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Braun, Ines [Verfasser]. "Die Verbrennung von Kohlenwasserstoffen in CO₂-O₂- sowie H₂O-O₂-Gemischen / Ines Braun." Karlsruhe : KIT-Bibliothek, 1998. http://d-nb.info/1198223294/34.
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Günther, Stefan [Verfasser], Thomas [Akademischer Betreuer] Braun, Elmar [Akademischer Betreuer] Wahle, and Thomas [Akademischer Betreuer] Brand. "Die Rolle skelettmuskelspezifischer Transkriptionsfaktoren und deren Co-Regulatoren während der Myogenese und Regeneration / Stefan Günther. Betreuer: Thomas Braun ; Elmar Wahle ; Thomas Brand." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2009. http://d-nb.info/102493733X/34.
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SCHIATTI, LUCIA. "Co-adaptive control strategies in assistive Brain-Machine Interfaces." Doctoral thesis, Università degli studi di Genova, 2018. http://hdl.handle.net/11567/929163.
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A large number of people with severe motor disabilities cannot access any of the
available control inputs of current assistive products, which typically rely on residual
motor functions. These patients are therefore unable to fully benefit from existent
assistive technologies, including communication interfaces and assistive robotics. In
this context, electroencephalography-based Brain-Machine Interfaces (BMIs) offer a
potential non-invasive solution to exploit a non-muscular channel for communication
and control of assistive robotic devices, such as a wheelchair, a telepresence
robot, or a neuroprosthesis. Still, non-invasive BMIs currently suffer from limitations,
such as lack of precision, robustness and comfort, which prevent their practical
implementation in assistive technologies.
The goal of this PhD research is to produce scientific and technical developments
to advance the state of the art of assistive interfaces and service robotics based on
BMI paradigms. Two main research paths to the design of effective control strategies
were considered in this project. The first one is the design of hybrid systems, based on
the combination of the BMI together with gaze control, which is a long-lasting motor
function in many paralyzed patients. Such approach allows to increase the degrees
of freedom available for the control. The second approach consists in the inclusion
of adaptive techniques into the BMI design. This allows to transform robotic tools and
devices into active assistants able to co-evolve with the user, and learn new rules of
behavior to solve tasks, rather than passively executing external commands.
Following these strategies, the contributions of this work can be categorized
based on the typology of mental signal exploited for the control. These include:
1) the use of active signals for the development and implementation of hybrid eyetracking
and BMI control policies, for both communication and control of robotic
systems; 2) the exploitation of passive mental processes to increase the adaptability
of an autonomous controller to the user’s intention and psychophysiological state,
in a reinforcement learning framework; 3) the integration of brain active and passive
control signals, to achieve adaptation within the BMI architecture at the level of
feature extraction and classification.
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Cherone, Jennifer M. (Jennifer Michelle). "Co-targeting among microRNAs is widespread and enriched in the brain." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/121877.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
MicroRNAs (miRNAs) play roles in diverse developmental processes and cellular differentiation. Distinct miRNAs have hundreds to thousands of conserved binding sites in mRNAs, but typically exert only modest repression on a single site. Co-targeting of individual mRNAs by multiple different miRNAs could be commonly used to achieve stronger and more complex patterns of repression. Comparing target sets of different miRNAs, we identified hundreds of pairs of miRNAs that share more mRNA targets than expected (often ~2-fold or more) relative to stringent controls. For one co-targeting pair, miR-138 and miR-137, we validated functional overlap in neuronal differentiation. Clustering of the pairing relationships revealed a group of 9 predominantly brain-enriched miRNAs that share many targets. In reporter assays, subsets of these miRNAs together repressed gene expression by 5- to 10-fold or more, sometimes exhibiting cooperative repression. Our results uncover an unexpected pattern in which certain combinations of miRNAs can collaborate to strongly repress particular targets, and suggest important developmental roles.
by Jennifer M. Cherone.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
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Isola, Phillip (Phillip John). "The Discovery of perceptual structure from visual co-occurrences in space and time." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/103203.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2015.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 83-92).
Although impressionists assure us that the world is just dabs of light, we cannot help but see surfaces and contours, objects and events. How can a visual system learn to organize pixels into these higher-level structures? In this thesis I argue that perceptual organization reflects statistical regularities in the environment. When visual primitives occur together much more often than one would expect by chance, we may learn to associate those primitives and to form a perceptual group. The first half of the thesis deals with the identification of such groups at the pixel level. I show that low-level image statistics are surprisingly effective at higher-level segmentation. I present an algorithm that groups pixels by identifying meaningful co-occurrences in an image's color statistics. Consider a zebra. Black-next-to-white occurs suspiciously often, hinting that these colors have a common cause. I model these co-occurrences using pointwise mutual information (PMI). If the PMI between two colors is high, then the colors probably belong to the same object. Grouping pixels with high PMI reveals object segments. Separating pixels with low PMI marks perceived boundaries. If simple color co-occurrences can tell us about object segments, what might more complex statistics tell us? The second half of the thesis investigates high dimensional visual data, such as image patches and video frames. In high dimensions, it is intractable to directly model co-occurrences. Instead, I show that modeling PMI can be posed as a simpler binary classification problem in which the goal is to predict if two primitives occur in the same spatial or temporal context. This allows us to model PMI associations between complex inputs. I demonstrate the effectiveness of this approach on three domains: discovering objects by associating image patches, discovering movie scenes by associating frames, and discovering place categories by associating geotagged photos. Together, these results shed light on how a visual system can learn to organize raw sensory input into meaningful percepts.
by Phillip Isola.
Ph. D.
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Cullen, Daniel Kacy. "Traumatically-induced degeneration and reactive astrogliosis in three-dimensional neural co-cultures." Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-11282005-210117/.
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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006.Robert McKeon, Committee Member ; Robert Lee, Committee Member ; Robert Guldberg, Committee Member ; Ravi Bellamkonda, Committee Member ; Michelle LaPlaca, Committee Chair. Vita.
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Kahsai, Tesfai Lily. "Distribution and modulatory roles of neuropeptides and neurotransmitters in the Drosophila brain." Doctoral thesis, Stockholms universitet, Zoologiska institutionen, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-42947.
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The central complex is a prominent neuropil found in the middle of the insect brain. It is considered as a higher center for motor control and information processing. Multiple neuropeptides and neurotransmitters are produced in neurons of the central complex, however, distribution patterns and functional roles of signaling substances in this brain region are poorly known. Thus, this thesis focuses on the distribution of signaling substances and on modulatory roles of neuropeptides in the central complex of Drosophila. Immunocytochemistry in combination with GAL4/UAS technique was used to visualize various signaling substances in the central complex. We revealed different central-complex neurons expressing the neuropeptides; Drosophila tachykinin (DTK), short neuropeptide F (sNPF), myoinhibitory peptide (MIP), allatostatin A, proctolin, SIFamide, neuropeptide F and FMRFamide. Subpopulations of DTK, sNPF and MIP-expressing neurons were found to co-localize a marker for acetylcholine. In addition, five metabotropic neurotransmitter receptors were found to be expressed in distinct patterns. Comparison of receptor/ligand distributions revealed a close match in most of the structures studied. By using a video-tracking assay, peptidergic modulation of locomotor behavior was studied. Different DTK and sNPF-expressing neurons innervating the central complex were revealed to modulate spatial distribution, number of activity-rest phases and activity levels, suggesting circuit dependent modulation. Furthermore, neurosecretory cells in the Drosophila brain that co-express three types of neuropeptides were shown to modulate stress responses to desiccation and starvation. In summary, we have studied two different neuropeptides (DTK and sNPF) expressed in interneuronal circuits and neurosecretory cells of the Drosophila brain in more detail. We found that these neuropeptides display multiple actions as neuromodulators and circulating hormones, and that their actions depend on where they are released.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: In press. Paper 3: Manuscript.
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Lakkadwala, Sushant. "Dual Functionalized Liposomes for Co-delivery of Anti-cancer Chemotherapeutics for Treatment of Brain Tumor." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29394.
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Glioblastoma is a hostile brain tumor associated with high infiltration leading to poor prognosis. Currently available treatment options are insufficient to increase median survival time. The combination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of selective and impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used various CPPs based on their physicochemical properties (TAT, penetratin, QLPVM and PFVYLI) and investigated the influence of insertion of CPP to Tf-liposomes on cytotoxic potential, cellular uptake, hemocompatibility and transport across the BBB both in vitro and in vivo. In addition, anti-tumor efficacy of dual functionalized liposomes was evaluated in vitro as well as in vivo. The liposomes were encapsulated with chemotherapeutics agents, doxorubicin and erlotinib for delivery to brain. Co-delivery of doxorubicin and erlotinib loaded Tf-CPP liposomes revealed significantly (p < 0.05) higher translocation more than 12 % across the co-culture endothelial barrier resulting in regression of tumor in the in vitro brain tumor model. The biodistribution of Tf-CPP liposomes demonstrated more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively compared to free drugs. Histological evaluation of tissue sections showed no signs of toxicity. In addition, Tf-Pen liposomes showed excellent antitumor efficacy by regressing ~90% of tumor in mice brain with significant increase in the median survival time (36 days). In conclusion, we have developed a high efficiency liposomal drug delivery carrier that can cross the BBB and co-deliver doxorubicin and erlotinib to desired target tumor site in vivo in mice, thereby 1) increased concentration of chemotherapeutics in brain, 2) regression in glioblastoma tumor size, 3) reducing the possibility of drug resistance in cancer cells, without eliciting undesired toxicity.National Institutes of Health (NIH Grant RO1 AG051574)
ND EPSCoR
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Andersson, Daniel. "Cooperative observation of multiple moving targets: an evolutionary approach." Thesis, University of Skövde, Department of Computer Science, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-822.
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The interest for cooperative robots has increased considerably in recent years and one of the research issues within this domain is how to evolve heterogeneity in a team. The research today is however either focusing on diversity in hardware (e.g. sensory system) or diversity of behaviour. This dissertation extends this research and presents experiments that attempts to 'co-evolve' heterogeneity at both the hardware level and the behavioural level. The results show that the team behaviour evolved depends on the complexity of the task where adding constraints or increasing the difficulty of the problem lead to better team behaviour.
Our belief was that the performance of the team should benefit from using robots that has been evolved at the hardware level together with the behavioural level. This, however, could not be proved to be true, but the idea that these two should be kept together in order to evolve heterogeneity in a team is still believed.
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Buason, Gunnar. "Competitive co-evolution of sensory-motor systems." Thesis, University of Skövde, Department of Computer Science, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-733.
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A recent trend in evolutionary robotics and artificial life research is to maximize self-organization in the design of robotic systems, in particular using artificial evolutionary techniques, in order to reduce the human designer bias. This dissertation presents experiments in competitive co-evolutionary robotics that integrate and extend previous work on competitive co-evolution of neural robot controllers in a predator-prey scenario with work on the ‘co-evolution’ of robot morphology and control systems. The focus here is on a systematic investigation of tradeoffs and interdependencies between morphological parameters and behavioral strategies through a series of predator-prey experiments in which increasingly many aspects are subject to self-organization through competitive co-evolution. The results show that there is a strong interdependency between morphological parameters and behavioral strategies evolved, and that the competitive co-evolutionary process was able to find a balance between and within these two aspects. It is therefore concluded that competitive co-evolution has great potential as a method for the automatic design of robotic systems.
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Zhao, Wanying. "An exploration of the integration of speech with co-speech gesture with non-invasive brain stimulation." Thesis, University of Hull, 2017. http://hydra.hull.ac.uk/resources/hull:16482.
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The current PhD project focuses on the integration of gesture with their co-occurring speech with the use of non-invasive brain stimulation. The project investigated ‘where’ and ‘when’ gesture-speech integration takes place. Building on the paradigm of Kelly et al., (2010) which provides a reaction time index of automatic gesture-speech integration, it was tested whether left middle temporal gyrus (pMTG) as well as left Inferior frontal gyrus (LIFG) are causally involved in gesture-speech integration. A follow-up study investigated the time window for this integration of gesture and speech in pMTG. This study found that gesture has a priming effect on the semantic retrieval of speech. This effect only manifested itself after gesture had been clearly understood and before the semantic analysis of speech. Based on the common coding hypothesis, this finding was interpreted in terms of gesture and speech originating from a common coding system, with both LIFG and pMTG as its neural underpining, enabling bi-directional influences between both domains.
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Bhat, G. "SOX17 IS A CO-EFFECTOR IN WNT/BETA-CATENIN MEDIATED BLOOD-BRAIN BARRIER DEVELOPMENT AND MAINTENANCE." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/463017.
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The presence of blood-brain barrier (BBB) at the level of endothelial cells (ECs) that
line the capillaries in the brain is a challenge while treating intracranial tumors or
many neurological disorders since BBB could block the passage of many solvents or
drugs entering from systemic circulation to brain parenchyma. Researchers are trying
to understand how BBB is induced during development and maintained in adult life
in order to develop new tools to enhance drug delivery across BBB. Many signaling
pathway that are active during BBB development are unraveled through mainly
reverse genetic approach and gene knock out studies. Wnt/β-catenin signaling well
known for its role in organ development, morphogenesis and in cancer causation is
also reported to be essential for BBB induction and maintenance in most vertebrates.
However many target molecules or effectors of this pathway remain to be identified.
Previously we have identified Sox17 a SoxF family transcription factor, as a
downstream molecule of Wnt/β-catenin signaling. It plays a key role in arterial
differentiation of the vasculature of different organs. We found that Sox17 is also
expressed at high levels in brain ECs throughout embryo development and in the
adult vasculature. EC-specific gain of function of β-catenin (GOF) increases Sox17
expression in BBB ECs and may induce ectopic expression of Sox17 also in the
choroid plexus vasculature that lacks the BBB.
We hypothesized therefore that Sox17 might be involved in BBB development and
maintenance downstream to the Wnt pathway. In Sox17 null mice we analyzed
different functional characteristics of BBB such as permeability control and specific
markers expression. The absence of this transcription factor leads to increase in BBB
permeability to high molecular weight molecules and marked increase in PLVAP, a
protein inversely related to maturation of BBB. We also observed significant
reduction in the β-catenin signaling itself by employing BAT-gal reporter in Sox17
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null background. In addition, many direct β-catenin targets like Axin2 and LEF1
were decreased upon Sox17 abrogation. These data suggested that Sox17 is not only
a target of β-catenin signaling but also could maintain steady state, detectable levels
of β-catenin signaling. We could rescue β-catenin signaling and correct BBB defects
by either inhibiting the β-catenin destruction complex or by employing GOF β-
catenin in Sox17 null background. Our study shows that Sox17 is an important
regulator of BBB and it partially acts by sustaining β-catenin signaling. Sox17
expression and signaling may be important in pathological conditions like
intracranial tumors and modulation of its activity could have clinical implications
and therapeutic benefits.
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Patel, Daywin. "Connexin30, expression in astrocytes, co-localization with connexin43 at gap junctions, and late developmental appearance in rat brain." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ35081.pdf.
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Schoof, Melanie Verfasser], and Ulrich [Akademischer Betreuer] [Schüller. "The transcriptional co-activator and lysine acetyltransferase CBP in brain and tumor development / Melanie Schoof ; Betreuer: Ulrich Schüller." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://nbn-resolving.de/urn:nbn:de:gbv:18-105444.
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Schoof, Melanie [Verfasser], and Ulrich [Akademischer Betreuer] Schüller. "The transcriptional co-activator and lysine acetyltransferase CBP in brain and tumor development / Melanie Schoof ; Betreuer: Ulrich Schüller." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/1214370527/34.
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Heinisch, Silke. "Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain." Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/9181.
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AnatomyPh.D.
Chemokines, immune proteins that induce chemotaxis and adhesion, and their G-protein coupled receptors distribute throughout the central nervous system (CNS), regulate neuronal patterning, and mediate neuropathology. These chemo-attractant molecules may provide a neuro-immune "link" by regulating CNS systems. The purpose of this study was to investigate the interactions of specific chemokines, stromal cell-derived factor (SDF)-1a/CXCL12, and fractalkine/CX3CL1, and their receptors, CXCR4 and CX3CR1, with the serotonin (5-hydroxytryptamine; 5-HT) and opioid systems using anatomical and electrophysiological techniques in the rat brain. In the serotonin dense midbrain raphe nuclei (RN), SDF-1a, CXCR4, fractalkine and CX3CR1 co-localize over 70% with 5-HT neurons. CX3CR1 also localizes to microglia in the RN and hippocampus. Functionally, SDF-1a (10 nM) increases spontaneous inhibitory postsynaptic current (sIPSC) frequency and evoked IPSC (eIPSC) amplitude, while decreasing paired-pulse ratio (PPR) selectively in 5-HT neurons, thus stimulating presynaptic GABA release at these neurons. Alternatively, fractalkine (10 nM) increases sIPSC and eIPSC amplitude without changing PPR selectively in 5-HT neurons, thereby elevating the postsynaptic GABA receptor number or sensitivity. These results are dose-dependent and receptor-mediated. Chemokine interactions with serotonin, a neurotransmitter regulating mood, may lead to therapies for depression comorbid with immune diseases. Additional immunohistochemical analysis in the brain shows CXCR4 and CX3CR1 neuronal co-localization with the mu-opioid receptor (MOR) in the hippocampus, cingulate cortex, periaqueductal grey (PAG), nucleus accumbens, ventral tegmental area, globus pallidus, but not in the striatum or habenular nuclei, suggesting region specific receptor interactions. Electrophysiological recordings following morphine, SDF-1?? or fractalkine in vitro treatment reveal morphine (10 ?M)-mediated hyperpolarization of the membrane potential and reduction of the input resistance of PAG neurons, however, SDF-1??and fractalkine at 10 nM do not impact either parameter. In combination, SDF-1? inhibits morphine's actions in all PAG neurons tested, and fractalkine blocks morphine-mediated changes in 60% of PAG neurons examined. Thus, CXCR4 as well as CX3CR1, although less consistently, both appear to desensitize MOR at the neuronal level. Chemokine-opioid receptor interactions may mediate novel mechanisms to treat neuro-inflammatory pain and opiate abuse. The combined anatomical and electrophysiological results support chemokines as neuromodulatory proteins that may provide communication between the nervous and immune systems.
Temple University--Theses
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TRATTARO, SEBASTIANO. "BRAIN ORGANOID MODELLING OF HUMAN CORTICOGENESIS:THE PARADIGM OF WEAVER SYNDROME." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/875973.
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Multiple strategies of brain organoidogenesis have enabled the investigation of human cerebral corticogenesis in-vitro with increasing accuracy. However, little is yet known about how closely the gene co-expression patterns seen in brain organoids (BO) match those of fetal cortex. Here we benchmarked BO against fetal corticogenesis by integrating transcriptomes from in-house differentiated cortical BO (CBO), other BO systems, human fetal brain samples processed in-house, and pre-natal cortices from the BrainSpan Atlas. We identified and ranked co-expression patterns and hubs of corticogenesis and CBO differentiation, highlighting well-preserved and variable trends across BO protocols, and we found heterochronicity of differentiation across BO models compared to fetal cortex. Once performed this benchmarking, we used CBO for disease-modelling of Weaver syndrome (WS), a rare disease characterized by intellectual disability. WS is associated with mutations in Polycomb repressive complex 2, a repressor of gene expression through H3K27me3. We differentiated patient-derived CBO and profiled their transcriptome and epigenome at different time-points, revealing upregulation of genes involved in neuronal maturation and migration as well as alteration of glucose metabolism in WS. Intersection of differentially expressed genes between WS- and control-CBO across stages with H3K27me3 ChIP-seq peaks, DNA-methylation profiles and dysregulated genes in CBO from a CRISPR/Cas9-engineered EZH2 KO revealed a set of PRC2 targets possibly mediating the WS intellectual disability phenotype. Our approach identified commonalities and divergences between state-of-the-art BO systems, providing a resource to query when modelling human corticogenesis, and identified molecular phenotypes and targets relevant for WS, generating the framework for future potential therapeutic intervention.
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Leibrand, Crystal R. "Structural and Functional Consequences of HIV-1 Viral Protein Tat and Morphine Co-Exposure at the Blood-Brain Barrier." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5472.
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According to UNAIDS 2016, over 37 million people worldwide were infected with human immunodeficiency virus (HIV) in 2016, with over 1.2 million people living with HIV in the United States. Of those, approximately one half will suffer from HIV-associated neurocognitive disorders (HAND), which is a spectrum of neurocognitive disorders ranging from asymptomatic neurocognitive impairment, to mild neurocognitive disorder, to HIV-associated dementia. While combination antiretroviral therapy (cART) has decreased the incidence of the most severe forms of HAND in patients with HIV, milder forms of HAND still persist. These defects can include decreased motor skills, cognitive abilities, memory, and attention. While patients with HIV are living longer thanks to cART, there are few to no long-term options for managing the neurocognitive defects caused by the chronic disease of HAND. Additionally, opiate abuse can increase both the incidence and severity of HAND. HAND may result due to poor antiretroviral drug (ARV) penetration across the blood-brain barrier (BBB). Thus, a better understanding of the effects of HIV and opiates on the BBB may result in improved therapies for HAND.
The Tat transgenic model was used to evaluate the effects of the HIV-1 viral protein Tat and morphine on blood-brain barrier leakiness using varied-sized paracellular compounds. Secondly, antiretroviral drug accumulation in the brain of Tat transgenic mice under Tat and/or morphine co-exposure was measured. Specifically, the single tablet regimen of Triumeq® (abacavir/lamivudine/dolutegravir) was studied in these mice and antiretroviral drug measured in both striatum and hippocampus brain regions and plasma via LC-MS/MS. Additionally, morphine and its metabolites were also measured via LC-MS/MS. Lastly, macrophage turnover within the caudate/putamen and phagocytic macrophage/microglia accumulation in the brain was measured in Tat transgenic mice under Tat and/or morphine conditions. Perivascular and parenchymal spaces were distinguished within the caudate/putamen, while overall phagocytic activity was measured in all other brain regions, including the nucleus accumbens, anterior cingulate cortex, primary motor cortex, somatosensory cortex, agranular insular cortex, and piriform cortex.
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Hood, Robert L. "Development of a Fiberoptic Microneedle Device for Simultaneous Co-Delivery of Fluid Agents and Laser Light with Specific Applications in the Treatment of Brain and Bladder Cancers." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51678.
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This dissertation describes the development of the fiberoptic microneedle device (FMD), a microneedle technology platform for fluid and light delivery, from general engineering characterization to specific applications in treating bladder and brain cancers. The central concept of the FMD is physical modification of silica fiberoptics and capillary tubes into sharp microneedles capable of penetrating a tissue's surface, enabling light and fluid delivery into the interstitial spaces. Initial studies sought to characterize the mechanical penetration and optical delivery of multimode fiberoptics and capillary tubes modified through a custom, CO2 laser melt-drawing technique. Additional work with multimode fibers investigated using an elastomeric lateral support medium to ensure robust penetration of small diameter fibers. These early experiments laid an engineering foundation for understanding the FMD technology.
Subsequent studies focused on developing the FMD to treat specific diseases. The first such investigation sought to leverage the high aspect ratio nature of FMDs made from long capillary tubes as a therapy delivery device deployable through the instrument channel of a urological cystoscope. The therapeutic strategy was to infuse single-walled carbon nanohorns (SWNHs), a carbon-based nanoparticle allowing surface modification and drug encapsulation, into the infiltrating front of later stage bladder tumors. The SWNHs primarily serve as exogenous chromophores, enabling a fluid-based control of photothermal heat generation created when the SWNHs interacted with laser energy from an interstitial FMD or a light-emitting fiber in the bladder's interior. The study described here primarily sought to characterize the dispersal of the infused SWNHs and the photothermal response of the particles when heated with a 1064 nm laser.
The FMD was also developed as a platform capable of conducting convection-enhanced delivery (CED), a therapeutic approach to treat invasive tumors of the central nervous system such as malignant glioma (MG). Intracranial CED involves the placement of small catheters local to the tumor site and slow infusion of a chemotherapeutic over long timeframes (12-72 hours). A primary challenge of this treatment approach is infused chemotherapeutics not dispersing sufficiently to reach the infiltrating cells in the tumor's margins. The hypothetical improvement provided by the FMD technology is using sub-lethal photothermal heating to sufficiently increase the diffusive and convective transport of an infusate to reach infiltrative cells in the tumor's periphery. Initial experiments sought to demonstrate and characterize a heat-mediated increase of volumetric dispersal in Agarose tissue phantoms and ex vivo tissue. Subsequent studies with in vivo rodent models determined the best laser parameters to achieve the desired levels of diffuse, sub-lethal heat generation and then demonstrated the hypothesis of increasing the rate of volumetric dispersal though concurrent local hyperthermia. This research was the first demonstration of photothermal augmentation of an interstitially infused fluid's dispersal rate, which may have uses outside of the CED approach to brain cancer exhibited here. Taken in sum, this manuscript describes the potency and versatility of the FMD technology platform through its development in various biomedical applications.Ph. D.
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Nieto, Montesinos Rita Milagros. "Vectorisation de molécules thérapeutiques aux tissus cérébraux." Thesis, Besançon, 2014. http://www.theses.fr/2014BESA0002/document.
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La présence de la glycoprotéine P (P-gp) dans la barrière hémato-encéphalique (BHE) conduit à l’échec de nombreuses thérapies ciblant le système nerveux central (SNC). Cependant la P-gp protège aussi le cerveau contre des composés nocifs, essentiellement lipophiles, endogènes et exogènes susceptibles de passer la BHE par diffusion simple. Par conséquent, toute inhibition de la P-gp qui vise à améliorer la distribution des agents pharmacologiques dans le cerveau doit prendre en compte la neurotoxicité potentielle de cette inhibition. Les premiers travaux ont montré que l’elacridar et le tariquidar, deux modulateurs de la P-gp de troisième génération, augmentaient la distribution dans le cerveau de plusieurs de ses substrats. Malheureusement, d’autres études plus récentes, suggèrent l’utilisation de doses élevées de l’elacridar et du tariquidar pour moduler efficacement l’activité de la P-gp dans la BHE. Néanmoins, ces doses élevées en co-administration avec des substrats de la P-gp peuvent être associées à des interactions pharmacocinétiques et à des profils toxiques, limitant ainsi l'utilisation de ces inhibiteurs.Dans ce contexte, l’objectif principal de cette thèse est d’obtenir une modulation transitoire mais efficace de la P-gp dans la BHE par administration intraveineuse de doses faibles mais thérapeutiques de l’elacridar et du tariquidar sous leur forme libre ou co-encapsulé dans les liposomes. Le lopéramide, substrat de la P-gp, a été également administré sous sa forme libre comme une preuve in vivo d’une inhibition efficace de la P-gp dans la BHE.L'administration simultanée de ces deux modulateurs de la P-gp n’a pas modifié leurs concentrations plasmatiques ou celles du lopéramide, mais a entraîné une importante distribution du lopéramide dans le cerveau en raison de leur activité inhibitrice non- compétitive. De plus, la co-encapsulation de l’elacridar et du tariquidar dans des immunoliposomes stabilisées stériquement a amélioré la demi-vie et la distribution dans le cerveau des ceux deux composés. Par conséquent, la distribution dans le cerveau du lopéramide a été considérablement augmentée, sans aucune modification de sa pharmacocinétique ou distribution tissulaire. Par ailleurs, la diminution partielle de l'activité inhibitrice du tariquidar par des liposomes vides suggère l’utilisation de ce nanovecteur comme une approche de bio-détoxification pour le traitement des surdoses de tariquidar. En résumé, cette thèse propose différentes approches pour exploiter pleinement l’elacridar et le tariquidar. Les résultats décrits dans ce manuscrit devraient ouvrir des pistes intéressantes pour atteindre une inhibition efficace de la P-gp dans la BHE et pour réussir des thérapies ciblant le système nerveux centralAlthough the P-glycoprotein (P-gp) represents an obstacle in several central nervous system (CNS) pharmacotherapies, the P-gp also protects the brain from intoxication by endogenous and exogenous harmful lipophilic compounds that otherwise could penetrate the blood-brain barrier (BBB) by simple diffusion. Therefore, any modulation of the efflux transporter has to consider the potential neurotoxicity of such modulation. Early studies showed that elacridar and tariquidar, two third-generation P-gp modulators, increase the distribution of several P-gp substrates in the brain. Unfortunately, recent studies suggest the use of high doses of elacridar and tariquidar to efficiently modulate the P-gp at the BBB. Nevertheless, when co-administered with P-gp substrates, these high doses may be associated with pharmacokinetic interactions and toxic profiles, thus limiting the use of these compounds.Hence, this thesis aimed to attain a transient but efficient modulation of the P-gp at the BBB using elacridar and tariquidar but avoiding the use of large doses of these compounds. For this purpose we took advantage of the possible in vivo intravenous co-administration of low but therapeutic doses of elacridar and tariquidar, under their free form or co-encapsulated in liposomes. The brain distribution of free loperamide was determined as an in vivo probe of full inhibition of the P-gp activity at the BBB.The concurrent administration of both free P-gp modulators does not modify their plasma concentrations or those of the P-gp substrate but significantly increased the brain uptake of loperamide as a result of their non-competitive modulatory activity. Moreover, the co-encapsulation of elacridar and tariquidar in targeted sterically stabilized immunoliposomes improved the half-lives and brain distribution of both compounds. Consequently, the brain uptake of free loperamide was significantly enhanced without any modification of its pharmacokinetics or tissue distribution. Moreover, the partial impairment of the modulatory activity of tariquidar by empty liposomes, supports the use of this nanocarrier as a bio-detoxifying approach for the treatment of tariquidar overdoses.In summary, this thesis proposes different approaches for full exploitation of elacridar and tariquidar. The findings described in this manuscript should open interesting avenues to achieve an efficient overcoming of the P-gp at the BBB and succeed CNS pharmacotherapies
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Martin-Aragón, Baudel Miguel Ángel Stanislas. "The role of cation chloride co-transporters (CCCs) as potential neuroprotective targets in ischaemic stroke." Thesis, Edinburgh Napier University, 2018. http://researchrepository.napier.ac.uk/Output/1499901.
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Stroke is one of the major causes of death and disability worldwide. The area that surrounds the infarcted core is the location of the continuing damage that takes place hours and days following an insult, and is referred to as the penumbra. By creating an oxygen deprived environment in the neuronal-like PC12 and NT2 cells and an in vivo photothrombotic model of stroke (PTS) in mice, two different strategies were created to replicate the conditions of an ischaemic brain. In differentiated PC12 and NT2 cells, following hypoxia, preferential activation of HIF-2α transcription and protein expression was detected. Increased expression of the neural progenitor stem cell-like markers, thought to be transcriptionally regulated by HIF-2α, were also observed. Furthermore, hypoxia caused loss of neuronal characteristics in differentiated cells. This is highly significant as it shows neuronal cells possess molecular mechanisms which could trigger recovery following ischaemic insult. The expression of the chloride co-transporters, NKCC1 and KCC2, mediators of the GABAergic response, was assessed following hypoxia in differentiated PC12 and NT2 cells and PTS. In PC12 and NT2 cells exposed to hypoxia, the expression of KCC2 was significantly decreased at both the transcript and protein level whereas NKCC1 expression remained unmodified. In the in vivo model, the development of the penumbra in the days following injury was assessed with specific markers allowing the identification of the penumbra up to 200 ❍m from the ischaemic core and a progressive neuronal loss was observed within. Our results show an increase in the number of neurons expressing NKCC1 in the penumbra up to 5 days following the insult when compared to the contralateral hemisphere. On the contrary, KCC2 positive cells were dramatically decreased in this area. In mice treated with bumetanide, an NKCC1 antagonist, a significant reduction in neuronal loss was observed. Our results show a reversal on the chloride co-transporters expression in vitro and in vivo and how treatments targeting these channels might represent a novel strategy to reduce the damage associated with stroke.
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Sygnecka, Katja. "Organotypic brain slice co-cultures of the dopaminergic system - A model for the identification of neuroregenerative substances and cell populations." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-188897.
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The development of new therapeutical approaches, devised to foster the regeneration of neuronal circuits after injury and/or in neurodegenerative diseases, is of great importance. The impairment of dopaminergic projections is especially severe, because these projections are involved in crucial brain functions such as motor control, reward and cognition. In the work presented here, organotypic brain slice co-cultures of (a) the mesostriatal and (b) the mesocortical dopaminergic projection systems consisting of tissue sections of the ventral tegmental area/substantia nigra (VTA/SN), in combination with the target regions of (a) the striatum (STR) or (b) the prefrontal cortex (PFC), respectively, were used to evaluate different approaches to stimulate neurite outgrowth: (i) inhibition of cAMP/cGMP turnover with 3’,5’ cyclic nucleotide phosphodiesterase inhibitors (PDE-Is), (ii) blockade of calcium currents with nimodipine, and (iii) the co-cultivation with bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs). The neurite growth-promoting properties of the tested substances and cell populations were analyzed by neurite density quantification in the border region between the two brain slices, using biocytin tracing or tyrosine hydroxylase labeling and automated image processing procedures. In addition, toxicological tests and gene expression analyses were conducted.
(i) PDE-Is were applied to VTA/SN+STR rat co-cultures. The quantification of neurite density after both biocytin tracing and tyrosine hydroxylase labeling revealed a growth promoting effect of the PDE2A-Is BAY60-7550 and ND7001. The application of the PDE10-I MP-10 did not alter neurite density in comparison to the vehicle control.
(ii) The effects of nimodipine were evaluated in VTA/SN+PFC rat co-cultures. A neurite growth-promoting effect of 0.1 µM and 1 µM nimodipine was demonstrated in a projection system of the CNS. In contrast, the application of 10 µM nimodipine did not alter neurite density, compared to the vehicle control, but induced the activation of the apoptosis marker caspase 3. The expression levels of the investigated genes, including Ca2+ binding proteins (Pvalb, S100b), immediate early genes (Arc, Egr1, Egr2, Egr4, Fos and JunB), glial fibrillary acidic protein, and myelin components (Mal, Mog, Plp1) were not significantly changed (with the exception of Egr4) by the treatment with 0.1 µM and 1 µM nimodipine.
(iii) Bulk BM-MSCs that were classically isolated by plastic adhesion were compared to the subpopulation Sca-1+Lin-CD45--derived MSCs (SL45-MSCs). The neurite growth-promoting properties of both MSC populations were quantified in VTA/SN+PFC mouse co-cultures. For this purpose, the MSCs were seeded on glass slides that were placed underneath the co-cultures. A significantly enhanced neurite density within the co-cultures was induced by both bulk BM-MSCs and SL45-MSCs. SL45-MSCs increased neurite density to a higher degree. The characterization of both MSC populations revealed that the frequency of fibroblast colony forming units (CFU-f ) is 105-fold higher in SL45-MSCs. SL45-MSCs were morphologically more homogeneous and expressed higher levels of nestin, BDNF and FGF2 compared to bulk BM-MSCs.
Thus, this work emphasizes the vast potential for molecular targeting with respect to the development of therapeutic strategies in the enhancement of neurite regrowth.
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Boveri, Monica. "Evaluation of blood-brain barrier in vitro models and application for studying barrier disruption induced by gram-positive bacteria." Artois, 2005. http://www.theses.fr/2005ARTO0402.
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The blood-brain barrier (BBB), located at the level of brain capillary endothelial cells (BCECs), separates the cerebral compartment from the systemic circulation, playing a fundamental role in maintaining the homeostasis of the central nervous system (CNS). The important role that BBB plays both under physiological and pathological conditions lead scientist to look for in vitro models to study the cellular and molecular mechanisms responsible for the permeability variations of this barrier. In regulatory toxicology and in the context of the current European Union political scenario, the development and validation of in vitro models is of outmost importance. The European Centre for the Validation of Alternative Methods (ECVAM) organised in 2003 a workshop on “BBB in vitro methods and their application in toxicology” to discuss the in vitro models available and their application in integrated testing strategies. Taking into consideration the outcomes of this workshop and according to the 3Rs concept (reduction, refinement and replacement), we replaced in a well-established BBB in vitro model the primary glial cells (GCs) necessary for the differentiation of BCECs with the C6 glial cell line, to avoid the use of animals. For the first time, we compared directly the structural and functional differentiation of BCECs induced by C6 cells towards GCs. Trans-endothelial electrical resistance (TEER) measurements showed that in the presence of C6 cells the values were always lower than in the presence of GCs. Permeability of the BCECs to both radioactive sucrose and FITC-inulin was 2. 5-fold higher when cells were co-cultured with C6 than with GCs. Immunocytochemistry studies showed less developed tight junction pattern in the presence of C6. P-gp expression and activity were lower in BCECs co-cultured with C6 than with GCs. The levels of VEGF in the culture medium were 40-fold higher in the presence of C6, suggesting that VEGF was one of the factors responsible for impairing the endothelial barrier co-cultured with C6 cells. Therefore, C6 cell line failed to replace primary GCs in a reliable BBB in vitro model. Furthermore, we used the BBB model consisting of BBCECs co-cultured with primary GCs to investigate the effects of the Gram-positive bacterial cell wall components lipoteichoic acid (LTA) and muramyl dipeptide (MDP) on the structure and function of BBB in vitro. The activation of GCs with LTA disrupted BBB integrity and LTA effect was potentiated by MDP. Immunocytochemistry analysis for tight junction associated proteins showed a delocalisation of AHNAK, revealing that LTA altered the tight junction pattern. LTA-activated GCs produced nitric oxide (NO) and the pro-inflammatory cytokines TNF-a and IL-1b, which contributed to LTA-induced BBB disruption, since the direct treatment of the endothelial monolayer with TNF-a, IL-1b or a NO donor increased BBB permeability. In addition, the pre-treatment of LTA-activated GCs with antibodies against these two cytokines blocked LTA effect and the presence of 1400W, inhibitor of inducible NO synthase (iNOS), partially reversed LTA-induced decreased TEER. This study showed for the first time that LTA impaired the BBB in vitro through glia activation and suggested that free-radical scavengers and inhibitors of iNOS and of pro-inflammatory cytokines could be major targets for the adjunctive therapy of CNS pathologies induced by Gram-positive bacteriaLa barrière hémato-encéphalique (BHE) située au niveau des cellules endothéliales des capillaires cérébraux (BCECs) sépare le cerveau de la circulation systémique, jouant un rôle fondamental dans l'homéostasie du système nerveux central (SNC). Le rôle important de la BHE tant en conditions physiologiques que pathologiques a conduit les chercheurs à mettre au point des modèles de BHE in vitro afin d’étudier les mécanismes cellulaires et moléculaires des variations de la perméabilité de cette barrière. La réglementation en toxicologie et la politique actuelle de l’Union Européenne, encourage fortement le développement et la validation de modèles in vitro. Le Centre Européen pour la Validation des Méthodes Alternatives (ECVAM) a organisé en 2003 une réunion de travail sur les "méthodes in vitro de BHE et leur application en toxicologie" pour évaluer les modèles in vitro disponibles et discuter de leur application dans des stratégies de tests. Suite à cette réunion et en suivant le concept "réduire, améliorer, remplacer" qui tient lieu de ligne de conduite dans la mise au point des méthodes alternatives à l’expérimentation animale, nous avons remplacé, dans le modèle habituellement utilisé au laboratoire, les cultures primaires de cellules gliales (GCs) nécessaires à la différenciation des cellules endothéliales cérébrales, par la lignée C6. Pour la première fois, l’induction des caractéristiques structurales et fonctionnelles de la BHE a donc été comparée dans les BCECs placées en présence de GCs ou de C6. Les mesures de la résistance électrique trans-endothéliale (TEER) montrent qu’en présence de C6 les valeurs sont toujours inférieures à celles obtenues en présence de GCs. De plus la perméabilité endothéliale au saccharose et à l’inuline est 2,5 fois plus élevée en présence de C6. Les études réalisées en immunofluorescence mettent en évidence une différenciation moins bonne des jonctions serrées en présence de C6. L’expression et l’activité de la P-gp sont fortement diminuées. La quantité de VEGF dosé dans les milieux de culture est 40 fois plus importante en présence de C6, ce qui pourrait expliquer la perméabilité élevée des BCECs co-cultivées avec les C6. Les résultats montrent donc que l’utilisation des C6 à la place des GCs ne permet pas d’obtenir un modèle fiable de BHE in vitro. Le modèle initial consistant en une co-culture de BCECs et de GCs a donc finalement été utilisé pour étudier l'effet de l'acide lipoteichoïque (LTA) et du muramyl dipeptide (MDP), composants de la paroi des bactéries Gram-positives, sur la structure et les fonctions de la BHE in vitro. L’activation des GCs par le LTA perturbe l'intégrité de la BHE. Cet effet est renforcé par le MDP. L’étude en immunofluorescence des protéines associées aux jonctions serrées montre une délocalisation d’AHNAK indiquant un effet du LTA sur les jonctions serrées. L’activation des GCs par le LTA a conduit à une sécrétion d’oxyde nitrique (NO) ainsi que de TNF-a et d’IL-1β, cytokines pro-inflammatoires. Ces composés contribueraient à la rupture de la BHE induite par le LTA. En effet le traitement direct des BCECs par le TNF-a ou l’IL-1β ou un donneur de NO augmente la perméabilité de la BHE. De plus, le prétraitement par des anticorps dirigés contre les deux cytokines, des GCs activées par le LTA, bloque l'effet du LTA. La présence d’un inhibiteur de la NO synthase inductible (le 1400W) limite l’augmentation de la perméabilité induite par le LTA. Cette étude prouve pour la première fois que l’activation des GCs par le LTA altère la BHE in vitro et montre que la NO synthase inductible et des cytokines pro-inflammatoires pourraient être les cibles thérapeutiques dans les pathologies du SNC induites par les bactéries Gram-positives
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Retore, Marciana. "CARACTERIZAÇÃO DA FIBRA DE CO-PRODUTOS AGROINDUSTRIAIS E SUA AVALIAÇÃO NUTRICIONAL PARA COELHOS EM CRESCIMENTO." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/10725.
Full textAbstract:
Conselho Nacional de Desenvolvimento Científico e TecnológicoTwo experiments were carried out in Rabbit Laboratory of Animal Science Department at Federal University of Santa Maria, RS, where were studied the influence of different fractions of fiber from agricultural by-products (citrus pulp, soybean hulls, linseed bran and corn gluten meal) on performance, digestibility coefficients, blood parameters and meat quality of rabbits submitted to diets. The diets were isoproteic and isoenergetic, 18% of crude protein and 3,000 kcal/kg of digestible energy, respectively. Eight New Zealand White rabbits were utilized to each treatment, from 40 to 89 days of age. At the first experiment, the treatments were: AHcontrol diet, with alfalfa hay; CP- total substitution of alfalfa hay by citrus pulp and SH- total substitution of alfalfa hay by soybean hulls. The animals of the treatments CP and SH showed similar performance, carcass weight and carcass dressing percentage to the animals of the treatment AH. The DM, OM, CP and NDF apparent digestibility coefficients were superior for the diet SH, due to fiber quality. Reductions on triglycerides, cholesterol, hemoglobin and glucose levels were observed in the blood of the animals fed with citrus pulp, because of the high cation-exchange capacity of this by-product. Meat tenderness was higher for those animals that consumed the diet with soybean hulls, due to better nutrients digestibility. The different fiber fractions from citrus pulp and soybean hulls do not affect animals performance and weight and dressing carcass, showing that these ingredients can substitute the alfalfa hay on rabbits diet. Fiber quality of citrus pulp decrease animals blood triglycerides and cholesterol levels. The lower amount of lignin in relation to cellulose and hemicellulose of the soybean hulls provides better nutrients digestibility coefficients. At the second experiment the treatments were: AH- control diet, with alfalfa hay; LB- total substitution of alfalfa hay by linseed bran and GM- total substitution of alfalfa hay by corn gluten meal (20% of crude protein). The animals from GM treatment showed similar performance in relation to the ones from AH treatment, although the carcass dressing percentage did not differ among the byproducts. Linseed bran proportioned lower performance, due to higher fiber hydration capacity and gel formation. The DM, OM, CP and NDF apparent digestibility coefficients were superior for GM treatment, due to fiber quality. Meat tenderness was higher for those animals that consumed the diet of the treatment GM because of the better digestibility coefficients. Corn gluten meal can substitute alfalfa hay on rabbits diet. Linseed bran, due to high amount of soluble fiber and high hydration capacity, affects animal performance and meat tenderness.
Dois experimentos foram realizados no Laboratório de Cunicultura do Departamento de Zootecnia, da Universidade Federal de Santa Maria, RS, onde se estudou a influência das diferentes frações de fibra advindas de co-produtos agroindustriais (polpa de citros, casca de soja, farelo de linhaça e farelo proteinoso de milho) sobre o desempenho, coeficientes de digestibilidade, parâmetros sanguíneos e características da carne de coelhos submetidos às dietas. As dietas foram isoprotéicas (18% PB) e isoenergéticas (3000 kcal/kg ED). Foram utilizados oito coelhos da raça Nova Zelândia Branca por tratamento, testados dos 40 aos 89 dias de idade. No primeiro experimento, os tratamentos foram: FA- ração controle, com feno de alfafa; PC- substituição total do feno de alfafa por polpa de citros e CS- substituição total do feno de alfafa por casca de soja. Os animais dos tratamentos PC e CS apresentaram desempenho, peso e rendimento de carcaça semelhantes aos animais do tratamento FA. Os coeficientes de digestibilidade aparente da MS, MO, PB e FDN foram superiores para a dieta com casca de soja, em função da qualidade de fibra deste ingrediente. Foi observado redução nos níveis séricos de triglicerídeo, colesterol, hemoglobina e glicose dos animais alimentados com polpa de citros, devido à alta capacidade de ligação catiônica deste co-produto. A maciez da carne foi superior para os animais que consumiram a dieta com casca de soja, em virtude da melhor digestibilidade dos nutrientes. As diferentes frações da fibra advindas da polpa de citros e casca de soja não afetam o desempenho dos animais e o peso e rendimento de carcaça, mostrando que estes ingredientes podem substituir o feno de alfafa na dieta de coelhos. A qualidade de fibra da polpa de citros reduz os níveis séricos de triglicerídeo e colesterol dos animais. A baixa quantidade de lignina em relação à celulose e hemicelulose da casca de soja propicia melhores coeficientes de digestibilidade dos nutrientes. No segundo experimento, os tratamentos foram: FA- ração controle, com feno de alfafa; FL- substituição total do feno de alfafa por farelo de linhaça e FP- substituição total do feno de alfafa por farelo proteinoso de milho (20% PB). Os animais do tratamento FP apresentaram desempenho semelhante aos animais do tratamento FA. Porém, o rendimento de carcaça não diferiu entre os co-produtos testados. O farelo de linhaça proporcionou desempenho inferior aos demais ingredientes, devido à alta capacidade de hidratação da fibra e formação de gel. Os coeficientes de digestibilidade aparente da MS, MO, PB e FDN foram superiores para o tratamento FP, em função da qualidade de fibra. A maciez da carne foi superior para os animais que consumiram a dieta do tratamento FP, em virtude da melhor digestibilidade dos nutrientes. O farelo proteinoso de milho pode substituir o feno de alfafa na dieta de coelhos. O farelo de linhaça, pela grande quantidade de fibra solúvel e alta capacidade higroscópica, prejudica o desempenho dos animais e maciez da carne.
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Oliveira, Melissa dos Santos. "Disponibilização de compostos funcionais em farelo de arroz fermentado em estado sólido." reponame:Repositório Institucional da FURG, 2009. http://repositorio.furg.br/handle/1/6066.
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A possibilidade de valoração de co-produtos e reciclagem de resíduos de processos agroindustriais utilizados em diferentes processos, inclusive os bioprocessos, está sendo amplamente investigada pelo mundo científico, que procura fontes alternativas para diversos produtos e suas aplicações. No alvo destas pesquisas está o farelo de arroz que, atualmente, é considerado um co-produto do beneficiamento do arroz que corresponde de 8 % a 10 % deste grão abundante no Rio Grande do Sul e constitui-se promissora fonte de proteínas, fibra dietética e compostos funcionais como antioxidantes, fosfolipídios, fenóis e ácido fítico. Este trabalho teve o objetivo de estudar a disponibilização de compostos funcionais em farelo de arroz, através da fermentação em estado sólido com Rhizopus oryzae. Durante o desenvolvimento do trabalho foi avaliado, no farelo de arroz fermentado, o efeito do processo fermentativo sobre a composição físico-química, o perfil de ácidos graxos, o conteúdo de fosfolipídios e a presença de compostos antioxidantes, bem como a atividade de enzimas durante o acompanhamento do processo fermentativo. O farelo de arroz utilizado foi fornecido pelo IRGA. O fungo agente fermentador foi Rhizopus oryzae e seus esporos foram propagados em agar batata dextrose, utilizando umar suspensão de Tween 80 (0,2 %), incubados durante 7 dias a 30 °C, até nova e completa esporulação do fungo. A fermentação foi realizada em biorreatores de bandejas onde o substrato (farelo de arroz) foi disposto e homogeneizado com a suspensão de esporos perfazendo a concentração inicial de 4,0x106 esporos.g-1 meio. A umidade do meio foi ajustada para 50 % e o processo ocorreu em estufa a 30 °C por 120 h. As amostras necessárias para as determinações analíticas foram coletadas no início do processo e a cada 24 h. Foram determinados os teores de umidade, cinzas, lipídios, proteína, fibra, açúcares redutores, aminoácidos digeríveis, ácido fítico, perfil de ácidos graxos com identificação e quantificação por cromatografia gasosa e fosfolipídios. Os compostos fenólicos dos fermentados foram extraídos com metanol a frio e quantificados por método espectrofotométrico com o reagente de Folin-Ciocalteau. A capacidade dos antioxidantes dos extratos do farelo fermentado foi estimada considerando o potencial em capturar os radicais 2,2-difenil-1-picrilidrazil (DPPH), inibir a peroxidação lipídica e a reação de escurecimento do guaiacol catalisada pela peroxidase. A fermentação em estado sólido reduziu em 40 %, 50 % e 60 %, significativamente (p<0,05), os teores lipídios, ácido fítico e açúcares redutores do farelo de arroz, respectivamente. O farelo fermentado apresentou teores aumentados de 30 % em cinzas, 50 % em fibras e 40 % em proteínas. A determinação de aminoácidos digeríveis indicou aumento de 27,6 % na digestibilidade das proteínas produzidas. O farelo de arroz fermentado por 24 h apresentou o maior conteúdo de compostos fenólicos totais (2200 µg ác.ferúlico/gfarelo), no entanto o extrato metanólico do farelo de arroz fermentado por 96 h inativou 50 % do DPPH reativo em 15 min (CE50 de 4,3 µg ác.ferúlico/mL). Este mesmo extrato reduziu em 57 % o valor do índice de peróxido no óleo de oliva após 30 dias de armazenamento. O extrato aquoso do farelo de arroz fermentado por 120 h foi o mais eficiente inibidor da reação de escurecimento catalisada pela peroxidase. Os teores de fosfolipídios foram aumentados em 1,8 mg P/g lipídio. No farelo fermentado os ácidos oléico, palmítico e linoléico foram os predominantes, ocorrendo ao longo da fermentação a redução dos ácidos graxos saturados (20 %) e o aumento dos ácidos graxos insaturados (5 %) Estes resultados indicam que a fermentação em estado sólido é uma poderosa ferramenta para agregar valor a este co-produto modificando a sua composição química e disponibilizando compostos de maior interesse, que podem ser aplicados em outros processos, subsidiando o agronegócio com alternativas para à sua sustentabilidade. O presente trabalho contribui com informações importantes para as etapas de investigação sobre a disponibilização destes biocompostos e suas futuras aplicações.
The possibility of co-product valuation and residue reuse of agroindustrial processes may be used in different processes, besides bioprocess is being investigated thoroughly by the scientific world which looks for alternative sources for several products and its applications. In the goal of these researches is rice bran, which is nowadays being considered a co-product of rice milling and corresponds from 8% to 10% of this abundant grain in Rio Grande do Sul. Thus, it is a promising source of proteins, dietary fiber and functional compounds like antioxidants, phospholipids, phenols and phytic acid. This work aimed to study the availability of functional compounds in rice bran through solid-state fermentation with Rhizopus oryzae. During the development of this work, the effect of the fermentative process was evaluated on fermented rice bran, that is, the physico-chemical composition, the fatty acid profile, phospholipids content and the presence of antioxidant compounds, as well as the enzyme activity during the fermentative process. Rice bran was supplied by IRGA (Instituto Rio Grandense de Arroz). The strain used for fermentation was from Rhizopus oryzae fungus and the spores were scraped from the slopes into aqueous emulsion of Tween 80 (0.2 %) incubated during 7 days at 30 °C until new and complete fungi sporulation. Fermentation was carried out in tray bioreactors, in which the substratum, rice bran, was placed and homogenized with spores suspension totalizing the initial concentration of 4.0x106 spores/g. The medium moisture was adjusted to 50 % and the process was carried out in a chamber at 30 ºC for 120 h. For analytical determination, the samples were withdrawn at the beginning of the process and each 24 h. The contents of moisture, ash, lipid, protein, fiber, reducing sugars, digestible aminoacids and phytic acid were determined, as well as the fatty acid profile, following identification and quantification by gaseous chromatography. The phenolic compounds were cold-extracted with methanol and quantified by spectrophotometer using the FolinCiocalteau reagent. The fermented bran extract antioxidant ability was estimated considering its potential in capturing DPPH radicals, inhibiting lipid peroxidation and guaiacol darkening reaction catalyzed by peroxidase enzyme. Solid-state fermentation reduced moisture, lipid, phytic acid and reducing sugars content of rice bran in, respectively, 24.6 %, 40 %, 50 % and 60 %. The fermented bran presented an increase of 30 % in ashes content, 50 % in fibers and 40 % in proteins. The digestible aminoacid determination indicated increase of 27.6 % in the digestibility of produced proteins. Rice bran fermented for 24 h showed the highest phenolic compound content (2200 µg ferulic acid/g bran), however the fermented rice bran methanolic extract at 96 h inactivated 50 % of the DPPH reagent in 15 min (CE50 of 4.3 µg ferulic acid/mL). This same extract reduced in 57% the peroxide index in olive oil after 30 days of storage. The fermented rice bran aqueous extract at 120 h was the most efficient inhibitor of the darkening reaction catalyzed by peroxidase. Phospholipids content were increased to 1.8 mgP/g lipid. Oleic, palmitic and linoleic fatty acids predominated in fermented bran, being observed a reduction in saturated fatty acids (20 %) and an increase (5 %) in unsaturated ones along the fermentation. These results point out that solid-state fermentation is a powerful tool to add value to rice bran, modifying its chemical composition in which components of major interest become available and can be applied to other processes, subsidizing agribusiness with important information for investigating steps related to these compounds, purifying method and application.
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Rothman, David J. "An Investigation of Neurological soft signs as a discriminating factor between Veterans with Post-traumatic Stress Disorder, mild Traumatic Brain Injury, and co-occurring Post-traumatic Stress Disorder and mild Traumatic Brain Injury." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5915.
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While multiple Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans suffer from mild Traumatic Brain Injury (mTBI), Post-traumatic Stress Disorder (PTSD), and co-morbid mTBI and PTSD, there remains difficulty disentangling the specific symptoms associated with each disorder using self-report and neurocognitive assessments. We propose that neurological soft signs (NSS), which are tasks associated with general neurologic compromise, may prove useful in this regard. Based on our review of the literature we hypothesized that individuals with PTSD would present with a greater number of NSS than controls or individuals with mTBI. Further, we hypothesized a synergistic effect, such that individuals with mTBI + PTSD would present with the greatest number of NSS. To test these hypotheses, we analyzed a subset of individuals (N=238) taken from a larger study of neurocognitive functioning in veterans. Participants completed a battery of neuropsychological measures, which included the Behavioral Dyscontrol Scale (BDS), the current study’s measure of NSS. A subset of other neuropsychological measures were also included to examine the utility of NSS over and above traditional neuropsychological measures. Individuals were removed from the study if they sustained a moderate/severe TBI or did not meet validity criteria on the Green’s Word Memory Test or the Negative Impression Management subscale of the Personality Assessment Inventory. Binomial logistic and multinomial logistic regression were used to examine the ability of NSS to discriminate between the study groups, first by themselves and then after the variance explained by the traditional neuropsychological measures was accounted for. Exploratory cluster analyses were performed on neuropsychological measures and NSS to identify profiles of cognitive performance in the data set. Results indicated that individuals in the mTBI and/or PTSD group had more NSS compared to controls. Of the individual NSS items only a go/no-go task of the BDS discriminated between groups, with worse performance among individuals in the mTBI, PTSD, and mTBI + PTSD group compared to controls. In contrast, the overall BDS score and individual NSS, in general, did not discriminate between the mTBI, PTSD, and mTBI + PTSD group. Overall, the current study suggests that, when eliminating participants who do not meet validity criteria, NSS do not aid in discriminating between individuals with mTBI, PTSD, and mTBI + PTSD.
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Di, Mauro Primiano Pio. "Development of novel and multifunctional polymeric nanoparticles for brain targeted drug delivery." Doctoral thesis, Universitat Ramon Llull, 2015. http://hdl.handle.net/10803/285236.
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Controlled release systems have become an innovative technique to treat diseases like cancer by the targeted delivery to individual cells and tissues. There is an urgent need to achieve efficacious and safe delivery with minimal nonspecific uptake by healthy tissues. Among the polymer-based nanoparticulate systems for drug delivery, nanoparticles (NPs) have represented a promising opportunity as delivery system due to their degradation in water-soluble compounds that enter the normal metabolic pathways of the organism and their capacity to modify pharmacokinetics and the drug tissue distribution profile.
An engineered and versatile targeted nano-platform for the delivery of paclitaxel (PTX) across the blood brain barrier (BBB) with the aim to improve its therapeutic effect on human glioma cells has been developed. A novel biodegradable polymer has been synthetized and custom tailored NPs have been obtained. The method allows to modify the targeted drug delivery for efficiently transport and release of active drug molecule across the BBB. Aiming a dual targeting strategy, functionalization with ligands known to be efficiently transported across BBB by a membrane receptor that also is over-expressed on human glioma cells has been employed to shuttle PTX from blood to brain and then target glioma cells. In vivo properties of the NPs have been explored to assess their biological profile and since the pressing need for careful evaluation, new strategies for NPs radiolabeling with the aim to investigate their in vivo fate, specifically stability in biological environments (stealthiness), biodistribution and pharmacokinetic, have been adopted.Los sistemas de liberación controlada de medicamentos, mediante la administración dirigida individualmente a células y tejidos, se han convertido en una técnica innovadora para tratar enfermedades como el cáncer. Existe una necesidad urgente para lograr una liberación eficaz y segura que incluya una mínima absorción no específica para los tejidos sanos. Entre los sistemas nanopartículados a base de polímeros para la administración de fármacos, las nanopartículas (NPs) han representado una oportunidad prometedora como sistema de suministro. Entre sus ventajas se puede destacar su perfil de degradación en compuestos hidrosolubles y no tóxicos, que se eliminan siguiendo las vías metabólicas normales del organismo. Por otro lado, presentan una elevada capacidad de modificar la farmacocinética y el perfil de distribución del medicamento en los tejidos. En esta tesis se ha desarrollado una nano-plataforma específica y versátil para la liberación de paclitaxel (PTX) a través de la barrera hematoencefálica (BHE) con el objetivo de mejorar su efecto terapéutico sobre las células de glioma humano. Se ha sintetizado un nuevo polímero biodegradable gracias al cual se han obtenido NPs personalizadas a medida. El método permite modificar el tipo administración dirigida de los fármacos para conseguir un transporte y una liberación de las moléculas de principio activo eficiente y segura. Se ha desarrollado el objetivo de seguir una estrategia de selección dual que consiste en transportar el PTX desde la sangre hasta el cerebro y luego dirigirse a las células de glioma. Para ello se ha empleado la funcionalización con marcadores capaces de atravesar eficientemente la BHE a través de un receptor de membrana que también está sobre-expresado en las células de glioma humano. Para evaluar el perfil biológico de las NPs se han explorado sus propiedades in vivo y dada la urgente necesidad de una evaluación fiable, se han adoptado nuevas estrategias para radiomarcar NPs con el objetivo de investigar su destino in vivo, la estabilidad en entornos biológicos, la biodistribución y la farmacocinética.
Els sistemes d'alliberament controlat de medicaments, mitjançant l'administració dirigida individualment a cèl•lules i teixits, s'han convertit en una tècnica innovadora per tractar malalties com el càncer. Hi ha una necessitat urgent per aconseguir un alliberament eficaç i segura que inclogui una mínima absorció no específica per als teixits sans. Entre els sistemes nanoparticulats a base de polímers per a l'administració de fàrmacs, les nanopartícules (NPs) han representat una oportunitat prometedora com a sistema de subministrament. Entre els seus avantatges es pot destacar el seu perfil de degradació en en compostos hidrosolubles i no tòxics, que s'eliminen seguint les vies metabòliques normals de l'organisme. D'altra banda, presenten una elevada capacitat de modificar la farmacocinètica i el perfil de distribució del medicament en els teixits. En aquesta tesi s'ha desenvolupat una nano‐plataforma específica i versàtil per a l'alliberament de paclitaxel (PTX) a través de la barrera hematoencefàlica (BHE) amb l'objectiu de millorar el seu efecte terapèutic sobre les cèl•lules de glioma humà. S'ha sintetitzat un nou polímer biodegradable gràcies al qual s'han obtingut NPs personalitzades a mida. El mètode permet modificar el tipus administració dirigida dels fàrmacs per aconseguir un transport i un alliberament de les molècules de principi actiu eficient i segura. S'ha desenvolupat l'objectiu de seguir una estratègia de selecció dual que consisteix a transportar el PTX des de la sang fins al cervell i després dirigir‐se a les cèl•lules de glioma. Per a això s'ha emprat la funcionalització amb marcadors capaços de travessar eficientment la BHE a través d'un receptor de membrana que també està sobre-expressat en les cèl•lules de glioma humà. Per avaluar el perfil biològic de les NPs s'han explorat les seves propietats in vivo i donada la urgent necessitat d'una avaluació fiable, s'han adoptat noves estratègies per radiomarcar NPs amb l'objectiu d'investigar la seva destinació in vivo, l'estabilitat en entorns biològics, la biodistribució i la farmacocinètica.
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Cullen, Daniel Kacy. "Traumatically-Induced Degeneration and Reactive Astrogliosis in 3-D Neural Co-Cultures: Factors Influencing Neural Stem Cell Survival and Integration." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/7584.
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Traumatic brain injury (TBI) results from a physical insult to the head and often results in temporary or permanent brain dysfunction. However, the cellular pathology remains poorly understood and there are currently no clinically effective treatments. The overall goal of this work was to develop and characterize a novel three-dimensional (3-D) in vitro paradigm of neural trauma integrating a robust 3-D neural co-culture system and a well-defined biomechanical input representative of clinical TBI. Specifically, a novel 3-D neuronal-astrocytic co-culture system was characterized, establishing parameters resulting in the growth and vitality of mature 3-D networks, potentially providing enhanced physiological relevance and providing an experimental platform for the mechanistic study of neurobiological phenomena. Furthermore, an electromechanical device was developed that is capable of subjecting 3-D cell-containing matrices to a defined mechanical insult, with a predicted strain manifestation at the cellular level. Following independent development and validation, these novel 3-D neural cell and mechanical trauma paradigms were used in combination to develop a mechanically-induced model of neural degeneration and reactive astrogliosis. This in vitro surrogate model of neural degeneration and reactive astrogliosis was then exploited to assess factors influencing neural stem cell (NSC) survival and integration upon delivery to this environment, revealing that specific factors in an injured environment were detrimental to NSC survival. This work has developed enabling technologies for the in vitro study of neurobiological phenomena and responses to injury, and may aid in elucidating the complex biochemical cascades that occur after a traumatic insult. Furthermore, the novel paradigm developed here may provide a powerful experimental framework for improving treatment strategies following neural trauma, and therefore serve as a valid pre-animal test-bed.
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Alvarez-Saavedra, Matias A. "The Snf2h and Snf2l Nucleosome Remodeling Proteins Co-modulate Gene Expression and Chromatin Organization to Control Brain Development, Neural Circuitry Assembly and Cognitive Functions." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/30304.
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Chromatin remodeling enzymes are instrumental for neural development as evidenced by their identification as disease genes underlying human disorders characterized by intellectual-disability. In this regard, the murine Snf2h and Snf2l genes show differential expression patterns during embryonic development, with a unique pattern in the brain where Snf2h is predominant in neural progenitors, while Snf2l expression peaks at the onset of differentiation. These observations led me to investigate the role of Snf2h and Snf2l in brain development by using conditionally targeted Snf2h and Snf2l mice.
I selectively ablated Snf2h expression in cortical progenitors, cerebellar progenitors, or postmitotic Purkinje neurons of the cerebellum, while Snf2l was deleted in the germline. I found that Snf2h plays diverse roles in neural progenitor expansion and postmitotic gene expression control, while Snf2l is involved in the precise timing of neural differentiation onset. Gene expression studies revealed that Snf2h and Snf2l co-modulate the FoxG1 and En1 transcription factors during cortical and cerebellar neurogenesis, respectively, to precisely control the transition from a progenitor to a differentiated neuron. Moreover, Snf2h is essential for the postmitotic neural activation of the clustered protocadherin genes, and does so by functionally interacting with the matrix-attachment region protein Satb2. My neurobehavioral studies also provided insight into how Snf2h loss in cerebellar progenitors results in cerebellar ataxia, while Snf2h loss in cortical progenitors, or in postmitotic Purkinje neurons of the cerebellum, resulted in learning and memory deficits, and hyperactive-like behavior.
Molecularly, Snf2h plays an important role in linker histone H1e dynamics and higher order chromatin packaging, as evidenced by loss of chromatin ultrastructure upon Snf2h deletion in progenitor and postmitotic neurons. I further demonstrated that Snf2h loss in a neuronal cell culture model results in reduced H1e deposition, and that overexpression of human SNF2H or SNF2L upon Snf2h knockdown rescues this biochemical dysfunction. My experiments suggest that Snf2h and Snf2l are regulatory nucleosome remodeling engines that co-modulate the gene expression programs necessary for proper brain development, maturation and function.
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Hubbard, Amy L. "Giving speech a hand fMRI of co-speech beat gesture processing in adult native English speakers, Japanese English as a second language speakers, typically-developing children, and children with autism spectrum disorder /." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1779835541&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Yao, Xi. "Un modèle en 3D d’adipocytes de type brun dérivés de cellules pluripotentes induites humaines pour le criblage in vitro de médicaments et pour la thérapie cellulaire contre l’obésité." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR6011.
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L'obésité est la conséquence d'un déséquilibre entre l'apport de calories et la dépense énergétique. Les thérapies basées sur la réduction de l'apport énergétique sont difficiles à suivre dans notre vie moderne et les médicaments anti obésité présentent d’importants effets secondaires. Des stratégies alternatives sont alors requises pour lutter contre l'obésité et les troubles métaboliques associés comme le diabète de type 2 et les maladies cardiovasculaires. Les adipocytes bruns et de type brun, encore appelés beige ou brite (BA), stockent la graisse, mais contrairement aux adipocytes blancs, les BA sont équipés pour brûler les lipides et consommer le glucose afin de dissiper l'énergie stockée. Les BA sécrètent également des adipokines qui vont cibler d'autres organes et pour participer à la régulation des paramètres métaboliques. Ainsi, les BA représentent des cibles cellulaires prometteuses pour lutter contre l'obésité en favorisant la dépense énergétique. Cependant, la rareté des BA chez l’homme adulte, qui est accentuée chez les patients obèses, est une limitation majeure pour un traitement de l’obésité basé sur le BA. La notion d’augmenter la masse de BA en greffant des progéniteurs de BA (BAP) chez des patients obèses a récemment émergée. La preuve de concept a été faite dans des modèles murins. Le prochain défi consiste à identifier une source abondante et fiable de BAP humains. Nous décrivons dans cette thèse la capacité des cellules souches pluripotentes induites humaines (hiPSCs) à générer des BAP et capables de se différencier avec une grande efficacité dans un modèle en 3D en adiposphères. Les hiPSC- adiposphères ont un profil d'expression de la matrice extracellulaire et des récepteurs couplés à la protéine G (GPCR) similaires aux adiposphères humaines dérivées de progéniteurs adipeux abdominaux sous-cutanés. Ces résultats montrent la pertinence physiologique du modèle hiPSC-adiposphères. De plus, les hiPSC-adiposphères contiennent plus de cellules UCP1 positives que les adiposphères abdominales. L’expression de UCP1 dans les hiPSC-adiposphères est augmentée suite à la stimulation par le 8-CPT-AMPc ou du 8-Br-GMPc de manière aiguë et chronique. Ceci indique que notre modèle 3D présente les caractéristiques métaboliques des adipocytes de type bruns et peut répondre à un criblage de molécules visant à augmenter la dépense énergétique.Enfin, l'enrichissement du modèle 3D en cellules endothéliales humaines (HDMEC) a été réalisé via une co-culture en suspension. La fonctionnalité des HDMECs intégrées dans les hiPSC-adiposhères a été testée in vitro par la visualisation de l’absorption de LDL. Nous avons aussi montré que les hiPSC-BAs et les HDMEC pouvaient générer des structures de type vascularisées dans le core de la sphère.En conclusion, le modèle hiPSC-adiposphère représente une source illimitée d’adipocytes d’intérêt thérapeutique qui pourrait, dans un avenir proche constituer un nouvel outil approprié à la fois pour la transplantation chez les patients atteint d’obésité morbide et pour le criblage de médicaments. Le potentiel thérapeutique des hiPSC-adiposphères sera tester prochainement dans un modèle de souris obèsesObesity results from an imbalance between calorie intake and energy expenditure. Therapies based to reduce energy intake are difficult to follow in our modern life, and drugs can display adverse effects. Alternative strategies are urgently required to fight obesity and associated metabolic disorders. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, BAs are equipped to burn glucose and lipids to dissipate energy stored. BAs also secrete adipokines that signal other organs and regulate metabolism. Therefore, BAs represent promising cell targets to promote energy expenditure and counteract obesity. However, the scarcity of BAs in human adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The proof of concept has been done in murin models. The next challenge is to identify an abundant and reliable source of human BAPs. We recently described the capacity of human induced pluripotent stem cells (hiPSCs) to generate BAPs. During my thesis, we established a procedure to generate hiPSC-BAP spheroids and a method for their differentiation at a high efficiency in hiPSC-brown-like adipospheres. The model was then enriched with Human Dermal Microvascular Endothelial Cells (HDMECs) to better mimic the adipose tissue microenvironment and to improve its therapeutic potential. BAPs derived from human iPSCs were maintained in suspension to form spheroids able to different into adipospheres. The structure of adipospheres was analysed by confocal microscopy and adipocytes were characterized at the molecular and metabolic levels. We generated adipospheres from two different hiPSC-BAP clones, which are able to fully differentiate from the surface to the core. We compared hiPSC-brown-like adipospheres with the ones generated by hanging drop method, and our model displays comparable pattern regarding to extracellular matrix and adipogenesis, despite the sizes are not defined. We also proved hiPSC-brown-like adipospheres promotes accumulation of brown-like adipocytes that are more biologically active compared to cells maintained in conventional monolayer cell cultures. In addition, hiPSC-brown-like adipospheres have a similar expression profile of extracellular matrix and G Protein-Coupled Receptors (GPCRs) compared with human adipospheres derived from subcutaneous abdominal adipose progenitors, suggested the physiological relevance of the hiPSC-adiposphere model. Moreover, hiPSC-adipospheres display a more brown-like adipogenic potential than abdominal adipospheres opening the opportunity and advantages for anti-obesity drug testing and cell based therapy to increase the BA mass in patients. Furthermore, hiPSC-adipospheres express UCP1 that can response to the stimulation of 8-CPT-cAMP or 8-Br-cGMP acutely and chronically, which indicated that our 3D model display metabolic characteristics of brown-like adipocytes. Finally, enrichment with HDMECs was performed via co culture in suspension. HDMECs functionality was tested in vitro by LDL-uptake. We proved that hiPSC-BAPs and HDMECs can co-culture in 3D and differentiate into vascularized hiPSC-brown-like adipospheres with functional tubular-like structure formed inside. Moreover, our co-cultured 3D model can secrete factors like VEGF and FGF2 to support vascularization which mimic in vivo situation.Altogether, the hiPSC-brown-like adipposphere model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for drug screening allowing discovery of novel and safe anti-obesity drugs
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Patel, Deven Chandrakant. "PREPARATION AND CHARACTERIZATION OF ELECTROSPUN POLY (D,L-LACTIDE-CO-GLYCOLIDE) SCAFFOLDS FOR VASCULAR TISSUE ENGINEERING AND THE ADVANCEMENT OF AN IN VITRO BLOOD BRAIN BARRIER MODEL." DigitalCommons@CalPoly, 2012. https://digitalcommons.calpoly.edu/theses/824.
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Developing an in vitro Blood Brain Barrier model that will replicate the physiological, anatomical, and functional characteristics of the native BBB has gained significant attention. Such a model would enable prediction of the penetration of CNS targeting drug candidates across the BBB, allow pre-screening and optimization strategies to be developed for new drugs and gene delivery formulations, and permit research groups to further understand how a dysfunctional BBB is involved in the pathogenesis of several neurological diseases.
The Tissue Engineering laboratory at the California Polytechnic State University, San Luis Obispo is currently in the process of developing a dynamic in vitro blood brain barrier model that will implement an in-house fabricated electrospun PLGA scaffold pressure sodded with C6 glial cells and BAECs (Bovie Aortic Endothelial Cells). The aims of this thesis were to upgrade and refine the existing electrospinner system, develop a BBB scaffold electrospinning protocol, and characterize and evaluate the consistency of the scaffolds fabricated using the protocol.
Ultimately, the electrospinner system was optimized in the following areas: the high voltage power supply, electrical layout and safety, as well as the syringe pump and stand. The modifications to the system will now permit new electrospinning strategies and ensure operator safety. The protocol developed for electrospinning scaffolds for the DIV-BBB system utilized 15 wt% PLGA in CHCl3 with a 4.5 ml/hr flow rate, an applied voltage of 18,000V with a negative polarity, and a gap distance of 25.4 cm.
Characterization and consistency studies revealed that scaffolds electrospun were statistically inconsistent with one another with regards to fiber diameter (P < 0.0001), porosity (P < 0.0001), and wall thickness (P < 0.0001). However, the scaffolds were mechanically consistent (P-value of 0.6134) according to the calculated Young's modulii. The average fiber diameter for the electrospun scaffolds was 2.556 µm, and had an average porosity of 70.06 µm2. Additionally, the wall thickness between the electrospun scaffolds ranged between 0.31 and 0.54 mm. The average Young's modulus of the electrospun scaffolds was determined to be 86.141 MPa. While the results associated with fiber diameter, porosity, and wall thickness were statistically inconsistent, it will be important to evaluate whether the variation between each scaffold will translate to a difference when conducting cellular studies after the DIV-BBB system is complete.
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Jöhnk, Bastian Verfasser], Gerhard [Akademischer Betreuer] [Gutachter] Braus, Stefanie [Gutachter] Pöggeler, Rolf [Gutachter] [Daniel, Ralf [Gutachter] Ficner, Kai [Gutachter] Heimel, and Michael S. [Gutachter] Weig. "Stress Response SCF Ubiquitin Ligase F box Protein Fbx15 Controls Nuclear Co repressor Localization and Virulence of the Opportunistic Human Fungal Pathogen Aspergillus fumigatus / Bastian Jöhnk. Betreuer: Gerhard Braus. Gutachter: Gerhard Braus ; Stefanie Pöggeler ; Rolf Daniel ; Ralf Ficner ; Kai Heimel ; Michael S. Weig." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2016. http://d-nb.info/1113288833/34.
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Sygnecka, Katja [Verfasser], Andrea [Akademischer Betreuer] Robitzki, Andrea [Gutachter] Robitzki, and Bernd [Gutachter] Heimrich. "Organotypic brain slice co-cultures of the dopaminergic system - A model for the identification of neuroregenerative substances and cell populations / Katja Sygnecka ; Gutachter: Andrea Robitzki, Bernd Heimrich ; Betreuer: Andrea Robitzki." Leipzig : Universitätsbibliothek Leipzig, 2015. http://d-nb.info/1239740050/34.
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Belwafi, Kais. "Conception d'une architecture embarquée adaptable pour le déploiement d'applications d'interface cerveau machine." Thesis, Cergy-Pontoise, 2017. http://www.theses.fr/2017CERG0896/document.
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L'objectif de ces travaux de recherche est l'étude et le développement d'un système ICM embarqué en utilisant la méthodologie de conception conjointe afin de satisfaire ses contraintes spécifiques. Il en a découlé la constitution d'un système ICM complet intégrant un système d'acquisition OpenBCI et un système de traitement à base de FPGA. Ce système pourrait être utilisé dans des contextes variés : médicale (pour les diagnostiques précoces des pathologies), technologique (informatique ubiquitaire), industriel (communication avec des robots), ludique (contrôler un joystick dans les jeux vidéo), etc. Dans notre contexte d’étude, la plateforme ICM proposée a été réalisée pour assister les personnes à mobilité réduite à commander les équipements domestiques. Nous nous sommes intéressés en particulier à l'étude et à l'implémentation des modules de filtrage adaptatif et dynamique, sous forme d'un coprocesseur codé en HDL afin de réduire son temps d'exécution car c'est le bloc le plus critique de la chaine ICM. Quant aux algorithmes d'extraction des caractéristiques et de classification, ils sont exécutés par le processeur Nios-II sous son système d'exploitation en ANSI-C. Le temps de traitement d'un trial par notre système ICM réalisé est de l'ordre de 0.4 s/trial et sa consommation ne dépasse guère 0.7 WThe main purpose of this thesis is to study and develop an embedded brain computer interface (BCI) system using HW/SW methodology in order to satisfy the system specifications. A complete BCI system integrated in an acquisition system (OpenBCI) and a hardware platform based on the FPGA were achieved. The proposed system can be used in a variety of contexts: medical (for early diagnosis of pathologies, assisting people with severe disabilities to control home devices system through thought), technological (ubiquitous computing), industrial (communication with Robots), games (control a joystick in video games), etc. In our study, the proposed ICM platform was designed to control home devices through the thought of people with severe disabilities. A particular attention has been given to the study and implementation of the filtering module, adaptive and dynamic filtering, in the form of a coprocessor coded in HDL in order to reduce its execution time as it is the critical block in the returned ICM algorithms. For the feature extraction and classification algorithms, they are executed in the Nios-II processor using ANSI-C language. The prototype operates at 200 MHz and performs a real time classification with an execution delay of 0.4 second per trial. The power consumption of the proposed system is about 0.7 W
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Mazzucotelli, Anne. "Activation du métabolisme énergétique par le co-activateur PGC-1Alpha et implication du récepteur nucléaire PPAR Alpha dans l’adipocyte blanc humain." Toulouse 3, 2007. http://thesesups.ups-tlse.fr/40/.
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L’accumulation de tissu adipeux prédispose au développement d’un certain nombre de désordres métaboliques parmi lesquels l’insulino-résistance et le syndrome métabolique. Une des stratégies envisagées est de convertir les adipocytes blancs en adipocytes présentant un phénotype oxydatif similaire à celui des adipocytes bruns. L’activation de la béta-oxydation et de la thermogenèse permettrait d’augmenter la dépense énergétique tout en utilisant les acides gras libérés par la lipolyse. Récemment, l’équipe a montré que la sur-expression de PGC1alpha dans des cultures primaires d’adipocytes blancs humains différenciés augmente l’expression de la protéine découplante UCP1 ainsi qu’une augmentation de l’oxydation. Afin d’avoir une vision plus large des gènes régulés par PGC1alpha dans l’adipocyte humain des expériences des puces à ADN ont été réalisées. Nous avons démontré que la sur-expression de PGC1alpha dans l’adipocyte humain induit l’expression de nombreux gènes impliqués dans le métabolisme énergétique et ceci indépendamment du récepteur nucléaire PPARgamma. Parallèlement, une augmentation de l’expression du récepteur nucléaire PPARalpha a été observée. PGC1alpha et PPARalpha ont été montré comme impliqués dans la régulation du gène de la glycérol kinase. Ainsi, la sur-expression de PGC1alpha dans l’adipocyte blanc permet la mise en place d’un cycle futile induit par la glycérol kinase ainsi qu’une augmentation de l’oxydation des acides gras ce qui pourrait limiter le relargage des acides gras dans la circulation. Ce résultat révèle une implication possible de PPARalpha dans la régulation de l’expression génique au niveau des adipocytes humains sur exprimant PGC1alpha. Plasma free fatty acids released from white adipose tissue may contribute to the metabolic abnormalities found in obese subjects. Expression of the transcriptional coactivator peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) in human adipocytes leads to a PPARgamma-dependent induction of the uncoupling protein UCP1 and promotes fat oxidation. The aim of the study was to get an exhaustive view of genes regulated by PGC-1alpha. We performed gene expression profiling using pangenomic microarrays. The identified 6 groups of genes: genes down regulated by Rosiglitazone, PGC1alpha or both and genes up regulated by Rosiglitazone, PGC1alpha or both. Among the large number of genes regulated by PGC-1alpha independently of PPARgamma, many genes were involved in mitochondrial metabolism. PGC-1alphaoverexpression induced mRNA expression of the glycerol kinase (GyK) as well as enzymatic activity. PPARalpha was also one of the PGC-1alphatargets. Its activation increased GyK expression and activity. PPARalpha was shown to bind and activate the GyK promoter in PGC-1alpha expressing human adipocytes. In vivo data in various mouse models confirmed the role of PGC-1alpha and PPARalpha in the regulation of GyK. The induction of GyK by PGC-1alpha and PPARalpha offers a new strategy to promote fat utilization in fat cells through the generation of a futile cycle between triglyceride hydrolysis and fatty acid reesterification. Moreover, this work reveals that PPARalpha controls gene expression in human white adipocytes
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Cangin, Causenge. "Association of depression with anaerobic muscle strengthening activity, moderate intensity physical activity, long term lipophilic statin usage, and selected co-morbidity: NHANES (National Health and Nutrition Examination Survey) 1999-2012." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1460067114.
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Lemoncello, Richard R. "A within-subjects experimental evaluation of the Television Assisted Prompting (TAP) system to maximize completion of home-delivered swallow strengthening exercises among individuals with co-occurring acquired swallowing and cognitive impairments." Thesis, Connect to title online (Scholars' Bank) Connect to title online (ProQuest), 2008. http://hdl.handle.net/1794/8948.
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Thesis (Ph. D.)--University of Oregon, 2008.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 150-162). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.
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FRANÇA, Clebia Pereira de. "Qualidade da torta e farelo de mamona de diferentes cultivares caracterizadas por espectroscopia NIR e análise multivariada." Universidade Federal de Campina Grande, 2010. http://dspace.sti.ufcg.edu.br:8080/jspui/handle/riufcg/804.
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CLEBIA PEREIRA DE FRANÇA - DISSERTAÇÃO PPGEA 2010..pdf: 11033989 bytes, checksum: 458970c54e3574daebe9028166c5ddeb (MD5)Made available in DSpace on 2018-05-24T20:13:38Z (GMT). No. of bitstreams: 1 CLEBIA PEREIRA DE FRANÇA - DISSERTAÇÃO PPGEA 2010..pdf: 11033989 bytes, checksum: 458970c54e3574daebe9028166c5ddeb (MD5) Previous issue date: 2010-02
Este trabalho foi realizado com o objetivo de estudar o potencial da espectrometria NIR e da quimiometria, para classificação de torta e farelo de mamona, submetida a diferentes tratamentos de detoxificação. Utilizaram-se os tratamentos químico com NaCl e Ca(OH)2 e térmico (40, 60, 80 e 100°C) para três cultivares de mamona a partir da torta e do farelo. A torta foi obtida em prensa mecânica das sementes e o farelo através de extração com solvente em Soxhlet. As medidas espectrais na região de 400 a 2500 nm e análise multivariada (PCA e SIMCA) foram empregadas para a identificação de padrões de agrupamento quanto ao processo de detoxificação. As medidas experimentais foram realizadas em duas etapas, em que na primeira foram utilizadas 180 amostras de torta e farelo de mamona da variedade BRS Paraguaçu, para otimização dos modelos quimiométricos. Cada classe foi constituída de 10 amostras representativas, tratadas com NaCl e Ca(OH)2 a 4% (m/m) e nas temperaturas de 40, 60, 80 e 100°, na segunda etapa, 605 amostras foram usadas com 15 unidades para cada classe de tratamento com Ca(OH)2 e NaCl a 1, 2 e 4% (m/m). Os espectros foram registrados em triplicatas autênticas para os tratamentos com 10 repetições para cada amostra. A partir dos espectros obtidos empregaram-se as técnicas multivariadas de PCA e SIMCA. Na PCA, observou-se no gráfico dos escores a formação de classes distintas com separação dos tratamentos com Ca(OH)2 e NaCl, além da sua combinação com incrementos de temperatura de 40, 60, 80 e 100°C. O agrupamento formado com duas componentes principais resultou em uma variância explicada superior a 95%. Com as informações da PCA desenvolveu-se um modelo SIMCA, para o qual foram previstos 100% de acerto para a classe da torta e farelo de mamona detoxificados da variedade Paraguaçu, referentes a primeira etapa, a PCA para as amostras tratadas com Ca( OH)2 e NaCl a 1, 2 e 4% (m/m) permitiu a identificação das amostras consideradasdetoxificadas para as variedades BRS Energia, BRS Paraguaçu e BRS 149 Nordestina. O tratamento a 4% (m/m) se destacou no gráfico dos escores por ser considerado 100% detoxificado, também ocorreu separação entre as classes BRS Paraguaçu e BRS 149 Nordestina em relação à BRS Energia. Com essas observações, a espectrometria NIR e a análise multivariada permitiram a identificação da torta e do farelo de mamona, considerados detoxificados de forma direta, não destrutiva, económica, rápida (30 s), sem o uso de reagentes caros e de geração resíduos químicos.
This work was carried out to study the potential of NIR spectroscopy and chemometrics for the classification of cake and castor meai under different treatments of detoxifícation. We used chemical treatments with NaCl and Ca (OH)2 and heat (40, 60, 80 and 100 °C) for three cultivars from the castor bean cake and meai. The cake was obtained from mechanical pressing of the seeds and bran by solvent extraction in Soxhlet. The spectral measurements in the region from 400 to 2500 nm and multivariate analysis (PCA and SIMCA) were used to identify patterns of grouping as the process of detoxifícation. The experimental measurements were performed in two stages: first stage was used 180 samples of cake and castor oil for the BRS Paraguaçu chemometric optimization. Each class was comprised of 10 representative samples treated with NaCl and Ca (OH)2 to 4% (w / w) and temperatures of 40, 60, 80 and 100 °C. In the second stage, 630 samples were used with 42 units for each class of treatment with Ca (OH)2 and NaCl at 1, 2 and 4% (w / w). The spectra were recorded in triplicate true for treatments with 10 repetitions for each sample. From the spectra obtained were employed multivariate techniques of PCA and SIMCA. In PCA, the graph of the scores observed the formation of separate classes with separate treatments with Ca(OH)2 and NaCl, and combinations of these with temperature increments of 40, 60, 80 and 100 °C. The group formed with two principal components explained variance resulted in a greater than 95%. With the information from the PCA was developed SIMCA model for which predicted 100% correct for the class of the pie and detoxified castor meai variety Paraguaçu on the first step. The PCA for the samples treated with Ca(OH)2 and NaCl at 1, 2 and 4% (w/ w) allowed the identifícation of samples considered detoxified for varieties Energy BRS, BRS 149 and BRS Paraguaçu Northeast. Treatment 4% (w/ w) stood out in the graph of the scores to be considered 100% detoxified. Also there was a separation between the classes Paraguaçu BRS and BRS 149 BRS for Northeast Energy. Given these observations, NIR spectrometry and multivariate analysis allowed the identifícation of the pie and detoxified castor meai considered a direct, non-destructive, inexpensive, rapid (30 s) without the use of expensive reagents and chemical waste generation.
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Hurdal, Monica Kimberly. "Mathematical and computer modelling of the human brain with reference to cortical magnification and dipole source localisation in the visual cortx." Thesis, Queensland University of Technology, 1998.
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Teo, Jason T. W. Information Technology & Electrical Engineering Australian Defence Force Academy UNSW. "Pareto multi-objective evolution of legged embodied organisms." Awarded by:University of New South Wales - Australian Defence Force Academy. School of Information Technology and Electrical Engineering, 2003. http://handle.unsw.edu.au/1959.4/38682.
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The automatic synthesis of embodied creatures through artificial evolution has become a key area of research in robotics, artificial life and the cognitive sciences. However, the research has mainly focused on genetic encodings and fitness functions. Considerably less has been said about the role of controllers and how they affect the evolution of morphologies and behaviors in artificial creatures. Furthermore, the evolutionary algorithms used to evolve the controllers and morphologies are pre-dominantly based on a single objective or a weighted combination of multiple objectives, and a large majority of the behaviors evolved are for wheeled or abstract artifacts. In this thesis, we present a systematic study of evolving artificial neural network (ANN) controllers for the legged locomotion of embodied organisms. A virtual but physically accurate world is used to simulate the evolution of locomotion behavior in a quadruped creature. An algorithm using a self-adaptive Pareto multi-objective evolutionary optimization approach is developed. The experiments are designed to address five research aims investigating: (1) the search space characteristics associated with four classes of ANNs with different connectivity types, (2) the effect of selection pressure from a self-adaptive Pareto approach on the nature of the locomotion behavior and capacity (VC-dimension) of the ANN controller generated, (3) the effciency of the proposed approach against more conventional methods of evolutionary optimization in terms of computational cost and quality of solutions, (4) a multi-objective approach towards the comparison of evolved creature complexities, (5) the impact of relaxing certain morphological constraints on evolving locomotion controllers. The results showed that: (1) the search space is highly heterogeneous with both rugged and smooth landscape regions, (2) pure reactive controllers not requiring any hidden layer transformations were able to produce sufficiently good legged locomotion, (3) the proposed approach yielded competitive locomotion controllers while requiring significantly less computational cost, (4) multi-objectivity provided a practical and mathematically-founded methodology for comparing the complexities of evolved creatures, (5) co-evolution of morphology and mind produced significantly different creature designs that were able to generate similarly good locomotion behaviors. These findings attest that a Pareto multi-objective paradigm can spawn highly beneficial robotics and virtual reality applications.
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Schweizer, Nadine. "Across Borders : A Histological and Physiological Study of the Subthalamic Nucleus in Reward and Movement." Doctoral thesis, Uppsala universitet, Institutionen för neurovetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-275165.
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The basal ganglia are the key circuitry controlling movement and reward behavior. Both locomotion and reward-related behavior are also modified by dopaminergic input from the substantia nigra and the ventral tegmental area (VTA). If the basal ganglia are severed by lesion or in disease, such as in Parkinson’s disease, the affected individuals suffer from severe motor impairments and often of affective and reward-related symptoms. The subthalamic nucleus (STN) is a glutamatergic key area of the basal ganglia and a common target for deep brain stimulation in Parkinson’s disease to alleviate motor symptoms. The STN serves not only motoric, but also limbic and cognitive functions, which is often attributed to a tripartite anatomical subdivision. However, the functional output of both VTA and STN may rely more on intermingled subpopulations than on a strictly anatomical subdivision. In this doctoral thesis, the role of subpopulations within and associated with the basal ganglia is addressed from both a genetic and a behavioral angle. The identification of a genetically defined subpopulation within the STN, co-expressing Paired-like homeodomain transcription factor 2 (Pitx2) and Vesicular glutamate transport 2 (Vglut2), made it possible to conditionally reduce glutamatergic transmission from this subgroup of neurons and to investigate its influence on locomotion and motivational behavior, giving interesting insights into the mechanisms possibly underlying deep brain stimulation therapy and its side-effects. We address the strong influence of the Pitx2-Vglut2 subpopulation on movement, as well as the more subtle changes in reward-related behavior and the impact of the alterations on the reward-related dopaminergic circuitry. We also further elucidate the genetic composition of the STN by finding new markers for putative STN subpopulations, thereby opening up new possibilities to target those cells genetically and optogenetically. This will help in future to examine both STN development, function in the adult central nervous system and defects caused by specific deletion. Eventually identifying and characterizing subpopulations of the STN can contribute to the optimization of deep brain stimulation and help to reduce its side-effects, or even open up possibilities for genetic or optogenetic therapy approaches.
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Vezenkov, Stoyan Raykov. "Pharmacological studies on the contribution of the neuropeptide proctolin to the cephalic control of singing behavior in grasshopper Chorthippus biguttulus (L. 1758)." Doctoral thesis, [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=974032557.
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Lommen, Jonathan Lyon Jacob. "Effects of Transcranial Direct-Current Stimulation on Gait Initiation in People with Parkinson’s Disease." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39959.
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Background: Gait initiation is a major issue in Parkinson’s disease (PD). Moreover, the effect of current treatment on motor deficits vary alongside individual differences and disease severity. In some cases, postural instability has been documented as a major side-effect and refractory symptom to dopaminergic medication. Despite these shortcomings, research involving other forms of therapy including deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), has evidenced the improvement of postural deficits in PD. In this regard, there is a strong rational for the modulation of subcortical brain activity via the application of non-invasive transcranial direct current stimulation (tDCS) to interconnected cortical brain structures. Purpose: Therefore, we sought to determine the effect of tDCS applied to the supplementary motor area (SMA), on gait initiation preparation and performance in PD. Methods: A within subjects repeated measures quasi-experimental design was used to investigate the effects of a 10-minute sham-controlled tDCS intervention. Clinically diagnosed participants (n=12) with idiopathic PD were tested on medication during two sessions that bookended one week. Those who had previously undergone other forms of brain stimulation, had diabetes, severe freezing of gait, or any other neurological or functional limitations that could interfere with gait initiation were excluded from the study. Statistical Analyses/Results: Two-way repeated measures ANOVAs with Bonferroni corrections and a post-hoc analyses when appropriate, revealed a significant reduction in the magnitude of center of pressure (CoP) displacement and velocity in the mediolateral (ML) direction following tDCS. Conclusions: Findings from this study provide insights that may guide scientific research regarding the effects of tDCS on gait initiation among those with PD. Additionally, our work may highlight the importance of ML postural stability for individuals with comorbid and/or pharmacologically induced postural instabilities.
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Sallagundala, Nagaraja. "Neuronal hypothalamic plasticity in chicken." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15600.
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Aufgabe der elektrophysiologischen Studie zur Charakterisierung der neuronalen hypothalamischen Plastizität beim Haushuhn war es, den Einfluss des Alters sowie GABAerger Substanzen auf die Feuerrate und die Temperatursensitivität (thermischer Koeffizient: TC) von Hypothalamusneuronen mittels extrazellulärer Ableitungen in Hirnschnitten zu untersuchen. Im Vergleich zu adulten Vögeln und Säugetieren wurde bei juvenilen Hühnern eine hohe neuronale Kältesensitivität nachgewiesen, die offensichtlich eine spezifische Eigenschaft juveniler Vögel ist. Die Ontogenese der neuronalen hypothalamischen Thermosensitivität ist deutlich artspezifisch. Einige Neurone wiesen eine inherente Kältesensitivität auf. Eine mögliche zentrale Rolle kältesensitiver Neurone im Rahmen der Thermoregulation juveniler Hühner wurde postuliert. Muscimol und Baclofen hemmen signifikant die Feuerrate der Hypothalamusneurone, unabhängig von der jeweiligen Thermosensitivität. Demgegenüber bewirken Bicucullin und CGP35348 einem Anstieg der Feuerrate. Nur bei kältesensitiven Neuronen wurde der TC signifikant durch GABAB-Rezeptor-Liganden verändert (signifikant erhöht durch Baclofen und durch CGP35348 gehemmt). Der Effekt von Muscimol und Baclofen auf Feuerrate und TC wurde durch Co-Perfusion mit einer 10-fach höheren Konzentration der entsprechenden Antagonisten Bicucullin und CGP35348 aufgehoben. Der wesentliche GABAerge Einfluss auf thermosensitive und –insensitive Hypothalamusneurone ist mit dem bei Säugetieren nachgewiesenen vergleichbar. Der einzige Unterschied betrifft die GABAB-Rezeptor vermittelte Änderung des TC. Beim Hühnerküken betraf dies die kältesensitiven und beim Säugetier die wärmesensitiven Neurone. Der grundlegende Mechanismus der GABAergen Beeinflussung thermosensitiver und –insensitiver Neurone scheint einen älteren evolutionären Ursprung zu haben. Eine funktionelle Rolle GABAerger Substanzen im Rahmen der zentralen Kontrolle der Körpertemperatur beim Vogel ist möglich.In the present electrophysiological studies, characterization of neuronal hypothalamic plasticity in the chicken aims to investigate the influence of age during development by extracellular recordings. High neuronal cold sensitivity has been found in juvenile chicken in contrast to adult mammals and birds. High hypothalamic cold sensitivity seems to be a specific characteristic feature in juvenile birds. Between species a species specificity of the early development of neuronal hypothalamic thermosensitivity could be clearly demonstrated. Existence of inherent nature to a certain degree suggests a possible thermoregulatory role of cold-sensitive neurons in chicken. The effects of the GABAergic substances on neuronal tonic activity (firing rate) and temperature sensitivity (temperature coefficient) in hypothalamic neurons have been examined. Muscimol and baclofen in equimolar concentrations significantly inhibited tonic activity, regardless of their type of thermosensitivity. In contrast bicuculline and CGP 35348 increased firing rate. Temperature coefficient was significantly changed by ligands of GABAB receptors, restricted to cold-sensitive neurons. The TC was significantly increased by baclofen and significantly decreased by CGP 35348. Effects of muscimol and baclofen on firing rate and TC were prevented by co-perfusion of appropriate antagonists bicuculline and CGP 35348, respectively in tenfold higher concentration. Thus the main effects of GABA in chicken are similar with that described in mammals. The only difference is in respect of the GABAB receptors mediated change restricted to cold-sensitive neurons in chicken but in mammals only seen in warm-sensitive neurons. However, the results indicate that the fundamental mechanism of GABAergic influence in chicken are conserved during evolution. The response of hypothalamic neurons to temperature changes suggest a possible functional role of GABAergic substances in the control of body temperature in birds.
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Akancha. "Co-Hydrolysis of Rice Bran Wax and Waste Plastics." Thesis, 2016. http://ethesis.nitrkl.ac.in/8442/1/2016_MT_711CH1151_Akancha.pdf.
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This work is a step towards the solution of both environmental safety and energy crisis.Tremendous use of plastic wares also leads to produce huge amount of plastics wastes.It is also pretty known that,plastics are non-biodegradable and possibly release toxic and greenhouse gases during incineration.Therefore,the investigation was the production and characterization of the oil obtained from co-pyrolysis of waste polypropylene and rice bran wax. The co-pyrolysis experiments were conducted in a semi-batch reactor within a temperature range of 400? to 650? which was obtained by Thermogravimetric analysis.The optimum pyrolytic oil at 550? i.e. 1:3 ratio(PP: RBW)has liquid yield of 80.5%,calorific value of 43.73 MJ/Kg.From physical characterization of oil,800.8 kg/m3 density,40.75? flash point and 43?fire point,shows a very close resemblance to diesel.The chemical composition of PP,RBW and 1:3 ratio analyzed by FTIR,GC-MS and NMR spectroscopy shows that the composition of all the three oils mainly contains aliphatic compounds and small amounts of oxygenated compounds.By determining the physical and chemical characterization,it can be stated that 1:3 ratio is a mixture of diesel and gasoline.After proper treatment and refining,the pyrolytic oil can be used as a substitute of fossil fuel.The solid residue of 1:3 ratio obtained after pyrolysis was characterized for its calorific value,SEM and BET analysis. The analysis proved that the char can be utilized as activated carbon and solid fuel.
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Hsiao, Shih-Jie, and 蕭仕傑. "Investigate Multitasking-Related Neural Co-Modulations among Independent Brain Processes." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/66760440127897369624.
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碩士國立交通大學
生醫工程研究所
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Driving is a complex task that requires drivers to pay attention all the time to control the cars. It takes only one split second of distraction can result in an accident. Distracted driving is regarded as an integrated task requiring different regions of the brain receive sensory data, coordinate information, make decision, and synchronize movement responses. Previous studies investigated electroencephalographic (EEG) dynamics associated with distracted driving. In this study, we further applied a novel independent modulator analysis (IMA) method to temporally independent EEG components to understand how the human executive control system coordinates different brain regions to simultaneously perform multiple tasks with different distractors. The behavioral results showed that the reaction time (RT) in response to the traffic event increased while multitasking. Moreover, the RT was longer when the distractor was presented in an auditory form versus a visual form. IMA results showed that there are performance-related independent modulators coordinating different brain regions while distracted driving. The component spectral fluctuations affected by the modulators were distinct between single- and dual-tasks. Specifically, more modulatory weights should project to the occipital region to deal with extra distracted stimulus in dual-tasks conditions. Comparison of modulatory weights between auditory and visual distractors showed that more modulatory weights projected to the frontal region while processing auditory distractor. This study provide valuable insights into the temporal dynamics of attentional modulation during multitasking as well as understanding of the underlying brain mechanisms that mediates the synchronization across brain regions and governs allocations of attention in distracted driving.
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Cunha, José Diogo Marques da Silva Branco da. "Sensorimotor rhythm brain-computer interface – A game-based online co-adaptive training." Master's thesis, 2018. http://hdl.handle.net/10451/36308.
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Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2018Brain-Computer Interface (BCI) technology translates brain signals into messages. BCI users are thus enabled to interact with the environment by thought, or more generally speaking by mental processes. Event-related desynchronization (ERD) based BCIs use the detection of changes in the spontaneous electroencephalogram (EEG) signal. Different mental processes induce power decreases (ERD) or increases (event-related synchronization, ERS) in different frequencies and different areas of the brain. These differences can be measured and classified. Operating a non-invasive EEG based sensorimotor rhythm BCI is a skill that typically requires extensive training. Lately, online co-adaptive feedback training approaches achieved promising results after short periods of training. Does this also mean that users can have meaningful BCI-based interactions after training, when the BCI is no longer adapting, like in a real- life scenario? To answer this question an online study was conducted with 20 naïve (first time) users. After a short (less than 20 minutes) setup, the users trained to gain BCI control by playing a Whack- A-Mole game where they would have to perform Motor Imagery (imagination of a specific movement- MI) to control a hammer to hit a mole. The game was played for about 30 minutes. During this time, the user learns to perform MI with online feedback from the game and the BCI parameters recurrently adapt to the user’s EEG patterns every~1minute. This recurrent adaptation allows different users to use slightly different strategies and produce ERDs in different frequencies and brain areas without loss of performance. After 30 minutes of training the adaptation was stopped and the users continued playing the game with the trained BCI for another 20 minutes. The BCI parameters were calibrated with data from the adaptive stage and kept fixed in the last 20 minutes. Our hypothesis is that once a system was co-adaptively trained it can maintain its performance without recurrent adaptation. Eighteen out of the twenty users were able to control the BCI and play the game. Seventeen out of the eighteen were able to improve or keep performance between adaptive and non-adaptive stage. These results seem to suggest that online co-adaptation is an effective way to gain BCI control.
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GAO, CHENG-HENG, and 高承亨. "The late effect to the heart after brain exposures to ﹑Co gamma rays." Thesis, 1986. http://ndltd.ncl.edu.tw/handle/60111270798556540023.
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Tsai, Wen-Feng, and 蔡汶峰. "Investigating brain activities and Neural Co-Modulations in motion sickness among passengers and drivers." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/5cu6s8.
Full textAbstract:
碩士國立交通大學
電控工程研究所
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Although the motion sickness related brain activities have been discussed by many of the previous studies, most of them investigate the passenger and there is no comparison between passengers and drivers in electroencephalogram (EEG) during motion sickness. In these previous studies, some results were found in different brain regions at the same time, but there was no more detailed discussion on why they occurred simultaneously. Therefore, the aim of this study attempts to explore the brain dynamic activities and neural co-modulations in motion sickness among passengers and drivers. This study recruited 18 subjects to participate in a motion sickness experiment, and simultaneously self-reported motion sickness level and EEG of subjects were recorded during the virtual-reality driving environment. Independent component analysis (ICA) was used to separate the filtered EEG signals into maximally temporally independent components (ICs). The decomposition enables the brain dynamics that are induced by the motion of the platform and motion sickness to be disassociated. Then, proceeded to co-modulation, reduced logarithmic spectra of ICs of interest, using principal component analysis, were decomposed by ICA again to find spectrally fixed and temporally independent modulators (IMs). The results of this study showed that the passenger’s alpha power had a significant increase with the motion sickness level in the parietal, left motor, right motor, and occipital midline areas, but the driver was a relatively slight increase. Furthermore, the alpha power of passenger was higher than the alpha power of driver in the high sickness section. Although the result of the alpha modulator was similar to that of the alpha power, but it was more significant than the alpha power in understanding the motion sickness among passengers and drivers. To conclude, this study illustrates the difference in motion sickness level and brain dynamics among passengers and drivers during motion sickness, especially in neural modulation.