A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Estimating parameters in stochastic systems:a variational Bayesian approach

This work is concerned with approximate inference in dynamical systems, from a variational Bayesian perspective. When modelling real world dynamical systems, stochastic differential equations appear as a natural choice, mainly because of their ability to model the noise of the system by adding a variation of some stochastic process to the deterministic dynamics. Hence, inference in such processes has drawn much attention. Here a new extended framework is derived that is based on a local polynomial approximation of a recently proposed variational Bayesian algorithm. The paper begins by showing that the new extension of this variational algorithm can be used for state estimation (smoothing) and converges to the original algorithm. However, the main focus is on estimating the (hyper-) parameters of these systems (i.e. drift parameters and diffusion coefficients). The new approach is validated on a range of different systems which vary in dimensionality and non-linearity. These are the Ornstein–Uhlenbeck process, the exact likelihood of which can be computed analytically, the univariate and highly non-linear, stochastic double well and the multivariate chaotic stochastic Lorenz ’63 (3D model). As a special case the algorithm is also applied to the 40 dimensional stochastic Lorenz ’96 system. In our investigation we compare this new approach with a variety of other well known methods, such as the hybrid Monte Carlo, dual unscented Kalman filter, full weak-constraint 4D-Var algorithm and analyse empirically their asymptotic behaviour as a function of observation density or length of time window increases. In particular we show that we are able to estimate parameters in both the drift (deterministic) and the diffusion (stochastic) part of the model evolution equations using our new methods.

The human factors of automatic speech recognition in control room systems

This thesis addresses the viability of automatic speech recognition for control room systems; with careful system design, automatic speech recognition (ASR) devices can be useful means for human computer interaction in specific types of task. These tasks can be defined as complex verbal activities, such as command and control, and can be paired with spatial tasks, such as monitoring, without detriment. It is suggested that ASR use be confined to routine plant operation, as opposed the critical incidents, due to possible problems of stress on the operators' speech.  It is proposed that using ASR will require operators to adapt a commonly used skill to cater for a novel use of speech. Before using the ASR device, new operators will require some form of training. It is shown that a demonstration by an experienced user of the device can lead to superior performance than instructions. Thus, a relatively cheap and very efficient form of operator training can be supplied by demonstration by experienced ASR operators. From a series of studies into speech based interaction with computers, it is concluded that the interaction be designed to capitalise upon the tendency of operators to use short, succinct, task specific styles of speech. From studies comparing different types of feedback, it is concluded that operators be given screen based feedback, rather than auditory feedback, for control room operation. Feedback will take two forms: the use of the ASR device will require recognition feedback, which will be best supplied using text; the performance of a process control task will require task feedback integrated into the mimic display. This latter feedback can be either textual or symbolic, but it is suggested that symbolic feedback will be more beneficial. Related to both interaction style and feedback is the issue of handling recognition errors. These should be corrected by simple command repetition practices, rather than use error handling dialogues. This method of error correction is held to be non intrusive to primary command and control operations. This thesis also addresses some of the problems of user error in ASR use, and provides a number of recommendations for its reduction.

Integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre for DNA probe immobilization

In this paper, we demonstrate the integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre (HC-PCF). In addition, we also show the fluorescence of Cy5-labelled DNA molecules immobilized within the hydrogel formed in two different types of HC-PCF. The 3D hydrogel matrix is designed to bind with the amino groups of biomolecules using an appropriate cross-linker, providing higher sensitivity and selectivity than the standard 2D coverage, enabling a greater number of probe molecules to be available per unit area. The HC-PCFs, on the other hand, can be designed to maximize the capture of fluorescence to improve sensitivity and provide longer interaction lengths. This could enable the development of fibre-based point-of-care and remote systems, where the enhanced sensitivity would relax the constraints placed on sources and detectors. In this paper, we will discuss the formation of such polyethylene glycol diacrylate (PEGDA) hydrogels within a HC-PCF, including their optical properties such as light propagation and auto-fluorescence.

Benefits of electronic vision enhancement systems (EVES) for the visually impaired

PURPOSE: To examine whether objective performance of near tasks is improved with various electronic vision enhancement systems (EVES) compared with the subject's own optical magnifier. DESIGN: Experimental study, randomized, within-patient design. METHODS: This was a prospective study, conducted in a hospital ophthalmology low-vision clinic. The patient population comprised 70 sequential visually impaired subjects. The magnifying devices examined were: patient's optimum optical magnifier; magnification and field-of-view matched mouse EVES with monitor or head-mounted display (HMD) viewing; and stand EVES with monitor viewing. The tasks performed were: reading speed and acuity; time taken to track from one column of print to the next; follow a route map, and locate a specific feature; and identification of specific information from a medicine label. RESULTS: Mouse EVES with HMD viewing caused lower reading speeds than stand EVES with monitor viewing (F = 38.7, P < .001). Reading with the optical magnifier was slower than with the mouse or stand EVES with monitor viewing at smaller print sizes (P < .05). The column location task was faster with the optical magnifier than with any of the EVES (F = 10.3, P < .001). The map tracking and medicine label identification task was slower with the mouse EVES with HMD viewing than with the other magnifiers (P < .01). Previous EVES experience had no effect on task performance (P > .05), but subjects with previous optical magnifier experience were significantly slower at performing the medicine label identification task with all of the EVES (P < .05). CONCLUSIONS: Although EVES provide objective benefits to the visually impaired in reading speed and acuity, together with some specific near tasks, some can be performed just as fast using optical magnification. © 2003 by Elsevier Inc. All rights reserved.

Deformation microstructure under nanoindentations in Cu using 3D x-ray structural microscopy

We have used a recently developed x-ray structural microscopy technique to make nondestructive, submicron-resolution measurements of the deformation microstructure below a 100mN maximum load Berkovich nanoindent in single crystal Cu. Direct observations of plastic deformation under the indent were obtained using a ~0.5 µm polychromatic microbeam and diffracted beam depth profiling to make micron-resolution spatially-resolved x-ray Laue diffraction measurements. The local lattice rotations underneath the nanoindent were found to be heterogeneous in nature as revealed by geometrically necessary dislocation (GND) densities determined for positions along lines beneath a flat indent face and under the sharp Berkovich indent blade edges. Measurements of the local rotation-axes and misorientation-angles along these lines are discussed in terms of crystallographic slip systems.

Multimodal Man-machine Interface and Virtual Reality for Assistive Medical Systems

The results of research the intelligence multimodal man-machine interface and virtual reality means for assistive medical systems including computers and mechatronic systems (robots) are discussed. The gesture translation for disability peoples, the learning-by-showing technology and virtual operating room with 3D visualization are presented in this report and were announced at International exhibition "Intelligent and Adaptive Robots–2005".

Next generation high density three-dimensional magnetic recording systems

This work is the first work using patterned soft underlayers in multilevel three-dimensional vertical magnetic data storage systems. The motivation stems from an exponentially growing information stockpile, and a corresponding need for more efficient storage devices with higher density. The world information stockpile currently exceeds 150EB (ExaByte=1x1018Bytes); most of which is in analog form. Among the storage technologies (semiconductor, optical and magnetic), magnetic hard disk drives are posed to occupy a big role in personal, network as well as corporate storage. However; this mode suffers from a limit known as the Superparamagnetic limit; which limits achievable areal density due to fundamental quantum mechanical stability requirements. There are many viable techniques considered to defer superparamagnetism into the 100's of Gbit/in2 such as: patterned media, Heat-Assisted Magnetic Recording (HAMR), Self Organized Magnetic Arrays (SOMA), antiferromagnetically coupled structures (AFC), and perpendicular magnetic recording. Nonetheless, these techniques utilize a single magnetic layer; and can thusly be viewed as two-dimensional in nature. In this work a novel three-dimensional vertical magnetic recording approach is proposed. This approach utilizes the entire thickness of a magnetic multilayer structure to store information; with potential areal density well into the Tbit/in2 regime. ^ There are several possible implementations for 3D magnetic recording; each presenting its own set of requirements, merits and challenges. The issues and considerations pertaining to the development of such systems will be examined, and analyzed using empirical and numerical analysis techniques. Two novel key approaches are proposed and developed: (1) Patterned soft underlayer (SUL) which allows for enhanced recording of thicker media, (2) A combinatorial approach for 3D media development that facilitates concurrent investigation of various film parameters on a predefined performance metric. A case study is presented using combinatorial overcoats of Tantalum and Zirconium Oxides for corrosion protection in magnetic media. ^ Feasibility of 3D recording is demonstrated, and an emphasis on 3D media development is emphasized as a key prerequisite. Patterned SUL shows significant enhancement over conventional "un-patterned" SUL, and shows that geometry can be used as a design tool to achieve favorable field distribution where magnetic storage and magnetic phenomena are involved. ^

Structure-based modeling of head -related transfer functions towards interactive customization of binaural sound systems

One of the most popular techniques for creating spatialized virtual sounds is based on the use of Head-Related Transfer Functions (HRTFs). HRTFs are signal processing models that represent the modifications undergone by the acoustic signal as it travels from a sound source to each of the listener's eardrums. These modifications are due to the interaction of the acoustic waves with the listener's torso, shoulders, head and pinnae, or outer ears. As such, HRTFs are somewhat different for each listener. For a listener to perceive synthesized 3-D sound cues correctly, the synthesized cues must be similar to the listener's own HRTFs. ^ One can measure individual HRTFs using specialized recording systems, however, these systems are prohibitively expensive and restrict the portability of the 3-D sound system. HRTF-based systems also face several computational challenges. This dissertation presents an alternative method for the synthesis of binaural spatialized sounds. The sound entering the pinna undergoes several reflective, diffractive and resonant phenomena, which determine the HRTF. Using signal processing tools, such as Prony's signal modeling method, an appropriate set of time delays and a resonant frequency were used to approximate the measured Head-Related Impulse Responses (HRIRs). Statistical analysis was used to find out empirical equations describing how the reflections and resonances are determined by the shape and size of the pinna features obtained from 3D images of 15 experimental subjects modeled in the project. These equations were used to yield “Model HRTFs” that can create elevation effects. ^ Listening tests conducted on 10 subjects show that these model HRTFs are 5% more effective than generic HRTFs when it comes to localizing sounds in the frontal plane. The number of reversals (perception of sound source above the horizontal plane when actually it is below the plane and vice versa) was also reduced by 5.7%, showing the perceptual effectiveness of this approach. The model is simple, yet versatile because it relies on easy to measure parameters to create an individualized HRTF. This low-order parameterized model also reduces the computational and storage demands, while maintaining a sufficient number of perceptually relevant spectral cues. ^

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.

Um algoritmo paralelo eficiente de migração reversa no tempo (rtm) 3d com granularidade fina

The reverse time migration algorithm (RTM) has been widely used in the seismic industry to generate images of the underground and thus reduce the risk of oil and gas exploration. Its widespread use is due to its high quality in underground imaging. The RTM is also known for its high computational cost. Therefore, parallel computing techniques have been used in their implementations. In general, parallel approaches for RTM use a coarse granularity by distributing the processing of a subset of seismic shots among nodes of distributed systems. Parallel approaches with coarse granularity for RTM have been shown to be very efficient since the processing of each seismic shot can be performed independently. For this reason, RTM algorithm performance can be considerably improved by using a parallel approach with finer granularity for the processing assigned to each node. This work presents an efficient parallel algorithm for 3D reverse time migration with fine granularity using OpenMP. The propagation algorithm of 3D acoustic wave makes up much of the RTM. Different load balancing were analyzed in order to minimize possible losses parallel performance at this stage. The results served as a basis for the implementation of other phases RTM: backpropagation and imaging condition. The proposed algorithm was tested with synthetic data representing some of the possible underground structures. Metrics such as speedup and efficiency were used to analyze its parallel performance. The migrated sections show that the algorithm obtained satisfactory performance in identifying subsurface structures. As for the parallel performance, the analysis clearly demonstrate the scalability of the algorithm achieving a speedup of 22.46 for the propagation of the wave and 16.95 for the RTM, both with 24 threads.

Regional Magma Plumbing and emplacement mechanisms of the Faroe-Shetland Sill Complex : Implications for magma transport and petroleum systems within sedimentary basins

Peer reviewed

Regional Magma Plumbing and emplacement mechanisms of the Faroe-Shetland Sill Complex : Implications for magma transport and petroleum systems within sedimentary basins

Peer reviewed