272 research outputs found
Integrated Detector Control and Calibration Processing at the European XFEL
The European X-ray Free Electron Laser is a high-intensity X-ray light source
currently being constructed in the area of Hamburg, that will provide spatially
coherent X-rays in the energy range between and
. The machine will deliver ,
consisting of up to , with a
repetition rate. The LPD, DSSC and AGIPD detectors are being developed to
provide high dynamic-range Mpixel imaging capabilities at the mentioned
repetition rates. A consequence of these detector characteristics is that they
generate raw data volumes of up to . In addition the
detector's on-sensor memory-cell and multi-/non-linear gain architectures pose
unique challenges in data correction and calibration, requiring online access
to operating conditions and control settings. We present how these challenges
are addressed within XFEL's control and analysis framework Karabo, which
integrates access to hardware conditions, acquisition settings (also using
macros) and distributed computing. Implementation of control and calibration
software is mainly in Python, using self-optimizing (py) CUDA code, numpy and
iPython parallels to achieve near-real time performance for calibration
application.Comment: Proceeding ICALEPS 201
Action–effect anticipation in infant action control
There is increasing evidence that action effects play a crucial role in action understanding and action control not only in adults but also in infants. Most of the research in infants focused on the learning of action–effect contingencies or how action effects help infants to infer goals in other persons’ actions. In contrast, the present research aimed at demonstrating that infants control their own actions by action–effect anticipation once they know about specific action–effect relations. About 7 and 9-month olds observed an experimenter demonstrating two actions that differed regarding the action–effect assignment. Either a red-button press or a blue-button press or no button press elicited interesting acoustical and visual effects. The 9-month olds produced the effect action at first, with shorter latency and longer duration sustaining a direct impact of action–effect anticipation on action control. In 7-month olds the differences due to action–effect manipulation were less profound indicating developmental changes at this age
Characterization of the Interaction between the Cohesin Subunits Rad21 and SA1/2
The cohesin complex is responsible for the fidelity of chromosomal segregation during mitosis. It consists of four core
subunits, namely Rad21/Mcd1/Scc1, Smc1, Smc3, and one of the yeast Scc3 orthologs SA1 or SA2. Sister chromatid cohesion
is generated during DNA replication and maintained until the onset of anaphase. Among the many proposed models of the
cohesin complex, the ï¾’coreï¾’ cohesin subunits Smc1, Smc3, and Rad21 are almost universally displayed as tripartite ring.
However, other than its supportive role in the cohesin ring, little is known about the fourth core subunit SA1/SA2. To gain
deeper insight into the function of SA1/SA2 in the cohesin complex, we have mapped the interactive regions of SA2 and
Rad21 in vitro and ex vivo. Whereas SA2 interacts with Rad21 through a broad region (301ï¾–750 aa), Rad21 binds to SA
proteins through two SA-binding motifs on Rad21, namely N-terminal (NT) and middle part (MP) SA-binding motif, located
At 60-81 aa of the N-terminus and 383ï¾–392 aa of the MP of Rad21, respectively. The MP SA-binding motif is a 10 amino acid,
a-helical motif. Deletion of these 10 amino acids or mutation of three conserved amino acids (L385, F389, and T390) in this ahelical
motif significantly hinders Rad21 from physically interacting with SA1/2. Besides the MP SA-binding motif, the NT SAbinding
motif is also important for SA1/2 interaction. Although mutations on both SA-binding motifs disrupt Rad21-SA1/2
interaction, they had no apparent effect on the Smc1-Smc3-Rad21 interaction. However, the Rad21-Rad21 dimerization was
reduced by the mutations, indicating potential involvement of the two SA-binding motifs in the formation of the two-ring
handcuff for chromosomal cohesion. Furthermore, mutant Rad21 proteins failed to significantly rescue precocious
chromosome separation caused by depletion of endogenous Rad21 in mitotic cells, further indicating the physiological
significance of the two SA-binding motifs of Rad21
Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis
The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection
CAST solar axion search with 3^He buffer gas: Closing the hot dark matter gap
The CERN Axion Solar Telescope (CAST) has finished its search for solar
axions with 3^He buffer gas, covering the search range 0.64 eV < m_a <1.17 eV.
This closes the gap to the cosmological hot dark matter limit and actually
overlaps with it. From the absence of excess X-rays when the magnet was
pointing to the Sun we set a typical upper limit on the axion-photon coupling
of g_ag < 3.3 x 10^{-10} GeV^{-1} at 95% CL, with the exact value depending on
the pressure setting. Future direct solar axion searches will focus on
increasing the sensitivity to smaller values of g_a, for example by the
currently discussed next generation helioscope IAXO.Comment: 5 pages, 2 figures. Last version uploade
Enteropathogenic Escherichia coli (EPEC) inactivate innate immune responses prior to compromising epithelial barrier function
Enteropathogenic Escherichia coli (EPEC) infection of the human small intestine induces severe watery diarrhoea linked to a rather weak inflammatory response despite EPEC's in vivo capacity to disrupt epithelial barrier function. Here, we demonstrate that EPEC flagellin triggers the secretion of the pro-inflammatory cytokine, interleukin (IL)-8, from small (Caco-2) and large (T84) intestinal epithelia model systems. Interestingly, IL-8 secretion required basolateral infection of T84 cells implying that flagellin must penetrate the epithelial barrier. In contrast, apical infection of Caco-2 cells induced IL-8 secretion but less potently than basolateral infections. Importantly, infection of Caco-2, but not T84 cells rapidly inhibited IL-8 secretion by a mechanism dependent on the delivery of effectors through a translocation system encoded on the locus of enterocyte effacement (LEE). Moreover, EPEC prevents the phosphorylation-associated activation of multiple kinase pathways regulating IL-8 gene transcription by a mechanism apparently independent of LEE-encoded effectors and four non-LEE-encoded effectors. Crucially, our studies reveal that EPEC inhibits the capacity of the cells to secrete IL-8 in response to bacterial antigens and inflammatory cytokines prior to disrupting barrier function by a distinct mechanism. Thus, these findings also lend themselves to a plausible mechanism to explain the absence of a strong inflammatory response in EPEC-infected humans
Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis
The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis
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