Modeling interannual dense shelf water export in the region of the Mertz Glacier Tongue (1992-2007)

1] Ocean observations around the Australian-Antarctic basin show the importance of coastal latent heat polynyas near the Mertz Glacier Tongue (MGT) to the formation of Dense Shelf Water (DSW) and associated Antarctic Bottom Water (AABW). Here, we use a regional ocean/ice shelf model to investigate the interannual variability of the export of DSW from the Adélie (west of the MGT) and the Mertz (east of the MGT) depressions from 1992 to 2007. The variability in the model is driven by changes in observed surface heat and salt fluxes. The model simulates an annual mean export of DSW through the Adélie sill of about 0.07 ± 0.06 Sv. From 1992 to 1998, the export of DSW through the Adélie (Mertz) sills peaked at 0.14 Sv (0.29 Sv) during July to November. During periods of mean to strong polynya activity (defined by the surface ocean heat loss), DSW formed in the Adélie depression can spread into the Mertz depression via the cavity under the MGT. An additional simulation, where ocean/ice shelf thermodynamics have been disabled, highlights the fact that models without ocean/ice shelf interaction processes will significantly overestimate rates of DSW export. The melt rates of the MGT are 1.2 ± 0.4 m yr−1 during periods of average to strong polynya activity and can increase to 3.8 ± 1.5 m/yr during periods of sustained weak polynya activity, due to the increased presence of relatively warmer water interacting with the base of the ice shelf. The increased melting of the MGT during a weak polynya state can cause further freshening of the DSW and ultimately limits the production of AABW

The role of immune checkpoints in cardiovascular disease

Immune checkpoint inhibitors (ICI) are monoclonal antibodies which bind to immune checkpoints (IC) and their ligands to prevent inhibition of T-cell activation by tumor cells. Currently, multiple ICI are approved targeting Cytotoxic T-lymphocyte antigen 4 (CTLA-4), Programmed Death Protein 1 (PD-1) and its ligand PD-L1, and Lymphocyte-activation gene 3 (LAG-3). This therapy has provided potent anti-tumor effects and improved prognosis for many cancer patients. However, due to systemic effects, patients can develop immune related adverse events (irAE), including possible life threatening cardiovascular irAE, like atherosclerosis, myocarditis and cardiomyopathy. Inhibition of vascular IC is associated with increased atherosclerotic burden and plaque instability. IC protect against atherosclerosis by inhibiting T-cell activity and cytokine production, promoting regulatory T-cell differentiation and inducing T-cell exhaustion. In addition, PD-L1 on endothelial cells might promote plaque stability by reducing apoptosis and increasing expression of tight junction molecules. In the heart, IC downregulate the immune response to protect against cardiac injury by reducing T-cell activity and migration. Here, inhibition of IC could induce life-threatening T-cell-mediated-myocarditis. One proposed purpose behind lymphocyte infiltration is reaction to cardiac antigens, caused by decreased self-tolerance, and thereby increased autoimmunity because of IC inhibition. In addition, there are several reports of ICI-mediated cardiomyopathy with immunoglobulin G expression on cardiomyocytes, indicating an autoimmune response. IC are mostly known due to their cardiotoxicity. However, t his review compiles current knowledge on mechanisms behind IC function in cardiovascular disease with the aim of providing an overview of possible therapeutic targets in prevention or treatment of cardiovascular irAEs

Nonequilibrium spectral diffusion due to laser heating in stimulated photon echo spectroscopy of low temperature glasses

A quantitative theory is developed, which accounts for heating artifacts in three-pulse photon echo (3PE) experiments. The heat diffusion equation is solved and the average value of the temperature in the focal volume of the laser is determined as a function of the 3PE waiting time. This temperature is used in the framework of nonequilibrium spectral diffusion theory to calculate the effective homogeneous linewidth of an ensemble of probe molecules embedded in an amorphous host. The theory fits recently observed plateaus and bumps without introducing a gap in the distribution function of flip rates of the two-level systems or any other major modification of the standard tunneling model.Comment: 10 pages, Revtex, 6 eps-figures, accepted for publication in Phys. Rev.

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

Cancer and heart disease:associations and relations

Emerging evidence supports that cancer incidence is increased in patients with cardiovascular (CV) disease and heart failure (HF), and patients with HF frequently die from cancer. Recently, data have been generated showing that circulating factors in relation to HF promote tumour growth and development in murine models, providing proof that a causal relationship exists between both diseases. Several common pathophysiological mechanisms linking HF to cancer exist, and include inflammation, neuro-hormonal activation, oxidative stress and a dysfunctional immune system. These shared mechanisms, in combination with risk factors, in concert may explain why patients with HF are prone to develop cancer. Investigating the new insights linking HF with cancer is rapidly becoming an exciting new field of research, and we herein review the most recent data. Besides insights in mechanisms, we call for clinical awareness, that is essential to optimize treatment strategies of patients having developed cancer with a history of HF. Finally, ongoing and future trials should strive for comprehensive phenotyping of both CV and cancer end points, to allow optimal usefulness of data, and to better describe and understand common characteristics of these two lethal diseases

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

The missing link: Predicting connectomes from noisy and partially observed tract tracing data

Our understanding of the wiring map of the brain, known as the connectome, has increased greatly in the last decade, mostly due to technological advancements in neuroimaging techniques and improvements in computational tools to interpret the vast amount of available data. Despite this, with the exception of the C. elegans roundworm, no definitive connectome has been established for any species. In order to obtain this, tracer studies are particularly appealing, as these have proven highly reliable. The downside of tract tracing is that it is costly to perform, and can only be applied ex vivo. In this paper, we suggest that instead of probing all possible connections, hitherto unknown connections may be predicted from the data that is already available. Our approach uses a 'latent space model' that embeds the connectivity in an abstract physical space. Regions that are close in the latent space have a high chance of being connected, while regions far apart are most likely disconnected in the connectome. After learning the latent embedding from the connections that we did observe, the latent space allows us to predict connections that have not been probed previously. We apply the methodology to two connectivity data sets of the macaque, where we demonstrate that the latent space model is successful in predicting unobserved connectivity, outperforming two baselines and an alternative model in nearly all cases. Furthermore, we show how the latent spatial embedding may be used to integrate multimodal observations (i.e. anterograde and retrograde tracers) for the mouse neocortex. Finally, our probabilistic approach enables us to make explicit which connections are easy to predict and which prove difficult, allowing for informed follow-up studies

Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats.

The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin

The Alps Paleoelevation and Paleoclimate Experiment: Reconstructing Eastward Propagation of Surface Uplift in the ALps (REAL)

Geological observations, geodynamic models, and seismic studies suggest Neogene eastward propagating surface uplift of the European Alps. Whereas 4DMB Phase I project APE focused on reconstructing surface uplift of the Central Alps, 4DMB Phase II project REAL aims at testing the predicted west-to-east surface uplift of the Alps by combining stable isotope paleoaltimetry and paleoclimate modeling. Stable isotope paleoaltimetry is based on the inverse relationship between elevation and the stable isotopic composition of meteoric water and provides a tool to reconstruct the elevation of mountain belts in the geological past. First, REAL explores applications of the δ-δ method (see Poster Phase I APE), which requires that various recorders of past rainfall are available in the rock record: soil carbonates from low-elevation (foreland) basins and hydrous minerals from high-elevation fault gouges/shear zones. Paleoelevation estimates are obtained by contrasting time-equivalent low- and high-elevation proxy data sets, provided that the isotopic composition of the fluids during mineral formation is estimated accurately. Whereas formation temperatures of fault gouge minerals (such as illite and syntectonic micas) can be readily estimated, we apply clumped isotope paleothermometry to provide robust estimates of meteoric water δ18O from the low-elevation foreland basin carbonate record. Second, meteoric water δ18O values are not only sensitive to local elevation, but also to the complex climatic changes resulting from different paleoenvironmental boundary conditions and regional topographic configuration. To isolate the contribution of each of these components δ-δ stable isotope paleoaltimetry is applied in combination with ECHAM5-wiso paleoclimate simulations for a number of topographic scenarios of diachronous surface uplift. This unique combination allows for the removal of climate change effects on the stable isotope data, and therefore improves the accuracy of paleoelevation reconstructions. Results from our ongoing Phase II project (spring 2021 - spring 2024): 1. Reveal that diachronous surface uplift would produce patterns of climate, δ18O in precipitation values, and isotopic lapse rates that are distinctly different from those of today and those produced by bulk surface uplift scenarios. Importantly, this signal would be detectable in stable isotope paleoaltimetry results (Boateng et al., in revision). 2. Present a Miocene (23–13 Ma) continental paleotemperature record from the northern Mediterranean region (Digne-Valensole basin, SE France), which indicates near-constant temperatures from 23.0-18.8 Ma, followed by a highly variable and warm climate during the Middle Miocene and rapid cooling after 14 Ma (Ballian et al., 2023). 3. Together with new and existing paleotemperature records, preliminary results of the δ-δ method show for the first time that (a) the Central Alps were already high during the Early Miocene and (b) the Eastern Alps were appreciably lower than the Central Alps during the Middle Miocene (Ballian et al., 2022)

Platform for automatic patient quality assurance via Monte Carlo simulations in proton therapy

For radiation therapy, it is crucial to ensure that the delivered dose matches the planned dose. Errors in the dose calculations done in the treatment planning system (TPS), treatment delivery errors, other software bugs or data corruption during transfer might lead to significant differences between predicted and delivered doses. As such, patient specific quality assurance (QA) of dose distributions, through experimental validation of individual fields, is necessary. These measurement based approaches, however, are performed with 2D detectors, with limited resolution and in a water phantom. Moreover, they are work intensive and often impose a bottleneck to treatment efficiency. In this work, we investigated the potential to replace measurement-based approach with a simulation-based patient specific QA using a Monte Carlo (MC) code as independent dose calculation engine in combination with treatment log files. Our developed QA platform is composed of a web interface, servers and computation scripts, and is capable to autonomously launch simulations, identify and report dosimetric inconsistencies. To validate the beam model of independent MC engine, in-water simulations of mono-energetic layers and 30 SOBP-type dose distributions were performed. Average Gamma passing ratio 99 ± 0.5% for criteria 2%/2 mm was observed. To demonstrate feasibility of the proposed approach, 10 clinical cases such as head and neck, intracranial indications and craniospinal axis, were retrospectively evaluated via the QA platform. The results obtained via QA platform were compared to QA results obtained by measurement-based approach. This comparison demonstrated consistency between the methods, while the proposed approach significantly reduced in-room time required for QA procedures