The crime drop and the security hypothesis

Major crime drops were experienced in the United States and most other industrialised countries for a decade from the early to mid-1990s. Yet there is little agreement over explanation or lessons for policy. Here it is proposed that change in the quantity and quality of security was a key driver of the crime drop. From evidence relating to vehicle theft in two countries it is concluded that electronic immobilisers and central locking were particularly effective. It is suggested that reduced car theft may have induced drops in other crime including violence. From this platform a broader security hypothesis, linked to routine activity and opportunity theory, is outlined

Design Practice and ‘Designing for All’

Accepted for publicationIt is essential that all designers with responsibility for the human-machine interface have access to information on the anthropometry and capabilities of the whole population of people who may wish to interact with the design in question. Current databases used by designers typically present only very limited information concerning people who are older and/or disabled. Furthermore, tables of data are known to be largely ineffective and designers prefer to see visualisations of design data. In order to establish the current situation regarding design in relation to the needs of older and disabled people, existing products, procedures and systems were investigated. The objective was to identify current practice and the needs of designers whilst attempting to ‘design for all’. This paper will report on the findings from these interviews to date, which will ultimately lead to a requirements specification to aid design for the needs of older and disabled people

Angular dependence of the bulk nucleation field Hc2 of aligned MgB2 crystallites

Studies on the new MgB2 superconductor, with a critical temperature Tc ~ 39 K, have evidenced its potential for applications although intense magnetic relaxation effects limit the critical current density, Jc, at high magnetic fields. This means that effective pinning centers must be added into the material microstructure, in order to halt dissipative flux movements. Concerning the basic microscopic mechanism to explain the superconductivity in MgB2, several experimental and theoretical works have pointed to the relevance of a phonon-mediated interaction, in the framework of the BCS theory. Questions have been raised about the relevant phonon modes, and the gap and Fermi surface anisotropies, in an effort to interpret spectroscopic and thermal data that give values between 2.4 and 4.5 for the gap energy ratio. Preliminary results on the anisotropy of Hc2 have shown a ratio, between the in-plane and perpendicular directions, around 1.7 for aligned MgB2 crystallites and 1.8 for epitaxial thin films. Here we show a study on the angular dependence of Hc2 pointing to a Fermi velocity anisotropy around 2.5. This anisotropy certainly implies the use of texturization techniques to optimize Jc in MgB2 wires and other polycrystalline components.Comment: 10 pages + 4 Figs.; Revised version accepted in Phys. Rev.

Targeting the Canonical Nuclear Factor-κB Pathway with a High-Potency IKK2 Inhibitor Improves Outcomes in a Mouse Model of Idiopathic Pneumonia Syndrome

Idiopathic pneumonia syndrome (IPS) is a noninfectious inflammatory disorder of the lungs that occurs most often after fully myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). IPS can be severe and is associated with high 1-year mortality rates despite existing therapies. The canonical nuclear factor-(NF) κB signaling pathway has previously been linked to several inflammatory disorders of the lung, including asthma and lung allograft rejection. It has never been specifically targeted as a novel IPS treatment approach, however. Here, we report that the IκB kinase 2 (IKK2) antagonist BAY 65-5811 or “compound A,” a highly potent and specific inhibitor of the NF-κB pathway, was able to improve median survival times and recipient oxygenation in a well-described mouse model of IPS. Compound A impaired the production of the proinflammatory chemokines CCL2 and CCL5 within the host lung after transplantation. This resulted in significantly lower numbers of donor lung infiltrating CD4+ and CD8+ T cells and reduced pulmonary inflammatory cytokine production after allograft. Compound A's beneficial effects appeared to be specific for limiting pulmonary injury, as the drug was unable to improve outcomes in a B6 into B6D2 haplotype-matched murine HSCT model in which recipient mice succumb to lethal acute graft-versus-host disease of the gastrointestinal tract. Collectively, our data suggest that the targeting of the canonical NF-κB pathway with a small molecule IKK2 antagonist may represent an effective and novel therapy for the specific management of acute lung injury that can occur after allogeneic HSCT

Alpha-decay branching ratios of near-threshold states in 19Ne and the astrophysical rate of 15O(alpha,gamma)19Ne

The 15O(alpha,gamma)19Ne reaction is one of two routes for breakout from the hot CNO cycles into the rp process in accreting neutron stars. Its astrophysical rate depends critically on the decay properties of excited states in 19Ne lying just above the 15O + alpha threshold. We have measured the alpha-decay branching ratios for these states using the p(21Ne,t)19Ne reaction at 43 MeV/u. Combining our measurements with previous determinations of the radiative widths of these states, we conclude that no significant breakout from the hot CNO cycle into the rp process in novae is possible via 15O(alpha,gamma)19Ne, assuming current models accurately represent their temperature and density conditions

High-throughput imaging assay for drug screening of 3D prostate cancer organoids

First Published June 11, 2021New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.Nicholas Choo, Susanne Ramm, Jennii Luu, Jean M. Winter, Luke A. Selth, Amy R. Dwyer … et al

Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites

Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.Benjamin Liffner, Juan Miguel Balbin, Gerald J. Shami, Ghizal Siddiqui, Jan Strauss, Sonja Frölich, Gary K. Heinemann, Ella May Edwards, Arne Alder, Jan Stephan Wichers, Darren J. Creek, Leann Tilley, Matthew W.A. Dixon, Tim-Wolf Gilberger, Danny W. Wilso

Type-1.5 superconductivity in multicomponent systems

In general a superconducting state breaks multiple symmetries and, therefore, is characterized by several different coherence lengths $\xi_i$, $i=1,...,N$. Moreover in multiband material even superconducting states that break only a single symmetry are nonetheless described, under certain conditions by multi-component theories with multiple coherence lengths. As a result of that there can appear a state where some coherence lengths are larger and some are smaller than the magnetic field penetration length $\lambda$: $\xi_1\leq \xi_2... < \sqrt{2}\lambda<\xi_M\leq...\xi_N$. That state was recently termed "type-1.5" superconductivity. This breakdown of type-1/type-2 dichotomy is rather generic near a phase transition between superconducting states with different symmetries. The examples include the transitions between $U(1)$ and $U(1)\times U(1)$ states or between $U(1)$ and $U(1)\times Z_2$ states. The later example is realized in systems that feature transition between s-wave and $s+is$ states. The extra fundamental length scales have many physical consequences. In particular in these regimes vortices can attract one another at long range but repel at shorter ranges. Such a system can form vortex clusters in low magnetic fields. The vortex clustering in the type-1.5 regime gives rise to many physical effects, ranging from macroscopic phase separation in domains of different broken symmetries, to unusual transport properties