A disaccharide that inhibits tumor necrosis factor alpha is formed from the extracellular matrix by the enzyme heparanase.

The activation of T cells by antigens or mitogens leads to the secretion of cytokines and enzymes that shape the inflammatory response. Among these molecular mediators of inflammation is a heparanase enzyme that degrades the heparan sulfate scaffold of the extracellular matrix (ECM). Activated T cells use heparanase to penetrate the ECM and gain access to the tissues. We now report that among the breakdown products of the ECM generated by heparanase is a trisulfated disaccharide that can inhibit delayed-type hypersensitivity (DTH) in mice. This inhibition of T-cell mediated inflammation in vivo was associated with an inhibitory effect of the disaccharide on the production of biologically active tumor necrosis factor alpha (TNF-alpha) by activated T cells in vitro; the trisulfated disaccharide did not affect T-cell viability or responsiveness generally. Both the in vivo and in vitro effects of the disaccharide manifested a bell-shaped dose-response curve. The inhibitory effects of the trisulfated disaccharide were lost if the sulfate groups were removed. Thus, the disaccharide, which may be a natural product of inflammation, can regulate the functional nature of the response by the T cell to activation. Such a feedback control mechanism could enable the T cell to assess the extent of tissue degradation and adjust its behavior accordingly.

SSB(N) quiet steering system study (Phase I).

Mode of access: Internet.

Executive-controlled adaptive systems,

At head of title: Microwave Research Institute, Polytechnic Institute of Brooklyn, Systems and Controls Group, R-688-58, PIB-616, contract no. DA-30-069-ORD-1560.

Digital processes for sampled data systems.

Includes bibliography.

An experimental analysis of operating conditions in cold roll-forming

A detailed literature survey confirmed cold roll-forming to be a complex and little understood process. In spite of its growing value, the process remains largely un-automated with few principles used in set-up of the rolling mill. This work concentrates on experimental investigations of operating conditions in order to gain a scientific understanding of the process. The operating conditions are; inter-pass distance, roll load, roll speed, horizontal roll alignment. Fifty tests have been carried out under varied operating conditions, measuring section quality and longitudinal straining to give a picture of bending. A channel section was chosen for its simplicity and compatibility with previous work. Quality measurements were measured in terms of vertical bow, twist and cross-sectional geometric accuracy, and a complete method of classifying quality has been devised. The longitudinal strain profile was recorded, by the use of strain gauges attached to the strip surface at five locations. Parameter control is shown to be important in allowing consistency in section quality. At present rolling mills are constructed with large tolerances on operating conditions. By reduction of the variability in parameters, section consistency is maintained and mill down-time is reduced. Roll load, alignment and differential roll speed are all shown to affect quality, and can be used to control quality. Set-up time is reduced by improving the design of the mill so that parameter values can be measured and set, without the need for judgment by eye. Values of parameters can be guided by models of the process, although elements of experience are still unavoidable. Despite increased parameter control, section quality is variable, if only due to variability in strip material properties. Parameters must therefore be changed during rolling. Ideally this can take place by closed-loop feedback control. Future work lies in overcoming the problems connected with this control.

Optimization of Discrete-Time, Stochastic Systems

* This research was supported by a grant from the Greek Ministry of Industry and Technology.

On the Feasibility of Steering Swallowable Microsystem Capsules Using Computer-Aided Magnetic Levitation

Swallowable capsule endoscopy is used for non-invasive diagnosis of some gastrointestinal (GI) organs. However, control over the position of the capsule is a major unresolved issue. This study presents a design for steering the capsule based on magnetic levitation. The levitation is stabilized with the aid of a computer-aided feedback control system and diamagnetism. Peristaltic and gravitational forces to be overcome were calculated. A levitation setup was built to analyze the feasibility of using Hall Effect sensors to locate the in- vivo capsule. CAD software Maxwell 3D (Ansoft, Pittsburgh, PA) was used to determine the dimensions of the resistive electromagnets required for levitation and the feasibility of building them was examined. Comparison based on design complexity was made between positioning the patient supinely and upright.

Sistema de conversão de energia eólica baseado no gerador de indução duplamente alimentado: análise e contribuição ao controle da máquina

The humanity reached a time of unprecedented technological development. Science has achieved and continues to achieve technologies that allowed increasingly to understand the universe and the laws which govern it, and also try to coexist without destroying the planet we live on. One of the main challenges of the XXI century is to seek and increase new sources of clean energy, renewable and able to sustain our growth and lifestyle. It is the duty of every researcher engage and contribute in this race of energy. In this context, wind power presents itself as one of the great promises for the future of electricity generation . Despite being a bit older than other sources of renewable energy, wind power still presents a wide field for improvement. The development of new techniques for control of the generator along with the development of research laboratories specializing in wind generation are one of the key points to improve the performance, efficiency and reliability of the system. Appropriate control of back-to-back converter scheme allows wind turbines based on the doubly-fed induction generator to operate in the variable-speed mode, whose benefits include maximum power extraction, reactive power injection and mechanical stress reduction. The generator-side converter provides control of active and reactive power injected into the grid, whereas the grid-side converter provides control of the DC link voltage and bi-directional power flow. The conventional control structure uses PI controllers with feed-forward compensation of cross-coupling dq terms. This control technique is sensitive to model uncertainties and the compensation of dynamic dq terms results on a competing control strategy. Therefore, to overcome these problems, it is proposed in this thesis a robust internal model based state-feedback control structure in order to eliminate the cross-coupling terms and thereby improve the generator drive as well as its dynamic behavior during sudden changes in wind speed. It is compared the conventional control approach with the proposed control technique for DFIG wind turbine control under both steady and gust wind conditions. Moreover, it is also proposed in this thesis an wind turbine emulator, which was developed to recreate in laboratory a realistic condition and to submit the generator to several wind speed conditions.

Testing of Interposer-Based 2.5D Integrated Circuits

The unprecedented and relentless growth in the electronics industry is feeding the demand for integrated circuits (ICs) with increasing functionality and performance at minimum cost and power consumption. As predicted by Moore's law, ICs are being aggressively scaled to meet this demand. While the continuous scaling of process technology is reducing gate delays, the performance of ICs is being increasingly dominated by interconnect delays. In an effort to improve submicrometer interconnect performance, to increase packing density, and to reduce chip area and power consumption, the semiconductor industry is focusing on three-dimensional (3D) integration. However, volume production and commercial exploitation of 3D integration are not feasible yet due to significant technical hurdles.

At the present time, interposer-based 2.5D integration is emerging as a precursor to stacked 3D integration. All the dies and the interposer in a 2.5D IC must be adequately tested for product qualification. However, since the structure of 2.5D ICs is different from the traditional 2D ICs, new challenges have emerged: (1) pre-bond interposer testing, (2) lack of test access, (3) limited ability for at-speed testing, (4) high density I/O ports and interconnects, (5) reduced number of test pins, and (6) high power consumption. This research targets the above challenges and effective solutions have been developed to test both dies and the interposer.

The dissertation first introduces the basic concepts of 3D ICs and 2.5D ICs. Prior work on testing of 2.5D ICs is studied. An efficient method is presented to locate defects in a passive interposer before stacking. The proposed test architecture uses e-fuses that can be programmed to connect or disconnect functional paths inside the interposer. The concept of a die footprint is utilized for interconnect testing, and the overall assembly and test flow is described. Moreover, the concept of weighted critical area is defined and utilized to reduce test time. In order to fully determine the location of each e-fuse and the order of functional interconnects in a test path, we also present a test-path design algorithm. The proposed algorithm can generate all test paths for interconnect testing.

In order to test for opens, shorts, and interconnect delay defects in the interposer, a test architecture is proposed that is fully compatible with the IEEE 1149.1 standard and relies on an enhancement of the standard test access port (TAP) controller. To reduce test cost, a test-path design and scheduling technique is also presented that minimizes a composite cost function based on test time and the design-for-test (DfT) overhead in terms of additional through silicon vias (TSVs) and micro-bumps needed for test access. The locations of the dies on the interposer are taken into consideration in order to determine the order of dies in a test path.

To address the scenario of high density of I/O ports and interconnects, an efficient built-in self-test (BIST) technique is presented that targets the dies and the interposer interconnects. The proposed BIST architecture can be enabled by the standard TAP controller in the IEEE 1149.1 standard. The area overhead introduced by this BIST architecture is negligible; it includes two simple BIST controllers, a linear-feedback-shift-register (LFSR), a multiple-input-signature-register (MISR), and some extensions to the boundary-scan cells in the dies on the interposer. With these extensions, all boundary-scan cells can be used for self-configuration and self-diagnosis during interconnect testing. To reduce the overall test cost, a test scheduling and optimization technique under power constraints is described.

In order to accomplish testing with a small number test pins, the dissertation presents two efficient ExTest scheduling strategies that implements interconnect testing between tiles inside an system on chip (SoC) die on the interposer while satisfying the practical constraint that the number of required test pins cannot exceed the number of available pins at the chip level. The tiles in the SoC are divided into groups based on the manner in which they are interconnected. In order to minimize the test time, two optimization solutions are introduced. The first solution minimizes the number of input test pins, and the second solution minimizes the number output test pins. In addition, two subgroup configuration methods are further proposed to generate subgroups inside each test group.

Finally, the dissertation presents a programmable method for shift-clock stagger assignment to reduce power supply noise during SoC die testing in 2.5D ICs. An SoC die in the 2.5D IC is typically composed of several blocks and two neighboring blocks that share the same power rails should not be toggled at the same time during shift. Therefore, the proposed programmable method does not assign the same stagger value to neighboring blocks. The positions of all blocks are first analyzed and the shared boundary length between blocks is then calculated. Based on the position relationships between the blocks, a mathematical model is presented to derive optimal result for small-to-medium sized problems. For larger designs, a heuristic algorithm is proposed and evaluated.

In summary, the dissertation targets important design and optimization problems related to testing of interposer-based 2.5D ICs. The proposed research has led to theoretical insights, experiment results, and a set of test and design-for-test methods to make testing effective and feasible from a cost perspective.

Process Monitoring and Defect Detection of Additive Manufacturing Using Inline Coherent Imaging

With applications ranging from aerospace to biomedicine, additive manufacturing (AM) has been revolutionizing the manufacturing industry. The ability of additive techniques, such as selective laser melting (SLM), to create fully functional, geometrically complex, and unique parts out of high strength materials is of great interest. Unfortunately, despite numerous advantages afforded by this technology, its widespread adoption is hindered by a lack of on-line, real time feedback control and quality assurance techniques. In this thesis, inline coherent imaging (ICI), a broadband, spatially coherent imaging technique, is used to observe the SLM process in 15 - 45 $\mu m$ 316L stainless steel. Imaging of both single and multilayer builds is performed at a rate of 200 $kHz$, with a resolution of tens of microns, and a high dynamic range rendering it impervious to blinding from the process beam. This allows imaging before, during, and after laser processing to observe changes in the morphology and stability of the melt. Galvanometer-based scanning of the imaging beam relative to the process beam during the creation of single tracks is used to gain a unique perspective of the SLM process that has been so far unobservable by other monitoring techniques. Single track processing is also used to investigate the possibility of a preliminary feedback control parameter based on the process beam power, through imaging with both coaxial and 100 $\mu m$ offset alignment with respect to the process beam. The 100 $\mu m$ offset improved imaging by increasing the number of bright A-lines (i.e. with signal greater than the 10 $dB$ noise floor) by 300\%. The overlap between adjacent tracks in a single layer is imaged to detect characteristic fault signatures. Full multilayer builds are carried out and the resultant ICI images are used to detect defects in the finished part and improve upon the initial design of the build system. Damage to the recoater blade is assessed using powder layer scans acquired during a 3D build. The ability of ICI to monitor SLM processes at such high rates with high resolution offers extraordinary potential for future advances in on-line feedback control of additive manufacturing.

Decolourisation of Acid orange 7 in a microbial fuel cell with a laccase-based biocathode: Influence of mitigating pH changes in the cathode chamber

Biocathodes may be a suitable replacement of platinum in microbial fuel cells (MFCs) if the cost of MFCs is to be reduced. However, the use of enzymes as bio-cathodes is fraught with loss of activity as time progresses. A possible cause of this loss in activity might be pH increase in the cathode as pH gradients in MFCs are well known. This pH increase is however, accompanied by simultaneous increase in salinity; therefore salinity may be a confounding variable. This study investigated various ways of mitigating pH changes in the cathode of MFCs and their effect on laccase activity and decolourisation of a model azo dye Acid orange 7 in the anode chamber. Experiments were run with catholyte pH automatically controlled via feedback control or by using acetate buffers (pH 4.5) of various strength (100 mM and 200 mM), with CMI7000 as the cation exchange membrane. A comparison was also made between use of CMI7000 and Nafion 117 as the transport properties of cations for both membranes (hence their potential effects on pH changes in the cathode) are different.

Évaluation du contrôle sensorimoteur chez les patients ayant une scoliose idiopathique de l'adolescent - Vers un biomarqueur des troubles sensorimoteur basé sur la stimulation vestibulaire galvanique

La scoliose est la pathologie déformante du rachis la plus courante de l’adolescence. Dans 80 % des cas, elle est idiopathique, signifiant qu’aucune cause n’a été associée. Les scolioses idiopathiques répondent à un modèle multifactoriel incluant des facteurs génétiques, environnementaux, neurologiques, hormonaux, biomécaniques et de croissance squelettique. Comme hypothèse neurologique, une anomalie vestibulaire provoquerait une asymétrie d’activation des voies vestibulospinales et des muscles paravertébraux commandés par cette voie, engendrant la déformation scoliotique. Certains modèles animaux permettent de reproduire ce mécanisme. De plus, des anomalies liées au système vestibulaire, comme des troubles de l’équilibre, sont observées chez les patients avec une scoliose. La stimulation vestibulaire galvanique permet d’explorer le contrôle sensorimoteur de l’équilibre puisqu’elle permet d’altérer les afférences vestibulaires. L’objectif de cette thèse est d’explorer le contrôle sensorimoteur en évaluant la réaction posturale provoquée par cette stimulation chez les patients et les participants contrôle. Dans la première étude, les patients sont plus déstabilisés que les contrôles et il n’y a pas de lien entre l’ampleur de l’instabilité et la sévérité de la scoliose. Dans la deuxième étude, à l’aide d’un modèle neuromécanique, un poids plus grand aux signaux vestibulaires a été attribué aux patients. Dans la troisième étude, un problème sensorimoteur est également observé chez les jeunes adultes ayant une scoliose, excluant ainsi que le problème soit dû à la maturation du système nerveux. Dans une étude subséquente, des patients opérés pour réduire leur déformation du rachis, montrent également une réaction posturale de plus grande amplitude à la stimulation comparativement à des participants contrôle. Ces résultats suggèrent que l’anomalie sensorimotrice ne serait pas secondaire à la déformation. Finalement, un algorithme a été développé pour identifier les patients ayant un problème sensorimoteur. Les patients montrant un contrôle sensorimoteur anormal ont également une réponse vestibulomotrice plus grande et attribuent plus de poids aux informations vestibulaires. Globalement, les résultats de cette thèse montrent qu’un déficit sensorimoteur expliquerait l’apparition de la scoliose mais pas sa progression. Le dysfonctionnement sensorimoteur n’est pas présent chez tous les patients. L’algorithme permettant une classification de la performance sensorimotrice pourrait être utile pour de futures études cliniques.

Image-Guided Precision Manipulation of Cells and Nanoparticles in Microfluidics

Manipulation of single cells and particles is important to biology and nanotechnology. Our electrokinetic (EK) tweezers manipulate objects in simple microfluidic devices using gentle fluid and electric forces under vision-based feedback control. In this dissertation, I detail a user-friendly implementation of EK tweezers that allows users to select, position, and assemble cells and nanoparticles. This EK system was used to measure attachment forces between living breast cancer cells, trap single quantum dots with 45 nm accuracy, build nanophotonic circuits, and scan optical properties of nanowires. With a novel multi-layer microfluidic device, EK was also used to guide single microspheres along complex 3D trajectories. The schemes, software, and methods developed here can be used in many settings to precisely manipulate most visible objects, assemble objects into useful structures, and improve the function of lab-on-a-chip microfluidic systems.

Analysis of the "Sonar Hopf" Cochlea

The "Sonar Hopf" cochlea is a recently much advertised engineering design of an auditory sensor. We analyze this approach based on a recent description by its inventors Hamilton, Tapson, Rapson, Jin, and van Schaik, in which they exhibit the "Sonar Hopf" model, its analysis and the corresponding hardware in detail. We identify problems in the theoretical formulation of the model and critically examine the claimed coherence between the described model, the measurements from the implemented hardware, and biological data.

Exploring coordination-driven self-assembly with autonomous chemical robots

The work presented herein focused on the automation of coordination-driven self assembly, exploring methods that allow syntheses to be followed more closely while forming new ligands, as part of the fundamental study of the digitization of chemical synthesis and discovery. Whilst the control and understanding of the principle of pre-organization and self-sorting under non-equilibrium conditions remains a key goal, a clear gap has been identified in the absence of approaches that can permit fast screening and real-time observation of the reaction process under different conditions. A firm emphasis was thus placed on the realization of an autonomous chemical robot, which can not only monitor and manipulate coordination chemistry in real-time, but can also allow the exploration of a large chemical parameter space defined by the ligand building blocks and the metal to coordinate. The self-assembly of imine ligands with copper and nickel cations has been studied in a multi-step approach using a self-built flow system capable of automatically controlling the liquid-handling and collecting data in real-time using a benchtop MS and NMR spectrometer. This study led to the identification of a transient Cu(I) species in situ which allows for the formation of dimeric and trimeric carbonato bridged Cu(II) assemblies. Furthermore, new Ni(II) complexes and more remarkably also a new binuclear Cu(I) complex, which usually requires long and laborious inert conditions, could be isolated. The study was then expanded to the autonomous optimization of the ligand synthesis by enabling feedback control on the chemical system via benchtop NMR. The synthesis of new polydentate ligands has emerged as a result of the study aiming to enhance the complexity of the chemical system to accelerate the discovery of new complexes. This type of ligand consists of 1-pyridinyl-4-imino-1,2,3-triazole units, which can coordinate with different metal salts. The studies to test for the CuAAC synthesis via microwave lead to the discovery of four new Cu complexes, one of them being a coordination polymer obtained from a solvent dependent crystallization technique. With the goal of easier integration into an automated system, copper tubing has been exploited as the chemical reactor for the synthesis of this ligand, as it efficiently enhances the rate of the triazole formation and consequently promotes the formation of the full ligand in high yields within two hours. Lastly, the digitization of coordination-driven self-assembly has been realized for the first time using an in-house autonomous chemical robot, herein named the ‘Finder’. The chemical parameter space to explore was defined by the selection of six variables, which consist of the ligand precursors necessary to form complex ligands (aldehydes, alkineamines and azides), of the metal salt solutions and of other reaction parameters – duration, temperature and reagent volumes. The platform was assembled using rounded bottom flasks, flow syringe pumps, copper tubing, as an active reactor, and in-line analytics – a pH meter probe, a UV-vis flow cell and a benchtop MS. The control over the system was then obtained with an algorithm capable of autonomously focusing the experiments on the most reactive region (by avoiding areas of low interest) of the chemical parameter space to explore. This study led to interesting observations, such as metal exchange phenomena, and also to the autonomous discovery of self assembled structures in solution and solid state – such as 1-pyridinyl-4-imino-1,2,3-triazole based Fe complexes and two helicates based on the same ligand coordination motif.