Arctic Ocean evidence for late Quaternary initiation of northern Eurasian ice sheets

A high-resolution multiparameter stratigraphy allows the identification of late Quaternary glacial and interglacial cycles in a central Arctic Ocean sediment core. Distinct sandy layers in the upper part of the otherwise fine-grained sediment core from the Lomonosov Ridge (lat 87.5°N) correlate to four major glacials since ca. 0.7 Ma. The composition of these ice-rafted terrigenous sediments points to a glaciated northern Siberia as the main source. In contrast, lithic carbonates derived from North America are also present in older sediments and indicate a northern North American glaciation since at least 2.8 Ma. We conclude that large-scale northern Siberian glaciation began much later than other Northern Hemisphere ice sheets

Arctic Ocean evidence for late Quaternary initiation of northern Eurasian ice sheets

A high-resolution multiparameter stratigraphy allows the identification of late Quaternary glacial and interglacial cycles in a central Arctic Ocean sediment core. Distinct sandy layers in the upper part of the otherwise fine-grained sediment core from the Lomonosov Ridge (lat 87.5°N) correlate to four major glacials since ca. 0.7 Ma. The composition of these ice-rafted terrigenous sediments points to a glaciated northern Siberia as the main source. In contrast, lithic carbonates derived from North America are also present in older sediments and indicate a northern North American glaciation since at least 2.8 Ma. We conclude that large-scale northern Siberian glaciation began much later than other Northern Hemisphere ice sheets

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

<p>Abstract</p> <p>Background</p> <p>DNA methylation in the <it>SHOX2 </it>locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with <it>SHOX2 </it>gene expression and/or copy number alterations. An amplification of the <it>SHOX2 </it>gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.</p> <p>Methods</p> <p><it>SHOX2 </it>expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect <it>SHOX2 </it>DNA methylation levels. <it>SHOX2 </it>expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.</p> <p>Results</p> <p>A hypermethylation of the <it>SHOX2 </it>locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the <it>SHOX2 </it>gene showed no difference.</p> <p>Conclusions</p> <p>Frequent gene amplification correlated with hypermethylation of the <it>SHOX2 </it>gene locus. This concerted effect qualifies <it>SHOX2 </it>DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.</p

Morphometrical Validation Of Histopathological Synovitis-Score

GesamtdissertationDie Diagnostik der Synovialitiden ist seit vielen Jahren klinisch definiert. Histopathologische Befunde an Synovektomiepräparaten oder Synovialisbiopsien spielen bei Diagnose und Therapie keine wesentliche Rolle. Trotz immer wieder festgestellter grundsätzlicher Diskrepanzen zwischen histopathologischem Befund und Schweregrad des Krankheitsbildes gibt es jedoch auch Hinweise auf Zusammenhänge zwischen Pathohistologie, Genese und Ausprägung einer Synovialitis. Neu entwickelt wurde ein histopathologisches Gradingsystem, das am Routine-HE Präparat drei Kriterien berücksichtigt, die jeweils mit Punktwerten von 0-3 bewertet werden, sodaß sich ein Summenscore von 0-9 ergibt (Synovitis-Score). Die Punktwerte werden geschätzt, eine genaue Quantifizierung erfolgte bisher nicht. Der Summenscore wird einem Entzündungsgrad zugeordnet, wobei 0-1 Punkt dem Entzündungsgrad 0, 2-3 Punkte dem Entzündungsgrad 1, 4-6 Punkte dem Entzündungsgrad 2 und 7-9 Punkte dem Entzündungsgrad 3 entsprechen. Der Entzündungsgrad korreliert mit verschiedenen Krankheitsbildern, wobei niedrige Scorewerte bei reaktiven Synovialitiden und Osteoarthritis beobachtet werden und hohe Scorewerte (ab einem Summenscore 5) bei rheumatoider Synovitis oder bei Psoriasisarthritis vorkommen. In der vorliegenden Arbeit wurde der geschätzte, semiquantitative Synovitis-Score quantifiziert. Methodisch wurde die computergestützte Bildanalyse (CAIA, computer assisted image analysis) eingesetzt. Abhängig vom untersuchten Merkmal kamen dabei primär automatisierte Verfahren nach selbstgeschriebenen Algorithmen oder interaktive Methoden zur Anwendung. Insgesamt wurden 2555 Einzelmessungen (EM) durchgeführt. 1549 EM waren automatisiert durchgeführte Operationen, 1006 EM wurden interaktiv angewandt. Entzündliche Infiltrate wurden in 887 EM quantifiziert, die Stromazelldichte in 524 EM, immunhistologische Überprüfungen wurden 138 mal durchgeführt. Deckzellschichtdicke (802 EM), Größe der Gewebsstücke (102 EM) und Größe der Nekrosen (102 EM) wurden interaktiv ermittelt. Die semiquantitativen Einschätzungen der Untersucher wurden bestätigt. Bei niedrigen und mittleren Entzündungsgraden ergaben sich keine signifikanten Unterschiede zwischen geschätzten Entzündungsgraduierungen und per CAIA gemessenen Entzündungsgraduierungen (n=52, p<0,01). Bei hohen Entzündungsgraden waren konventionell erhobener Synovitis-Score und CAIA-Score voneinander verschieden (n=18, p<0,01), was an einem hohen Anteil von high grade Entzündungen in der Gruppe 2 lag. Vergleicht man die high grade Entzündungen des CAIA-Scores der Gruppe 2 mit dem konventionellen Score, so ergibt sich eine Übereinstimmung von 17/18 Fällen (94,4%) hinsichtlich der biologischen Wertigkeit, sodaß auch bei den hohen Entzündungsgraden hinsichtlich der biologischen Wertigkeit eine hohe Übereinstimmung besteht.Die geschätzten Punktwerte und die Summenscores wurden somit hinsichtlich ihrer Aussage zur Genese einer Synovialitis bestätigt. Bei den Messungen fiel auf, daß bei höheren Summenwerten auch häufig vermehrt fibrinoide Nekrosen vorhanden waren. Eine Korrelation mit den Krankheitsbildern ergab, daß fibrinoide Nekrosen signifikant mit rheumatoider Arthritis und Psoriasiaarthritis assoziiert waren. Dieser Befund wurde bisher nicht im Synovitis-Score aufgenommen. Es erscheint ratsam, den Synovitis-Score um einen Punkt anzuheben, wenn Nekrosen mehr als 25% der Gewebefläche einnehmen.The diagnosis of synovitis is predominantly clinical defined as yet. Histopathological reports are more or less nonrelevant in diagnosis and therapy. A new grading system, which can be performed on routine HE-sections, enables the classification as low synovitis, moderate synovitis or strong synovitis and the correlation to reactive synovitis or destructive synovitis (rheumtoid arthritis, psoriatic arthritis). Three criteria (enlargement of synovial lining cell layer, activation of synovial stroma, inflammatory infiltrate) are rated with points from 0 to 3, adding of points leads to the synovitis-score and to the inflammatory grade. The synovitis-score and the inflammatory grade was therefore estimated until now. In order to validate the score, computer assisted image analysis was performed on 70 specimen in more than 2500 measurements. The estimation of the investigators were confirmed, the estimated synovitis-scores and inflammatory grades were verified concerning the genesis of synovitis

Intellectual Property Protection and Sustainability - Keys to Crowdfunding Success?

This study uses signaling theory to examine how intellectual property protection and sustainability influence the success of reward-based crowdfunding campaigns. Beyond that, we study how sustainability moderates the relationship between signaling quality through intellectual property protection and crowdfunding success. To test our hypotheses, we create a novel measure for intellectual property protection by using Machine-learning-based content analyses to build an intellectual property protection dictionary and then apply this dictionary to analyze 22,310 campaigns from the reward-based crowdfunding platform IndieGoGo between March 2015 and February 2023. Our findings from regression analyses suggest that signaling mechanisms conveyed through intellectual property protection embedded in campaign descriptions or sustainability indicated by campaign categories show a significant and positive relationship with crowdfunding success. However, sustainability emerges as a nuanced moderating influence, tempering the positive relationship between quality signals through intellectual property protection and crowdfunding success

Arctic Ocean evidence for late Quaternary initiation of northern Eurasian sheets

A high-resolution multiparameter stratigraphy allows the identification of late Quaternary glacial and interglacial cycles in a central Arctic Ocean sediment core. Distinct sandy layers in the upper part of the otherwise fine-grained sediment core from the Lomonosov Ridge (lat 87.5°N) correlate to four major glacials since ca. 0.7 Ma. The composition of these ice-rafted terrigenous sediments points to a glaciated northern Siberia as the main source. In contrast, lithic carbonates derived from North America are also present in older sediments and indicate a northern North American glaciation since at least 2.8 Ma. We conclude that large-scale northern Siberian glaciation began much later than other Northern Hemisphere ice sheets