Evolution of regulatory complexes: a many-body system

The recent advent of large-scale genomic sequence data and improvement of sequencing technologies has enabled population genetics to advance from a mostly abstract theoretical basis to a quantitative molecular description. However, functional units in DNA are typically combinations of interacting nucleotide segments, and evolutionary forces acting on these segments can result in very complicated population dynamics. The goal is to formulate these interactions in such a way that the macroscopic features are independent of the microscopic details, as in statistical mechanics. In this thesis, I discuss the evolutionary dynamics of regulatory sequences, which control the production of protein in cells. One of the primary forms of regulation occurs through interactions of proteins called transcription factors, with binding sites in the DNA sequence, and the strength of these interactions influence the individual's fitness in the population. What makes this an ideal model system for quantitative analysis of genomic evolution, is the possibility of inferring this relationship. Compared to prokaryotes and yeast, gene regulation is much more complex in higher eukaryotes. Regulatory information is organized in modules with multiple binding sites that are linked to a common function. In Chapter. 2, we show that binding site complexes are commonly formed by local sequence duplications, as opposed to forming from scratch by single point mutations. We also show that the underlying regulatory grammar is in tune with this mechanism such that the duplication events confer an adaptive advantage. Regulatory complexes resemble a many-particle system whose function emerges from the collective dynamics of its elements. In Chapter. 3, we develop a thermodynamic framework to characterize the effective affinity of site complexes to multiple transcription factors with cooperative binding. These affinities are the phenotype, or trait of binding complexes on which selection acts, and we characterize their evolution. From the yeast genome polymorphism data, we infer a fitness landscape as a function of binding affinity by using the novel method developed in Chapter.~ 4. This method of quantitative trait analysis can deal with long-range correlations between sites which arise in asexual populations. Our fitness landscape quantitatively predicts the amount of conservation of the phenotype, as well as the amount of compensatory changes between sites. Our results open a new avenue to understand the regulatory "grammar" of eukaryotic genomes based on quantitative evolution models. They prove that a combination of theoretical models, high-throughput experimental measurements, and analysis of genomic variation is necessary for a proper quantitative understanding of biological systems

Treatment of Syrian Phosphogypsum using Acids and Bases

Phosphogypsum is a technologically enhanced naturally occurring radioactive material (TE-NORM) that contains radionuclides from 238U and 232Th decay series which are of most radio-toxicity. The reduction in concentration of radionuclides content from PG was based on leaching of 226Ra, 210Pb, U and 40K using different chemicals.The factors which affect the leaching process such as leaching reagent, concentration of the proposed reagent, liquid-solid ratio, contact time, temperature and multi leaching effect were optimized. Based on the experimental results, about 79.4%, 57.9%, 65.7% and 89.8% of U, 226Ra, 210Pb and 40K respectively, were successfully removed from the PG under optimum conditions ( HNO3, concentration (4M), liquid-solid ratio mL-gr(1-1), contact time (2h), temperature (60°C) and three leaching steps). Using this treatment of PG waste leads to obtain a decontaminated product that can be safely used in many industrial applications. Keywords: Phosphogypsum waste, Leaching process, Radioactive materials, TENORM

Investigations of elastin recoil on molecular and macroscopic levels.

Elastin is one of the most hydrophobic proteins, and it is extremely flexible when hydrated. The driving force for recoil is the decrease in entropy of the protein and/or the hydrating solvent. This dissertation is a study of both mechanisms. Following an introduction (Chapter 1), Chapters 2 and 3 investigate the recoil mechanism on the molecular level in the hydrating solvent and in the protein, respectively. Chapter 4 examines macroscopic properties of recoil by thermomechanics. Conclusions are discussed in Chapter 5. Using double quantum NMR, the deuterated water ordering at the elastin surface was studied quantitatively as a function of stretch and in the presence of solutes known to modulate the hydrophobic effect: polyethylene glycol (PEG), sulfate ion, a kosmotrope, and perchlorate ion, a chaotrope. When the purified elastin is stretched, a nearly one order of magnitude increase in the ordering of water is observed, and this is due to the increase in water exposed to the hydrophobic surface. When PEG and sulfate ions are added to the solvent, ordering of the water is significantly decreased due to a more compact protein with reduced solvent exposed surface area. At concentrations below 0.3 mol/kg perchlorate ion, only minor changes in the magnitude of the ordered water signal are observed because perchlorate interacts with peptide bonds and does not decrease exposed hydrophobic surface area. Ordering of elastin was studied using static 13C NMR to assess the amplitude of backbone motions in the mature elastic material. It was found that the residual shielding anisotropy is small, 1 – 3 ppm and within the experimental resolution of this experiment, no stretch induced ordering was observed. Thus, cross-linked elastin is dynamically disordered much like soluble minielastins. The thermomechanical experiments show that elastin is stiffer in the presence of PEG, sulfate and high perchlorate concentrations. These solutes do not interact with the protein and decrease the volume and the length of the fiber, confirming the increase in compaction. Also, they decrease the heat liberated, the change in entropy and the internal energy with stretch. Thus, the hydrophobic effect is the major player in elastin recoil

Where is My Next Hop ? The Case of Indian Ocean Islands

Internet has become a foundation of our modern society. However, all regions or countries do not have the same Internet access regarding quality especially in the Indian Ocean Area (IOA). To improve this quality it is important to have a deep knowledge of the Internet physical and logical topology and associated performance. However, these knowledges are not shared by Internet service providers. In this paper, we describe a large scale measurement study in which we deploy probes in different IOA countries, we generate network traces, develop a tool to extract useful information and analyze these information. We show that most of the IOA traffic exits through one point even if there exists multiple exit points

Optimisation of road safety treatment strategies through crash modification factors and simulation

Road safety has become an intensively studied topic with an overarching aim of better understanding why road crashes occur and thus to reduce both frequency and severity. If it is known why road crashes occur, agencies should be able to better apply more effective and efficient road safety improvement strategies. The aim of the traffic engineer is to design and provide a safe travel environment to the road user. While road crashes cannot be completely prevented, a sound understanding of the causative factors helps to minimise crash rate. Crash occurrences can be viewed as a result of the interaction of numerous variables including road geometry, vehicle condition, and operational conditions such as speed and traffic volume. The main objective of this research was to evaluate traffic and geometric road features and their influences on the safety performance of road intersections, roundabouts, and road segments by estimating suitable crash modification factors (CMFs). To accomplish the study objective, crash prediction models (CPMs) were developed using a generalised linear model (GLM) technique, i.e. Poisson or negative binomial (NB) distribution. The regional area of Toowoomba City, Australia was adopted as the case study. Traffic, geometric, and crash data on 106 road intersections for the years 2008-2015, as well as 49 roundabouts and 84 roadway segments for years the 2010-2015 were used for crash modelling and evaluation. The NB distribution was adopted in preference to Poisson distribution as the data showed over-dispersion. Several goodness-of-fit (GOF) tests were performed on the developed models to identify the better-fitting models. These models were then validated using both the estimation and validation datasets. An accurate identification of hazardous road locations (HRLs) prevents wasted resources that may result if possible improvements at such locations are identified with less accuracy. The Empirical-Bayes (EB) approach was employed to identify the HRLs in the study area. This approach was adopted to provide more accurate safety estimation by accounting for the regression-to-the-mean bias usually associated with the road crash data. The HRLs were then ranked based on their potential for safety improvement (PSI) value, which is the difference between the expected and predicted road crashes at each location. The top 10 poorly performing locations for each of theroad intersections, roundabouts, and road segments were identified for further investigation. The CMFs identify any change in the safety performance resulting from implementing a particular treatment. In this study, CMFs were used to estimate the effect of the various proposed safety treatments at identified HRLs. The cross-sectional method (regression approach) was applied to estimate CMFs for individual safety treatment. This method has been considered recently and has not been extensively applied, however, it can be considered as a viable alternative method to estimate the CMFs in cases where observational before-and-after studies are not practical due to data restrictions. In order to estimate the variation in the values of CMF with different sites characteristics, the crash modification functions (CMFunctions) were developed. Using CMFunctions, the safety effects of various traffic and geometric elements of different road facilities (i.e., intersections, roundabouts, and roadway segments) were investigated. The study also notes that while there has been substantial research in the broad area, very few studies have been undertaken to estimate CMFs for the combined effect of multiple safety treatments. However, the four most suitable techniques for estimating combined CMFs were reviewed and applied together to propose effective safety measures for the HRLs. Since there were variations in the estimation of combined CMFs using the four techniques, the average values were adopted as the best approach to estimate the effect of combined treatments. The results demonstrated that multiple treatments have higher safety effects (i.e., lower CMF) than single treatments. The results also indicated that the effect of treatments on road safety does not depend on the number of treatments that have been applied but rather depend on environment. The traffic simulation software PTV VISSIM 9.0 was employed to assess the traffic operational performance before and after safety treatment implementation. The top 10 HRLs for each of the road facilities were simulated and evaluated under different scenarios in terms of level of service (LOS), traffic delay, travel time, and average speed. The results showed that there is no significant degradation of traffic operations expected at treated locations. Finally, a benefit analysis was conducted to estimate the savings during the 10 years after applying the proposed treatments. The crash reduction factors and crash costs were utilised to estimate the crash cost reduction that was associated with single and combined treatments. Such estimation can support road authorities and practitioners to select the final treatment plans for the identified HRLs by undertaking benefit-cost analysis to assist the decision-making process. Contributions of this research can be summarised as: (i) to develop CPMs for different types of road facilities, (ii) to develop CMFunctions to estimate the variation in the values of CMF with different sites characteristics, (iii) to propose a methodology to identify the most appropriate safety treatments (single and multiple treatments) using CMFs, costing and simulation packages. The research has also identified some important aspects for future research to extend the present work

Judicial enforceability of economic, social and cultural rights in Bangladesh : a critical evaluation

The implementation of economic, social and cultural rights (esc rights) continues to pose uncertainties in the modern world. Given that many states constitutionally treat such rights as aspirational and not justiciable, it is difficult to enforce them judicially at the domestic level. Bangladesh has embodied these rights in Part ii of its Constitution as a social welfare goal of the State. This article takes Bangladesh as a case study and examines the international legal framework for the implementation of esc rights at the domestic level. Making a comparison with other jurisdictions, such as India and South Africa, the article examines the approach of the judiciary of Bangladesh (the Supreme Court) in giving effect to these rights. Lastly, the article argues that the court should devise appropriate and effective enforcement mechanisms for these rights

Laparoscopic versus open surgery for treatment of colorectal cancer

Background: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer in United States and has the second highest cancer related mortality rate after lung cancer. Cancer of the colon is equally frequent in men and women while cancer of the rectum occur 20-50% more frequently in men. This study aimed to compare the outcome of laparoscopic and open approach in surgical management of colorectal carcinoma and to better selection of the best procedure for treatment of colorectal cancer.Patients and Method: This prospective randomized study included 18 cases who underwent colorectal surgeries during the period October, 2019 till October, 2020 in the Surgery Unit at Zagazig Faculty of Medicine. These patients were subdivided into equal two groups: 9 cases underwent the open approach while the remaining 9 cases underwent the laparoscopic approach, with a period of one year follow up postoperative. Results: Intraoperatively, the laparoscopic group showed some cons like total operative time (p = 0.001) and time needed for dissection (p < 0.001), which were significantly higher when compared to the open group. In the postoperative period, close monitoring of all clinical and laboratory parameters was performed with bedside imaging by ultrasound in indicated cases. The laparoscopic group took the upper hand over open group regarding day of first motion, when to start oral intake and hospital stay (p = <0.001, <0.001 and 0.002 respectively).Conclusion: Analysis of the scientific literature confirmed that for the curative treatment of colon and rectal cancer, laparoscopy is not inferior to open surgery with respect to overall survival, disease-free survival and rate of recurrence

Determination of Temperature Zoning for the Great Lakes Region of Africa Based on Superpave System

"Majority of the countries in the Great Lakes region of Africa still rely on the traditional Penetration grading approach for characterizing asphalt binder, as opposed to the more recent and reliable approach of SuperPave (Superior Performing Asphalt Pavements). This paper outlines the steps and criteria of selecting Performance Grade (PG) of bitumen to be used in selected countries of the Great Lakes region, based on the SuperPave approach. In Superpave, high-temperature (HT) Performance Grade required for a given region of project is determined based on a rutting damage model. HT equation is a function of layer thickness, climatic conditions, and latitude of the site (Mohseni et al, 2005); whereas, Low-temperature (LT) Performance Grade is selected using an algorithm developed from LTPP climatic data, and that relates the minimum pavement temperature to minimum air temperature, latitude, and depth (Mohseni, 1998). Study of climatic conditions of selected countries (Uganda, Kenya and Tanzania) in the great lakes region shows that the maximum pavement design temperature is 64 ºC, while the minimum pavement design temperature is -10 ºC. Further, the temperature zoning is distributed into three geographical areas, namely PG 64-10, PG 58-10 and PG 52-10 according to the collected and studied data.

Anti- Forensics: The Tampering of Media

In the context of forensic investigations, the traditional understanding of evidence is changing where nowadays most prosecutors, lawyers and judges heavily rely on multimedia signs. This modern shift has allowed the law enforcement to better reconstruct the crime scenes or reveal the truth of any critical event.In this paper we shed the light on the role of video, audio and photos as forensic evidences presenting the possibility of their tampering by various easy-to-use, available anti-forensics softwares. We proved that along with the forensic analysis, digital processing, enhancement and authentication via forgery detection algorithms to testify the integrity of the content and the respective source of each, differentiating between an original and altered evidence is now feasible. These operations assist the court to attain higher degree of intelligibility of the multimedia data handled and assert the information retrieved from each that support the success of the investigation process

Evaluation of the efficacy of low-level laser in improving the symptoms of burning mouth syndrome

Background: Burning mouth syndrome (BMS) is common condition that affects menopause women, patients suffer from sever burning sensation. Up to now there is no definitive treatment for this disease. Present study was undertaken to evaluate the efficacy of low-level laser (LLL) in improving t he symptoms of burning mouth syndrome. Material and Methods: Twenty patients with BMS were enrolled in this study; they were divided in two groups randomly. In the laser group, in each patient, 10 areas on the oral mucosa were selected and underwent LLL irradiation at a wavelength of 630 nm, and a power of 30 mW for 10 seconds twice a week for 4 weeks. In the placebo group, silent/off laser therapy was carried out during the same period in the same areas. Burning sensation and quality of life were evaluated. Results: Burning sensation severity and quality of life in the two groups after intervention were different significant statistically, ( P = 0.004, P = 0.01 respectively) .Patients in laser group had better results. Conclusions: It can be concluded that low level laser might decrease the intensity of burning mouth syndrom