Loess stratigraphy in Dutch and Belgian Limburg

Ziel dieser Veröffentlichung ist es, für einen Abschnitt entlang des Albert Kanals in Niederländisch und Belgisch Limburg eine Übersicht zur Lössstratigraphie zu erstellen. Die Arbeit gründet sich vor allem auf Feldaufnahmen und Schwermineralanalysen. An Talhängen und zwischen Flussterrassen kam es zur Sedimentation und Erhaltung mächtiger, reich gegliederter Lössablagerungen. Die Wände des Albert Kanals, Lössaufschlüsse im angrenzenden Gebiet und vier große archäologische Ausgrabungen wurden untersucht. Auf Grund von charakteristischen lithologischen und paläopedologischen Leithorizonten, mineralogischen und chronologischen Daten und deren Korrelation mit Lössaufschlüssen in Hessen wurde eine lössstratigraphische Übersicht für die Zeit seit dem Holstein-Interglazial erstellt, welche sich mit Ozean- und Eisisotopenabfolgen sowie mit festländischen Pollenzonen korrelieren lassen. Es lassen sich vier glaziale Lösszyklen und fünf interglaziale Paläoböden auf der Rothem Terrasse der Maas ausmachen.researc

Evidence of Presence of the Eltville Tuff Layer in Dutsch and Belgian Limbourg and the Consequences for the Loess Stratigraphy

Anfang 1979 ist zum ersten Male in den Niederlanden ein vulkanischer Tuff in den Lößablagerungen von Süd-Limburg gefunden worden (Meijs 1980a). Auf Grund der stratigraphischen Lage, des makroskopischen Aussehens und der mineralogischen Zusammensetzung wurde dieser Tuff mit dem Eltviller Tuff korreliert. In dieser Veröffentlichung werden die Korrelierungsbeweisgründe eingehend behandelt und mit den Ergebnissen mikromorphologischer und röntgenologischer Untersuchungen ergänzt. Die Entdeckung des Eltviller Tuffs in dieser Region gerade unter dem Kesselt-Paläoboden (= Nagelbeek Horizont) bedeutet, daß dieser Paläoboden ein stratigraphisches Äquivalent des E4-Naßbodens ist. Dieses steht im Widerspruch mit der in Belgien und den Niederlanden herrschenden Ansicht, laut der der Kesselt-Paläoboden mit dem im Denekamp Interstadial geformten Stillfried-B Paläoboden korreliert wird (z. B. Zagwijn & Paepe 1968). Der letztgenannte Paläoboden liegt aber stratigraphisch unter dem Eltviller Tuff und ist ungefähr 10.000 Jahr älter als der E4-Naßboden (Semmel 1967, Vogel & van der Hammen 1967).researc

Loci influencing blood pressure identified using a cardiovascular gene-centric array

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.</p

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Preliminary Excavation Report on the Middle Palaeolithic Valley Settlements at Veldwezelt-Hezerwater (prov. of Limburg)

Voorlopig opgravingsrapport van de middenpaleolithische valleinederzettingen te Veldwezelt-Hezerwater (prov. Limburg) Het laboratorium voor prehistorie aan de Katholieke Universiteit te Leuven organiseerde in 1998, 1999, 2000 & 2001 vier archeologische opgravingscampagnes in de leemgroeve van de N.V. Vandersanden in Veldwezelt-Hezerwater. De opgravingen werden uitgevoerd in nauwe samenwerking met het Instituut voor het Archeologisch Patrimonium (IAP) van de Vlaamse Gemeenschap en het Provinciaal Gallo-Romeins Museum te Tongeren. De succesvolle opgravingen die te Veldwezelt-Hezerwater georganiseerd werden, leverden de voorbije jaren archeologische resten op van vermoedelijk tenminste vijf verschillende kampen van de Neanderthaler die in de vallei van het Hezerwater, een bijriviertje van de Maas, gelegen waren

Loci influencing blood pressure identified using a cardiovascular gene-centric array.

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P &lt; 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention