First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

Modelling cost-effective clearing solutions for invasive alien trees: A case study on wilding conifers.

Accurate on-site identification of appropriate alien clearing methods can realize significant cost savings for heterogenous sites. We developed a cost-based model accounting for site parameters such as infestation density, slope, obstructive vegetation density and site-access. These parameters are combined with a unit-costing sub-module to identify the most cost-effective clearing method for a particular site. The model was tested in the heterogenous Cape Fynbos biome of South Africa for three clearing methods for Pinus: traditional felling, drill-and-fill, and the arial-basal bark application (ABBA) method. The model accounts for the above-mentioned site parameters after which it is calibrated with the unit-costing for each method. Various scenarios consisting of different combinations of above-mentioned site parameters are then applied to identify the cost-effective solution for any particular combination of site parameters. Results favoured the drill-and-fill method in most cases, with the ABBA method reserved for sites with isolated Pines situated in dense fynbos with difficult access at slope gradients of 45° and higher. At these site combinations, ground teams experience longer walk times which reduces their productivity to such an extent that ABBA is comparatively more cost-effective. Traditional felling turned out to be prohibitively expensive because of team composition (mandatory higher safety and supervision requirements required for chainsaw operations) and slower on-site walking due to heavier equipment. The information enables site managers to do more accurate planning since the model will ensure that a cost-effective method is chosen for any particular site. It is then up to the manager to implement the chosen clearing method in a cost-efficient way.

Characterization of physiologically regulated vectors for the treatment of ischemic disease.

A high therapeutic index is as important for gene-based therapies as it is for chemotherapy or radiotherapy. One approach has been transcriptional targeting through the use of tissue-specific regulatory elements. A more versatile approach would be to use a regulatory element that is controlled via a parameter common to a broad range of diseases. Ischemia is characteristic of a number of pathologies that range from vascular occlusion through to cancer. The state of low oxygen, hypoxia, triggers a transcriptional signaling pathway that is mediated by transcription factors binding to a specific enhancer, the hypoxia response element (HRE). These observations have therefore led to the use of HREs to drive gene expression in a number of target tissues from tumors to cardiac muscle. To translate these observations into a clinically useful vector system we have now assessed the potency of a number of naturally derived HREs in various configurations combined with minimal promoters. The optimal HRE has been introduced into a single transcription unit retroviral vector that can deliver regulated gene expression in response to hypoxia. An important feature of this new physiologically regulated vector is the combination of low basal expression and high-level activated expression that is on a par with that obtained with the cytomegalovirus immediate-early (CMV IE) promoter. The role of elements that stabilize mRNA in the presence of hypoxia has also been assessed. These hypoxia-regulated vectors may have utility for restricting the delivery of therapeutic proteins to tumors and ischemic sites.