Assessing uncertainty in housing stock infiltration rates and associated heat loss: English and UK case studies

Strategies to reduce domestic heating loads by minimizing the infiltration of cold air through adventitious openings located in the thermal envelopes of houses are highlighted by the building codes of many countries. Consequent reductions of energy demand and CO2e emission are often unquantified by empirical evidence. Instead, a mean heating season infiltration rate is commonly inferred from an air leakage rate using a simple ratio scaled to account for the physical and environmental properties of a dwelling. The scaling does not take account of the permeability of party walls in conjoined dwellings and so cannot differentiate between the infiltration of unconditioned ambient air that requires heating, and conditioned air from adjacent dwellings that does not. A stochastic method is presented that applies a theoretical model of adventitious infiltration to predict distributions of mean infiltration rates and the associated total heat loss in any stock of dwellings during heating hours. The method is applied to the English and UK housing stocks and provides probability distribution functions of stock infiltration rates and total heat loss during the heating season for two extremes of party wall permeability. The distributions predict that up to 79% of the current English stock could require additional purpose-provided ventilation to limit negative health consequences. National models predict that fewer dwellings are under-ventilated. The distributions are also used to predict that infiltration is responsible for 3–5% of total UK energy demand, 11–15% of UK housing stock energy demand, and 10–14% of UK housing stock carbon emissions

Extinction filters mediate the global effects of habitat fragmentation on animals

Habitat loss is the primary driver of biodiversity decline worldwide, but the effects of fragmentation (the spatial arrangement of remaining habitat) are debated. We tested the hypothesis that forest fragmentation sensitivity—affected by avoidance of habitat edges—should be driven by historical exposure to, and therefore species’ evolutionary responses to disturbance. Using a database containing 73 datasets collected worldwide (encompassing 4489 animal species), we found that the proportion of fragmentation-sensitive species was nearly three times as high in regions with low rates of historical disturbance compared with regions with high rates of disturbance (i.e., fires, glaciation, hurricanes, and deforestation). These disturbances coincide with a latitudinal gradient in which sensitivity increases sixfold at low versus high latitudes. We conclude that conservation efforts to limit edges created by fragmentation will be most important in the world’s tropical forests

Examining Ligand-based Stabilization of Proteins in Cells with MEK1 Kinase Inhibitors

Here we describe the evaluation of a cell-based ligand binding assay using DiscoveRx’s enzyme-fragment complementation technology performed in two independent laboratories. The assay is based on the ability of certain ligands to bind to a protein leading to a ligand•protein complex that has a different stability than the free protein. The assay employed a pro-labeled-tagged MEK1 kinase stably expressed in A549 cells and this was used to evaluate focused sets of compounds containing known MEK1inhibitors. An assay using a pro-labeled tagged G9A expressed in A549 cells was used as a counterscreen. In one study it was found that the majority of MEK1 inhibitors were either found as inactive (43%) or showed an inhibitory response (16%) in the cell-based MEK1 assay however seven compounds showed a specific activation response consistent with stabilization of MEK1 in cells. Examination of these stabilizing compounds showed that three of these were analogs of hypothemycin, a known covalent allosteric MEK1 inhibitor, while the remaining compounds covered one structural class. Both laboratories were able to confirm activity in the cell-based MEK1 assay for certain known MEK1 inhibitors and that this activity was highly selective over the G9a counterscreen assay. This study supports that the MEK1 cellular protein stability assay is sensitive to certain MEK1 inhibitors, often noncompetitive inhibitors with respect to ATP. The cellular stability assay format could be useful to rapidly filter kinase inhibitor hit lists for allosteric kinase inhibitors and confirm target engagement in cells

Respiratory function, and resting calorimeter measures from adult males with (BeMD) and without (Control) Becker’s muscle dystrophy.

<p>Respiratory function, and resting calorimeter measures from adult males with (BeMD) and without (Control) Becker’s muscle dystrophy.</p

Anthropometric measures from adult males with (BeMD) and without (CTRL) Becker’s muscle dystrophy.

<p>Anthropometric measures from adult males with (BeMD) and without (CTRL) Becker’s muscle dystrophy.</p

Pilot data of average REE over time in Control Participants.

<p>Pilot data of average REE over time in Control Participants.</p

Prediction Equations correlation with measured REE in Adults with BeMD.

<p>Prediction Equations correlation with measured REE in Adults with BeMD.</p

REE and Fat Mass (Kg) relationship in BeMD (closed circles) and Control (open circles) participants.

<p>Kg = Kilograms; REE = Resting Energy Expenditure; Kcal = Kilocalories.</p

REE and Body Mass (Kg) relationship in BeMD (closed circles) and Control (open circles) participants.

<p>Kg = Kilograms; REE = Resting Energy Expenditure; Kcal = Kilocalories.</p

Relationship between GM ACSA and REE in BeMD (closed circles) and Control (open circles) participants.

<p>GM = Gastrocnemius Medialis; ACSA = Anatomical Cross Sectional Area; cm = centimetres; REE = Resting Energy Expenditure; Kcal = Kilocalories.</p