Optimization of production of anti-cancer vaccines based on dendritic cells

Cancer remains as one of the top killing diseases in first world countries. It’s not a single, but a set of various diseases for which different treatment approaches have been taken over the years. Cancer immunotherapy comes as a “new” breath on cancer treatment, taking use of the patients’ immune system to induce anti-cancer responses. Dendritic Cell (DC) vaccines use the extraordinary capacity of DCs’ antigen presentation so that specific T cell responses may be generated against cancer. In this work, we report the ex vivo generation of DCs from precursors isolated from clinical-grade cryopreserved umbilical cord blood (UCB) samples. After the thawing protocol for cryopreserved samples was optimized, the generation of DCs from CD14+ monocytes, i.e., moDCs, or CD34+ hematopoietic stem cells (HSCs), i.e, CD34-derived DCs, was followed and their phenotype and function evaluated. Functional testing included the ability to respond to maturation stimuli (including enzymatic removal of surface sialic acids), Ovalbumin-FITC endocytic capacity, cytokine secretion and T cell priming ability. In order to evaluate the feasibility of using DCs derived from UCB precursors to induce immune responses, they were compared to peripheral blood (PB) moDCs. We observed an increased endocytosis capacity after moDCs were differentiated from monocyte precursors, but almost 10-fold lower than that of PB moDCs. Maturation markers were absent, low levels of inflammatory cytokines were seen and T cell stimulatory capacity was reduced. Sialidase enzymatic treatment was able to mature these cells, diminishing endocytosis and promoting higher T cell stimulation. CD34-derived DCs showed higher capacity for both maturation and endocytic capacity than moDCs. Although much more information was acquired from moDCs than from CD34-derived DCs, we conclude the last as probably the best suited for generating an immune response against cancer, but of course much more research has to be performed.

Machine diagnosis based on artificial immune systems

Nowadays, many of the manufactory and industrial system has a diagnosis system on top of it, responsible for ensuring the lifetime of the system itself. It achieves this by performing both diagnosis and error recovery procedures in real production time, on each of the individual parts of the system. There are many paradigms currently being used for diagnosis. However, they still fail to answer all the requirements imposed by the enterprises making it necessary for a different approach to take place. This happens mostly on the error recovery paradigms since the great diversity that is nowadays present in the industrial environment makes it highly unlikely for every single error to be fixed under a real time, no production stop, perspective. This work proposes a still relatively unknown paradigm to manufactory. The Artificial Immune Systems (AIS), which relies on bio-inspired algorithms, comes as a valid alternative to the ones currently being used. The proposed work is a multi-agent architecture that establishes the Artificial Immune Systems, based on bio-inspired algorithms. The main goal of this architecture is to solve for a resolution to the error currently detected by the system. The proposed architecture was tested using two different simulation environment, each meant to prove different points of views, using different tests. These tests will determine if, as the research suggests, this paradigm is a promising alternative for the industrial environment. It will also define what should be done to improve the current architecture and if it should be applied in a decentralised system.

Electro-Optical/Infrared sensor turret integration on an aircraft - structural im-pact on LOCKHEED MARTIN C-130H and design methodology

The growing need to patrol and survey large maritime and terrestrial areas increased the need to integrate external sensors on aircraft in order to accomplish those patrols at increasingly higher altitudes, longer range and not depending upon vehicle type. The main focus of this work is to elaborate a practical, simple, effective and efficient methodology for the aircraft modification procedure resulting from the integration of an Elec-tro-Optical/Infra-Red (EO/IR) turret through a support structure. The importance of the devel-opment of a good methodology relies on the correct management of project variables as time, available resources and project complexity. The key is to deliver a proper tool for a project de-sign team that will be used to create a solution that fulfils all technical, non-technical and certi-fication requirements present in this field of transportation. The created methodology is inde-pendent of two main inputs: sensor model and aircraft model definition, and therefore it is in-tended to deliver the results for different projects besides the one that was presented in this work as a case study. This particular case study presents the development of a structure support for FLIR STAR SAPHIRE III turret integration on the front lower fuselage bulkhead (radome) of the LOCKHEED MARTIN C-130 H. Development of the case study focuses on the study of local structural analysis through the use of Finite Element Method (FEM). Development of this Dissertation resulted in a cooperation between Faculty of Science and Technology - Universidade Nova de Lisboa and the company OGMA - Indústria Aeronáutica de Portugal

Scaling In-Memory databases on multicores

Current computer systems have evolved from featuring only a single processing unit and limited RAM, in the order of kilobytes or few megabytes, to include several multicore processors, o↵ering in the order of several tens of concurrent execution contexts, and have main memory in the order of several tens to hundreds of gigabytes. This allows to keep all data of many applications in the main memory, leading to the development of inmemory databases. Compared to disk-backed databases, in-memory databases (IMDBs) are expected to provide better performance by incurring in less I/O overhead. In this dissertation, we present a scalability study of two general purpose IMDBs on multicore systems. The results show that current general purpose IMDBs do not scale on multicores, due to contention among threads running concurrent transactions. In this work, we explore di↵erent direction to overcome the scalability issues of IMDBs in multicores, while enforcing strong isolation semantics. First, we present a solution that requires no modification to either database systems or to the applications, called MacroDB. MacroDB replicates the database among several engines, using a master-slave replication scheme, where update transactions execute on the master, while read-only transactions execute on slaves. This reduces contention, allowing MacroDB to o↵er scalable performance under read-only workloads, while updateintensive workloads su↵er from performance loss, when compared to the standalone engine. Second, we delve into the database engine and identify the concurrency control mechanism used by the storage sub-component as a scalability bottleneck. We then propose a new locking scheme that allows the removal of such mechanisms from the storage sub-component. This modification o↵ers performance improvement under all workloads, when compared to the standalone engine, while scalability is limited to read-only workloads. Next we addressed the scalability limitations for update-intensive workloads, and propose the reduction of locking granularity from the table level to the attribute level. This further improved performance for intensive and moderate update workloads, at a slight cost for read-only workloads. Scalability is limited to intensive-read and read-only workloads. Finally, we investigate the impact applications have on the performance of database systems, by studying how operation order inside transactions influences the database performance. We then propose a Read before Write (RbW) interaction pattern, under which transaction perform all read operations before executing write operations. The RbW pattern allowed TPC-C to achieve scalable performance on our modified engine for all workloads. Additionally, the RbW pattern allowed our modified engine to achieve scalable performance on multicores, almost up to the total number of cores, while enforcing strong isolation.