Distribution of lifetimes of kinetochore-microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization

Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an {\it in-vitro} experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the {\it in-vitro} experiments provided the experiment is repeated sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.Comment: This is an author-created, un-copyedited version of an article accepted for publication in "Physical Biology" (IOP). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Doctor of Philosophy

dissertationCell division is a complex process that involves carefully orchestrated chemical and mechanical events. Tight regulation is vital during division, since a breakdown in control mechanisms can lead to serious disorders such as cancer. A key step in division is the movement of chromosomes to specific locations in the cell with remarkable precision. In higher eukaryotes, the movement of chromosomes has been well observed over the course of hundreds of years. Yet, the mechanisms underlying chromosome motility and the control of precise chromosome localizations in the cell are poorly understood. More recently, a wealth of experimental data has become available for bacterial division. Despite the long supported theory that bacteria and eukaryotes differ widely when undergoing division, it is emerging that similar mechanisms for motility and cell cycle control might be at play in both cell types. Mathematical modeling is useful in the study of these dynamic cellular environments, where it is difficult to experimentally uncover the mechanisms that drive a multitude of mechanical and chemical events. In this dissertation, we develop various mathematical models that address the question of how dynamic polymers can move large objects such as chromosomes in higher eukaryotes and in bacteria. Then, we develop models that address how chemical and mechanical signals can be coordinated to control the precise localization of a chromosome. The mathematical models proposed here employ stochastic differential equations, ordinary differential equations and partial differential equations. The models are numerically simulated to obtain solutions for various parameter values, but we also use tools from bifurcation theory, asymptotic and perturbation methods for our model analysis. Our mathematical models can not only reproduce the experimental data at hand, but also make predictions about the mechanisms underlying chromosome motility in dividing cells

Sexual orientation, gender identity and non-discrimination - The Albanian labor legislation and its effects on employment and vocational training potentials

Albania is undergoing an important moment in its integration process to European Union. In this context, the Albanian legislation should compare with the best international standards, in guaranteeing the implementation of the rule of law, democratic principals, the citizen’s equity and the observance of fundamental human rights and freedoms. The promotion, protection and the guaranteeing of the fundamental rights and freedoms of the individual, including the LGBT person’s rights, must have the same attention and consideration, irrespective of the fact that the individual is being part of a social minor group, or part of the majority of the society. The community of the Lesbians, Gays, Bisexuals and Transgender (LGBT) in Albania, based on the legislation in force, should enjoy equal rights and freedoms like all other members of the society. The Constitution of the Republic of Albania, the Albanian labour legislation and the legislation generally, are inspired in accordance with the non-discrimination principles, objectives and definitions of international acts, promoting and expressing protection of human rights and freedoms in general, and in particular in the field of employment and vocational training. This paper will analyze, if the sexual orientation, is one of the causes of discrimination for employment and vocational training, in Albanian legislation, especially how it is expressed this issue on the Constitution of the Republic of Albania, the Albanian Labour Code, the Albanian law “On the protection against discrimination” ect

Drivers of internationalization of territorial development. The case of Albania

Mechanisms and trajectories triggered by globalization have largely influenced territorial development across the globe. Countries have tried to address territorial development with alternative fortunes due to the interlinked international and domestic economic, political, and social contingencies. In terms of sustainable land use, there have been enormous differences between the developed and under-developed countries. To overcome these territorial management imbalances, international actors have activated a number of initiatives aiming for a more coherent territorial development across the globe. Relevant actors like the United Nations Agencies, international development agencies, and the European Union EU have launched numerous territorial agendas aiming the assessment of the necessary actions to achieve a major balanced use of the territory. This paper explores the path of the drivers of a progressive internationalization of spatial planning practices. Its focus will be on Albania, which has recently introduced the reform of its national spatial development system, aiming at addressing its territorial challenges

Stochastic Analysis of a Mammalian Circadian Clock Model: Small Protein Number Effects

The circadian clock, responsible for coordinating organism function with daily and seasonal changes in the day-night cycle, is controlled by a complex protein network that constitutes a robust biochemical oscillator. Deterministic ordinary differential equation models have been used extensively to model the behavior of these central clocks. However, due to the small number of proteins involved in the circadian oscillations, mathematical models that track stochastic variations in the numbers of clock proteins may reveal more complex and biologically relevant behaviors. In this paper, we compare the response of a robust yet detailed deterministic model for the mammalian circadian clock with its corresponding stochastic version that takes into account low protein number noise. We then use signal analysis techniques in order to examine differences in behavior among components of the stochastic system oscillator. This approach reveals differences in the system response between the stochastic and deterministic model and also allows us to extend bifurcation analysis into the stochastic domain. From our analysis of the unfitted stochastic model, we propose novel explanations of some previous experimental results

The Research of Listeria Monocytogenes in the Fresh Meat of the Broilers in Poultry Abattoir Konsoni in Kosova

This study is initiated to define the level of contamination and possible contaminant factors of broiler's fresh meat with Listeria monocytogenes in poultry's abattoir Konsoni and realized from November 2013 to march 2014, where 72 samples of the fresh meat were tested. These samples were taken from carcasses of the broilers in abattoir during the process of slaughter in different phases. The analytical procedure is realized by using the norm horizontal method ISO 11290. From 72 samples analyzed, 18 samples resulted positive for Listeria spp. Biochemical test and CAMP-test confirmed 7 samples positive for Listeria monocytogenes. From all the samples analyzed, when expressing them in a percentage 25% resulted positive for Listeria spp, whereas 9.72% are positive with Listeria monocytogenes. The data taken tell that from 18 positive samples,16 of them were taken after the phase of eviscerating or as it is called ―cold part of the abattoir. The presence of the Listeria monocytogenes in the ―cold parts of the abattoir is related to the psychrophile nature of listeria. From the data gained we can conclude that the main origin of Listeria monocytogenes are the broilers itself, which they carry this bacterium in their viscera and after the evisceration it contaminates the carcasses and the premises of the abattoir.Keywords: Listeria monocytogenes, poultry’s abattoir, meat, carcass

New consideration for Biodiesel laboratory scale production using modeling and simulation techniques

Biodiesel is a material serving as a promising energy alternative to cover the demand of clean sustainable energy sources. Conventional biodiesel production is done by transesterification method using stirred tank reactor and homogeneous base or acid catalyst then followed by purification process. However, there are some disavantages related with this method. They include soap formation, sensitivity to free fatty acid (FFA) content and purification difficulties.Transesterification process depends upon a number of process parameters which are required to be optimized in order to maximize the biodiesel yield. In this paper we have worked for flow sheet constructions of Biodiesel small plant using computer simulating software. All the conclusion results will be shown in simulation part of paper. The core objective of this paper would to design and develop a profitable biodiesel production plantby examining all models