Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure

The LUX-ZEPLIN (LZ) Experiment

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts

Mantle heat drives hydrothermal fluids responsible for carbonate-hosted base metal deposits: evidence from 3He/4He of ore fluids in the Irish Pb-Zn ore district

There is little consensus on whether carbonate-hosted base metal deposits, such as the world-class Irish Zn+Pb ore field, formed in collisional or extensional tectonic settings. Helium isotopes have been analysed in ore fluids trapped in sulphides samples from the major base metal deposits of the Irish Zn-Pb ore field in order to quantify the involvement of mantle-derived volatiles, that require melting to be realised, as well as test prevailing models for the genesis of the ore fields. 3He/4He ratios range up to 0.2 Ra, indicating that a small but clear mantle helium contribution is present in the mineralising fluids trapped in galena and marcasite. Sulfides from ore deposits with the highest fluid inclusion temperatures (~200°C) also have the highest 3He/4He (&gt; 0.15 Ra). Similar 3He/4He are recorded in fluids from modern continental regions that are undergoing active extension. By analogy we consider that the hydrothermal fluids responsible for the carbonate-hosted Irish base metal mineralization circulated in thinned continental crust, undergoing extension, and demonstrates that enhanced mantle heat flow is ultimately responsible for driving fluid convection

LUX-ZEPLIN (LZ) Technical Design Report

In this Technical Design Report (TDR) we describe the LZ detector to be built at the Sanford Underground Research Facility (SURF). The LZ dark matter experiment is designed to achieve sensitivity to a WIMP-nucleon spin-independent cross section of three times ten to the negative forty-eighth square centimeters

LUX-ZEPLIN (LZ) Conceptual Design Report

The design and performance of the LUX-ZEPLIN (LZ) detector is described as of March 2015 in this Conceptual Design Report. LZ is a second-generation dark-matter detector with the potential for unprecedented sensitivity to weakly interacting massive particles (WIMPs) of masses from a few GeV/c2 to hundreds of TeV/c2. With total liquid xenon mass of about 10 tonnes, LZ will be the most sensitive experiment for WIMPs in this mass region by the end of the decade. This report describes in detail the design of the LZ technical systems. Expected backgrounds are quantified and the performance of the experiment is presented. The LZ detector will be located at the Sanford Underground Research Facility in South Dakota. The organization of the LZ Project and a summary of the expected cost and current schedule are given

The LUX-ZEPLIN (LZ) radioactivity and cleanliness control programs

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above 1.4×10−48cm2 for a WIMP mass of 40GeV/c2 and a 1000days exposure. LZ achieves this sensitivity through a combination of a large 5.6t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented