Reconstructing Neogene surface uplift of the Alps: Integrating stable isotope paleoaltimetry and paleoclimate modelling

Paleoaltimetry - the reconstruction of the elevation of mountain ranges in the geological past - is key to understanding the geodynamic drivers of surface uplift. Simultaneously, surface uplift of Earth’s major mountain ranges redirected atmospheric flow and impacted climate globally. At a smaller scale, mountain building affects regional climate and biodiversity. Stable isotope paleoaltimetry is a powerful tool to quantify the past elevation of mountain ranges. It is based on the inverse relationship between the stable isotopic composition of meteoric waters and elevation, which is represented by the so-called isotopic lapse rate. However, variations in climatic parameters modify isotopic lapse rates and impact moisture transport over the continents and consequently affect paleoelevation reconstructions. Here, we show the results of a combined stable isotope paleoaltimetry and paleoclimate modeling approach in the European Alps. This approach allows for an improved and more realistic estimation of isotopic lapse rates, large-scale isotope-in-precipitation patterns over Europe and hence Alpine paleoaltimetry calculations. The European Alps are an ideal target for a combined paleoaltimetry - climate modeling approach, given that they are (a) one of the most-studied mountain ranges for which many geoscientific data are available, and (b) sufficiently small and oriented near-parallel to dominant atmospheric circulation patterns. The latter implies that no major global climatic changes are expected in response to Alpine surface uplift, as opposed to e.g. the Andes or the Tibet-Himalaya mountain ranges. Results from 4D-MB SPP phase 1 and 2 show that: (1) Changing the surface elevation of even a small orogen can complicate stable isotope paleoaltimetry by mixing the elevation and climate signal in a more complex way than commonly assumed. Climate models can help separate these signals and constrain surface uplift histories. (2) The Central Alps were already high during the Early and Middle Miocene, whereas the Eastern Alps were still at significantly lower elevations, thereby confirming that surface uplift propagated from west to east, as would be expected from oblique continent-continent collision. Together, the results highlight the importance and viability of this combined, interdisciplinary approach. Based on the results from 4D-MB SPP phase 1 and 2, we propose that future efforts to reconstruct surface uplift of mountain ranges follow this state-of-the-art approach, while keeping local limitations to proxy material availability and access to facilities in mind

Bacteriological quality and intake of acidified drinking water in Wistar rats is pH-dependent

The effects of acidification of drinking water on bacteriological quality and water intake in adult, male Wistar rats. was studied in 2 consecutive experiments. HCl was used to aeidify water to pH 2.5, 3.0 and 3.5. Control groups received untreatedtap or demineralized water. Acidification of water with HCl to pH 2.5 effectively prevented growth of aerobic bacteria in the drinking water bottles after a number of days, but also caused a reproducible decline in water intake when compared to untreated water. A reduced water intake may indicate disturbed wellbeing and may interfere with experimental results. Acidification to pH 3.0 also kept bacteriological counts low and did not reduce water intake when compared to rats drinkingnon-acidified water. Acidification to pH 3.5 led to high bacteriological counts after a few days. On the basis of these 2 experiments, acidification of drinking water with 1101 to pH 3.0 is advised

Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker

Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration. Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cance

When the Medium is the Message:A Meta-Analysis of Creative Media Advertising Effects

Creative media advertising is a specific type of unconventional advertising in which a regular physical object serves as a medium to carry an advertising message. To better understand the workings of this type of advertising, we conducted a meta-analysis. In this study, we explore the direct effects of creative media advertising, several moderators, and the possible underlying mechanisms. The results show that exposure to creative (versus traditional) media advertising has an overall positive effect on brand association strength and persuasion (i.e., ad attitude, brand attitude, purchase intentions, and electronic word of mouth [eWOM]). Both these effects are moderated by metaphor use, meaning that the effects are stronger when the physical object is a good metaphor for the message it carries. Furthermore, indirect (e.g., social media, printed picture) exposure to the message positively moderates the effect of creative media advertising on brand association strength but not on persuasion. Brand familiarity does not play a moderating role. Finally, a meta-analytic structural equation modeling (SEM) procedure was used to show that the main underlying mechanism of creative media advertising persuasiveness is surprise—and not perceived persuasive intent. For practitioners, this study shows that creative media ads are more effective when leveraging surprise and metaphors

Staying true with the help of others: doxastic self-control through interpersonal commitment

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective

Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer

BRCA1/2 mutation carriers diagnosed with breast cancer have a strongly elevated life-time risk of developing a contralateral tumour. We studied the contralateral breast cancer risk in 164 patients from 83 families with a proven BRCA1 mutation in relation to the age at diagnosis of the first primary breast cancer. In the actuarial outcomes after 10 years’ follow-up, 40% of the 124 BRCA1-patients diagnosed with breast cancer < 50 years had developed contralateral breast cancer, vs 12% of the 40 patients > 50 years at first diagnosis (Plogrank= 0.02). These data suggest that age at diagnosis of the first tumour should be taken into account when prophylactic mastectomy in BRCA1-patients is considered. © 2000 Cancer Research Campaig

Decrease in the orbital period of dwarf nova OY Carinae

We have measured the orbital light curve of dwarf nova OY Carinae on 8 separate occasions between 1997 September and 2005 December. The measurements were made in white light using CCD photometers on the Mt Canopus 1 m telescope. The time of eclipse in 2005 December was 168 +- 5 s earlier than that predicted by the Wood et al.(1989) ephemeris. Using the times of eclipse from our measurements and the compilation of published measurements by Pratt et al (1999) we find that the observational data are inconsistent with a constant period and indicate that the orbital period is decreasing by 5+-1 X 10^-12 s/s. This is too fast to be explained by gravitational radiation emission. It is possible that the change is cyclic with a period greater than about 80 years. This is much longer than typical magnetic activity cycles and may be due to the presence of a third object in the system. Preliminary estimates suggest that this is a brown dwarf with mass about 0.016 Msun and orbital radius >= 17 AU.Comment: 4 pages 2 figures. MNRAS submitted Final proofread version. Discussion modified with figure showing fits and residuals to models, statistical significance of fits added and minor typographical edit

Reply to Comment by Vincent et al.

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143706/1/tect20719.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143706/2/tect20719_am.pd

Miocene (23–13 Ma) continental paleotemperature record from the northern Mediterranean region (Digne-Valensole Basin, SE France) within a global climatic framework

During the Middle Miocene, the Earth’s climate transitioned from a warm phase, the Miocene Climatic Optimum (MCO, 16.9–14.7 Ma), to a colder phase associated by formation of major ice sheets on Antarctica. This climatic shift, the Middle Miocene Climatic Transition (MMCT, 14.7–13.8 Ma), considerably impacted not only the structure and formation of major ecosystems (e.g. Jimenez-Moreno & Suc, 2005) it also affected global ocean circulation (Holbourn et al., 2014), terrestrial temperatures as well as precipitation patterns (e.g. Methner et al., 2020). While the MCO and the subsequent MMCT are well described in marine records, knowledge about the magnitude and rate of terrestrial paleoclimate changes is often limited by lack of temporal resolution and reliable quantitative proxy records (Steinthorsdottir et al., 2021). Here, we present a long-term (23–13 Ma) biostratigraphically-controlled terrestrial stable (δ18O, δ13C) and clumped (Δ47) isotope paleosol carbonate record from the northern Mediterranean region (Digne-Valensole basin, SE France). When comparing the northern Mediterranean δ18O, δ13C and Δ47 record with age-equivalent counterparts from central Europe (Northern Alpine Foreland Basin, Switzerland), our Δ47 results from the Digne-Valensole basin reveal two important features: 1) Relatively warm and constant carbonate formation temperatures (ca. 30°C) for the Early Miocene (23–18.6 Ma) followed by 2) intensified temperature fluctuations with high values (ca. 37°C) at the onset of the MCO, most probably amplified by changes in seasonality of pedogenic carbonate formation. The combined Northern Alpine foreland and northern Mediterranean records display a coherent climate pattern for the Middle Miocene circum-Alpine foreland. In both records, high-amplitude, rapid changes in Δ47 temperatures (ca. 18°C within 400 ka) characterize the onset of the MCO and MMCT. We furthermore identify warm peaks during the MCO and a distinct fall in apparent Δ47-based temperatures at ca. 14 Ma that is in very good temporal agreement with oceanic isotope records and coincides with the documented global cooling following the MCT. Collectively, these data contribute to understanding of the dynamics and variability in atmospheric circulation controlling Middle to Late Miocene temperature dynamics in the Northern Mediterranean region

Molecular profiles of BRCA1-mutated and matched sporadic breast tumours: relation with clinico-pathological features

About 5–10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA1, have been identified. While distinct tumour features can be used to estimate the likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not yet possible to categorize a BRCA1 mutated tumour. The aim of the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgical breast tumour specimens. The expression profiles of 6 frozen breast tumour tissues with a proven BRCA1 gene mutation were weighed against those from 12 patients without a known family history but who had similar clinico-pathological characteristics. In addition two fibroblast cultures, the breast cancer cell-line HCC1937 and its corresponding B-lymphoblastoid cell line (heterozygous for mutation BRCA1 5382insC) and an epithelial ovarian cancer cell line (A2780) were studied. Using a high density membrane based array for screening of RNA isolated from these samples and standard algorithms and software, we were able to distinguish subgroups of sporadic cases and a group consisting mainly of BRCA1-mutated breast tumours. Furthermore this pilot analysis revealed a gene cluster that differentially expressed genes related to cell substrate formation, adhesion, migration and cell organization in BRCA1-mutated tumours compared to sporadic breast tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co