Haemophilus influenzae Outer Membrane Proteins-Structure, Function and Virulence Mechanisms

Haemophilus influenzae is a Gram-negative bacterium that is classified by the presence or absence of a polysaccharide capsule, termed “typeable” and “non-typeable” H. influenzae (NTHi), respectively. Depending on the capsular polysaccharide composition and antigenicity, typeable isolates are further subdivided into six serotypes designated a–f. H. influenzae type b (Hib) has been the most common serotype causing invasive disease, for example, meningitis, epiglottitis, septicaemia, and osteomyelitis in former decades. Since the introduction of a Hib vaccine, the incidence of invasive Hib disease has significantly decreased. In contrast, the levels of invasive disease caused by other H. influenzae types, that is, NTHi and H. influenzae serotype f (Hif), is increasing, suggesting that NTHi and Hif are emerging pathogens. The mechanisms behind this emergence are not fully understood. To circumvent the bactericidal activities of the host antimicrobial peptides, complement system and nutritional immunity, many bacterial species, including H. influenzae, have evolved with several outer membrane proteins (OMPs) that play a role in subverting the host defense systems.This study covers the structural and functional analysis of three H. influenzae OMPs; Protein E (PE) from NTHi, Haemophilus Surface Fibril (Hsf) from Hib and, finally, Protein H (PH) from Hif, to understand the molecular pathogenicity of H. influenzae. We successfully crystallized and solved the atomic structure of the ubiquitous multifunctional surface protein PE at 1.8 Å resolution. The detailed structure of PE highlights how this important virulence factor of H. influenzae has the capacity to simultaneously interact with host Vitronectin (Vn), Laminin (Ln), or Plasminogen (PLG), promoting bacterial pathogenesis. We also showed that H. influenzae acquired hemin on the surface via PE, and shared it with hemin-depleted co-cultured bacteria, that is, PE worked as a hemin storage reservoir for H. influenzae. The trimeric autotransporter Hsf interacts with Vn, contributing to Hib serum resistance, better adherence and internalization into host cells. In silico analysis and experimental results demonstrated that the architecture of the trimeric autotransporter Hsf is not straight but rather a twisted, doubled over “hairpin-like” structure. We characterized PH as Vn-binding protein of Hif and discovered that it recognized the C-terminal part of Vn (aa 352–362). We found that PH-dependent Vn binding resulted in better survival of Hif in human serum and increased bacterial adherence to alveolar epithelial cells. Structural information of these OMPs will increase knowledge of H. influenzae virulence mechanisms. In addition, to develop vaccines or drugs against H. influenzae, targeting of OMPs are a potential key to provide protection against infectious Haemophilus spp. disease. Hence, functional studies on OMPs of H. influenzae in combination with the structural data provide a deeper understanding of host-pathogen interactions

Identifying Network-Biomarkers of Breast Cancer Survivability

One of the key challenges of breast cancer research is to predict whether a patient identified with specific subtype or treated with a specific therapy is going to survive or die. Current studies find small subsets of gene biomarkers able to accurately predict the response to therapy. In these studies, the selected genes are not necessarily functionally related, and hence, they may not correctly indicate the molecular mechanism behind breast cancer survivability. Also, several studies have shown there is a very low overlap between the different respective biomarkers subsets for the same cancer disease. To improve the robustness of classification performance and stability of detected biomarkers, recent methods take existing knowledge on relations between genes into account in the classifier, by aggregating functionality related genes to produce discriminative gene subnetworks called network-biomarkers. In this paper, given a breast cancer dataset of patients with different subtypes treated with a given therapy drug, we devised network-based machine learning approach by integrating protein protein interaction network (PPI) with gene expression data (1) to identify the network-biomarkers of breast cancer survivability a) based on subtypes and b) based on therapy and (2) to predict the survivability of breast cancer patients a) based on subtypes b) treated with a therapy drug. We used the concept of seed gene for identification of network-biomarkers with distance 2, 3 and 4 from seed gene protein and our method found distance 3 and $4$ are the distance that gives us best result for identifying survivability of breast cancer patient based on subtype and therapy respectively. To solve the class imbalance problem in some subtypes, we implemented ADASYN. We obtained best classification performance using random forest where the geometric mean, F1-measure and accuracy are respectively 0.867, 0.850 and 87.00% for subtype specific study, and 0.829, 0.807 and 83.77%, for therapy specific

Modified Cascaded H-Bridge Multilevel Inverter Using Particle Swarm Optimization

For more than two decades,multilevel inverters in different topologies and control strategies have been involved in many applications.In contrast to conventional three-level inverters,they are more efficient and better suited for applications requiring high power and high voltage levels.The current multilevel inverter topologies available in the market include diode clamped or neutral point clamped (NPC),capacitor clamped or flying capacitor (FC), and cascaded H-bridge (CHB).It is essential to produce an effective power converter from the perspective of cost,efficiency and output quality.These factors have lead to develop a new family of multilevel inverters known as modified CHB-MLIs of a single and three phases for five,nine and thirteen levels.This topology of the modified inverters requires fewer components compared to existing inverters (particularly in the higher levels) and requires fewer carrier signals and gate drives. Therefore,the overall cost and complexity are greatly reduced,particularly for higher output voltage levels.An important issue in the power electronic converters is the modulation control method in order to produce high quality output with a minimum distortion.As there exist many strategies for modulation, still the low-switching frequency technique is widely accepted in higher power applications.There are different optimization aims for different applications utilizing the low-switching frequency technique it is possible to increase the number of output voltage levels and produce a better sinusoidal output waveform and efficiency.The modified CHB-MLIs for five, nine and thirteen levels have a reduced number of DC power supplies and switches when compared to the conventional CHB topologies designed for the same number of voltage levels.The aim of this thesis is to investigate the performance of modified CHB-MLIs of a single and three phases for five,nine and thirteen levels based on cascaded multilevel inverter using low-switching frequency modulation scheme.The modulation method for obtaining the optimum switching angles based on Newton Raphson (NR) and Particle Swarm Optimization (PSO)control techniques have been proposed.A NR and PSO control techniques were presented for selective harmonics elimination (SHE) solution in a modified CHB-MLIs.These control techniques have been implemented through closed-loop control system using DSP TMS320F2812.In this thesis, the complete switching angles of the SHE has been developed by using a heuristic optimization technique namely PSO by solving the non-linear equation of the output voltage waveform and later validated with the conventional method NR.To validity of a low power prototype of the modified CHB-MLIs have been designed and implemented;analytical,simulation,and experimental results have been provided.The relative merits of the proposed modulation scheme based on the NR and PSO have been assessed based on modified inverters output quality and efficiency.Investigations of the proposed modulation scheme based on PSO have been revealed that the switching pattern of the adopted inverters has the capability of producing output voltage with minimal THD and high efficiency of the modified inverters.The results acquired from the simulation results the superiority of PSO over the conventional methods NR,where the THD reduction values in the three developed CHB-MLI namely five-level, nine level,and thirteen level are 15%,7.8%,and 5.2%, respectively

Towards Constructive Cost Analysis for demand based Reusable Domain Specific Components

The prevailing software development methodology embraced by a majority of organisations is characterised by its agility. The neglect of normal analysis and design procedures is a consequence of the significant pressures associated with designing a product within specified time and budget constraints. This phenomenon could potentially result in a death of software of superior quality, while simultaneously impeding the constructive reuse of components. In the majority of component approaches, the demand of domain specific sofwatre components occurs during the later stages. In this paper, various components can be identified as demand based reusbale domain specific software components, which might also help in reusing these components in the subsequent increments. The strategy for extraction of components & procedure for reusing the existing components is described and a sample case to realize the same is presented.Still there is a dire need to early identify  the demand based domain specific sofwatre components  and perform the constructive cost analysis for the reusable  domain specific software components. The issues related to the estimation of cost reuse measures are still challenging. This paper presents the constructuve cost analysis for the demand based reusable domain specific sofwtare components and proposes reuse measures for the family of applications with the quantized values. By analyzing these cost measures, the budget and effort in the development can be reduced. The results are estimated from the HR Portal domain specific softwrae application as a case study and its respective scenario has been explored in a better manner

Education: the quest for the lost wisdom in the maze of knowledge

A novel method to assess the complex Education process has been devised. The technique involves the quantification of Learning Outcome, which has hitherto been largely subjective and cumbersome despite the technological advance in learning and teaching aids. The new technique presents an objective assessment in a mathematical form. The approach is an innovated Metric Suit based on a measure of Entropy related to learning outcome. The ‘Information’ entropy is computed and used as a measure of Knowledge. Another learning outcome is the proper application of relevant knowledge termed ‘Wisdom’. Wisdom can also be measured using entropy computations. In this sense, entropy is related to the factor of disorder. The various parameters are represented by random variables. Because the amount of the required computations is very large, only the most effective of variables will be considered. The results obtained so far are encouraging. However, more tests on the proposed Metric Suit from various areas of application will further ascertain its robustness. Comprehensive tests and thorough analyses will provide a strong basis for evaluation judgment. The model treats the education process as a communications channel. The transfer of information between the sender and the recipient depends on the amount of uncertainty presented by each of the components that constitute the system. The computations of “Entropy” involve all the programs that constitute a discipline at university level

The JK System to Detect Plagiarism

In this research a system, referred to as Jubair-Khaireddin (JK), has been developed to assess the degree of similarity between two programs even though they look superficially dissimilar. The JK system has the capability to detect deliberate attempts of plagiarism. Reverse engineering technique is used to bring each suspected program back to its initial specification stage. This operation enables us to extract the structure of the program which is an important factor in detecting plagiarism. This can be achieved through the extraction of the Static Execution Tree (SET) for each program. The SET is then transformed into Terminating Binary Sequence (TBS). The TBSs generated from the tested programs are compared in order to get similar branches. Reengineering technique is then applied on these similar branches in order to compute its entropy (information content). The entropy is computed to prove or disprove the existence of similarities between programs. The JK system has been tested on different Java programs with different modifications, and proved successful in detecting almost all cases including those of partially plagiarised programs.Facultad de Informátic

Utilization of waste as a constituent ingredient for enhancing thermal performance of bricks – a review paper

In view of the environmental regulations, practitioners have been inclined to use bricks with higher insulation capability, however with minimal attention to sustainable material composition, let alone waste material. From a research perspective, in the wake of the growing concerns for the environment, the use of waste material to develop bricks which can exhibit suitable characteristics attributed to the material composition has been on the rise. However, the extant literature on utilization of waste materials for brick mix design has neglected to provide detailed literature review on the influence of waste materials on the thermal performance of bricks. Methods: This paper provides detailed review of research conducted on thermal properties of bricks produced from various types of waste. Influence of the method of manufacturing and type of waste on thermal performance of bricks is discussed. A sustainability selection criteria format is provided to assist optimal decision making in considering alternative sustainable waste material. Findings: A sustainability selection criteria format is provided to assist optimal decision making in considering alternative sustainable waste material. Applications: The outcome of this paper can serve as a common reference for practitioners and researchers attempting to seek out solutions for further improving overall quality of thermally insulated waste-incorporated bricks, paving the way for more focused research on waste utilization in the development of more sustainable wall material based on the current brick production process

The unique structure of Haemophilus influenzae protein E reveals multiple binding sites for host factors.

Haemophilus influenzae protein E (PE) is a multifunctional adhesin, involved in direct interactions with lung epithelial cells and host proteins, including plasminogen and the extracellular matrix proteins vitronectin and laminin. We recently crystallized PE and successfully collected X-ray diffraction data to 1.8 Å. Here we solved the structure of a recombinant version of PE and analyzed different functional regions. It is a dimer in solution and in the asymmetric unit of the crystals. The dimer has a structure that resembles a flattened β-barrel. It is however not a true β-barrel as there are differences in both the hydrogen bonding pattern and the shape. Each monomer consisted of a 6-stranded antiparallel β-sheet with a rigid α-helix at the C-terminal tethered to the concave side of the sheet by a disulfide bridge. The laminin/plasminogen binding region (residues 41-68) is exposed, while the vitronectin binding region (residues 84-108) is partially accessible in the dimer. The dimerized PE explains the simultaneous interaction with laminin and vitronectin. In addition, we found this unique adhesin being present in many bacterial genera of the family Pasteurallaceae and also orthologues in other unrelated species (Enterobacter cloacae and Listeria monocytogenes). Peptides corresponding to the surface-exposed regions PE24-37, PE74-89, and PE134-156 were immunogenic in the mouse. Importantly, these peptide-based antibodies also recognised PE at the bacterial surface. Taken together, our detailed structure of PE explains how this important virulence factor of H. influenzae simultaneously interacts with host vitronectin, laminin or plasminogen promoting bacterial pathogenesis

Particle Swarm Optimization (PMO) Algorithm With Reduced Number Of Switches In Multilevel Inverter (MLI)

In this work, a three-phase of multilevel inverter (MLI) with reduced number of switches components based on Newton Raphson (NR) and Particle Swarm Optimization (PSO) techniques were presented. The Selective Harmonic Elimination Pulse-Width Modulation (SHE-PWM) is a powerful technique for harmonic minimization in multilevel inverter within allowable limits. NR and PSO techniques were used to determine the switching angles by solving the non-linear equation's analysis of the output voltage waveform of the modified CHB-MLI in order to control the fundamental component. A comparison has been made between NR and PSO techniques related to optimization in order minimize harmonic distortion. The main aims of this paper cover design, modeling, construction the modified topology of the CHB-MLI for a three phase five levels inverter. The controllers based on NR and PSO were applied to the modified multilevel inverter. The inverter offers much less THD using PSO scheme compared with the NR scheme. The performance of the proposed controllers based on NR and PSO techniques done by using MATLAB/Simulink of results are compared

Aggregated Modelling Analysis Of Power Flow From Wind Power Plant Into Grid System Using MATLAB/ SIMULINK Software

In consistent with the growth in demand, complexity of electric power systems has evolved to meet the requirements of supply. Power is generated from non-renewable, fossil fuels and nuclear fuel while renewable energy resources mainly include solar and wind. Power from Wind plants WP has shown a fast growth in the last decades due to their economic benefits especially at areas with the proper wind speed and the possibility to connect wind generators in distribution or transmission power networks. Conventional power unit generators are of high generation capacities, therefore smaller numbers are required in power plant, in other hand wind turbines WP are of smaller capacities therefore, Wind Power Plants (WPPs) consist of dozens or hundreds of low-power units. Time domain simulations of WPPs may take too much time if detailed models are considered in such studies while reduced order models used in interconnection studies of synchronous machines with full converter technology significantly reduce computational time (1, 2). The performance of all models is evaluated based on time domain simulations in the Simulink/MATLAB environment. The work includes the simulation of 50 MW WPP constructed from 18 MW doubly fed induction generators (DFIGs) aggregated (reduced) to one system of Nx2.78 MW generation capacity interconnected to existing conventional system network through 132 kV grid. The analysis includes active and power flow at the farm and the PCC terminals also power flow at PCC has been assessed for different level of WP penetration. Outputs from the MATLAB/SIMULINK modeling and simulation introduces the level of the grid voltage, current active and reactive power in the PCC and the wind farm terminal