The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. ...Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies.
3-D tracking in a miniature time projection chamber Vahsen, S.E.; Hedges, M.T.; Jaegle, I. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2015, Letnik:
788, Številka:
C
Journal Article
Recenzirano
Odprti dostop
The three-dimensional (3-D) detection of millimeter-scale ionization trails is of interest for detecting nuclear recoils in directional fast neutron detectors and in direction-sensitive searches for ...weakly interacting massive particles (WIMPs), which may constitute the Dark Matter of the universe. We report on performance characterization of a miniature gas target Time Projection Chamber (TPC) where the drift charge is avalanche-multiplied with Gas Electron Multipliers (GEMs) and detected with the ATLAS FE-I3 Pixel Application Specific Integrated Circuit (ASIC). We report on measurements of gain, gain resolution, point resolution, diffusion, angular resolution, and energy resolution with low-energy X-rays, cosmic rays, and alpha particles, using the gases Ar:CO2 (70:30) and He:CO2 (70:30) at atmospheric pressure. We discuss the implications for future, larger directional neutron and Dark Matter detectors. With an eye to designing and selecting components for these, we generalize our results into analytical expressions for detector performance whenever possible. We conclude by demonstrating the 3-D directional detection of a fast neutron source.
Determination of Z coordinate from track width in MiniTPC Feng, D.C.; Garcia-Sciveres, M.; Kadyk, J.A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2017, Letnik:
851
Journal Article
Recenzirano
A gas-filled Time Projection Chamber and a radioactive neutron source were used to study recoil tracks produced by scattering of the multi-MeV neutrons on gas nuclei. Since the event readout is ...triggered by the first electron arrival, the initial time and position in the electron drift direction are unknown, leading to a translational uncertainty in this direction. By using the track width due to electron diffusion, the coordinate along the drift direction was determined. With a suitable width calibration at a known drift distance, it is found that width measurements of the track can provide useful information for establishing a well-defined gas fiducial volume for the interactions. The coordinate determination is also sufficiently precise that it can be used as a third parameter in kinematic reconstruction of the neutron collision, providing improved knowledge of the neutron collision process. Despite a wide range of track ionization levels resulting from the broad spectrum of neutron energies and varying angles of scatter, the coordinate determination is not sensitive to the track ionization.
Efforts in design and optimization of catalyst layers for polymer electrolyte fuel cells hinge on mathematical models that link electrode composition and microstructure with effective ...physico-chemical properties. A pivotal property of these layers and the focus of this work is the proton conductivity, which is largely determined by the morphology of the ionomer. However, available relations between catalyst layer composition and proton conductivity are often adopted from general theories for random heterogeneous media and ignore specific features of the microstructure, e.g., agglomerates, film-like structures, or the hierarchical porous network. To establish a comprehensive understanding of the peculiar structure-property relations, we generated synthetic volumetric images of the catalyst layer microstructure. In a mesoscopic volume element, we modeled the electrolyte phase and calculated the proton conductivity using numerical tools. Varying the ionomer morphology in terms of ionomer film coverage and thickness revealed two limiting cases: the ionomer can either form a thin film with high coverage on the catalyst agglomerates; or the ionomer exists as voluminous chunks that connect across the inter-agglomerate space. Both cases were modeled analytically, adapting relations from percolation theory. Based on the simulated data, a novel relation is proposed, which links the catalyst layer microstructure to the proton conductivity over a wide range of morphologies. The presented analytical approach is a versatile tool for the interpretation of experimental trends and it provides valuable guidance for catalyst layer design. The proposed model was used to analyze the formation of the catalyst layer microstructure during the ink stage. A parameter study of the initial ionomer film thickness and the ionomer dispersion parameter revealed that the ionomer morphology should be tweaked towards well-defined films with high coverage of catalyst agglomerates. These implications match current efforts in the experimental literature and they may thus provide direction in electrode materials research for polymer electrolyte fuel cells.
The sterol regulatory element-binding protein (SREBP) transcription factor family is a critical regulator of lipid and sterol homeostasis in eukaryotes. In mammals, SREBPs are highly active in the ...fed state to promote the expression of lipogenic and cholesterogenic genes and facilitate fat storage. During fasting, SREBP-dependent lipid/cholesterol synthesis is rapidly diminished in the mouse liver; however, the mechanism has remained incompletely understood. Moreover, the evolutionary conservation of fasting regulation of SREBP-dependent programs of gene expression and control of lipid homeostasis has been unclear. We demonstrate here a conserved role for orthologs of the NAD(+)-dependent deacetylase SIRT1 in metazoans in down-regulation of SREBP orthologs during fasting, resulting in inhibition of lipid synthesis and fat storage. Our data reveal that SIRT1 can directly deacetylate SREBP, and modulation of SIRT1 activity results in changes in SREBP ubiquitination, protein stability, and target gene expression. In addition, chemical activators of SIRT1 inhibit SREBP target gene expression in vitro and in vivo, correlating with decreased hepatic lipid and cholesterol levels and attenuated liver steatosis in diet-induced and genetically obese mice. We conclude that SIRT1 orthologs play a critical role in controlling SREBP-dependent gene regulation governing lipid/cholesterol homeostasis in metazoans in response to fasting cues. These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis.
The four receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth. Ligand ...binding triggers a conformational change in the receptor negative regulatory region (NRR) that enables ADAM protease cleavage at a juxtamembrane site that otherwise lies buried within the quiescent NRR. Subsequent intramembrane proteolysis catalysed by the -secretase complex liberates the intracellular domain (ICD) to initiate the downstream Notch transcriptional program. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer, making the Notch pathway a compelling target for new drugs. Although -secretase inhibitors (GSIs) have progressed into the clinic, GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways and cause intestinal toxicity, attributed to dual inhibition of Notch1 and 2 (ref. 11). To elucidate the discrete functions of Notch1 and Notch2 and develop clinically relevant inhibitors that reduce intestinal toxicity, we used phage display technology to generate highly specialized antibodies that specifically antagonize each receptor paralogue and yet cross-react with the human and mouse sequences, enabling the discrimination of Notch1 versus Notch2 function in human patients and rodent models. Our co-crystal structure shows that the inhibitory mechanism relies on stabilizing NRR quiescence. Selective blocking of Notch1 inhibits tumour growth in pre-clinical models through two mechanisms: inhibition of cancer cell growth and deregulation of angiogenesis. Whereas inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, inhibition of either receptor alone reduces or avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors. Our studies emphasize the value of paralogue-specific antagonists in dissecting the contributions of distinct Notch receptors to differentiation and disease and reveal the therapeutic promise in targeting Notch1 and Notch2 independently.
Over the last decade, theory and modeling have become essential tools to navigate the parameter space that governs activity and stability of electrocatalyst systems for polymer electrolyte fuel ...cells. This perspective covers essential phenomena from atomic scale to nanoscale and discusses the impact of the key parameters at play. It is centered around the development of first-principles electrochemical methods as a foremost goal in the field. The general modeling framework entails at its core a self-consistency problem that must be solved to relate the metal phase potential to descriptors of catalyst activity and stability. Density functional theory has captured a central role in this rapidly evolving field. The article puts more than usual emphasis on aspects of the multifaceted challenges in fuel cell electrocatalysis that at present lie beyond the capabilities of density functional theory; they include metal charging and solvent effects. Following the general discussion of the theoretical-computational framework, an approach for “deciphering” the oxygen reduction reaction is demonstrated; it reconciles reaction pathways and free energy profiles obtained from density functional theory simulations with kinetic modeling of surface reactions and effective kinetic parameters. Another section dwells on the importance of metal charging phenomena that are especially important for the catalytic function of nanoporous media. The penultimate section exposes the ambivalent role of Pt oxide formation in modulating catalytic properties for the oxygen reduction reaction as well as for catalyst corrosion.
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•Prospects for first principles electrochemical modeling.•Role of oxygen chemisorption and oxide formation for catalyst activity and stability.•Importance of the metal charging relation in electrocatalysis.•Theoretical methodology for deciphering the ORR.•Statistical modeling of catalyst degradation phenomena.
Messenger RNA regulation is a critical mode of controlling gene expression. Regulation of mRNA stability and translation is linked to controls of poly(A) tail length. Poly(A) lengthening can ...stabilize and translationally activate mRNAs, whereas poly(A) removal can trigger degradation and translational repression. Germline granules (for example, polar granules in flies, P granules in worms) are ribonucleoprotein particles implicated in translational control. Here we report that the Caenorhabditis elegans gene gld-2, a regulator of mitosis/meiosis decision and other germline events, encodes the catalytic moiety of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in early embryos. Importantly, the GLD-2 protein sequence has diverged substantially from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and belongs to the Bicaudal-C family of RNA binding proteins. We suggest that GLD-2 is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to specific mRNAs by a binding partner, thereby targeting those mRNAs for polyadenylation and increased expression.
Electron avalanches in liquid argon mixtures Kim, J.G.; Dardin, S.M.; Kadel, R.W. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2004, Letnik:
534, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We have observed stable avalanche gain in liquid argon when mixed with small amounts of xenon (xe) in the high electric field (
>
7
MV/cm) near the point of a chemically etched needle in a ...point–plane geometry. We identify two gain mechanisms, one pressure dependent, and the other independent of the applied pressure. We conclude that the pressure-dependent signals are from avalanche gain in gas bubbles at the tip of the needle, while the pressure-independent pulses are from avalanche gain in liquid. We measure the decay time spectra of photons from both types of avalanches. The decay times from the pressure-dependent pulses decrease (increase) with the applied pressure (high voltage), while the decay times from the pressure-independent pulses are approximately independent of pressure or high voltage. For our operating conditions, the collected charge distribution from avalanches is similar for 60 or 122
keV photon sources. With krypton additives, instead of Xe, we measure behavior consistent with only the pressure-dependent pulses. Neon and TMS were also investigated as additives, and designs for practical detectors were tested.
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