189 research outputs found
Site-specific recombinatorics : in situ cellular barcoding with the Cre Lox system
Background: Cellular barcoding is a recently developed biotechnology tool that enables the familial identification of progeny of individual cells in vivo. In immunology, it has been used to track the burst-sizes of multiple distinct responding T cells over several adaptive immune responses. In the study of hematopoiesis, it revealed fate heterogeneity amongst phenotypically identical multipotent cells. Most existing approaches rely on ex vivo viral transduction of cells with barcodes followed by adoptive transfer into an animal, which works well for some systems, but precludes barcoding cells in their native environment such as those inside solid tissues. Results: With a view to overcoming this limitation, we propose a new design for a genetic barcoding construct based on the Cre Lox system that induces randomly created stable barcodes in cells in situ by exploiting inherent sequence distance constraints during site-specific recombination. We identify the cassette whose provably maximal code diversity is several orders of magnitude higher than what is attainable with previously considered Cre Lox barcoding approaches, exceeding the number of lymphocytes or hematopoietic progenitor cells in mice. Conclusions: Its high diversity and in situ applicability, make the proposed Cre Lox based tagging system suitable for whole tissue or even whole animal barcoding. Moreover, it can be built using established technology
Quantum optimal control in quantum technologies. Strategic report on current status, visions and goals for research in Europe
Quantum optimal control, a toolbox for devising and implementing the shapes of external fields that accomplish given tasks in the operation of a quantum device in the best way possible, has evolved into one of the cornerstones for enabling quantum technologies. The last few years have seen a rapid evolution and expansion of the field. We review here recent progress in our understanding of the controllability of open quantum systems and in the development and application of quantum control techniques to quantum technologies. We also address key challenges and sketch a roadmap for future developments
Quantum optimal control in quantum technologies. Strategic report on current status, visions and goals for research in Europe
Quantum optimal control, a toolbox for devising and implementing the shapes
of external fields that accomplish given tasks in the operation of a quantum
device in the best way possible, has evolved into one of the cornerstones for
enabling quantum technologies. The last few years have seen a rapid evolution
and expansion of the field. We review here recent progress in our understanding
of the controllability of open quantum systems and in the development and
application of quantum control techniques to quantum technologies. We also
address key challenges and sketch a roadmap for future developments.Comment: this is a living document - we welcome feedback and discussio
Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells
The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo
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The 1430s: a cold period of extraordinary internal climate variability during the early Spörer Minimum with social and economic impacts in north-western and central Europe
Changes in climate affected human societies throughout the last millennium. While European cold periods
in the 17th and 18th century have been assessed in detail, earlier cold periods received much less attention due to sparse information available. New evidence from proxy archives, historical documentary sources and climate model simulations permit us to provide an interdisciplinary, systematic assessment of an exceptionally cold period in the 15th century. Our assessment includes the role of internal, unforced climate variability and external forcing in shaping extreme climatic conditions and the impacts on and responses of the medieval society in north-western and central Europe. Climate reconstructions from a multitude of natural and anthropogenic archives indicate that the 1430s were the coldest decade in north-western and central Europe in the 15th century. This decade is characterised by cold winters and average to warm summers resulting in a strong seasonal cycle in temperature. Results from comprehensive climate models indicate consistently that these conditions occurred by chance due to the partly chaotic internal variability within the climate system. External forcing like volcanic eruptions tends to reduce simulated temperature seasonality and cannot explain the reconstructions. The strong seasonal cycle in temperature reduced food production and led to increasing food prices, a subsistence crisis and a famine in parts of Europe. Societies were not prepared to cope with failing markets and interrupted trade routes. In response to the crisis, authorities implemented numerous measures of supply policy and adaptation such as the installation of grain storage capacities to be prepared for future food production shortfalls
MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing
Conditional knockout mouse strategies identify the histone methyltranferase MLL2 as a key player in epigenetic reprogramming of female gametes
Differences Between Household Income from Surveys and Registers and How These Affect the Poverty Headcount: Evidence from the Austrian SILC
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
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