Applying uncertainty considerations to energy conservation equations

When applying computer simulation tools in practice uncertainties abound, for example in material properties and boundary conditions. To facilitate the quantification of the effects of uncertainties, the differential, factorial and Monte Carlo methods have been implemented within a simulation tool, ESP-r. These methods require multiple simulations to extract statistical measures of model uncertainty. An alternative approach is to embed uncertainty considerations within the simulation tool's algorithms. The principle advantages of this approach are that the uncertainty is quantified at all times and therefore requires only a single simulation. Coupled with this, it is possible to take control action based on the prevailing effects of uncertainties. This paper details the mathematical techniques required to integrate uncertainty considerations within the energy conservation equations when applied to the simulation of buildings. A comparison is made between the use of this novel approach and traditional mechanisms of assessing uncertainty

History and development of validation with the ESP-r simulation program

It is well recognised that validation of dynamic building simulation programs is a long-term complex task. There have been many large national and international efforts that have led to a well-established validation methodology comprising analytical, inter-program comparison and empirical validation elements, and a significant number of tests have been developed. As simulation usage increases, driven by such initiatives as the European Energy Performance of Buildings Directive, such tests are starting to be incorporated into national and international standards. Although many program developers have run many of the developed tests, there does not appear to have been a systematic attempt to incorporate such tests into routine operation of the simulation programs. This paper reports work undertaken to address this deficiency. The paper summarizes the tests that have been applied to the simulation program ESP-r. These tests have been developed within International Energy Agency Annexes, within CEN standards, within various large-scale national projects, and by the UK's Chartered Institution of Building Services Engineers. The structure used to encapsulate the tests allows developers to ensure that recent code modifications have not resulted in unforeseen impacts on program predictions, and allows users to check for themselves against benchmarks

Do Clinical Guidelines for Whole Body Computerised Tomography in Trauma Improve Diagnostic Accuracy and Reduce Unnecessary Investigations? A Systematic Review and Narrative Synthesis.

Introduction Whole body computerised tomography has become a standard of care for the investigation of major trauma patients. However, its use varies widely, and current clinical guidelines are not universally accepted. We undertook a systematic review of the literature to determine whether clinical guidelines for whole body computerised tomography in trauma increase its diagnostic accuracy. Materials and methods A systematic review of Medline, Cinhal and the Cochrane database, supplemented by a manual search of relevant papers was undertaken, with narrative synthesis. Studies comparing clinical guidelines to physician gestalt for the use of whole body computerised tomography in adult trauma were included. Results A total of 887 papers were identified from the electronic databases, and 1 from manual searches. Of these, seven papers fulfilled the inclusion criteria. Two papers compared clinical guidelines with routine practice: one found increased diagnostic accuracy while the other did not. Two papers investigated the performance of established clinical guidelines and demonstrated moderate sensitivity and low specificity. Two papers compared different components of established triage tools in trauma. One paper devised a de novo clinical decision rule, and demonstrated good diagnostic accuracy with the tool. The outcome criteria used to define a ‘positive’ scan varied widely, making direct comparisons between studies impossible. Conclusions Current clinical guidelines for whole body computerised tomography in trauma may increase the sensitivity of the investigation, but the evidence to support this is limited. There is a need to standardise the definition of a ‘clinically significant’ finding on CT to allow better comparison of diagnostic studies

Germination Ecology of Two Savanna Tree Species, Tamarindus indica and Prosopis africana

Various methods of seed scarification including concentrated sulphuric acid, alcohol; methanol, ethanol, iso-propanol, butanol and hot water (100°C), were applied on seeds of Tamarindus indica L. and Prosopis africana Guill and Peri., to improve germination and assess seed vigor. The highest germination and germination energy (Germ. En.) for T. indica occurred following pre-treatment in methanol for 10 minutes (70% germination; 42, Germ. En.), while better response was obtained for P. africana following pretreatment in ethanol for 10 minutes (58% germination; 38, Germ. En.), and Conc. H2SO4, for 5 minutes (60% germination; 38, Germ. En.)

Influence of cardiac autonomic neuropathy on cardiac repolarisation during incremental adrenaline infusion in type 1 diabetes

Aims/hypothesis We examined the effect of a standardised sympathetic stimulus, incremental adrenaline (epinephrine) infusion on cardiac repolarisation in individuals with type 1 diabetes with normal autonomic function, subclinical autonomic neuropathy and established autonomic neuropathy. Methods Ten individuals with normal autonomic function and baroreceptor sensitivity tests (NAF), seven with subclinical autonomic neuropathy (SAN; normal standard autonomic function tests and abnormal baroreceptor sensitivity tests); and five with established cardiac autonomic neuropathy (CAN; abnormal standard autonomic function and baroreceptor tests) underwent an incremental adrenaline infusion. Saline (0.9% NaCl) was infused for the first hour followed by 0.01 μg kg−1 min−1 and 0.03 μg kg−1 min−1 adrenaline for the second and third hours, respectively, and 0.06 μg kg−1 min−1 for the final 30 min. High resolution ECG monitoring for QTc duration, ventricular repolarisation parameters (T wave amplitude, T wave area symmetry ratio) and blood sampling for potassium and catecholamines was performed every 30 min. Results Baseline heart rate was 68 (95% CI 60, 76) bpm for the NAF group, 73 (59, 87) bpm for the SAN group and 84 (78, 91) bpm for the CAN group. During adrenaline infusion the heart rate increased differently across the groups (p = 0.01). The maximum increase from baseline (95% CI) in the CAN group was 22 (13, 32) bpm compared with 11 (7, 15) bpm in the NAF and 10 (3, 18) bpm in the SAN groups. Baseline QTc was 382 (95% CI 374, 390) ms in the NAF, 378 (363, 393) ms in the SAN and 392 (367, 417) ms in the CAN groups (p = 0.31). QTc in all groups lengthened comparably with adrenaline infusion. The longest QTc was 444 (422, 463) ms (NAF), 422 (402, 437) ms (SAN) and 470 (402, 519) ms (CAN) (p = 0.09). T wave amplitude and T wave symmetry ratio decreased and the maximum decrease occurred earlier, at lower infused adrenaline concentrations in the CAN group compared with NAF and SAN groups. AUC for the symmetry ratio was different across the groups and was lowest in the CAN group (p = 0.04). Plasma adrenaline rose and potassium fell comparably in all groups. Conclusions/interpretation Participants with CAN showed abnormal repolarisation in some measures at lower adrenaline concentrations. This may be due to denervation adrenergic hypersensitivity. Such individuals may be at greater risk of cardiac arrhythmias in response to physiological sympathoadrenal challenges such as stress or hypoglycaemia

Report and Application of a Tool Compound Data Set

Small molecule tool compounds have enabled profound advances in life science research. These chemicals are potent, cell active, and selective, and, thus, are suitable for interrogating biological processes. For these chemicals to be useful they must be correctly characterized and researchers must be aware of them. We mined the ChEMBL bioactivity database to identify high quality tool compounds in an unbiased way. We identified 407 best-in-class compounds for 278 protein targets, and these are reported in an annotated data set. Additionally, we developed informatics functions and a web application for data visualization and automated pharmacological hypothesis generation. These functions were used to predict inhibitors of the Chromobox Protein Homologue 5 (CBX5) mediated gene repression pathway that currently lacks appropriate inhibitors. The predictions were subsequently validated by a highly specific cell based assay, revealing new chemical modulators of CBX5-mediated heterochromatin formation. This data set and associated functions will help researchers make the best use of these valuable compounds

Cardiac autonomic regulation and repolarization during acute experimental hypoglycemia in Type 2 diabetes

Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in T2DM patients. Our aim was to examine changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and eleven age, BMI-matched nondiabetic controls underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0mmol/L) or hypoglycemia (2.5mmol/L) for one hour. Heart rate, blood pressure, heart rate variability were assessed every thirty minutes and corrected QT (QTc) and T wave morphology every 60 minutes. Heart rate initially increased in T2DM participants but then fell towards baseline despite maintained hypoglycemia at 1 hour, accompanied by reactivation of vagal tone. In nondiabetic participants, vagal tone remained depressed during sustained hypoglycemia. Diabetic participants exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T wave symmetry and Principal Component Analysis (PCA) ratio compared with the nondiabetic group. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears time-dependent. T2DM individuals demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes

Charged hydrogenic problem in a magnetic field: Non-commutative translations, unitary transformations, and coherent states

An operator formalism is developed for a description of charged electron-hole complexes in magnetic fields. A novel unitary transformation of the Hamiltonian that allows one to partially separate the center-of-mass and internal motions is proposed. We study the operator algebra that leads to the appearance of new effective particles, electrons and holes with modified interparticle interactions, and their coherent states in magnetic fields. The developed formalism is used for studying a two-dimensional negatively charged magnetoexciton $X^-$. It is shown that Fano-resonances are present in the spectra of internal $X^-$ transitions, indicating the existence of three-particle quasi-bound states embedded in the continuum of higher Landau levels.Comment: 9 pages + 2 figures, accepted in PRB, a couple of typos correcte

Prolonged prothrombotic effects of antecedent hypoglycemia in individuals with type 2 diabetes

OBJECTIVE Hypoglycemia has been linked to persistent increases in cardiovascular (CV) mortality in type 2 diabetes after the event. Our aim was to examine acute and downstream effects of hypoglycemia on markers of thrombosis risk and inflammation in type 2 diabetes. RESEARCH DESIGN AND METHODS Twelve individuals with type 2 diabetes with no history of CV disease and 11 age- and BMI-matched volunteers without diabetes underwent paired hyperinsulinemic-euglycemic (glucose 6 mmol/L for two 60-min periods) and hypoglycemic (glucose 2.5 mmol/L for two 60-min periods) clamps on separate occasions on day 0. Fibrin clot properties, platelet reactivity, and inflammatory markers were measured at baseline, end of and after recovery from the initial clamp, day 1, and day 7 using validated assays and electron microscopy. RESULTS Euglycemic hyperinsulinemia reduced platelet reactivity, decreased fibrin clot density, and improved fibrinolytic efficiency in both groups. Platelet reactivity and aggregation increased during acute hypoglycemia in both groups, resolving at recovery. In type 2 diabetes, clot lysis times and clot maximum absorbance increased up to day 7 (P = 0.002 and 0.001 vs. euglycemia, respectively), but clots from control subjects without diabetes showed limited changes. Fibrin network density increased Δ 1.15 ± 0.28 fibers/μm2 at day 7 after the hypoglycemic clamp (P < 0.01 for glycemic arm), whereas fibrinogen and complement C3 increased after hypoglycemia up to day 7 in type 2 diabetes only. CONCLUSIONS Antecedent hypoglycemia has acute and persistent prothrombotic effects, lasting at least 7 days, that were enhanced in individuals with type 2 diabetes. These findings identify mechanisms by which hypoglycemia might increase short- and medium-term risk of CV mortality

Pathway-Based High-Throughput Chemical Screen Identifies Compounds That Decouple Heterochromatin Transformations

Heterochromatin protein 1 (HP1) facilitates the formation of repressive heterochromatin domains by recruiting histone lysine methyltransferase enzymes to chromatin, resulting in increased levels of histone H3K9me3. To identify chemical inhibitors of the HP1-heterochromatin gene repression pathway, we combined a cell-based assay that utilized chemical-mediated recruitment of HP1 to an endogenous active gene with high-throughput flow cytometry. Here we characterized small molecule inhibitors that block HP1-mediated heterochromatin formation. Our lead compounds demonstrated dose-dependent inhibition of HP1-stimulated gene repression and were validated in an orthogonal cell-based system. One lead inhibitor was improved by a change in stereochemistry, resulting in compound 2, which was further used to decouple the inverse relationship between H3K9 and H3K4 methylation states. We identified molecular components that bound compound 2, either directly or indirectly, by chemical affinity purification with a biotin-tagged derivative, followed by quantitative proteomic techniques. In summary, our pathway-based chemical screening approach resulted in the discovery of new inhibitors of HP1-mediated heterochromatin formation while identifying exciting new molecular interactions in the pathway to explore in the future. This modular platform can be expanded to test a wide range of chromatin modification pathways yielding inhibitors that are cell permeable and function in a physiologically relevant setting