An Indirect Genetic Algorithm for Set Covering Problems

This paper presents a new type of genetic algorithm for the set covering problem. It differs from previous evolutionary approaches first because it is an indirect algorithm, i.e. the actual solutions are found by an external decoder function. The genetic algorithm itself provides this decoder with permutations of the solution variables and other parameters. Second, it will be shown that results can be further improved by adding another indirect optimisation layer. The decoder will not directly seek out low cost solutions but instead aims for good exploitable solutions. These are then post optimised by another hill-climbing algorithm. Although seemingly more complicated, we will show that this three-stage approach has advantages in terms of solution quality, speed and adaptability to new types of problems over more direct approaches. Extensive computational results are presented and compared to the latest evolutionary and other heuristic approaches to the same data instances.

Enhanced Direct and Indirect Genetic Algorithm Approaches for a Mall Layout and Tenant Selection Problem

During our earlier research, it was recognised that in order to be successful with an indirect genetic algorithm approach using a decoder, the decoder has to strike a balance between being an optimiser in its own right and finding feasible solutions. Previously this balance was achieved manually. Here we extend this by presenting an automated approach where the genetic algorithm itself, simultaneously to solving the problem, sets weights to balance the components out. Subsequently we were able to solve a complex and non-linear scheduling problem better than with a standard direct genetic algorithm implementation.

An Indirect Genetic Algorithm for a Nurse Scheduling Problem

This paper describes a Genetic Algorithms approach to a manpower-scheduling problem arising at a major UK hospital. Although Genetic Algorithms have been successfully used for similar problems in the past, they always had to overcome the limitations of the classical Genetic Algorithms paradigm in handling the conflict between objectives and constraints. The approach taken here is to use an indirect coding based on permutations of the nurses, and a heuristic decoder that builds schedules from these permutations. Computational experiments based on 52 weeks of live data are used to evaluate three different decoders with varying levels of intelligence, and four well-known crossover operators. Results are further enhanced by introducing a hybrid crossover operator and by making use of simple bounds to reduce the size of the solution space. The results reveal that the proposed algorithm is able to find high quality solutions and is both faster and more flexible than a recently published Tabu Search approach.

'An Indirect Genetic Algorithm for Set Covering Problems'

This paper presents a new type of genetic algorithm for the set covering problem. It differs from previous evolutionary approaches first because it is an indirect algorithm, i.e. the actual solutions are found by an external decoder function. The genetic algorithm itself provides this decoder with permutations of the solution variables and other parameters. Second, it will be shown that results can be further improved by adding another indirect optimisation layer. The decoder will not directly seek out low cost solutions but instead aims for good exploitable solutions. These are then post optimised by another hill-climbing algorithm. Although seemingly more complicated, we will show that this three-stage approach has advantages in terms of solution quality, speed and adaptability to new types of problems over more direct approaches. Extensive computational results are presented and compared to the latest evolutionary and other heuristic approaches to the same data instances.

'Enhanced Direct and Indirect Genetic Algorithm Approaches for a Mall Layout and Tenant Selection Problem'

During our earlier research, it was recognised that in order to be successful with an indirect genetic algorithm approach using a decoder, the decoder has to strike a balance between being an optimiser in its own right and finding feasible solutions. Previously this balance was achieved manually. Here we extend this by presenting an automated approach where the genetic algorithm itself, simultaneously to solving the problem, sets weights to balance the components out. Subsequently we were able to solve a complex and non-linear scheduling problem better than with a standard direct genetic algorithm implementation.

Using Causal Models for the Calculation of Direct and Indirect Effects: An Example From Occupational Health

International audience

Indirect child mortality estimation technique to identify trends of under-five mortality in Ethiopia.

Background: In sub-Saharan African countries, the chance of a child dying before the age of five years is high. The problem is similar in Ethiopia, but it shows a decrease over years. Methods: The 2000; 2005 and 2011 Ethiopian Demographic and Health Survey results were used for this work. The purpose of the study is to detect the pattern of under-five child mortality overtime. Indirect child mortality estimation technique is adapted to examine the under-five child mortality trend in Ethiopia. Results: From the result, it was possible to see the trend of under-five child mortality in Ethiopia. The under-five child mortality shows a decline in Ethiopia. Conclusion: From the study, it can be seen that there is a positive correlation between mother and child survival which is almost certain in any population. Therefore, this study shows the trend of under-five mortality in Ethiopia and decline over time.

Comparative assessment of seller’s staining test (SST) and direct fluorescent antibody test for rapid and accurate laboratory diagnosis of rabies.

Background: Rabies causes 55, 000 annual human deaths globally and about 10,000 people are exposed annually in Nigeria. Diagnosis of animal rabies in most African countries has been by direct microscopic examination. In Nigeria, the Seller’s stain test (SST) was employed until 2009. Before then, both SST and dFAT were used concurrently until the dFAT became the only standard method. Objective: This study was designed to assess the sensitivity and specificity of the SST in relation to the ‘gold standard’ dFAT in diagnosis of rabies in Nigeria. Methods: A total of 88 animal specimens submitted to the Rabies National Reference Laboratory, Nigeria were routinely tested for rabies by SST and dFAT. Results: Overall, 65.9% of the specimens were positive for rabies by SST, while 81.8% were positive by dFAT. The sensitivity of SST in relation to the gold standard dFAT was 81.0% (95% CIs; 69.7% - 88.6%), while the specificity was 100% (95% CIs; 76% - 100%). Conclusion: The relatively low sensitivity of the SST observed in this study calls for its replacement with the dFAT for accurate diagnosis of rabies and timely decisions on administration of PEP to prevent untimely deaths of exposed humans.

Wind turbine indirect ice detection and operational analysis

Wind energy is one of the most promising and fast growing sector of energy production. Wind is ecologically friendly and relatively cheap energy resource available for development in practically all corners of the world (where only the wind blows). Today wind power gained broad development in the Scandinavian countries. Three important challenges concerning sustainable development, i.e. energy security, climate change and energy access make a compelling case for large-scale utilization of wind energy. In Finland, according to the climate and energy strategy, accepted in 2008, the total consumption of electricity generated by means of wind farms by 2020, should reach 6 - 7% of total consumption in the country [1]. The main challenges associated with wind energy production are harsh operational conditions that often accompany the turbine operation in the climatic conditions of the north and poor accessibility for maintenance and service. One of the major problems that require a solution is the icing of turbine structures. Icing reduces the performance of wind turbines, which in the conditions of a long cold period, can significantly affect the reliability of power supply. In order to predict and control power performance, the process of ice accretion has to be carefully tracked. There are two ways to detect icing – directly or indirectly. The first way applies to the special ice detection instruments. The second one is using indirect characteristics of turbine performance. One of such indirect methods for ice detection and power loss estimation has been proposed and used in this paper. The results were compared to the results directly gained from the ice sensors. The data used was measured in Muukko wind farm, southeast Finland during a project 'Wind power in cold climate and complex terrain'. The project was carried out in 9/2013 - 8/2015 with the partners Lappeenranta university of technology, Alstom renovables España S.L., TuuliMuukko, and TuuliSaimaa.

Synthesis of fluorescent dendrimeric antigen efficiently internalized by human dendritic cells

A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups has been synthetized. The synthesis implies a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD).[1] The introduction of a cystamine core allows the incorporation of this dendrons into a 1,8-naphthalimide fluorofore functionalized with a maleimide group. The fluorescence properties of this DeAn has been studied and compared with the properties of an equivalent dendron possessing amino-terminal groups. This DeAn has been used as a synthetic antigen in a biomedical assay that tests the amoxicillin sensitivity of dendritic cells (DC) from tolerant and allergic patients.

DESIGN, SYNTHESIS AND APPLICATIONS OF FLUORESCENT AND ELECTROCHEMICAL PROBES

“Seeing is believing” the proverb well suits for fluorescent imaging probes. Since we can selectively and sensitively visualize small biomolecules, organelles such as lysosomes, neutral molecules, metal ions, anions through cellular imaging, fluorescent probes can help shed light on the physiological and pathophysiological path ways. Since these biomolecules are produced in low concentrations in the biochemical pathways, general analytical techniques either fail to detect or are not sensitive enough to differentiate the relative concentrations. During my Ph.D. study, I exploited synthetic organic techniques to design and synthesize fluorescent probes with desirable properties such as high water solubility, high sensitivity and with varying fluorescent quantum yields. I synthesized a highly water soluble BOIDPY-based turn-on fluorescent probe for endogenous nitric oxide. I also synthesized a series of cell membrane permeable near infrared (NIR) pH activatable fluorescent probes for lysosomal pH sensing. Fluorescent dyes are molecular tools for designing fluorescent bio imaging probes. This prompted me to design and synthesize a hybrid fluorescent dye with a functionalizable chlorine atom and tested the chlorine re-activity for fluorescent probe design. Carbohydrate and protein interactions are key for many biological processes, such as viral and bacterial infections, cell recognition and adhesion, and immune response. Among several analytical techniques aimed to study these interactions, electrochemical bio sensing is more efficient due to its low cost, ease of operation, and possibility for miniaturization. During my Ph.D., I synthesized mannose bearing aniline molecule which is successfully tested as electrochemical bio sensor. A Ferrocene-mannose conjugate with an anchoring group is synthesized, which can be used as a potential electrochemical biosensor.

Pressure Induced Structural Changes and Gas Diffusion Pathways in Monomeric Fluorescent Proteins

Fluorescent proteins (FPs) are extremely valuable biochemical markers which have found a wide range of applications in cellular and molecular biology research. The monomeric variants of red fluorescent proteins (RFPs), known as mFruits, have been especially valuable for in vivo applications in mammalian cell imaging. Fluorescent proteins consist of a chromophore caged in the beta-barrel protein scaffold. The photophysical properties of an FP is determined by its chromophore structure and its interactions with the protein barrel. Application of hydrostatic pressure on FPs results in the modification of the chromophore environment which allows a systematic study of the role of the protein-chromophore interactions on photophysical properties of FPs. Using Molecular Dynamics (MD) computer simulations, I investigated the pressure induced structural changes in the monomeric variants mCherry, mStrawberry, and Citrine. The results explain the molecular basis for experimentally observed pressure responses among FP variants. It is found that the barrel flexibility, hydrogen bonding interactions and chromophore planarity of the FPs can be correlated to their contrasting photophysical properties at vaious pressures. I also investigated the oxygen diffusion pathways in mOrange and mOrange2 which exhibit marked differences in oxygen sensitivities as well as photostability. Such computational identifications of structural changes and oxygen diffusion pathways are important in guiding mutagenesis efforts to design fluorescent proteins with improved photophysical properties.

Synthetic approaches to flexible fluorescent conjugated polymers

Conjugated polymers (CPs) are intrinsically fluorescent materials that have been used for various biological applications including imaging, sensing, and delivery of biologically active substances. The synthetic control over flexibility and biodegradability of these materials aids the understanding of the structure-function relationships among the photophysical properties, the self-assembly behaviors of the corresponding conjugated polymer nanoparticles (CPNs), and the cellular behaviors of CPNs, such as toxicity, cellular uptake mechanisms, and sub-cellular localization patterns. ^ Synthetic approaches towards two classes of flexible CPs with well-preserved fluorescent properties are described. The synthesis of flexible poly( p-phenylenebutadiynylene)s (PPBs) uses competing Sonogashira and Glaser coupling reactions and the differences in monomer reactivity to incorporate a small amount (∼10%) of flexible, non-conjugated linkers into the backbone. The reaction conditions provide limited control over the proportion of flexible monomer incorporation. Improved synthetic control was achieved in a series of flexible poly(p-phenyleneethynylene)s (PPEs) using modified Sonogashira conditions. In addition to controlling the degree of flexibility, the linker provides disruption of backbone conjugation that offers control of the length of conjugated segments within the polymer chain. Therefore, such control also results in the modulation of the photophysical properties of the materials. ^ CPNs fabricated from flexible PPBs are non-toxic to cells, and exhibit subcellular localization patterns clearly different from those observed with non-flexible PPE CPNs. The subcellular localization patterns of the flexible PPEs have not yet been determined, due to the toxicity of the materials, most likely related to the side-chain structure used in this series. ^ The study of the effect of CP flexibility on self-assembly reorganization upon polyanion complexation is presented. Owing to its high rigidity and hydrophobicity, the PPB backbone undergoes reorganization more readily than PPE. The effects are enhanced in the presence of the flexible linker, which enables more efficient π-π stacking of the aromatic backbone segments. Flexibility has minimal effects on the self-assembly of PPEs. Understanding the role of flexibility on the biophysical behaviors of CPNs is key to the successful development of novel efficient fluorescent therapeutic delivery vehicles.^

Assessment of resting energy expenditure in pediatric mitochondrial diseases with indirect calorimetry

Mitochondrial diseases (MD) are the most frequent inborn errors of metabolism. In affected tissues, MD can alter cellular oxygen consumption rate leading to potential decreases in whole-body resting energy expenditure (REE), but data on pediatric children are absent. We determined, using indirect calorimetry (IC), whole-body oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and REE in pediatric patients with MD and healthy controls. Another goal was to assess the accuracy of available predictive equations for REE estimation in this patient population. IC data were obtained under fasting and resting conditions in 20 MD patients and 27 age and gender-matched healthy peers. We determined the agreement between REE measured with IC and REE estimated with Schofield weight and FAO/WHO/UNU equations. Mean values of VO2, VCO2 (mL·min-1·kg-1) or RQ did not differ significantly between patients and controls (P = 0.085, P = 0.055 and P = 0.626 respectively). Accordingly, no significant differences (P = 0.086) were found for REE (kcal·day-1 kg-1) either. On the other hand, although we found no significant differences between IC-measured REE and Schofield or FAO/WHO/UNU-estimated REE, Bland-Altman analysis revealed wide limits of agreement and there were some important individual differences between IC and equation-derived REE. VO2, VCO2, RQ and REE are not significantly altered in pediatric patients with MD compared with healthy controls. The energy demands of pediatric patients with MD should be determined based on IC data in order to provide the best possible personalized nutritional management for these children.