A see-saw in Pacific Subantarctic Mode Water formation driven by atmospheric modes

Subantarctic Mode Water (SAMW) in the Pacific forms in two distinct pools in the south central and southeast Pacific, which subduct into the ocean interior and impact global storage of heat and carbon. Wintertime thickness of the central and eastern SAMW pools vary predominantly out of phase with each other, by up to ±150 m between years, resulting in an interannual thickness see‐saw. The thickness in the eastern (central) pool is found to be strongly positively (negatively) correlated with both the Southern Annular Mode (SAM) and El Niño Southern Oscillation (ENSO). The relative phases of the SAM and ENSO set the SAMW thickness, with in phase reinforcing modes in 2005‐2008 and 2012‐2017 driving strong differences between the pools. Between 2008‐2012 out of phase atmospheric modes result in less coherent SAMW patterns. SAMW thickness is dominated by local formation driven by SAM and ENSO modulated wind stress and turbulent heat fluxes

Decadal-scale thermohaline variability in the Atlantic sector of the Southern Ocean

An enhanced Altimetry Gravest Empirical Mode (AGEM), including both adiabatic and diabatic trends, is developed for the Antarctic Circumpolar Current (ACC) south of Africa using updated hydrographic CTD sections, Argo data, and satellite altimetry. This AGEM has improved accuracy compared to traditional climatologies and other proxy methods. The AGEM for the Atlantic Southern Ocean offers an ideal technique to investigate the thermohaline variability over the past two decades in a key region for water mass exchanges and transformation. In order to assess and attribute changes in the hydrography of the region, we separate the changes into adiabatic and diabatic components. Integrated over the upper 2000 dbar of the ACC south of Africa, results show mean adiabatic changes of 0.16 ± 0.11°C decade−1 and 0.006 ± 0.014 decade−1, and diabatic differences of −0.044 ± 0.13°C decade−1 and −0.01 ± 0.017 decade−1 for temperature and salinity, respectively. The trends of the resultant AGEM, that include both adiabatic and diabatic variability (termed AD-AGEM), show a significant increase in the heat content of the upper 2000 dbar of the ACC with a mean warming of 0.12 ± 0.087°C decade−1. This study focuses on the Antarctic Intermediate Water (AAIW) mass where negative diabatic trends dominate positive adiabatic differences in the Subantarctic Zone (SAZ), with results indicating a cooling (−0.17°C decade−1) and freshening (−0.032 decade−1) of AAIW in this area, whereas south of the SAZ positive adiabatic and diabatic trends together create a cumulative warming (0.31°C decade−1) and salinification (0.014 decade−1) of AAIW

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

Thrombin-Activatable Fibrinolysis Inhibitor Binds To Streptococcus Pyogenes By Interacting With Collagen-Like Proteins A And B

Regulation of proteolysis is a critical element of the host immune system and plays an important role in the induction of pro- and anti-inflammatory reactions in response to infection. Some bacterial species take advantage of these processes and recruit host proteinases to their surface in order to counteract the host attack. Here we show that Thrombin-activatable Fibrinolysis Inhibitor (TAFI), a zinc-dependent procarboxypeptidase, binds to the surface of group A streptococci of an M41 serotype. The interaction is mediated by the streptococcal collagen-like surface proteins A and B (Sc1A and Sc1B), and the streptococcal-associated TAFI is then processed at the bacterial surface via plasmin and thrombin-thrombomodulin. These findings suggest an important role for TAFI in the modulation of host responses by streptococci

Thrombin-Activatable Fibrinolysis Inhibitor Binds To Streptococcus Pyogenes By Interacting With Collagen-Like Proteins A And B

Regulation of proteolysis is a critical element of the host immune system and plays an important role in the induction of pro- and anti-inflammatory reactions in response to infection. Some bacterial species take advantage of these processes and recruit host proteinases to their surface in order to counteract the host attack. Here we show that Thrombin-activatable Fibrinolysis Inhibitor (TAFI), a zinc-dependent procarboxypeptidase, binds to the surface of group A streptococci of an M41 serotype. The interaction is mediated by the streptococcal collagen-like surface proteins A and B (Sc1A and Sc1B), and the streptococcal-associated TAFI is then processed at the bacterial surface via plasmin and thrombin-thrombomodulin. These findings suggest an important role for TAFI in the modulation of host responses by streptococci

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

A passive Stokes flow rectifier for Newtonian fluids

Non-linear effects of the Navier-Stokes equations disappear under the Stokes regime of Newtonian fluid flows disallowing the fluid flow rectification. Here we show mathematically and experimentally that passive flow rectification of Newtonian fluids is obtainable under the Stokes regime of both compressible and incompressible flows by introducing nonlinearity into the otherwise linear Stokes equations. Asymmetric flow resistances arise in shallow nozzle/diffuser microchannels with deformable ceiling, in which the fluid flow is governed by a non-linear coupled fluid-solid mechanics equation. Fluid flow rectification has been demonstrated for low-Reynolds-number flows (Re ~ O(0.001)-O(1)) of common Newtonian fluids such as air, water, and alcohol. This mechanism can pave the way for regulating the low-Reynolds-number fluid flows with potential applications in precise low-flow-rate micropumps, drug delivery systems, etc

Using XDAQ in Application Scenarios of the CMS Experiment

XDAQ is a generic data acquisition software environment that emerged from a rich set of of use-cases encountered in the CMS experiment. They cover not the deployment for multiple sub-detectors and the operation of different processing and networking equipment as well as a distributed collaboration of users with different needs. The use of the software in various application scenarios demonstrated the viability of the approach. We discuss two applications, the tracker local DAQ system for front-end commissioning and the muon chamber validation system. The description is completed by a brief overview of XDAQ.Comment: Conference CHEP 2003 (Computing in High Energy and Nuclear Physics, La Jolla, CA

The CMS Event Builder

The data acquisition system of the CMS experiment at the Large Hadron Collider will employ an event builder which will combine data from about 500 data sources into full events at an aggregate throughput of 100 GByte/s. Several architectures and switch technologies have been evaluated for the DAQ Technical Design Report by measurements with test benches and by simulation. This paper describes studies of an EVB test-bench based on 64 PCs acting as data sources and data consumers and employing both Gigabit Ethernet and Myrinet technologies as the interconnect. In the case of Ethernet, protocols based on Layer-2 frames and on TCP/IP are evaluated. Results from ongoing studies, including measurements on throughput and scaling are presented. The architecture of the baseline CMS event builder will be outlined. The event builder is organised into two stages with intelligent buffers in between. The first stage contains 64 switches performing a first level of data concentration by building super-fragments from fragments of 8 data sources. The second stage combines the 64 super-fragments into full events. This architecture allows installation of the second stage of the event builder in steps, with the overall throughput scaling linearly with the number of switches in the second stage. Possible implementations of the components of the event builder are discussed and the expected performance of the full event builder is outlined.Comment: Conference CHEP0

End stage renal disease patients have a skewed T cell receptor Vβ repertoire

Background: End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed. Results: A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4 %, P < 0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing. Conclusions: ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity