Review of UK microgeneration. Part 1 : policy and behavioural aspects

A critical review of the literature relating to government policy and behavioural aspects relevant to the uptake and application of microgeneration in the UK is presented. Given the current policy context aspiring to zero-carbon new homes by 2016 and a variety of minimum standards and financial policy instruments supporting microgeneration in existing dwellings, it appears that this class of technologies could make a significant contribution to UK energy supply and low-carbon buildings in the future. Indeed, achievement of a reduction in greenhouse gas emissions by 80% (the UK government's 2050 target) for the residential sector may entail substantial deployment of microgeneration. Realisation of the large potential market for microgeneration relies on a variety of inter-related factors such as microeconomics, behavioural aspects, the structure of supporting policy instruments and well-informed technology development. This article explores these issues in terms of current and proposed policy instruments in the UK. Behavioural aspects associated with both initial uptake of the technology and after purchase are also considered

Convergent Validity of a Single Question with Multiple Classification Options for Depression Screening in Medical Settings

The purpose of this study was to assess the convergent validity of a single depression question with multiple classification options for depression screening. Participants were 40 medical inpatients. The age range of our sample was 18 to 85 years (M = 56.15, SD = 17.66). A clinical interview and the BDI-II were administered. The correlation between patients’ self-rating classification of depression and their BDI-II classification was significant, rs(38) = .90, p < .01. Follow-up repeated-measures chi-square revealed a statistically significant association between BDI-II classification and patients’ self-rating classification, χ2(9, N = 40) = 47.79, p < .005. Significant positive standardized residuals revealed a clear linear relationship between BDI-II and patient self-rating classifications. Our data support the use of a single depression question with multiple classification options as a useful and valid means of quickly screening for the presence of depression by frontline health care professionals

Molecular architecture of potassium chloride co-transporter KCC2

KCC2 is a neuron specific K+-Cl− co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia. Despite significant accumulating data on the biology and electrophysiological properties of KCC2, structure-function relationships remain poorly understood. Here we used calixarene detergent to solubilize and purify wild-type non-aggregated and homogenous KCC2. Specific binding of inhibitor compound VU0463271 was demonstrated using surface plasmon resonance (SPR). Mass spectrometry revealed glycosylations and phosphorylations as expected from functional KCC2. We show by electron microscopy (EM) that KCC2 exists as monomers and dimers in solution. Monomers are organized into “head” and “core” domains connected by a flexible “linker”. Dimers are asymmetrical and display a bent “S-shape” architecture made of four distinct domains and a flexible dimerization interface. Chemical crosslinking in reducing conditions shows that disulfide bridges are involved in KCC2 dimerization. Moreover, we show that adding a tag to the C-terminus is detrimental to KCC2 function. We postulate that the conserved KCC2 C-ter may be at the interface of dimerization. Taken together, our findings highlight the flexible multi-domain structure of KCC2 with variable anchoring points at the dimerization interface and an important C-ter extremity providing the first in-depth functional architecture of KCC2

Rapid Discovery of Pyrido[3,4- d ]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach

Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft mode

End-to-end numerical modeling of the Roman Space Telescope coronagraph

The Roman Space Telescope will have the first advanced coronagraph in space, with deformable mirrors for wavefront control, low-order wavefront sensing and maintenance, and a photon-counting detector. It is expected to be able to detect and characterize mature, giant exoplanets in reflected visible light. Over the past decade the performance of the coronagraph in its flight environment has been simulated with increasingly detailed diffraction and structural/thermal finite element modeling. With the instrument now being integrated in preparation for launch within the next few years, the present state of the end-to-end modeling is described, including the measured flight components such as deformable mirrors. The coronagraphic modes are thoroughly described, including characteristics most readily derived from modeling. The methods for diffraction propagation, wavefront control, and structural and thermal finite-element modeling are detailed. The techniques and procedures developed for the instrument will serve as a foundation for future coronagraphic missions such as the Habitable Worlds Observatory.Comment: 113 pages, 85 figures, to be published in SPIE Journal of Astronomical Telescopes, Instruments, and System

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models

Insulin-Like Peptides and the Target of Rapamycin Pathway Coordinately Regulate Blood Digestion and Egg Maturation in the Mosquito Aedes aegypti

Mosquitoes are insects that vector many serious pathogens to humans and other vertebrates. Most mosquitoes must feed on the blood of a vertebrate host to produce eggs. In turn, multiple cycles of blood feeding promote frequent contacts with hosts and make mosquitoes ideal disease vectors. Both hormonal and nutritional factors are involved in regulating egg development in the mosquito, Aedes aegypti. However, the processes that regulate digestion of the blood meal remain unclear.Here we report that insulin peptide 3 (ILP3) directly stimulated late phase trypsin-like gene expression in blood fed females. In vivo knockdown of the mosquito insulin receptor (MIR) by RNA interference (RNAi) delayed but did not fully inhibit trypsin-like gene expression in the midgut, ecdysteroid (ECD) production by ovaries, and vitellogenin (Vg) expression by the fat body. In contrast, in vivo treatment with double-stranded MIR RNA and rapamycin completely blocked egg production. In vitro experiments showed that amino acids did not simulate late phase trypsin-like gene expression in the midgut or ECD production by the ovaries. However, amino acids did enhance ILP3-mediated stimulation of trypsin-like gene expression and ECD production.Overall, our results indicate that ILPs from the brain synchronize blood meal digestion and amino acid availability with ovarian ECD production to maximize Vg expression by the fat body. The activation of digestion by ILPs may also underlie the growth promoting effects of insulin and TOR signaling in other species

A DNA-based molecular probe for optically reporting cellular traction forces

We developed molecular tension probes (TPs) that report traction forces of adherent cells with high spatial resolution, can be linked to virtually any surface, and obviate monitoring deformations of elastic substrates. TPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific forces. We applied TPs to reveal that cellular traction forces are heterogeneous within focal adhesions and localized at their distal edges