A Modular Open-Technology Device to Measure and Adjust Concentration of Sperm Samples for Cryopreservation

Repositories for aquatic germplasm can safeguard the genetic diversity of species of interest to aquaculture, research, and conservation. The development of such repositories is impeded by a lack of standardization both within laboratories and across the research community. Protocols for cryopreservation are often developed ad hoc and without close attention to variables, such as sperm concentration, that strongly affect the success and consistency of cryopreservation. The wide dissemination and use of specialized tools and devices can improve processing reliability, provide data logging, produce custom hardware to address unique problems, and save costs, time, and labor. The goal of the present work was to develop a low-cost and open-technology approach to standardize the concentration of sperm samples prior to cryopreservation. The specific objectives were to: 1) fabricate and test a peristaltic pump and optical evaluation module (POEM); 2) fabricate and test a prototype of the modular, open-technology concentration measurement and adjustment system (CMAS), which incorporated the POEM; 3) identify opportunities to extend the CMAS to microliter volumes through low-cost resin 3-D printing, and 4) identify strategies from this work that can be applied to future open fabrication efforts. The POEM and CMAS were prototyped and tested with biological samples. A relationship between optical signal and cell concentration of channel catfish (Ictalurus punctatus) sperm samples was established by linear regression. In a blind trial, cell concentrations were estimated with the POEM and correlated closely to their known concentrations (linear regression R2 = 0.9945) in a range of 1 × 108 to 4 × 109 cells/mL. The CMAS was able to estimate and adjust the concentration of a sample of the marine microalgae Tetraselmis chuii as a preparatory step for cryopreservation. To explore the possible use of the CMAS with microliter sample volumes in future work, evaluation of low-cost resin 3-D printing showed that this technology can approach conventional microfabrication techniques in feature quality and resolution. The development of the CMAS as open technology can provide opportunities for community-level standardization in cryopreservation of aquatic germplasm, invite new users, makers, and developers into the open-technology community, and increase the reach and capabilities of aquatic germplasm repositories

Computational fluid dynamics indicators to improve cardiovascular pathologies

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.Postprint (published version

Characterisation of the rif and stevor Multigene Families in Plasmodium falciparum Isolates Sampled From Natural Infections

Parasite-derived variant surface antigens (VSA) expressed on the infected erythrocyte surface are important targets of naturally acquired protective immune responses against malaria. The three major VSA-encoding multigene families of Plasmodium falciparum, var, rif and stevor, exhibit high inter- and intra-strain genomic variability. The VSA component encoded by the var gene family, PfEMP1, comprises the major cytoadhesive ligand and the major antigenic target of protective antibodies. However, other VSA families, including those encoded by the rif and stevor multigene families, may also play important roles in malaria pathogenesis and immunity. However, the biological relevance of non-PfEMP1 VSA remains largely unknown. This thesis represents the first extensive analysis of sequence diversity and expression patterns of rif and stevor variant gene families in African field isolates of P. falciparum. The work details the characterization of rif and stevor gene repertoires of P. falciparum parasites from diverse geographical locations and identification of conserved genes in both P. falciparum and the related chimpanzee malaria parasite P. reichenowi. Both capillary sequencing and clone-free, 454 deep sequencing methods have been used to study changes in variant gene expression during asexual development of wild and culture-adapted isolates. Isolate- and stage-specific transcription patterns of rif and stevor genes were observed, and the major sets of transcripts in multiple isolates, including parasites that have been selected for different cytoadhesive phenotypes (resetting and adhesion to human brain endothelial cell lines) identified. The role of RIFIN antigens in the natural acquisition of antibodies to malaria was tested using a strain transcendent variant PF3D7_1253700 (PFL2585c). The hypervariable region of this RIFIN, expressed as a recombinant protein was used to purify naturally acquired human antibodies from sera from malaria-immune African adults. These antibodies recognized native RIFIN antigen on the surface of intact trophozoites showing that RIFINs for additional targets of naturally acquired antibodies that recognize the surface of parasite-infected red blood cells

Design automation and analysis of three-dimensional integrated circuits

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004.Includes bibliographical references (p. 165-176).This dissertation concerns the design of circuits and systems for an emerging technology known as three-dimensional integration. By stacking individual components, dice, or whole wafers using a high-density electromechanical interconnect, three-dimensional integration can achieve scalability and performance exceeding that of conventional fabrication technologies. There are two main contributions of this thesis. The first is a computer-aided design flow for the digital components of a three-dimensional integrated circuit (3-D IC). This flow primarily consists of two software tools: PR3D, a placement and routing tool for custom 3-D ICs based on standard cells, and 3-D Magic, a tool for designing, editing, and testing physical layout characteristics of 3-D ICs. The second contribution of this thesis is a performance analysis of the digital components of 3-D ICs. We use the above tools to determine the extent to which 3-D integration can improve timing, energy, and thermal performance. In doing so, we verify the estimates of stochastic computational models for 3-D IC interconnects and find that the models predict the optimal 3-D wire length to within 20% accuracy. We expand upon this analysis by examining how 3-D technology factors affect the optimal wire length that can be obtained. Our ultimate analysis extends this work by directly considering timing and energy in 3-D ICs. In all cases we find that significant performance improvements are possible. In contrast, thermal performance is expected to worsen with the use of 3-D integration. We examine precisely how thermal behavior scales in 3-D integration and determine quantitatively how the temperature may be controlled during the circuit placement process. We also show how advanced packaging(cont.) technologies may be leveraged to maintain acceptable die temperatures in 3-D ICs. Finally, we explore two issues for the future of 3-D integration. We determine how technology scaling impacts the effect of 3-D integration on circuit performance. We also consider how to improve the performance of digital components in a mixed-signal 3-D integrated circuit. We conclude with a look towards future 3-D IC design tools.by Shamik Das.Ph.D

Towards efficient neurosurgery: Image analysis for interventional MRI

Interventional magnetic resonance imaging (iMRI) is being increasingly used for performing imageguided neurosurgical procedures. Intermittent imaging through iMRI can help a neurosurgeon visualise the target and eloquent brain areas during neurosurgery and lead to better patient outcome. MRI plays an important role in planning and performing neurosurgical procedures because it can provide highresolution anatomical images that can be used to discriminate between healthy and diseased tissue, as well as identify location and extent of functional areas. This is of significant clinical utility as it helps the surgeons maximise target resection and avoid damage to functionally important brain areas. There is clinical interest in propagating the pre-operative surgical information to the intra-operative image space as this allows the surgeons to utilise the pre-operatively generated surgical plans during surgery. The current state of the art neuronavigation systems achieve this by performing rigid registration of pre-operative and intra-operative images. As the brain undergoes non-linear deformations after craniotomy (brain shift), the rigidly registered pre-operative images do not accurately align anymore with the intra-operative images acquired during surgery. This limits the accuracy of these neuronavigation systems and hampers the surgeon’s ability to perform more aggressive interventions. In addition, intra-operative images are typically of lower quality with susceptibility artefacts inducing severe geometric and intensity distortions around areas of resection in echo planar MRI images, significantly reducing their utility in the intraoperative setting. This thesis focuses on development of novel methods for an image processing workflow that aims to maximise the utility of iMRI in neurosurgery. I present a fast, non-rigid registration algorithm that can leverage information from both structural and diffusion weighted MRI images to localise target lesions and a critical white matter tract, the optic radiation, during surgical management of temporal lobe epilepsy. A novel method for correcting susceptibility artefacts in echo planar MRI images is also developed, which combines fieldmap and image registration based correction techniques. The work developed in this thesis has been validated and successfully integrated into the surgical workflow at the National Hospital for Neurology and Neurosurgery in London and is being clinically used to inform surgical decisions

f3d — a file format and tools for storage and manipulation of volumetric data sets

Different file formats for storage and manipulation of volumetric data exist today, but none of them has been accepted as a standard by the volume visualization and volume graphics communities until now. This paper tries to change this situation by proposing a new, freely available file format f3d, which, as we believe, fulfills the demands of research and educational environments. We hope that this new format will be accepted by the above mentioned communities and thus will provide a basis for improved communication between different groups and applications.

Brain-muscle axis during treatment of minimal hepatic encephalopathy with L-ornithine L-aspartate

Abstract Background: Minimal Hepatic Encephalopathy (MHE) is a fluctuant cognitive deficit, and a common complication of cirrhosis, with significant health and socioeconomic consequences. Oral L-Ornithine L-Aspartate (LOLA) has been proposed to treat MHE but mechanism and efficacy are unknown. This study hypothesises LOLA treatment will correlate with improvements in: 1) Cognitive function (primary endpoints) 2) Relation to Brain-muscle axis (secondary endpoints) Design and methods: This double-blinded placebo-controlled trial included 34 patients (LOLA n=14, placebo n=20) over 12 weeks. All underwent psychometric testing (PHES, CogstateTM, Stroop, Short Form-36). Secondary endpoints included brain volume, white matter microstructure, brain function (proton MR spectroscopy/ functional MRI); muscle power (handgrip strength, 6-minute-walk-test); anthropometry (upper limb skinfold); muscle metabolome (lateral vastus muscle biopsy LC-MS analysis). Results: Significantly more patients receiving LOLA reported improved energy levels, specifically in Vitality (SF36 subdomain). No differences in PHES, Cogstate and Stroop test performance occured. Change-in-biceps skinfold thickness demonstrated significant gain with LOLA compared to placebo, without differences in power. LC-MS experiments were not discriminatory. Whole Brain differences in FA and RD suggested reduced brain oedema (subcortical volume reduction and global white matter changes). No significant group differences in fMRI task/ resting activation were seen. Spectroscopy of ACC showed significantly higher unresolved glutamine-glutamate (Glx) complex levels with LOLA, also correlating with increased PPI use, and may represent LOLA-driven increased Krebs-cycling or a function of altered gut microbiome. Conclusion: No cognitive benefits were demonstrated. Improved quality of life measures maybe a nutritional consequence also relating to increased biceps skinfold thickness with LOLA. Effects on brain oedema are postulated. Future studies need higher powering to allow subanalysis by aetiology, and smaller voxels at basal ganglia are recommended. Attempts to replicate rising ACC Glx with LOLA and regions of interest identified on fMRI subanalysis may be fruitful.Open Acces

Numerical Techniques for Stochastic Optimization

This is a comprehensive and timely overview of the numerical techniques that have been developed to solve stochastic programming problems. After a brief introduction to the field, where accent is laid on modeling questions, the next few chapters lay out the challenges that must be met in this area. They also provide the background for the description of the computer implementations given in the third part of the book. Selected applications are described next. Some of these have directly motivated the development of the methods described in the earlier chapters. They include problems that come from facilities location, exploration investments, control of ecological systems, energy distribution and generation. Test problems are collected in the last chapter. This is the first book devoted to this subject. It comprehensively covers all major advances in the field (both Western and Soviet). It is only because of the recent developments in computer technology, that we have now reached a point where our computing power matches the inherent size requirements faced in this area. The book demonstrates that a large class of stochastic programming problems are now in the range of our numerical capacities