Structure-Guided Design and Biophysical Characterization of Novel Anti-HIV Reagents

Despite over 30 years of effort, an HIV-1 vaccine that elicits protective antibodies still does not exist. Recent clinical studies have identified that during natural infection about 20% of the population is capable of mounting a potent and protective antibody response. Closer inspection of these individuals reveal that a subset of these antibodies, recently termed potent VRC01-like (PVL), derive exclusively from a single human germline heavy chain gene. Induced clonal expansion of the B cell encoding this gene is the first step through which PVL antibodies may be elicited. Unfortunately, naturally occurring HIV gp120s fail to bind to this germline, and as a result cannot be used as the initial prime for a vaccine regimen. We have determined the crystal structure of an important germline antibody that is a promising target for vaccine design efforts, and have set out to engineer a more likely candidate using computationally-guided rational design.

In addition to prevention efforts on the side of vaccine design, recently characterized broadly neutralizing anti-HIV antibodies have excellent potential for use in gene therapy and passive immunotherapy. The separation distance between functional Fabs on an antibody is important due to the sparse distribution of envelop spikes on HIV compared to other viruses. We set out to build and characterize novel antibody architectures by incorporating structured linkers into the hinge region of an anti-HIV antibody b12. The goal was to observe whether these linkers increased the arm-span of the IgG dimer. When incorporated, flexible Gly4Ser repeats did not result in detectable extensions of the IgG antigen binding domains, by contrast to linkers including more rigid domains such as β2-microglobulin, Zn-α2-glycoprotein, and tetratricopeptide repeats (TPRs). This study adds an additional set of linkers with varying lengths and rigidities to the available linker repertoire, which may be useful for the modification and construction of antibodies and other fusion proteins.

Rate and Microstructure Effects on the Dynamics of Carbon Nanotube Foams

Soft hierarchical materials often present unique functional properties that are sensitive to the geometry and organization of their micro- and nano-structural features across different lengthscales. Carbon Nanotube (CNT) foams are hierarchical materials with fibrous morphology that are known for their remarkable physical, chemical and electrical properties. Their complex microstructure has led them to exhibit intriguing mechanical responses at different length-scales and in different loading regimes. Even though these materials have been studied for mechanical behavior over the past few years, their response at high-rate finite deformations and the influence of their microstructure on bulk mechanical behavior and energy dissipative characteristics remain elusive.

In this dissertation, we study the response of aligned CNT foams at the high strain-rate regime of 10² - 10⁴ s^-1. We investigate their bulk dynamic response and the fundamental deformation mechanisms at different lengthscales, and correlate them to the microstructural characteristics of the foams. We develop an experimental platform, with which to study the mechanics of CNT foams in high-rate deformations, that includes direct measurements of the strain and transmitted forces, and allows for a full field visualization of the sample’s deformation through high-speed microscopy.

We synthesize various CNT foams (e.g., vertically aligned CNT (VACNT) foams, helical CNT foams, micro-architectured VACNT foams and VACNT foams with microscale heterogeneities) and show that the bulk functional properties of these materials are highly tunable either by tailoring their microstructure during synthesis or by designing micro-architectures that exploit the principles of structural mechanics. We also develop numerical models to describe the bulk dynamic response using multiscale mass-spring models and identify the mechanical properties at length scales that are smaller than the sample height.

The ability to control the geometry of microstructural features, and their local interactions, allows the creation of novel hierarchical materials with desired functional properties. The fundamental understanding provided by this work on the key structure-function relations that govern the bulk response of CNT foams can be extended to other fibrous, soft and hierarchical materials. The findings can be used to design materials with tailored properties for different engineering applications, like vibration damping, impact mitigation and packaging.

TWO-DIMENSIONAL ARRAY OF ION TRAPS ON A PLANAR CHIP

We investigate a planar ion chip design with a two-dimensional array of linear ion traps for the scalable quantum information processor. The segmented electrodes reside in a single plane on a substrate and a grounded metal plate, a combination of appropriate rf and DC potentials are applied to them for stable ion confinement, and the trap axes are located above the surface at a distance controlled by the electrodes' lateral extent and the substrate's height as discussed. The potential distributions are calculated using static electric field qualitatively. This architecture is conceptually simple and many current microfabrication techniques are feasible for the basic structure. It may provide a promising route for scalable quantum computers.

Design of antenna-coupled lumped-element titanium nitride KIDs for long-wavelength multi-band continuum imaging

Many applications in cosmology and astrophysics at millimeter wavelengths including CMB polarization, studies of galaxy clusters using the Sunyaev-Zeldovich effect (SZE), and studies of star formation at high redshift and in our local universe and our galaxy, require large-format arrays of millimeter-wave detectors. Feedhorn and phased-array antenna architectures for receiving mm-wave light present numerous advantages for control of systematics, for simultaneous coverage of both polarizations and/or multiple spectral bands, and for preserving the coherent nature of the incoming light. This enables the application of many traditional "RF" structures such as hybrids, switches, and lumped-element or microstrip band-defining filters.

Simultaneously, kinetic inductance detectors (KIDs) using high-resistivity materials like titanium nitride are an attractive sensor option for large-format arrays because they are highly multiplexable and because they can have sensitivities reaching the condition of background-limited detection. A KID is a LC resonator. Its inductance includes the geometric inductance and kinetic inductance of the inductor in the superconducting phase. A photon absorbed by the superconductor breaks a Cooper pair into normal-state electrons and perturbs its kinetic inductance, rendering it a detector of light. The responsivity of KID is given by the fractional frequency shift of the LC resonator per unit optical power.

However, coupling these types of optical reception elements to KIDs is a challenge because of the impedance mismatch between the microstrip transmission line exiting these architectures and the high resistivity of titanium nitride. Mitigating direct absorption of light through free space coupling to the inductor of KID is another challenge. We present a detailed titanium nitride KID design that addresses these challenges. The KID inductor is capacitively coupled to the microstrip in such a way as to form a lossy termination without creating an impedance mismatch. A parallel plate capacitor design mitigates direct absorption, uses hydrogenated amorphous silicon, and yields acceptable noise. We show that the optimized design can yield expected sensitivities very close to the fundamental limit for a long wavelength imager (LWCam) that covers six spectral bands from 90 to 400 GHz for SZE studies.

Excess phase (frequency) noise has been observed in KID and is very likely caused by two-level systems (TLS) in dielectric materials. The TLS hypothesis is supported by the measured dependence of the noise on resonator internal power and temperature. However, there is still a lack of a unified microscopic theory which can quantitatively model the properties of the TLS noise. In this thesis we derive the noise power spectral density due to the coupling of TLS with phonon bath based on an existing model and compare the theoretical predictions about power and temperature dependences with experimental data. We discuss the limitation of such a model and propose the direction for future study.

MODIFIED DIRECT TWOS-COMPLEMENT PARALLEL ARRAY MULTIPLICATION ALGORITHM FOR COMPLEX MATRIX OPERATION

A direct twos-complement parallel array multiplication algorithm is introduced and modified for digital optical numerical computation. The modified version overcomes the problems encountered in the conventional optical twos-complement algorithm. In the array, all the summands are generated in parallel, and the relevant summands having the same weights are added simultaneously without carries, resulting in the product expressed in a mixed twos-complement system. In a two-stage array, complex multiplication is possible with using four real subarrays. Furthermore, with a three-stage array architecture, complex matrix operation is straightforwardly accomplished. In the experiment, parallel two-stage array complex multiplication with liquid-crystal panels is demonstrated.

MODIFIED ENGAGEMENT METHOD FOR MATRIX OPERATION

We describe a modified engagement method for matrix operation based on a two-dimensional crossed-ring interconnection network, Our method incorporates fewer steps than that reported by Bocker et al. [Appl. Opt. 22, 804 (1983)], and its performance is found to be the most efficient (minimum steps) in comparison with other systolic and/or engagement methods for matrix operation. Thus, it may be helpful for other optical and electronic implementations of matrix operations. One compact optoelectronic integrity approach for implementing the modified engagement method is briefly described. (C) 1995 Optical Society of America

Optical intrinsically fuzzy mathematical morphology for gray-scale image processing

Intrinsically fuzzy morphological erosion and dilation are extended to a total of eight operations that have been formulated in terms of a single morphological operation--biased dilation. Based on the spatial coding of a fuzzy variable, a bidirectional projection concept is proposed. Thus, fuzzy logic operations, arithmetic operations, gray-scale dilation, and erosion for the extended intrinsically fuzzy morphological operations can be included in a unified algorithm with only biased dilation and fuzzy logic operations. To execute this image algebra approach we present a cellular two-layer processing architecture that consists of a biased dilation processor and a fuzzy logic processor. (C) 1996 Optical Society of America

Hit-or-miss representation of a pattern spectrum and its optical implementation

We demonstrate that a pattern spectrum can be decomposed into the union of hit-or-miss transforms with respect to a series of structure-element pairs. Moreover we use a Boolean-logic function to express the pattern spectrum and show that the Boolean-logic representation of a pattern spectrum is composed of hit-or-miss min terms. The optical implementation of a pattern spectrum is based on an incoherent optical correlator with a feedback operation. (C) 1996 Optical Society of America

Morphological ordered gray-scale erosion for optical image processing

An ordered gray-scale erosion is suggested according to the definition of hit-miss transform. Instead of using three operations, two images, and two structuring elements, the developed operation requires only one operation and one structuring element, but with three gray-scale levels. Therefore, a union of the ordered gray-scale erosions with different structuring elements can constitute a simple image algebra to program any combined image processing function. An optical parallel ordered gray-scale erosion processor is developed based on the incoherent correlation in a single channel. Experimental results are also given for an edge detection and a pattern recognition. (C) 1998 Society of Photo-Optical Instrumentation Engineers. [S0091-3286(98)00306-7].

Optoelectronic quotient-selected modified signed-digit division

A novel optoelectronic quotient-selected modified signed-digit division technique is proposed. This division method generates one quotient digit per iteration involving only one shift operation, one quotient selection operation and one addition/subtraction operation. The quotient digit can be selected by observing three most significant digits of the partial remainder independent of the divisor. Two algorithms based on truth-table look-up and binary logic operations are derived. For optoelectronic implementation, an efficient shared content-addressable memory based architecture as well as compact logic array processor based architecture with an electron-trapping device is proposed. Performance evaluation of the proposed optoelectronic quotient-selected division shows that it is faster than the previously reported convergence division approach. Finally, proof-of-principle experimental results are presented to verify the effectiveness of the proposed technique. (C) 2001 Society of Photo-Optical Instrumentation Engineers.

One-step digit-set-restricted modified signed-digit adder using an incoherent correlator based on a shared content-addressable memory

An efficient one-step digit-set-restricted modified signed-digit (MSD) adder based on symbolic substitution is presented. In this technique, carry propagation is avoided by introducing reference digits to restrict the intermediate carry and sum digits to {1,0} and {0,1}, respectively. The proposed technique requires significantly fewer minterms and simplifies system complexity compared to the reported one-step MSD addition techniques. An incoherent correlator based on an optoelectronic shared content-addressable memory processor is suggested to perform the addition operation. In this technique, only one set of minterms needs to be stored, independent of the operand length. (C) 2002 society or Photo-Optical Instrumentation Engineers.

Control de un sistema de accionamientos de traslación basado en correa para un manipulador de cinemática paralela

[ES]Este Trabajo de Fin de Grado “Control de un sistema de accionamientos de traslación basado en correa para un manipulador de cinemática paralela” tiene como objetivo principal la implementación de un sistema de control que nos permita manejar un manipulador de cinemática paralela de dos grados de libertad accionado mediante dos motores eléctricos de corriente continua. Como componente central de este sistema de control, se dispondrá de un ordenador portátil cuyo procesador será el encargado de ejecutar las acciones necesarias para que pueda llevarse a cabo esta actividad de control. De esta forma, la tarea más importante y laboriosa a llevar cabo en este proyecto será el desarrollo de un aplicación de control que, corriendo en el citado ordenador, permitirá al usuario manejar el manipulador de cinemática paralela en cuestión. Para ello, esta aplicación deberá ser capaz de interpretar las ordenes de movimiento dadas por el usuario y transmitirlas al procesador del mencionado ordenador. Además de todo lo anterior, para completar el desarrollo del sistema de control, será necesaria la implementación de diversos sensores que se encargarán de detectar y transmitir las señales necesarias para evitar situaciones de emergencia en el que el manipulador estuviese a punto de chocar con algún objeto o persona. En conclusión, mediante el cumplimiento de los objetivos de este Trabajo de Fin de Grado, se va a disponer de un sistema de control sencillo, intuitivo y fácilmente operable, que va a permitir a cualquier futuro usuario del mismo el manejo de un robot de cinemática paralela.

Heterometallic Complexes as Models of Enzymatic Active Sites

This dissertation describes studies on two multinucleating ligand architectures: the first scaffold was designed to support tricopper complexes, while the second platform was developed to support tri- and tetrametallic clusters.

In Chapter 2, the synthesis of yttrium (and lanthanide) complexes supported by a tripodal ligand framework designed to bind three copper centers in close proximity is described. Tricopper complexes were shown to react with dioxygen in a 1:1 [Cu₃]/O₂ stoichiometry to form intermediates in which the O–O bond was fully cleaved, as characterized via UV-Vis spectroscopy and determination of the reaction stoichiometry. Pre-arrangement of the three Cu centers was pivotal to cooperative O₂ activation, as mono-copper complexes reacted differently with dioxgyen. The reactivity of the observed intermediates was studied with various substrates (reductants, O-atom acceptors, H-atom donors, Brønsted acids) to determine their properties. In Chapter 3, the reactivity of the same yttrium-tricopper complex with nitric oxide was explored. Reductive coupling to form a trans-hyponitrite complex (characterized by X-ray crystallography) was observed via cooperative reactivity by an yttrium and a copper center on two distinct tetrametallic units. The hyponitrite complex was observed to release nitrous oxide upon treatment with a Brønsted acid, supporting its viability as an intermediate in nitric oxide reduction to nitrous oxide.

In Chapter 4, a different multinucleating ligand scaffold was employed to synthesize heterometallic triiron clusters containing one oxide and one hydroxide bridges. The effects of the redox-inactive, Lewis acidic heterometals on redox potential was studied by cyclic voltammetry, unveiling a linear correlation between redox potential and heterometal Lewis acidity. Further studies on these complexes showed that the Lewis acidity of the redox-inactive metals also affected the oxygen-atom transfer reactivity of these clusters. Comparisons of this reactivity with manganese systems, collaborative efforts to reassign the structures of related manganese oxo-hydroxo clusters, and synthetic attempts to access related dioxo clusters are also described.

In Appendix A, ongoing efforts to synthesize new clusters supported by the same multinucleating ligand platform are described. Studies of novel approaches towards ligand exchange in tetrametallic clusters and incorporation of new supporting and bridging ligand motifs in trinuclear complexes are presented.

Design and evaluation of an optical switching node

[EN]For a good development of elastic optical networks, the design of flexible optical switching nodes is required. This work analyses the previously proposed flexible architectures and, based on the most appropriate, which is the Architecture on Demand (AoD), proposes a specific configuration of the node that includes spatial and spectral switching and the wavelength conversion functionality with a low blocking probability and the minimum amount of modules; the characteristics of the traffic that the designed node is able to cope with are specified in the last chapter. An evaluation of the designed node is also done, and, compared to the other architectures, it is shown that the Architecture on Demand gives better results than others and that it has a higher potential for future developments.

Marketing study

The findings are presented of a marketing survey conducted in the lake Victoria region. The research concentrated on consumers, trader /processors serving local markets, industrial processors serving mainly international markets, and fishers. The market for fish from Lake Victoria is traced from the consumer to the producer, including as many components of the chain as possible. The components are dealt with in individual sections which comprise a profile of a typical consumer/trader-processor/industrial processor /fisher, a list of survey sites, a map showing locations, a note on potential biases within the individual survey, a list of hypotheses or study topics for all surveys except for that of industrial processors, detailed analyses and also the pertinent questionnaire.