Shadow Price Guided Genetic Algorithms

The Genetic Algorithm (GA) is a popular global search algorithm. Although it has been used successfully in many fields, there are still performance challenges that prevent GA’s further success. The performance challenges include: difficult to reach optimal solutions for complex problems and take a very long time to solve difficult problems. This dissertation is to research new ways to improve GA’s performance on solution quality and convergence speed. The main focus is to present the concept of shadow price and propose a two-measurement GA. The new algorithm uses the fitness value to measure solutions and shadow price to evaluate components. New shadow price Guided operators are used to achieve good measurable evolutions. Simulation results have shown that the new shadow price Guided genetic algorithm (SGA) is effective in terms of performance and efficient in terms of speed

CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact

The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.Instituto de BiotecnologíaFil: Ishizaki, Takahiro. Umeå University. Department of Molecular Biology; SueciaFil: Ishizaki, Takahiro. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Hernandez, Sophia. Umeå University. Department of Molecular Biology; SueciaFil: Hernandez, Sophia. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paoletta, Martina. Umeå University. Department of Molecular Biology; SueciaFil: Paoletta, Martina. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Sanderson, Theo. Francis Crick Institute; Reino UnidoFil: Bushell, Ellen S. C. Umeå University. Department of Molecular Biology; SueciaFil: Bushell, Ellen S. C. The Laboratory for Molecular Infection Medicine Sweden (MIMS); Sueci

En funksjonell studie av det essensielle amidotransferasekomplekset MurT/CobQ i Streptococcus pneumoniae

The bacterial cell wall is responsible for maintaining cell shape and gives protection from osmotic lysis caused by turgor pressure. The major component of the cell wall in Gram-positive bacteria is the structurally complex biopolymer peptidoglycan. Streptococcus pneumoniae (Pneumococcus) is a Gram-positive human pathogen responsible for an estimated 1-2 million deaths annually worldwide. Studies of its cell wall synthesis machinery are of high academic interest and it can contribute to drug target discoveries, which have the potential to improve treatments in the future. The recently discovered essential amidotransferase complex MurT/CobQ, encoded by the operon murTcobQ, is in S. pneumoniae responsible for the amidation the peptidoglycan precursor lipid II. The amidation of the second residue γ-glutamate to isoglutamine in lipid II has previously been shown to be necessary for the transpeptidase activity of the peptidoglycan synthesising proteins, known as penicillin binding proteins (PBPs). What biological role this amidation plays is currently not known. In the present work depletion of MurT/CobQ expression has been used extensively to study how low levels of amidated lipid II affects the phenotype of S. pneumoniae. The sensitivity against the β−lactam antibiotics cefotaxime and ampicillin did not appear to be significantly affected by MurT/CobQ depletion, and neither did lysozyme resistance. The non-essential PBP1a is the only PBP to have reported residual transpeptidase activity with non-amidated lipid II in vitro. This proved difficult to demonstrate in vivo, and as such the results of these experiments were inconclusive. It was shown that depletion of MurT/CobQ severely affected the pneumococcal cells ability to properly divide, with septal cell wall synthesis being inhibited. The cells were still able to synthesize cell wall peripherally, strongly indicating that there is a difference between the septal and peripheral cell wall synthesising machineries in their ability to utilize non-amidated lipid II as substrate. The depletion of MurT/CobQ also affected the ability of the muralytic fratricide protein CbpD to successfully lyse cells, further strengthening the existing theory that this enzyme attacks the septal region of dividing cells. Furthermore this work demonstrated that in vivo, the PBPs are able to cross-link the stem peptides of the cell wall using non-amidated lipid II as substrate. Here it was shown that while the cell walls of normal pneumococcal cells contained a small amount of non-amidated stem-peptide dimers, cells depleted of MurT/CobQ contained significantly higher amounts of non-amidated stem-peptide dimers. Den bakterielle cellveggen gir bakteriecellene sin form og beskytter dem fra osmotisk lysis. Hovedkomponenten i celleveggen hos grampositive bakterier den komplekse biopolymeren peptidoglykan. Streptococcus pneumoniae er en grampositiv, humanpatogen bakterie som er ansvarlig for mellom 1-2 millioner dødsfall årlig på verdensbasis, og studier av celleveggssyntesen kan potensielt lede til forbedrede behandlingsmetoder i fremtiden. Det nylig oppdagede essensielle amidotransferasekomplekset MurT/CobQ, kodet av operonet murTcobQ, er ansvarlig for amideringen av peptidoglykanforløperen lipid II i S. pneumoniae. Amideringen av aminosyren γ−glutamat til isoglutamin i lipid II er tidligere vist å være nødvendig for transpeptidaseaktiviteten til de peptidoglykansyntetiserende enzymene (PBPer). Hvilken biologisk rolle denne amideringen spiller er for øyeblikket ukjent. I dette arbeidet har depletion (underuttrykk) av MurT/CobQ uttrykk blitt brukt for å studere hvordan lave konsentrasjoner av amidert lipid II påvirker fenotype hos S. pneumoniae. Sensitiviteten mot β−laktam antibiotikaene cefotaxim og ampicillin, samt lysozym ble ikke signifikant påvirket av MurT/CobQ depletion. Det ikke-essensielle enzymet PBP1a er det eneste som tidligere har vist en viss aktivitet med uamidert lipid II in vitro. Dette viste seg å være vanskelig å demonstrere in vivo, og resultatene fra disse forsøkene var mangelfulle. Arbeidet har vist at depletion av MurT/CobQ påvirker streptokokk-cellenes evne til å dele seg ved at den septale celleveggssyntesen blir inhibert. Cellene evnet fremdeles å syntetisere ny cellevegg i lengderetningen, noe som indikerer at der er en forskjell mellom de septale og perifere celleveggssyntesemaskinerienes evne til å bruke uamidert lipid II. Depletion av MurT/CobQ førte også til at det muralytiske fratricidproteinet CbpD ikke klarer å lysere celler, noe som bidrar til å styrke den rådende teorien om at dette proteinet angriper septum hos pneumokokker i delingsfasen. Videre viser denne studien at in vivo så evner PBPene å inkorporere og kryssbinde uamidert lipid II til en viss grad i celleveggen. Det ble vist at mens celleveggen til normale celler inneholdt en liten mengde uamiderte peptid-dimerer, så inneholdt MurTCobQ-depleted celler et signifikant høyere nivå av uamiderte peptid-dimerer.M-M

Nature-inspired survivability: Prey-inspired survivability countermeasures for cloud computing security challenges

As cloud computing environments become complex, adversaries have become highly sophisticated and unpredictable. Moreover, they can easily increase attack power and persist longer before detection. Uncertain malicious actions, latent risks, Unobserved or Unobservable risks (UUURs) characterise this new threat domain. This thesis proposes prey-inspired survivability to address unpredictable security challenges borne out of UUURs. While survivability is a well-addressed phenomenon in non-extinct prey animals, applying prey survivability to cloud computing directly is challenging due to contradicting end goals. How to manage evolving survivability goals and requirements under contradicting environmental conditions adds to the challenges. To address these challenges, this thesis proposes a holistic taxonomy which integrate multiple and disparate perspectives of cloud security challenges. In addition, it proposes the TRIZ (Teorija Rezbenija Izobretatelskib Zadach) to derive prey-inspired solutions through resolving contradiction. First, it develops a 3-step process to facilitate interdomain transfer of concepts from nature to cloud. Moreover, TRIZ’s generic approach suggests specific solutions for cloud computing survivability. Then, the thesis presents the conceptual prey-inspired cloud computing survivability framework (Pi-CCSF), built upon TRIZ derived solutions. The framework run-time is pushed to the user-space to support evolving survivability design goals. Furthermore, a target-based decision-making technique (TBDM) is proposed to manage survivability decisions. To evaluate the prey-inspired survivability concept, Pi-CCSF simulator is developed and implemented. Evaluation results shows that escalating survivability actions improve the vitality of vulnerable and compromised virtual machines (VMs) by 5% and dramatically improve their overall survivability. Hypothesis testing conclusively supports the hypothesis that the escalation mechanisms can be applied to enhance the survivability of cloud computing systems. Numeric analysis of TBDM shows that by considering survivability preferences and attitudes (these directly impacts survivability actions), the TBDM method brings unpredictable survivability information closer to decision processes. This enables efficient execution of variable escalating survivability actions, which enables the Pi-CCSF’s decision system (DS) to focus upon decisions that achieve survivability outcomes under unpredictability imposed by UUUR

Reduction of critical mass in a chemotaxis system by external application of a chemoattractant

In this paper we study non-negative radially symmetric solutions of a parabolic-elliptic Keller-Segel system. The system describes the chemotactic movement of cells under the additional circumstance that an external application of a chemo attractant at a distinguished point is introduced

Review of the demand driven funding system

In 2012, the Australian Government lifted previously imposed limits on the funding of bachelor-degree students at public universities. This new system was called ‘demand driven’ because it allowed universities to respond to student demand and allowed more students to benefit from higher education. On 12 November 2013 Minister for Education, the Hon Christopher Pyne, appointed a review panel to look at and make recommendations in relation to the demand driven funding arrangements. The review panel comprised the Hon Dr David Kemp and Mr Andrew Norton and is known as the Norton-Kemp review. The panel looked at the impacts of the demand driven system and whether it is increasing participation, improving access to students from poorer backgrounds and rural and regional areas, and meeting the skill needs of the economy. It explored whether there were any adverse impacts on quality and considered the long term sustainability of the system. The report found that public universities have responded well to changes under the demand driven system and improved access for all students. It found the new system has allowed universities to be more responsive to student needs, driven innovation and lifted quality. The reviewers made 19 findings and 17 recommendations, including extending the demand driven system to diplomas, advanced diplomas and associate degrees, and to private universities and non-university higher education providers such as TAFEs. The reviewers believe that extending the demand driven system will expand opportunities for students, and lead to further innovation in courses and modes of delivery, and in the quality of teaching and graduates

Security measurement as a trust in cloud computing service selection and monitoring

With the increase in the number of cloud service offerings by the cloud service providers nowadays, selecting the appropriate service provider becomes difficult for customers. This is true since most of the cloud service providers offer almost similar services at different costs. Thus, making cloud service selection a tedious process for customers. The selection of the cloud services from the security standpoint needs a distinct consideration from both the academia and the industry. Security is an important factor in cloud computing. Thus, any exploited vulnerability will have a negative effect on cloud computing adoption by customers. Hence, little attention has been paid to cloud service monitoring and selection from a security perspective. To solve this issue, we propose a security measurement as a trust (SMaaT) in the cloud computing selection. Finally, we propose Analytical Hierarchical Process (AHP) for service selection from the customers’ perspective

Towards privacy-aware mobile-based continuous authentication systems

User authentication is used to verify the identify of individuals attempting to gain access to a certain system. It traditionally refers to the initial authentication using knowledge factors (e.g. passwords), or ownership factors (e.g. smart cards). However, initial authentication cannot protect the computer (or smartphone), if left unattended, after the initial login. Thus, continuous authentication was proposed to complement initial authentication by transparently and continuously testing the users\u27 behavior against the stored profile (machine learning model). Since continuous authentication utilizes users\u27 behavioral data to build machine learning models, certain privacy and security concerns have to be addressed before these systems can be widely deployed. In almost all of the continuous authentication research, non-privacy-preserving classification methods were used (such as SVM or KNN). The motivation of this work is twofold: (1) studying the implications of such assumption on continuous authentication security, and users\u27 privacy, and (2) proposing privacy-aware solutions to address the threats introduced by these assumptions. First, we study and propose reconstruction attacks and model inversion attacks in relation to continuous authentication systems, and we implement solutions that can be effective against our proposed attacks. We conduct this research assuming that a certain cloud service (which rely on continuous authentication) was compromised, and that the adversary is trying to utilize this compromised system to access a user\u27s account on another cloud service. We identify two types of adversaries based on how their knowledge is obtained: (1) full-profile adversary that has access to the victim\u27s profile, and (2) decision value adversary who is an active adversary that only has access to the cloud service mobile app (which is used to obtain a feature vector). Eventually, both adversaries use the user\u27s compromised feature vectors to generate raw data based on our proposed reconstruction methods: a numerical method that is tied to a single attacked system (set of features), and a randomized algorithm that is not restricted to a single set of features. We conducted experiments using a public data set where we evaluated the attacks performed by our two types of adversaries and two types of reconstruction algorithms, and we have shown that our attacks are feasible. Finally, we analyzed the results, and provided recommendations to resist our attacks. Our remedies directly limit the effectiveness of model inversion attacks; thus, dealing with decision value adversaries. Second, we study privacy-enhancing technologies for machine learning that can potentially prevent full-profile adversaries from utilizing the stored profiles to obtain the original feature vectors. We also study the problem of restricting undesired inference on users\u27 private data within the context of continuous authentication. We propose a gesture-based continuous authentication framework that utilizes supervised dimensionality reduction (S-DR) techniques to protect against undesired inference attacks, and meets the non-invertibility (security) requirement of cancelable biometrics. These S-DR methods are Discriminant Component Analysis (DCA), and Multiclass Discriminant Ratio (MDR). Using experiments on a public data set, our results show that DCA and MDR provide better privacy/utility performance than random projection, which was extensively utilized in cancelable biometrics. Third, since using DCA (or MDR) requires computing the projection matrix from data distributed across multiple data owners, we proposed privacy-preserving PCA/DCA protocols that enable a data user (cloud server) to compute the projection matrices without compromising the privacy of the individual data owners. To achieve this, we propose new protocols for computing the scatter matrices using additive homomorphic encryption, and performing the Eigen decomposition using Garbled circuits. We implemented our protocols using Java and Obliv-C, and conducted experiments on public datasets. We show that our protocols are efficient, and preserve the privacy while maintaining the accuracy