Rethinking Distributed Caching Systems Design and Implementation

Distributed caching systems based on in-memory key-value stores have become a crucial aspect of fast and efficient content delivery in modern web-applications. However, due to the dynamic and skewed execution environments and workloads, under which such systems typically operate, several problems arise in the form of load imbalance. This thesis addresses the sources of load imbalance in caching systems, mainly: i) data placement, which relates to distribution of data items across servers and ii) data item access frequency, which describes amount of requests each server has to process, and how each server is able to cope with it. Thus, providing several strategies to overcome the sources of imbalance in isolation. As a use case, we analyse Memcached, its variants, and propose a novel solution for distributed caching systems. Our solution revolves around increasing parallelism through load segregation, and solutions to overcome the load discrepancies when reaching high saturation scenarios, mostly through access re-arrangement, and internal replication.Os sistemas de cache distribuídos baseados em armazenamento de pares chave-valor em RAM, tornaram-se um aspecto crucial em aplicações web modernas para o fornecimento rápido e eficiente de conteúdo. No entanto, estes sistemas normalmente estão sujeitos a ambientes muito dinâmicos e irregulares. Este tipo de ambientes e irregularidades, causa vários problemas, que emergem sob a forma de desequilíbrios de carga. Esta tese aborda as diferentes origens de desequilíbrio de carga em sistemas de caching distribuído, principalmente: i) colocação de dados, que se relaciona com a distribuição dos dados pelos servidores e a ii) frequência de acesso aos dados, que reflete a quantidade de pedidos que cada servidor deve processar e como cada servidor lida com a sua carga. Desta forma, demonstramos várias estratégias para reduzir o impacto proveniente das fontes de desequilíbrio, quando analizadas em isolamento. Como caso de uso, analisamos o sistema Memcached, as suas variantes, e propomos uma nova solução para sistemas de caching distribuídos. A nossa solução gira em torno de aumento de paralelismo atraves de segregação de carga e em como superar superar as discrepâncias de carga a quando de sistema entra em grande saturação, principalmente atraves de reorganização de acesso e de replicação intern

Nomadic fog storage

Mobile services incrementally demand for further processing and storage. However, mobile devices are known for their constrains in terms of processing, storage, and energy. Early proposals have addressed these aspects; by having mobile devices access remote clouds. But these proposals suffer from long latencies and backhaul bandwidth limitations in retrieving data. To mitigate these issues, edge clouds have been proposed. Using this paradigm, intermediate nodes are placed between the mobile devices and the remote cloud. These intermediate nodes should fulfill the end users’ resource requests, namely data and processing capability, and reduce the energy consumption on the mobile devices’ batteries. But then again, mobile traffic demand is increasing exponentially and there is a greater than ever evolution of mobile device’s available resources. This urges the use of mobile nodes’ extra capabilities for fulfilling the requisites imposed by new mobile applications. In this new scenario, the mobile devices should become both consumers and providers of the emerging services. The current work researches on this possibility by designing, implementing and testing a novel nomadic fog storage system that uses fog and mobile nodes to support the upcoming applications. In addition, a novel resource allocation algorithm has been developed that considers the available energy on mobile devices and the network topology. It also includes a replica management module based on data popularity. The comprehensive evaluation of the fog proposal has evidenced that it is responsive, offloads traffic from the backhaul links, and enables a fair energy depletion among mobiles nodes by storing content in neighbor nodes with higher battery autonomy.Os serviços móveis requerem cada vez mais poder de processamento e armazenamento. Contudo, os dispositivos móveis são conhecidos por serem limitados em termos de armazenamento, processamento e energia. Como solução, os dispositivos móveis começaram a aceder a estes recursos através de nuvens distantes. No entanto, estas sofrem de longas latências e limitações na largura de banda da rede, ao aceder aos recursos. Para resolver estas questões, foram propostas soluções de edge computing. Estas, colocam nós intermediários entre os dispositivos móveis e a nuvem remota, que são responsáveis por responder aos pedidos de recursos por parte dos utilizadores finais. Dados os avanços na tecnologia dos dispositivos móveis e o aumento da sua utilização, torna-se cada mais pertinente a utilização destes próprios dispositivos para fornecer os serviços da nuvem. Desta forma, o dispositivo móvel torna-se consumidor e fornecedor do serviço nuvem. O trabalho atual investiga esta vertente, implementado e testando um sistema que utiliza dispositivos móveis e nós no “fog”, para suportar os serviços móveis emergentes. Foi ainda implementado um algoritmo de alocação de recursos que considera os níveis de energia e a topologia da rede, bem como um módulo que gere a replicação de dados no sistema de acordo com a sua popularidade. Os resultados obtidos provam que o sistema é responsivo, alivia o tráfego nas ligações no core, e demonstra uma distribuição justa do consumo de energia no sistema através de uma disseminação eficaz de conteúdo nos nós da periferia da rede mais próximos dos nós consumidores

Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly

The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule’s assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.United States. Office of Naval Research (Presidential Early Career Award for Scientists and Engineers)National Institutes of Health (U.S.) (U01 EB014976

SoS: self-organizing substrates

Large-scale networked systems often, both by design or chance exhibit self-organizing properties. Understanding self-organization using tools from cybernetics, particularly modeling them as Markov processes is a first step towards a formal framework which can be used in (decentralized) systems research and design.Interesting aspects to look for include the time evolution of a system and to investigate if and when a system converges to some absorbing states or stabilizes into a dynamic (and stable) equilibrium and how it performs under such an equilibrium state. Such a formal framework brings in objectivity in systems research, helping discern facts from artefacts as well as providing tools for quantitative evaluation of such systems. This thesis introduces such formalism in analyzing and evaluating peer-to-peer (P2P) systems in order to better understand the dynamics of such systems which in turn helps in better designs. In particular this thesis develops and studies the fundamental building blocks for a P2P storage system. In the process the design and evaluation methodology we pursue illustrate the typical methodological approaches in studying and designing self-organizing systems, and how the analysis methodology influences the design of the algorithms themselves to meet system design goals (preferably with quantifiable guarantees). These goals include efficiency, availability and durability, load-balance, high fault-tolerance and self-maintenance even in adversarial conditions like arbitrarily skewed and dynamic load and high membership dynamics (churn), apart of-course the specific functionalities that the system is supposed to provide. The functionalities we study here are some of the fundamental building blocks for various P2P applications and systems including P2P storage systems, and hence we call them substrates or base infrastructure. These elemental functionalities include: (i) Reliable and efficient discovery of resources distributed over the network in a decentralized manner; (ii) Communication among participants in an address independent manner, i.e., even when peers change their physical addresses; (iii) Availability and persistence of stored objects in the network, irrespective of availability or departure of individual participants from the system at any time; and (iv) Freshness of the objects/resources' (up-to-date replicas). Internet-scale distributed index structures (often termed as structured overlays) are used for discovery and access of resources in a decentralized setting. We propose a rapid construction from scratch and maintenance of the P-Grid overlay network in a self-organized manner so as to provide efficient search of both individual keys as well as a whole range of keys, doing so providing good load-balancing characteristics for diverse kind of arbitrarily skewed loads - storage and replication, query forwarding and query answering loads. For fast overlay construction we employ recursive partitioning of the key-space so that the resulting partitions are balanced with respect to storage load and replication. The proper algorithmic parameters for such partitioning is derived from a transient analysis of the partitioning process which has Markov property. Preservation of ordering information in P-Grid such that queries other than exact queries, like range queries can be efficiently and rather trivially handled makes P-Grid suitable for data-oriented applications. Fast overlay construction is analogous to building an index on a new set of keys making P-Grid suitable as the underlying indexing mechanism for peer-to-peer information retrieval applications among other potential applications which may require frequent indexing of new attributes apart regular updates to an existing index. In order to deal with membership dynamics, in particular changing physical address of peers across sessions, the overlay itself is used as a (self-referential) directory service for maintaining the participating peers' physical addresses across sessions. Exploiting this self-referential directory, a family of overlay maintenance scheme has been designed with lower communication overhead than other overlay maintenance strategies. The notion of dynamic equilibrium study for overlays under continuous churn and repairs, modeled as a Markov process, was introduced in order to evaluate and compare the overlay maintenance schemes. While the self-referential directory was originally invented to realize overlay maintenance schemes with lower overheads than existing overlay maintenance schemes, the self-referential directory is generic in nature and can be used for various other purposes, e.g., as a decentralized public key infrastructure. Persistence of peer identity across sessions, in spite of changes in physical address, provides a logical independence of the overlay network from the underlying physical network. This has many other potential usages, for example, efficient maintenance mechanisms for P2P storage systems and P2P trust and reputation management. We specifically look into the dynamics of maintaining redundancy for storage systems and design a novel lazy maintenance strategy. This strategy is algorithmically a simple variant of existing maintenance strategies which adapts to the system dynamics. This randomized lazy maintenance strategy thus explores the cost-performance trade-offs of the storage maintenance operations in a self-organizing manner. We model the storage system (redundancy), under churn and maintenance, as a Markov process. We perform an equilibrium study to show that the system operates in a more stable dynamic equilibrium with our strategy than for the existing maintenance scheme for comparable overheads. Particularly, we show that our maintenance scheme provides substantial performance gains in terms of maintenance overhead and system's resilience in presence of churn and correlated failures. Finally, we propose a gossip mechanism which works with lower communication overhead than existing approaches for communication among a relatively large set of unreliable peers without assuming any specific structure for their mutual connectivity. We use such a communication primitive for propagating replica updates in P2P systems, facilitating management of mutable content in P2P systems. The peer population affected by a gossip can be modeled as a Markov process. Studying the transient spread of gossips help in choosing proper algorithm parameters to reduce communication overhead while guaranteeing coverage of online peers. Each of these substrates in themselves were developed to find practical solutions for real problems. Put together, these can be used in other applications, including a P2P storage system with support for efficient lookup and inserts, membership dynamics, content mutation and updates, persistence and availability. Many of the ideas have already been implemented in real systems and several others are in the way to be integrated into the implementations. There are two principal contributions of this dissertation. It provides design of the P2P systems which are useful for end-users as well as other application developers who can build upon these existing systems. Secondly, it adapts and introduces the methodology of analysis of a system's time-evolution (tools typically used in diverse domains including physics and cybernetics) to study the long run behavior of P2P systems, and uses this methodology to (re-)design appropriate algorithms and evaluate them. We observed that studying P2P systems from the perspective of complex systems reveals their inner dynamics and hence ways to exploit such dynamics for suitable or better algorithms. In other words, the analysis methodology in itself strongly influences and inspires the way we design such systems. We believe that such an approach of orchestrating self-organization in internet-scale systems, where the algorithms and the analysis methodology have strong mutual influence will significantly change the way future such systems are developed and evaluated. We envision that such an approach will particularly serve as an important tool for the nascent but fast moving P2P systems research and development community

Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining

Comparative Evaluation of Marginal and Internal Adaptation of Class II Zirconia Ceramic Inlays Vs Feldspathic Ceramic Inlays With and Without a Resin Base and Different Interface Treatments: An In Vitro Scanning Electron Microscopic study.

AIM : The aim of this in vitro study is to evaluate and compare the marginal adaptation and internal adaptation of Class II Zirconia ceramic inlays to Feldspathic ceramic inlays with and without a resin base and different interface treatments using Scanning Electron Microscopic analysis. METHODOLOGY : 40 extracted lower mandibular teeth were selected and cleaned and stored in 0.1% thymol solution at 4ºC and they were embedded in tooth coloured acrylic resin. All the forty teeth were divided into 4 groups of 10 teeth each. The Group 1A had Zirconia ceramic inlays with a flowable composite base, Group 1B had Zirconia Ceramic inlays without a base, Group 2A had Feldspathic ceramic inlays with a flowable composite base and Group 2B had Feldspathic ceramic inlay without a base. Class II MO cavity preparation was done in all the teeth and flowable composite resin base applied on the pulpal floor and axial wall alone for group 1A and 2A. The groups 1B and 2B served as control groups. The group 1 inlays were fabricated with Zirconia inlays by CAD/CAM and the group 2 inlays were fabricated by hot-pressing of Feldspathic ceramic. The under surface of the inlays underwent sand blasting using 27μm of aluminium oxide particles at 2 bar pressure and the cavities underwent soft air abrasion interface treatment with 100μm sodium bicarbonate particles at 3 bar pressure. The inlays were luted with dual cure resin cement under 5kg mechanical load with a dental surveyor. The samples were left for 24 hours for complete polymerization and the teeth samples were embedded in clear acrylic resin. The samples were sectioned mesio-distally using diamond discs and they were subjected to Scanning electron microscopic evaluation for marginal and internal adaptation of all the inlays. The values were recorded and tabulated RESULT : One-way ANOVA and Post hoc Tukey HSD tests were done and was found out that the marginal adaptation of the zirconia ceramic inlays was statistically significant to feldspathic ceramic inlays. The internal adaptation of the ceramic inlays with flowable composite base in both the groups were statistically significant to the groups without the base. CONCLUSION : It was concluded that, the ceramic inlays luted in the presence of a flowable composite base had better adaptation than the inlays luted directly to the tooth. Zirconia ceramic inlays (manufactured by CAD/CAM) with a flowable composite resin base had better marginal and internal adaptation than zirconia ceramic inlays without base and feldspathic ceramic inlays (manufactured by hot pressing) with and without a base

Designing peer-to-peer overlays:a small-world perspective

The Small-World phenomenon, well known under the phrase "six degrees of separation", has been for a long time under the spotlight of investigation. The fact that our social network is closely-knitted and that any two people are linked by a short chain of acquaintances was confirmed by the experimental psychologist Stanley Milgram in the sixties. However, it was only after the seminal work of Jon Kleinberg in 2000 that it was understood not only why such networks exist, but also why it is possible to efficiently navigate in these networks. This proved to be a highly relevant discovery for peer-to-peer systems, since they share many fundamental similarities with the social networks; in particular the fact that the peer-to-peer routing solely relies on local decisions, without the possibility to invoke global knowledge. In this thesis we show how peer-to-peer system designs that are inspired by Small-World principles can address and solve many important problems, such as balancing the peer load, reducing high maintenance cost, or efficiently disseminating data in large-scale systems. We present three peer-to-peer approaches, namely Oscar, Gravity, and Fuzzynet, whose concepts stem from the design of navigable Small-World networks. Firstly, we introduce a novel theoretical model for building peer-to-peer systems which supports skewed node distributions and still preserves all desired properties of Kleinberg's Small-World networks. With such a model we set a reference base for the design of data-oriented peer-to-peer systems which are characterized by non-uniform distribution of keys as well as skewed query or access patterns. Based on this theoretical model we introduce Oscar, an overlay which uses a novel scalable network sampling technique for network construction, for which we provide a rigorous theoretical analysis. The simulations of our system validate the developed theory and evaluate Oscar's performance under typical conditions encountered in real-life large-scale networked systems, including participant heterogeneity, faults, as well as skewed and dynamic load-distributions. Furthermore, we show how by utilizing Small-World properties it is possible to reduce the maintenance cost of most structured overlays by discarding a core network connectivity element – the ring invariant. We argue that reliance on the ring structure is a serious impediment for real life deployment and scalability of structured overlays. We propose an overlay called Fuzzynet, which does not rely on the ring invariant, yet has all the functionalities of structured overlays. Fuzzynet takes the idea of lazy overlay maintenance further by eliminating the need for any explicit connectivity and data maintenance operations, relying merely on the actions performed when new Fuzzynet peers join the network. We show that with a sufficient amount of neighbors, even under high churn, data can be retrieved in Fuzzynet with high probability. Finally, we show how peer-to-peer systems based on the Small-World design and with the capability of supporting non-uniform key distributions can be successfully employed for large-scale data dissemination tasks. We introduce Gravity, a publish/subscribe system capable of building efficient dissemination structures, inducing only minimal dissemination relay overhead. This is achieved through Gravity's property to permit non-uniform peer key distributions which allows the subscribers to be clustered close to each other in the key space where data dissemination is cheap. An extensive experimental study confirms the effectiveness of our system under realistic subscription patterns and shows that Gravity surpasses existing approaches in efficiency by a large margin. With the peer-to-peer systems presented in this thesis we fill an important gap in the family of structured overlays, bringing into life practical systems, which can play a crucial role in enabling data-oriented applications distributed over wide-area networks

Complexity in financial market. Modeling psychological behavior in agent-based models and order book models

The fundamental idea developed throughout this work is the introduction of new metrics in Social Sciences (Economics, Finance, opinion dynamics, etc). The concept of metric, that is the concept of measure, is usually neglected by mainstream theories of Economics and Finance. Financial Markets are the natural starting point of such an approach to Social Sciences because a systematic approach can be undertaken and the methods of Physics has shown to be very effective. In fact since a decade there exists a very huge amount of high frequency data from stock exchanges which permit to perform experimental procedures as in Natural Sciences. Financial markets appear as a perfect playground where models can be tested and where repeatability of empirical evidences are well-established features differently from, for instance, Macro-Economy and Micro-Economy. Thus Finance has been the first point of contact for the interdisciplinary application of methods and tools deriving from Physics and it has been also the starting point of this work. We investigated the origin of the so-called Stylized Facts of financial markets (i.e. the statistical properties of financial time series) in the framework of agent-based models. We found that Stylized Facts can be interpreted as a finite size effect in terms of the number of effectively independent agents (i.e. strategy) which results to be a key variable to understand the self-organization of financial markets. As a second issue we focused our attention on the order book dynamics both from a theoretical and a data oriented point of view. We developed a zero intelligence model in order to investigate the role of vanishing liquidity in the price response to incoming orders. Within the framework of this model we have analyzed the effect of the introduction of strategies pointing out that simple strategic behaviors can explain bursts of intermittency and long memory effects. On the other hand we quantitatively showed that there exists a feedback effect in markets called self-fulfilling prophecy which is the mechanism through which technical trading can exist and work. This feature is a very interesting quantitative evidence of a self-reinforcement of agents’ belief. Last but not least nowadays we live in a computerized and networked society where many of our actions leave a digital trace and affect other people’s actions. This has lead to the emergence of a new data-driven research field. In this work we highlighted how non financial data can be used to track financial activity, in detail we investigate query log volumes, i.e. the volumes of searches for a specific query done by users in a search engine, as a proxy for trading volumes and we find that users’ activity on Yahoo! search engine anticipates trading volume by one-two days. Differently from Finance, Economics is far from being an ideal candidate to export the methodology of Natural Sciences because of the lack of empirical data since controlled (and repeatable) experiments are totally artificial while real experiments are almost incontrollable and non repeatable due to a high degree of non stationarity of economical systems. However, the application of method deriving from complexity to the Economics of Growth is one of the more important achievement of the work here developed. The basic idea is to study the network defined by international trade flows and introduce a (non-monetary) metric to measure the complexity and the competitiveness of countries’ productive system. In addition we are able to define a metric for products’ quality which overcomes traditional economic measure for the quality of products given in terms of hours of qualified labour needed to produce a good. The method developed provides some impressive results in predicting economical growth of countries and offers many opportunities of improvements and generalizations

Revealing the Mechanism of Thiopeptide Antibiotics at Atomistic Resolution : Implications for Rational Drug Design

For decades drug design has primarily focused on small molecules that bind to well-formed tight binding pockets, such as the catalytic centers of enzymes. Recently, there is increasing interest to design compounds that disrupt or stabilize biomacromolecular interfaces (e.g. protein–protein, protein–DNA, protein–RNA, protein–lipid interfaces). These non-traditional drug targets hold great therapeutic potential as they govern cellular pathways. In contrast to traditional drug targets, where computational methods are now routinely and productively used to complement experiments, the use of computer-based approaches for the study and design of interfacial modulators is still in its infancy. The current thesis is a first detailed study into understanding the effects of modulators of a protein–RNA interface and developing computer-based approaches for their design. This work focuses on the 23S-L11 subunit of the ribosomal GTPase-associated region (GAR), a prototypic protein–RNA interface of high relevance in the development of novel antibacterials. The GAR is the target of naturally occuring thiopeptide antibiotics. These unique molecules are effective inhibitors of bacterial protein synthesis, but are currently unused in human antibacterial therapy due to their low aqueous solubility. Their mechanism of action is explored in the current thesis, enabling the design and proposition of new chemical scaffolds targeting their binding site. The specific challenges associated with the 23-SL11-thiopeptide system, such as the inherent flexibility of the protein–RNA composite environment and the size and structural complexity of the thiopeptide ligands, are addressed by a combination of computational chemistry approaches at different levels of granularity and a steady feedback with experimental data to validate and improve the computational techniques. These approaches range from quantummechanics for deriving optimized intramolecular parameters and partial atomic charges for the thiopeptide compounds, to molecular dynamics simulations accounting for the binding site’s flexibility, to molecular docking studies for predicting the binding modes of different thiopeptides and derivatives. All-atom molecular dynamics simulations were conducted, providing a detailed understanding of the effect of thiopeptide binding at a previously unmet resolution. The findings of this work, coupled with previous experimental knowledge, strongly support the hypothesis that restricting the binding site’s conformational flexibility is an important component of the thiopeptide antibiotics’ mode of action. With the help of an MD-docking-MD workflow and an energy decomposition analysis crucial residues of the binding site and pharmacologically relevant moieties within the ligand structures could be identified. A 4D-pharmacophore model is presented that was derived from a refined 23S-L11-thiopeptide complex and additionally accounts for the dynamic stability of molecular interactions formed between the antibiotic and the ribosomal binding site as the fourth dimension. The results of this thesis revealed, for the first time, a plausable description of the thiopeptide antibiotics’ mode of action, down to the details of their pharmacologically relevant parts and provide a computational framework for the design of new ligands

The Conformational Universe of Proteins and Peptides: Tales of Order and Disorder

Proteins represent one of the most abundant classes of biological macromolecules and play crucial roles in a vast array of physiological and pathological processes. The knowledge of the 3D structure of a protein, as well as the possible conformational transitions occurring upon interaction with diverse ligands, are essential to fully comprehend its biological function.In addition to globular, well-folded proteins, over the past few years, intrinsically disordered proteins (IDPs) have received a lot of attention. IDPs are usually aggregation-prone and may form toxic amyloid fibers and oligomers associated with several human pathologies. Peptides are smaller in size than proteins but similarly represent key elements of cells. A few peptides are able to work as tumor markers and find applications in the diagnostic and therapeutic fields. The conformational analysis of bioactive peptides is important to design novel potential drugs acting as selective modulators of specific receptors or enzymes. Nevertheless, synthetic peptides reproducing different protein fragments have frequently been implemented as model systems in folding studies relying on structural investigations in water and/or other environments.This book contains contributions (seven original research articles and five reviews published in the journal Molecules) on the above-described topics and, in detail, it includes structural studies on globular folded proteins, IDPs and bioactive peptides. These works were conducted usingdifferent experimental methods