TCR Translocations at the Normal-malignant T Cell Interface

Hematopoiesis is the process leading to production and maturation of peripheral blood cells. All blood cells are derived from hematopoietic stem cells (HSCs) which reside in hematopoietic organs. In mammals, the site of hematopoiesis changes during development, which is sequentially taking place in different organs starting with primitive erythrocytes in the yolk sac, the aorta-gonad mesonephros (AGM) region, the fetal lever, and finally the bone marrow (BM) during adulthood. Blood cells are short-lived, and with a daily demand for more than a billion new hematopoietic cells, a continuous replenishment of progenitor cells committed to specific hematopoietic lineages is required. HSCs are at the top of the hematopoietic hierarchy, and are the only source of progenitors. HSCs comprise 0.005-0.01% of the bone marrow, and their unique properties, i.e. the ability of self-renewal and multi-lineage differentiation potential in combination with a specific stem cell microenvironment/ niche, enable these cells to sustain the hematopoietic system. These cells differentiate into progenitor cells, either into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP), which in due course differentiate into mature blood cells, providing cells to the myeloid or lymphoid system respectively 6. CLPs carry the potential to give rise to B cells, T cells (via the thymus) and NK cells, whereas CMPs have the potential to differentiate into erythrocytes, megakaryocytes, macrophages, and granulocytes. Dendritic cells can arise from both progenitor types. The process of hematopoietic lineage determination is tightly regulated by the BM microenvironment’s extrinsic factors, such as growth factors and cytokines mediated by cell-cell interactions, which sustain survival and proliferation of committed cells. Equally important in determining cell fate are the lineage- and cell-type-specific gene expression signatures (intrinsic factors). These signatures are based on the up and down regulation of transcription factors apparently regulated by the epigenetic-micro RNAs regulatory circuit. The strict regulation of both extrinsic and intrinsic signals is of utmost importance, as deregulation of the expression of these factors could result in hematopoietic malignancies such as leukemia or lymphoma. Such deregulation of gene expression is usually caused by irreversible molecular-cytogenetic changes introduced into the genomic DNA sequence. These changes can be caused by mutations, translocations and deletions concerning genes involved in cell cycle, differentiation, proliferation, and self-renewal processes. During the last decade it has become evident that, next to genetic aberrations, epigenetic alterations can also contribute to tumorigenesis, for example through gene silencing due to aberrant methylation.

Distributed optical fibre sensing for high space‐time resolution ocean velocity observations: A case study From a macrotidal channel

Despite significant recent technological advances, oceanographic observations on horizontal scales of meters to a few kilometres prove challenging. Exploiting legacy seafloor cables presents a disruptive prospect to address this gap, as it may provide low-cost sustained observations with high space-time resolution, enabled through novel opto-electronic interrogation of optical fibers within the cables. Here, we demonstrate this approach in a renewable tidal energy cable embedded within a region with a strong barotropic tide. By making remote measurements continuously over 12 hr, we obtain the distributed differential strain experienced by 2 km of offshore cable from a diverse range of oceanic flow processes, with an along-cable resolution of 2.04 m. We successfully identify: (a) nearshore wave breaking and its modulation by changes in water depth; (b) along-cable tidal velocity, shown to be linearly related to the differential strain; and (c) high-frequency motions consistent with 3-dimensional turbulent processes, either of natural origin or from flow-cable interaction. These inferences are supported by nearby conventional measurements of water depth and velocity

Observation of a large lee wave in the Drake Passage

Lee waves are thought to play a prominent role in Southern Ocean dynamics, facilitating a transfer of energy from the jets of the Antarctic Circumpolar Current to microscale, turbulent motions important in water mass transformations. Two EM-APEX profiling floats deployed in the Drake Passage during the Diapycnal and Isopycnal Mixing Experiment (DIMES) independently measured a 120 ± 20-m vertical amplitude lee wave over the Shackleton Fracture Zone. A model for steady EM-APEX motion is developed to calculate absolute vertical water velocity, augmenting the horizontal velocity measurements made by the floats. The wave exhibits fluctuations in all three velocity components of over 15 cm s−1 and an intrinsic frequency close to the local buoyancy frequency. The wave is observed to transport energy and horizontal momentum vertically at respective peak rates of 1.3 ± 0.2 W m−2 and 8 ± 1 N m−2. The rate of turbulent kinetic energy dissipation is estimated using both Thorpe scales and a method that isolates high-frequency vertical kinetic energy and is found to be enhanced within the wave to values of order 10−7 W kg−1. The observed vertical flux of energy is significantly larger than expected from idealized numerical simulations and also larger than observed depth-integrated dissipation rates. These results provide the first unambiguous observation of a lee wave in the Southern Ocean with simultaneous measurements of its energetics and dynamics

The imprint of Southern Ocean overturning on seasonal water mass variability in Drake Passage

Seasonal changes in water mass properties are discussed in thermohaline coordinates from a seasonal climatology and repeat hydrographic sections. The SR1b CTD transects along Drake Passage are used as a case study. The amount of water within temperature and salinity classes and changes therein are used to estimate dia-thermal and dia-haline transformations. These transformations are considered in combination with climatologies of surface buoyancy flux to determine the relative contributions of surface buoyancy fluxes and subsurface mixing to changes in the distribution of water in thermohaline coordinates. The framework developed provides unique insights into the thermohaline circulation of the water masses that are present within Drake Passage, including the erosion of Antarctic Winter Water (AAWW) during the summer months and the interaction between the Circumpolar Deep Waters (CDW) and Antarctic Intermediate Water (AAIW). The results presented are consistent with summertime wind-driven inflation of the CDW layer and deflation of the AAIW layer, and with new AAIW produced in the winter as a mixture of CDW, remnant AAWW, and surface waters. This analysis therefore highlights the role of surface buoyancy fluxes in the Southern Ocean overturning

Ocean mixing beneath Pine Island Glacier ice shelf, West Antarctica

Ice shelves around Antarctica are vulnerable to an increase in ocean-driven melting, with the melt rate depending on ocean temperature and the strength of flow inside the ice-shelf cavities. We present measurements of velocity, temperature, salinity, turbulent kinetic energy dissipation rate, and thermal variance dissipation rate beneath Pine Island Glacier ice shelf, West Antarctica. These measurements were obtained by CTD, ADCP, and turbulence sensors mounted on an Autonomous Underwater Vehicle (AUV). The highest turbulent kinetic energy dissipation rate is found near the grounding line. The thermal variance dissipation rate increases closer to the ice-shelf base, with a maximum value found ∼0.5 m away from the ice. The measurements of turbulent kinetic energy dissipation rate near the ice are used to estimate basal melting of the ice shelf. The dissipation-rate-based melt rate estimates is sensitive to the stability correction parameter in the linear approximation of universal function of the Monin-Obukhov similarity theory for stratified boundary layers. We argue that our estimates of basal melting from dissipation rates are within a range of previous estimates of basal melting

Mesoscale eddy dissipation by a “zoo” of submesoscale processes at a western boundary

Mesoscale eddies are ubiquitous dynamical features that tend to propagate westward and disappear along ocean western boundaries. Using a multiscale observational study, we assess the extent to which eddies dissipate via a direct cascade of energy at a western boundary. We analyze data from a ship‐based microstructure and velocity survey, and an 18‐month mooring deployment, to document the dissipation of energy in anticyclonic and cyclonic eddies impinging on the topographic slope east of the Bahamas, in the North Atlantic Ocean. These observations reveal high levels of turbulence where the steep and rough topographic slope modified the intensified northward flow associated with, in particular, anticyclonic eddies. Elevated dissipation was observed both near‐bottom and at mid depths (200–800 m). Near‐bottom turbulence occurred in the lee of a protruding escarpment, where elevated Froude numbers suggest hydraulic control. Energy was also radiated in the form of upward‐propagating internal waves. Elevated dissipation at mid depths occurred in regions of strong vertical shear, where the topographic slope modified the vertical structure of the northward eddy flow. Here, low Richardson numbers and a local change in the isopycnal gradient of potential vorticity (PV) suggest that the elevated dissipation was associated with horizontal shear instability. Elevated mid‐depth dissipation was also induced by topographic steering of the flow. This led to large anticyclonic vorticity and negative PV adjacent to the topographic slope, suggesting that centrifugal instability underpinned the local enhancement in dissipation. Our results provide a mechanistic benchmark for the realistic representation of eddy dissipation in ocean models

Dissipation of mesoscale eddies at a western boundary via a direct energy cascade

The fate of mesoscale eddy kinetic energy represents a large source of uncertainty in the global ocean energy budget. Satellite altimetry suggests that mesoscale eddies vanish at ocean western boundaries. However, the fate of the eddies’ kinetic energy remains poorly known. Here we show that the generation of small-scale turbulence as eddy flow impinges on the steep and corrugated slope of an ocean western boundary plays a dominant role in the regional decay of mesoscale eddy kinetic energy. We compare altimetry-based estimates of mesoscale eddy kinetic energy decline with measurements of turbulent dissipation. Mesoscale eddies are found to decay at a rate of 0.016 ± 0.012 GW and 0.023 ± 0.017 GW for anticyclonic and cyclonic eddies, respectively, similar to the observed turbulent dissipation rate of 0.020 ± 0.011 GW. This demonstrates that a major direct transfer of mesoscale eddy kinetic energy to small, dissipative scales can be effectively triggered by the eddies’ interaction with the western boundary topography

Antarctic circumpolar current impacts on internal wave life cycles

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 48(8), (2021): e2020GL089471, https://doi.org/10.1029/2020GL089471.Major gaps exist in our understanding of the pathways between internal wave generation and breaking in the Southern Ocean, with important implications for the distribution of internal wave-driven mixing, the sensitivity of ocean mixing rates and patterns to changes in the ocean environment, and the necessary ingredients of mixing parameterizations. Here we assess the dominant processes in internal wave evolution by characterizing wave and mesoscale flow scales based on full-depth in situ measurements in a Southern Ocean mixing hot spot and a ray tracing calculation. The exercise highlights the importance of Antarctic Circumpolar Current jets as a dominant influence on internal wave life cycles through advection, the modification of wave characteristics via wave-mean flow interactions, and the set-up of critical layers for both upward- and downward-propagating waves. Our findings suggest that it is important to represent mesoscale flow impacts in parameterizations of internal wave-driven mixing in the Southern Ocean.The SOFine project was funded by the UK Natural Environmental Research Council (NERC) (grant NE/G001510/1). S. Waterman is currently supported by the National Science and Engineering Research Council of Canada (NSERC) Discovery Grant Program (NSERC-2020-05799). A. Meyer acknowledges current support from the ARC Centre of Excellence for Climate Extremes (CE170100023) and previous support from the joint CSIRO-University of Tasmania Quantitative Marine Science (QMS) program. A. N. Garabato acknowledges the support of the Royal Society and the Wolfson Foundation

Seasonal variability of sea surface height in the coastal waters and deep basins of the Nordic Seas

Sea surface height measured by the Envisat radar altimeter over open ocean and from leads in sea ice are combined to generate a complete view of variability in the Nordic Seas, geographically and seasonally. The observed seasonal variability is decomposed using empirical orthogonal functions, and is consistent with seasonal variations in steric and dynamic forcing. Wintertime increase in sea surface height on the east Greenland shelf is hypothesised to be caused by wind-forced downwelling, which provides direct evidence for the regional play of coastal dynamics. High levels of eddy kinetic energy around the sea ice edge in Fram Strait, and off east Greenland and Svalbard are consistent with the interaction of the wind with the ice edge

Internal waves and turbulence in the Antarctic Circumpolar Current

Author Posting. © American Meteorological Society, 2013. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 43 (2013): 259–282, doi:10.1175/JPO-D-11-0194.1.This study reports on observations of turbulent dissipation and internal wave-scale flow properties in a standing meander of the Antarctic Circumpolar Current (ACC) north of the Kerguelen Plateau. The authors characterize the intensity and spatial distribution of the observed turbulent dissipation and the derived turbulent mixing, and consider underpinning mechanisms in the context of the internal wave field and the processes governing the waves’ generation and evolution. The turbulent dissipation rate and the derived diapycnal diffusivity are highly variable with systematic depth dependence. The dissipation rate is generally enhanced in the upper 1000–1500 m of the water column, and both the dissipation rate and diapycnal diffusivity are enhanced in some places near the seafloor, commonly in regions of rough topography and in the vicinity of strong bottom flows associated with the ACC jets. Turbulent dissipation is high in regions where internal wave energy is high, consistent with the idea that interior dissipation is related to a breaking internal wave field. Elevated turbulence occurs in association with downward-propagating near-inertial waves within 1–2 km of the surface, as well as with upward-propagating, relatively high-frequency waves within 1–2 km of the seafloor. While an interpretation of these near-bottom waves as lee waves generated by ACC jets flowing over small-scale topographic roughness is supported by the qualitative match between the spatial patterns in predicted lee wave radiation and observed near-bottom dissipation, the observed dissipation is found to be only a small percentage of the energy flux predicted by theory. The mismatch suggests an alternative fate to local dissipation for a significant fraction of the radiated energy.SW acknowledges the support of the Grantham Institute for Climate Change, Imperial College London. ACNG acknowledges the support of a NERC Advanced Research Fellowship (Grant NE/C517633/1). KLP acknowledges support from Woods Hole Oceanographic Institution bridge support funds.2013-08-0