A note on symmetry reductions of the Lindblad equation: transport in constrained open spin chains

We study quantum transport properties of an open Heisenberg XXZ spin 1/2 chain driven by a pair of Lindblad jump operators satisfying a global `microcanonical' constraint, i.e. conserving the total magnetization. We will show that this system has an additional discrete symmetry which is particular to the Liouvillean description of the problem. Such symmetry reduces the dynamics even more than what would be expected in the standard Hilbert space formalism and establishes existence of multiple steady states. Interestingly, numerical simulations of the XXZ model suggest that a pair of distinct non-equilibrium steady states becomes indistinguishable in the thermodynamic limit, and exhibit sub-diffusive spin transport in the easy-axis regime of anisotropy Delta > 1.Comment: 14 pages with 5 pdf figures, revised version, as accepted by New Journal of Physic

FCHO controls AP2's initiating role in endocytosis through a Ptdlns(4,5)P-2-dependent switch

Clathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo adaptor AP2 requires membrane-localized Fer/Cip4 homology domain-only proteins (FCHO). Here, live-cell enhanced total internal reflection fluorescence-structured illumination microscopy shows that FCHO marks sites of clathrin-coated pit (CCP) initiation, which mature into uniform-sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Epidermal growth factor potential receptor substrate number 15 (Eps15) ring. We dissect the network of interactions between the FCHO interdomain linker and AP2, which concentrates, orients, tethers, and partially destabilizes closed AP2 at the plasma membrane. AP2's subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with phosphatidylinositol 4,5-bisphosphate, clathrin, cargo, and CME accessory factors. FCHO can now relocate toward a CCP's outer edge to engage and activate further AP2s to drive CCP growth/maturation

Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial.

BACKGROUND:Ilorasertib (ABT-348) inhibits Aurora and VEGF receptor (VEGFR) kinases. Patients with advanced solid tumours participated in a phase 1 dose-escalation trial to profile the safety, tolerability, and pharmacokinetics of ilorasertib. METHODS:Ilorasertib monotherapy was administered at 10-180 mg orally once daily (Arm I, n = 23), 40-340 mg orally twice daily (Arm II, n = 28), or 8-32 mg intravenously once daily (Arm III, n = 7), on days 1, 8, and 15 of each 28-day cycle. RESULTS:Dose-limiting toxicities were predominantly related to VEGFR inhibition. The most frequent treatment-emergent adverse events ( > 30%) were: fatigue (48%), anorexia (34%), and hypertension (34%). Pharmacodynamic markers suggested that ilorasertib engaged VEGFR2 and Aurora B kinase, with the VEGFR2 effects reached at lower doses and exposures than Aurora inhibition effects. In Arm II, one basal cell carcinoma patient (40 mg twice daily (BID)) and one patient with adenocarcinoma of unknown primary site (230 mg BID) had partial responses. CONCLUSIONS:In patients with advanced solid tumours, ilorasertib treatment resulted in evidence of engagement of the intended targets and antitumour activity, but with maximum inhibition of VEGFR family kinases occurring at lower exposures than typically required for inhibition of Aurora B in tissue. CLINICAL TRIAL REGISTRATION:NCT01110486

From sustainable community to Big Society: ten years learning with the Imagine approach

Community is a key word in the current UK political vocabulary. As part of Big Society or as a sustainable means to develop social coherence, community has been an area of focus which has attained UK political party interest since 2003. In 1999 the Imagine method was first hinted at in the Earthscan book: ‘Sustainability Indicators: measuring the immeasurable’. The approach allows citizens to learn about and self-evaluate their own sustainability by developing their own sustainability indicators in a manner which is participatory and evidence-based. Communities could make use of the approach, not in an attempt to arrive at some ‘absolute’ value of sustainability, but in striving to achieve a self-knowing sense of how sustainable they are, by their own measured indicators and to use this evaluation in discourse with other agencies such as local and national government. The tone of Imagine is to empower citizens to own their own sustainability and to plan for sustainable futures. The method, developed for spatial and temporal sustainability assessment, has been trialled by countries in the Mediterranean region within Coastal Area Management Programmes (CAMPs). Building off this engagement with geographically and culturally diverse communities, the method has been supported by the Homes and Communities Agency (HCA) in the UK and developed into a teaching module which has been subsequently tested at undergraduate, postgraduate, continuing professional development (CPD), Virtual Learning Environment (VLE) and working with practitioners, as a hands-on Masterclass . The resulting course: Creating Sustainable Communities (CSC) has now been introduced to 20 UK Universities and has seen use by 7. This paper tracks the development of the Imagine method, explores its major elements and sets out the learning impacts it has had to-date