. Minor differences between cow strains indicated that both are suitable for pasture-based feeding systems. However, short-term trials cannot give a conclusion for the whole lactation, and fertility and health traits should be included

Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

Temperature, pressure, gas stoichiometry, and residence time were varied to control the yield and product distribution of the palladium-catalyzed aminocarbonylation of aromatic bromides in both a silicon microreactor and a packed-bed tubular reactor. Automation of the system set points and product sampling enabled facile and repeatable reaction analysis with minimal operator supervision. It was observed that the reaction was divided into two temperature regimes. An automated system was used to screen steady-state conditions for offline analysis by gas chromatography to fit a reaction rate model. Additionally, a transient temperature ramp method utilizing online infrared analysis was used, leading to more rapid determination of the reaction activation energy of the lower temperature regimes. The entire reaction spanning both regimes was modeled in good agreement with the experimental data

Indikatoren zur Ausbildung im Hochschulbereich: Studie zum Innovationssystem Deutschlands Nr. 10-2003

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