Protein-Binding Microarray Analysis of Tumor Suppressor AP2α Target Gene Specificity

Cheap and massively parallel methods to assess the DNA-binding specificity of transcription factors are actively sought, given their prominent regulatory role in cellular processes and diseases. Here we evaluated the use of protein-binding microarrays (PBM) to probe the association of the tumor suppressor AP2α with 6000 human genomic DNA regulatory sequences. We show that the PBM provides accurate relative binding affinities when compared to quantitative surface plasmon resonance assays. A PBM-based study of human healthy and breast tumor tissue extracts allowed the identification of previously unknown AP2α target genes and it revealed genes whose direct or indirect interactions with AP2α are affected in the diseased tissues. AP2α binding and regulation was confirmed experimentally in human carcinoma cells for novel target genes involved in tumor progression and resistance to chemotherapeutics, providing a molecular interpretation of AP2α role in cancer chemoresistance. Overall, we conclude that this approach provides quantitative and accurate assays of the specificity and activity of tumor suppressor and oncogenic proteins in clinical samples, interfacing genomic and proteomic assays

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Energy audit of air conditioning systems

The work presented here consists in developing an audit methodology, with appropriate simulation tools and benchmarks. Several case studies are used to support, to test and to illustrate these developments. Each case study is described according to a standard format, in order to make the data easy to re-use in the future. The audit of the HVAC system consists in analyzing the information available about actual energy performances and in identifying the most attractive retrofit opportunities. Focus is given here to cooling energy consumption, but it could never be completely dissociated from heating requirements. An example of case study is presented in the paper to give a first idea of what could be the (difficult) task of the energy auditor. One of the main difficulties comes from the too many information lacks. Filling these lacks would require, in most case, more detailed energy records on site. Simulation models may help a lot, for a better interpretation of on site records and also for a safe identification of the most promising retrofit opportunities. Such models and examples of simulations are presented in the paper

Commissioning-orientated building loads calculations. Application to the CA-MET building in Namur (Belgium).

The parallel use of whole building simulation and monitoring of building energy consumptions (heating, cooling, lighting and other electricity consumptions) represents a potential “high-level” commissioning tool in order to verify, either as a one shot campaign or as a continuous process, the correct operation of a building. The most advanced approaches use on-line building simulation to continuously compare the real performance of the building to a base line provided by simulation. In that context, different levels of building loads calculation can be used, ranging from rough methods like eg degree day methods to detailed multizone building simulation. The former methods use aggregated information about the buildings (“global” parameters like the heat loss coefficient for instance) and provide as outputs average quantities (energy consumption for a given average controlled temperature) while the latter require a high number of parameters and deliver very detailed results (hourly evolution of demands in each zone of the building). A major question concerns the suitability of the different approaches in a commissioning context. This papers illustrates the use of different calculation methods (heating and cooling loads) for the particular case of an office building located in Namur (Belgium), which is the object of an intensive re-commissioning activity for several years. Very global methods are used as well as detailed computer simulations using TRNSYS Multizone building types 46 and 56. In the latter case, the model is calibrated using reference periods and can serve as a baseline indicator of the energy consumption in the building. The complexity of the building (300 m long, modular architecture, presence of an atrium-like internal street) required some simplifications in the modelling associated to a specific methodology to extrapolate the results got from the simulation of a relatively small part of the building to the whole picture. The paper will explain the advantages and disadvantages of each approach, the required information and the limits of the results. The potential use of the different calculation levels for the implementation in a continuous commissioning process will be examinated as conclusion of the work

A functional test procedure for the improved commissioning of a VAV system

In the context of the IEA40 research project, a specification of a “Functional Test Procedure” was progressively developed using the CA-MET building in Namur as real size test bench for the application and validation of the procedure. The target system is a typical VAV system devoted to the ventilation, cooling and air conditioning functions. The procedure consists in a series of operations to be applied to the system, considered as a set of connected components and taking into account the following constraints: - time availability - intrinsic limitations of the system - reference performances The proposed procedure is divided in two sets of actions: - a number of preliminary actions allowing to take the best benefit of the subsequent phases: o identification of available measurement points o identification of actuators characteristics o identification of control strategies o aeraulic network calculations o selection of measurement techniques and experimental design - the verification tasks themselves: The philosophy of the verification process is to bring the system into a number of states whoch allowed each specific checks to be carried out. The organisation of the procedure tries to optimize the time spent for commissioning by logically sequencing the operations according to the following order: - test in manual operation - test in manual stop - test in normal operation - test at maximum flowrate - test at minimum flowrate - test in automatic stop The paper will provide the specific operations to be carried out at each step and will illustrate the whole process with the prototyping work performed on the CA-MET building in Namur

Re-commissioning of a VAV air cistribution system.

Three years after its start up, the building considered here is not yet providing a satisfactory comfort to its occupants. Too cold and too hot environmental conditions were too often encountered in different occupied zones, mainly in mid-season and in summertime. The execution of a re- commissioning process would support in resolving these problems. Previous verifications allowed us to confirm that almost all HVAC components considered are technically “correct” and that almost all problems are coming from mistakes committed when installing and tuning these components. The re-commissioning presented in this paper is based on both calculation and experimental data

About the use of simulation models and of functional tests in commissioning of HVAC systems.

peer reviewe

Polygeneration and HVAC

Decentralized cogeneration may help in energy conservation if a large enough amount of heat can be actually recovered. This restriction is becoming more and more severe because of the growing effectiveness of modern power plants. Re-conversion of heating into cooling is not competitive with the use of modern vapor compression chillers. It may just help to extend a little the time during which the co-generation plant can be effectively used. A co-generation plant should not be sized above 30% of the maximal heating power in order to stay energy efficient. The results of a long term case study are summarized in the paper. These results show the incidence of the plant over-sizing : in this case, the system is consuming more than a classical solutio

The main results of a european research project : improvement of transport safety by control of fog production in a chamber ("FOG")

The issue of transport safety is identified as a major goal in the European Union. The mid term objective declared in the European White Paper for Transport aims at halving the number of deaths on the roads by 2010. Low visibility conditions, especially due to fog, increase the risk of major accidents (chain collision) and a number of innovative products are developed by the automotive industry, including equipment manufacturers, in order to increase the level of safety of the cars passengers and drivers. Testing of these products require the simulation or artificial reproduction of adequate low visibility (fog) conditions with good stability and reproductibility characteristics. The main objective of the “FOG” project was to develop a prototype of innovative fog chamber in which the mechanistic production of fog (by high pressure spraying of water) in a chamber was assisted by an efficient control of the indoor climate. This prototype was installed in a new building constructed on the campus of the University of Liège in Arlon (Belgium). The developments of the project also include a number of additional products enhancing the capabilities of the prototype: - an improved fog production spraying device, including an optimized management - a laser-based visibility measurement device - a reduced scale transmissiometer - a combined indoor climate - fog production simulation software All these products were successfully tested in the conclusive part of the project making the prototype fully operational and ready for use by researchers in the field of transport safety as well as industrial products manufacturers. The capability of the testing facility to test the interaction with the driver was also investigated. The paper will present the major developments of the project and the potential future perspectives of the work