Dissertations / Theses on the topic 'Combined or multimodal treatments'

El TDAH és un trastorn neuroevolutiu de l’atenció i la impulsivitat de naturalesa crònica que afecta un 4% de la població i que freqüentment s’associa amb altres trastorns, com els problemes de conducta i les dificultats en l’aprenentatge. Actualment hi ha base empírica sobre el seu origen genètic i biològic, encara que el seu curs evolutiu i el seu pronòstic estan molt influenciats per factors ambientals. És per això que un abordatge adequat del procés d’avaluació i d’intervenció d’aquest trastorn ha de contemplar de forma primerenca els contextos en què el nen es desenvolupa (escola, família i comunitat) i ha de comptar amb un equip multidisciplinari. En aquesta línia, las modalitats d’intervenció que han evidenciat ser més efectives són les medicacions psicoestimulants, les intervencions psicosocials i els tractaments que combinen ambdues modalitats terapèutiques. L’estimulant més utilitzat per al TDAH, el metilfenidat, és el fàrmac més prescrit en psiquiatria infantil i s’ha constatat la seva efectivitat de forma reiterada. No obstant això, s’ha d’administrar amb cautela perquè presenta limitacions que a vegades no en compensen l’administració, com el efectes no desitjats, el desconeixement sobre els efectes a llarg termini o els escassos estudis sobre eficàcia i seguretat en nens preescolars. Aquests troballes ens fan considerar les intervencions psicosocials, que també són una bona opció terapèutica. Les intervencions psicosocials validades empíricament serveixen d’entrenament a pares i mestres per manejar el trastorn, com també al mateix nen, tot i que en menor mesura, per exercitar les seves habilitats socioemocionals. La finalitat d’aquestes teràpies és que paral•lelament o tres la formació, s’implementen intervencions conductuals, cognitiu-conductuals, escolars i sòcio-emocionals en els contexts naturals del nen. Encara que està provada la eficàcia d’aquestes modalitat d’intervenció de forma aïllada, s’han trobat millores superiors amb els tractaments combinats o multimodals, que cobren un ampli ventall de dificultats i plànols de funcionament, permetent en ocasions reduir la dosi de medicació amb un manteniment dels efectes positius. Però, malauradament, encara s’observa una relativa carència d’estudis que incloguin tractaments combinats per al TDAH infantil, si més no a España. En el millor del casos, les intervencions han estat breus i intensives. Tanmateix, no s’han publicat estudis sobre l’eficàcia d’aquestes intervencions per millorar variables com el clima escolar i familiar d’aquests nens. L’objectiu, doncs, d’aquest projecte és analitzar l’eficàcia relativa i diferencial d’un tractament combinat (medicació estimulant + entrenament a pares i mestres) versus un de farmacològic, durant un curs escolar, per millorar diverses variables relacionades amb el nen hiperactiu, com també amb els seus mestres i pares (símptomes, rendiment acadèmic, clima escolar i familiar, autoeficàcia percebuda i coneixements sobre TDAH).
El TDAH es un trastorno neuro-evolutivo de la atención, la actividad y la impulsividad de naturaleza crónica, que afecta a un 4% de la población, asociándose frecuentemente con otros trastornos, como los problemas de conducta y las dificultades de aprendizaje. En la actualidad, hay evidencia empírica sobre su origen genético y biológico, aunque su curso evolutivo y pronóstico están enormemente influidos por factores ambientales. De ahí que un adecuado abordaje del proceso de evaluación e intervención de este trastorno deba contemplar de forma temprana los contextos donde el niño se desenvuelve (escuela, familia y comunidad), contando con un equipo multidisciplinar. En esta línea, las modalidades de intervención que han mostrado ser más efectivas son las medicaciones estimulantes, las intervenciones psicosociales y los tratamientos que combinan ambas opciones terapéuticas. El estimulante más utilizado para el TDAH, el metilfenidato, es el fármaco más prescrito en psiquiatría infantil y se ha constatado reiteradamente su efectividad. Pero se debe administrar con cautela porque presenta limitaciones que en ocasiones no compensan su administración, como sus efectos indeseados; el desconocimiento sobre sus efectos a largo plazo; y los escasos estudios sobre su eficacia y seguridad en niños preescolares. Estos hallazgos nos instan a considerar las intervenciones psicosociales, que son también una buena opción terapéutica. Las intervenciones psicosociales validadas empíricamente son el entrenamiento a padres y a maestros en el manejo del trastorno, y en menor medida el entrenamiento en habilidades socio-emocionales al propio niño. La finalidad de estas terapias es que paralelamente o tras la formación, se implementen intervenciones conductuales, cognitivo-conductuales, escolares y socio-emocionales en los contextos naturales del niño. Sin embargo, a pesar de la eficacia de estas modalidades de intervención de forma aislada, se han mostrado mejoras superiores con los tratamientos combinados o multimodales, que cubren un amplio abanico de dificultades y planos de funcionamiento, permitiendo en ocasiones reducir la dosis de medicación con un mantenimiento de los efectos positivos. Pero desafortunadamente, aún se observa una relativa carencia de estudios que incluyan tratamientos combinados para el TDAH infantil, al menos en España. Y en el mejor de los casos, las intervenciones han sido muy breves e intensivas. Asimismo, no se han publicado estudios sobre la eficacia de estas intervenciones para mejorar variables como el clima escolar y familiar de estos niños. Precisamente, el objetivo de este proyecto es analizar la eficacia relativa y diferencial de un tratamiento combinado (medicación estimulante+entrenamiento a padres y maestros) versus farmacológico, durante un curso escolar, para mejorar diversas variables relacionadas con el niño hiperactivo, sus maestros y sus padres (síntomas, rendimiento académico, clima escolar y familiar, autoeficacia percibida y conocimientos sobre TDAH).
ADHD is a neuro-developmental disorder of attention, impulsivity and activity of a chronic nature, affecting 4% of the population, frequently associated with other disorders such as behavioral problems and learning disabilities. Today, there is empirical evidence on genetic and biological origin, although its clinical course and prognosis are greatly influenced by environmental factors. Hence, an adequate management of the process of assessment and intervention for this disorder should contemplate early contexts where the child develops (school, family and community), with a multidisciplinary team. In this stratum, the interventions that have proven most effective are stimulant medications, psychosocial interventions and treatments that combine both options. The stimulant used for ADHD, methylphenidate, is the most prescribed drug in child psychiatry and has been found repeatedly to be effective. But it should be administered with caution, because it has limitations, like its side effects, the lack of long-term effects, and the few studies on efficacy and safety in preschool children. These findings urge us to consider psychosocial interventions, which are also a good option. Empirically valid psychosocial interventions are parent training and teachers in the management of the disorder, and less training in socio-emotional skills the child itself. The purpose of these therapies is that, - parallel or after the training -, behavioral, cognitive-behavioral, and socio-emotional interventions would be implemented in the child's natural settings. However, despite the effectiveness of these modalities of intervention in isolation, greater improvement has been shown with combined or multimodal treatments covering a wide range of problems, allowing sometimes to reduce the dose of medication, with a maintenance of positive effects. But unfortunately there is still a relative lack of studies involving combined treatments for childhood ADHD, at least in Spain. And in most cases, interventions have been very brief and intensive. Also, there are no published studies on the effectiveness of these interventions to improve variables such as school and family environment of these children. The precise purpose of this project is to analyze the relative and differential efficacy of combined treatment (stimulant medication + training for parents and teachers) versus drug, during a school year, in order to improve various variables related to the hyperactive child, their teachers and their parents (symptoms, academic performance, school and family evironment, self-efficacy and knowledge about ADHD).

Product matching in e-commerce is an area that faces more and more challenges with growth in the e-commerce marketplace as well as variation in the quality of data available online for each product. Product matching for e-commerce provides competitive possibilities for vendors and flexibility for customers by identifying identical products from different sources. Traditional methods in product matching are often conducted through rule-based methods and methods tackling the issue through machine learning usually do so through unimodal systems. Moreover, existing methods would tackle the issue through product identifiers which are not always unified for each product. This thesis provides multimodal approaches through product name, description, and image to the problem area of product matching that outperforms unimodal approaches. Three multimodal approaches were taken, one unsupervised and two supervised. The unsupervised approach uses straight-forward embedding space to nearest neighbor search that provides better results than unimodal approaches. One of the supervised multimodal approaches uses Siamese network on the embedding space which outperforms the unsupervised multi- modal approach. Finally, the last supervised approach instead tackles the issue by exploiting distance differences in each modality through logistic regression and a decision system that provided the best results.
Produktmatchning inom e-handel är ett område som möter fler och fler utmaningar med hänsyn till den tillväxt som e-handelsmarknaden undergått och fortfarande undergår samt variation i kvaliteten på den data som finns tillgänglig online för varje produkt. Produktmatchning inom e-handel är ett område som ger konkurrenskraftiga möjligheter för leverantörer och flexibilitet för kunder genom att identifiera identiska produkter från olika källor. Traditionella metoder för produktmatchning genomfördes oftast genom regelbaserade metoder och metoder som utnyttjar maskininlärning gör det vanligtvis genom unimodala system. Dessutom utnyttjar mestadels av befintliga metoder produktidentifierare som inte alltid är enhetliga för varje produkt mellan olika källor. Denna studie ger istället förslag till multimodala tillvägagångssätt som istället använder sig av produktnamn, produktbeskrivning och produktbild för produktmatchnings-problem vilket ger bättre resultat än unimodala metoder. Tre multimodala tillvägagångssätt togs, en unsupervised och två supervised. Den unsupervised metoden använder embeddings vektorerna rakt av för att göra en nearest neighborsökning vilket gav bättre resultat än unimodala tillvägagångssätt. Ena supervised multimodal tillvägagångssätten använder siamesiska nätverk på embedding utrymmet vilket gav resultat som överträffade den unsupervised multimodala tillvägagångssättet. Slutligen tar den sista supervised metoden istället avståndsskillnader i varje modalitet genom logistisk regression och ett beslutssystem som gav bästa resultaten.

Workers are challenged by the increasingly complex multitasking environments they experience. To interact effectively with these environments, they must avoid overload. When workers get overloaded (when their mental demands exceed the resource capacity) quality drops, performance degrades, and safety suffers. What is largely unknown, however, is whether these results translate to postural tasks. Postural stability exhibits an entirely different set of challenges: injury, the danger of slips and falls, and risks associated with aging workers or those who have mental or physical challenges. An assembly line worker, for example, must assume different postures, interact with the product in some way, and react to visual and auditory alarms. Mistakes could be dangerous. It is clearly important, then, to understand the interactive effects of mental and postural workload. The goal of this research was to quantify the effects of mental and postural demands on overall workload. To accomplish this, we implemented three studies that were designed to capture the synergistic effects of different task types on overall workload and compare different types of workload measures against each other to help further design research in the area. We designed a dual-task mental/postural protocol to test the differential effects of a series of cognitive demands found in dual-task postural studied. The results of the first study depict a clear picture: the addition of an auditory task to unstable seating decreases postural sway. Based solely on this result, it might be concluded that workload did not increase. Using the same protocol while measuring mental workload however, we found that workload did in fact increase both subjectively and objectively, even when similar postural benefit was found. Even as performance seemed to improve, the participant moved nearer to possible overload and performance decrement (a condition we did not induce in this research). Based on the differences found between the different measures, we believe the importance of measuring overall workload as well as individual task performance in cognitive/postural dual-task research is very high.
Ph. D.

The aim of this project was to investigate the anticancer activity of the anti-diabetic drug metformin, individually or combined in various settings with chemotherapy, on in vitro models of colorectal cancer (CRC). I found that metformin reduced cell proliferation by inducing cell cycle arrest in the G0/G1 phase, but did not lead to cell death. The anti-proliferative action of metformin resulted mediated by the inactivation of the mTOR pathway and of IGF1R protein. However, the drug only transiently arrested cell growth, since its effects were reversed after drug removal. When I combined the biguanide with the chemotherapy drugs commonly used to treat CRC I observed different responses in the cell lines analysed that reflected their genetic background and their different sensitivities to both the biguanide and chemotherapy. I found that metformin added before chemotherapy drugs antagonised their effects in the majority of the treatments. On the contrary, its administration after long chemotherapeutic treatments significantly reduced the cell viability. I noted that metformin better inhibits cell proliferation in cell lines with rapid growth. I have also assessed the dual treatment combination of metformin with different drugs that target specific genes or proteins (targeted therapies), focusing on BRAF-mutant cell lines. For most of the tested treatments the simultaneous administration of metformin and target drugs gave no advantages over the single drugs, and often resulted in antagonism. Overall, our results show that although further investigations are still needed to elucidate the results of the treaments including metformin, these data suggest that caution should be used in administering chemotherapy to indviduals taking metformin.

Two ultrasound systems were studied to investigate the effects of positional and volumetric prostate variations on dosimetry over the course of external radiation therapy. A 2D system, currently used at the Montreal General Hospital for patient repositioning, was compared to a 3D system invented recently. Prostate variations were quantified from ultrasound images acquired daily during a 2003 clinical study. A method was devised to introduce ultrasound information in a Monte Carlo Treatment Planning System previously developed at McGill. Patient repositioning was evaluated for both systems using dose-volume histograms of Voxel Monte Carlo dose calculation. Repositioning with the 3D system, neglecting volume changes, was found to bring the target dose to within 1 % of the planned dose, rather than the 12 % of the clinical 2D system. However, when considering the varying 3D volumes, the dose could only be corrected to within 7 %. These results indicate that the 3D system provides not only a more accurate assessment of prostate displacements, but also volumetric information that significantly affects the dosimetry.

Neuropsychotherapy is a new philosophy in the treatment of mental disorders that bases its principles in the application of the information we have about the brain activations and brain functioning to adjust the therapy to them, in order to center the process in how the brain evolves to its normal activations. New tools in the field of neuroimaging have helped in this process, providing accurate and detailed information about how the particular brain of each patient works. Between the many neuroimaging techniques available nowadays, the functional magnetic resonance (fMRI) stands out by its high spatial resolution, which allows a better knowledge of which brain area is activated before each stimulus or while performing each activity. The disadvantages this technique presents in terms of size of the scanner and restriction of movements give light to another technique, more suitable in certain domains: the electroencephalography (EEG), which provides a greater freedom of movement and higher temporal resolution. For the purposes of this PhD Thesis, both techniques will be compared, in order to find which one better suits our interests. For doing so, another factor will be taken into account. Due to the limitations the neuroimaging techniques have in terms of presentation of the stimuli, we are not able to expose the subject to certain kinds of real life situations. There is where the virtual reality (VR) enters the scene. With VR we are able to move the subject to a virtual world where any kind of stimulus is possible. In the case of neuropsychotherapy, it will allow the exposition of the patient to a situation related to his disorder, in a safer and more controlled environment. In fact, virtual reality has been widely used for the treatment of psychological disorders; but, until now, it has not been applied during the assessment of the disease. For the aims of this Thesis, virtual environments will be used for the assessment of subjects before and after undergoing a psychological treatment for a specific disorder, using neuroimaging techniques to find useful information that could help during the therapeutic process. As an example of disorder, the phobia to small animals (spiders and cockroaches) has been chosen, although the conclusions of this study could be extended to other kinds of psychological disorders. Before being able to assure that the brain activations obtained are related to the disorder and not to other issues, it is needed to measure the sense of presence the subjects felt during the virtual experience. This is why before the assessment of a psychological disorder, a study of the sense of presence in a virtual environment was introduced. This study also helped in the decision of which neuroimaging technique apply in the second part of the Thesis. EEG and fMRI were used for the measure of presence in the same virtual environments, and the results in terms of brain activations were compared. Presence was also measured by means of questionnaires, the traditional subjective way of measuring it. As a result of this study it is expected to check if VR could effectively stimulate presence and which neuroimaging technique is more appropriate for the targets of this Thesis. To sum up, the initial hypotheses of this Thesis are that: 1- The new neuroimaging techniques can provide of useful information to use during neuropsychotherapy. 2- Virtual reality would help in the assessment of the disorder, improving the accuracy in the way the subjects are exposed to the stimuli. 3- The environments used would be immersive enough so the patient will feel present in them and feel them as real. For fulfilling these objectives, each of the two courses of work (study of presence and assessment of a mental disorder) was divided in two parts. In total, four studies were developed: 1- Study of the sense of presence in a virtual environment using fMRI: the aim of this part of the Thesis was to check if the environments were able to stimulate the sense of presence, correlating the results with those given to questionnaires. 2- Study of the sense of presence in a virtual environment using EEG: the aim here was to compare the brain activations obtained with EEG with those from the previous study, and if the responses of the questionnaires were equivalent despite being in a less intrusive scanner. As a result of these two studies, it was decided that the environments were immersive enough to induce the sense of presence, and that the best neuroimaging technique for the next part of the Thesis was the fMRI, due to the higher spatial resolution it brought. 3- Assessment of a psychological disorder, pre-treatment: once decided the study will continue with fMRI, the areas related to a specific disorder (small animals¿ phobia) were studied using VR as stimulus. Until now, the assessment has been done using real animals as stimuli but not using VR, which here is hypothesized to allow a better approach to the phobic experience than the view of photographs or videos of real animals. 4- Assessment of the state of subjects with a psychological disorder, post-treatment: once the patients had underwent a treatment to cure the disorder, they were assessed again to check if the brain areas related to the phobia stopped being activated after it. As a result of this second part of the Thesis, the brain areas related to the phobia (that stopped being activated after the treatment) were obtained, and this information is hoped to be useful in future neuropsychotherapeutic works, for the better adjustment of the disorder. In conclusion, this PhD Thesis studies the advantages that the new neuroimaging techniques and virtual reality could bring to the study of neuropsychotherapy.
Clemente Bellido, M. (2014). Contributions to Neuropsychotherapy of the Combined Use of Neuroimaging and Virtual Exposure for Assessment in Psychological Treatments [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/37234
TESIS

La cirrosi, la causa més freqüent d’hipertensió portal (HTP) en els països occidentals, és considerada una malaltia amb múltiples fases, que evoluciona des d'etapes inicials asimptomàtiques a un estat de cirrosi descompensada amb diverses manifestacions clíniques, les quals representen la principal causa de mort i de trasplantament hepàtic a tot el món. Per tant, caldria adaptar les diferents teràpies per a la cirrosi a cadascuna de les fases de la malaltia. Malgrat els avenços realitzats en les últimes dècades per entendre millor la fisiopatologia de la HTP i poder desenvolupar noves estratègies farmacològiques, fins al moment, els beta-bloquejants no selectius (BBNS) continuen sent la base del tractament dels pacients cirròtics amb HTP per a reduir la pressió portal (PP) i prevenir l'hemorràgia per varius. Aquesta tesi doctoral se centra en l'estudi de noves estratègies terapèutiques per al tractament de la cirrosi hepàtica en diferents etapes de la malaltia. Concretament, hem provat dos nous potencials fàrmacs orals, sols o en combinació amb d’altres fàrmacs convencionals, per veure la seva eficàcia en diversos models d’experimentació animal d’HTP: el model de lligadura de la vena porta (LVP), el de lligadura del conducte biliar (LCB), i el model d’intoxicació per tetraclorur de carboni (CCl4). Tres estudis conformen aquesta tesi. En el primer estudi, es va avaluar la utilitat de la droxidopa, un fàrmac pro-adrenèrgic que ja s'utilitza en humans per a altres indicacions, en el tractament de les alteracions hemodinàmiques i renals associades a la cirrosi hepàtica; en el segon estudi, es van testar combinacions de droxidopa amb d’altres fàrmacs que disminueixen la PP (BBNS o estatines), per tal d'intentar aconseguir un efecte sinèrgic i, en el tercer estudi, es va dur a terme una comparació, pel que fa a la reducció de la PP i la toxicitat, de l’efecte de les estatines convencionals (simvastatina, atorvastatina) amb el NCX 6560, una atorvastatina alliberadora d'òxid nítric (ON). La droxidopa va produir un efecte diürètic i natriürètic destacat, i va millorar les alteracions sistèmiques i hemodinàmiques de les rates amb HTP mitjançant l'augment de la pressió arterial mitjana i la resistència de l’artèria mesentèrica superior conjuntament amb una reducció del flux sanguini en l'artèria mesentèrica superior. El tractament crònic amb propranolol més droxidopa va reduir la PP, tot mantenint l'increment en la diüresi i la natriüresi de la droxidopa. Ni la combinació aguda de carvedilol més droxidopa, ni la combinació amb atorvastatina, van aconseguir un efecte sinèrgic. La comparació entre les diferents estatines va mostrar un major efecte tòxic d'aquests fàrmacs en un model que reprodueix una funció hepàtica deteriorada i colèstasi (especialment amb el tractament amb simvastatina), i el NCX 6560 va millorar la HTP de manera similar a l'atorvastatina en dos models cirròtics (LCB i CCl4), però amb menor toxicitat i un millor perfil vasoprotector intrahepàtic. En conjunt, els resultats d’aquesta tesi apunten a un potencial ús terapèutic de la droxidopa per al tractament dels pacients cirròtics amb ascites refractària i síndrome hepatorenal tipus 2, fins i tot en aquells pacients que estan en tractament amb propranolol, i a un ús més segur del NCX 6560 en el potencial tractament a llarg termini de la HTP amb estatines.
Cirrhosis, the most frequent cause of portal hypertension (PHT) in Western countries, is considered a multistage disease progressing from asymptomatic initial stages to decompensated cirrhosis with multiple clinical manifestations, which are a leading cause of death and liver transplantation worldwide. Therefore, therapies in liver cirrhosis should be adapted to each stage of the disease. Although many advances has been made in the last decades to understand the pathophysiology of PHT and develop new pharmacological approaches, up to now, non-selective beta-blockers (NSBB) still remain the mainstay of treatment in cirrhotic patient with PHT in order to reduce portal pressure (PP) and prevent variceal bleeding. The present doctoral thesis focuses on the study of new therapeutic strategies for the management of liver cirrhosis at different stages of the disease. In particular, two potential oral new drugs were tested, alone or in combination with other conventional drugs, to see their efficacy in several experimental animal models of PHT: the portal vein ligation (PVL), the bile duct ligation (BDL), and the carbon tetrachloride (CCl4) models. Three studies constitute this thesis. In the first study, the pro-adrenergic drug droxidopa, already used in humans for other indications, was evaluated for the management of the hemodynamic and renal alterations associated with liver cirrhosis; in the second study, combinations of droxidopa with other PP-lowering drugs (NSBB or statins) were performed in order to achieve a synergistic effect and, in the third study, a comparison of conventional statins (simvastatin, atorvastatin) with the nitric oxide (NO)-donating atorvastatin NCX 6560, in terms of PP lowering effect and toxicity, was also carried out. Droxidopa produced a marked diuretic and natriuretic effect, and improved the systemic and hemodynamic alterations of portal hypertensive rats by increasing mean arterial pressure and superior mesenteric artery resistance and by reducing superior mesenteric artery blood flow. A chronic treatment with propranolol plus droxidopa reduced PP, maintaining the increase in diuresis and natriuresis caused by droxidopa. Neither the acute combination of carvedilol plus droxidopa nor the combination with atorvastatin achieved a synergistic effect. The comparison among statins showed a magnified toxic effect of these drugs in a model that mimics a deteriorated liver function and cholestasis (especially with simvastatin treatment), and NCX 6560 improved PHT similarly to atorvastatin in two cirrhotic models (BDL and CCl4), but with less toxicity and a better intrahepatic vasoprotective profile. Altogether, the results presented in this thesis point to a potential therapeutic use of droxidopa in the management of cirrhotic patients with refractory ascites and type-2 hepatorenal syndrome, even in those patients on propranolol therapy, and to a safer use of NCX 6560 in the potential long-term statin treatment of PHT.

Master of Science
Food Science Institute
Randall K. Phebus
Due to the potential of Shiga toxin-producing Escherichia coli (STEC) contamination, beef processors use various antimicrobial interventions throughout the slaughter and fabrication processes to reduce risks of contaminating the food supply. Certain antimicrobials are approved and marketed for spraying onto chilled subprimal cuts; however, administering these treatments through commercial-scale equipment against foodborne pathogens is not fully validated. This study evaluated the efficacy of three common antimicrobial sprays, individually (Study 1) and combined (Study 2), against a rifampicin-resistant STEC cocktail (O26, O45, O103, O111, O121, O145, and O157:H7) using a commercial style subprimal spray cabinet. For Study 1, beef subprimals (n=16) were mist-inoculated with the cocktail (ca. 5 log CFU/cm²), followed by spray-treatment with individual antimicrobials [200 ppm peracetic acid (PAA), 2% Centron™ (sulfuric acid, sodium sulfate anhydrous and water mixture; CEN), 4.5% lactic acid (LA), or water (W)]. Study 1 was designed as randomized generalized block. After each treatment phase, STEC population reductions were quantified. As individual antimicrobial treatments, LA and PAA provided greater (P ≤ 0.05) STEC reductions (0.5 and 0.6 ± 0.08 log CFU/cm², respectively) compared to water (0.2 ± 0.08 log CFU/cm²), but the CEN reduction (0.4 ± 0.10 log CFU/cm²) was statistically similar to W. To test the efficacy of combined treatments on subprimal cuts in Study 2, a split-plot design was used using three replications. The inoculated subprimals (n=4) were first treated with PAA, LA, CEN, or W; vacuum packaged; and stored for 72 hours at 4°C. Each subprimal was then divided (n=16) and treated with each of the four antimicrobials as a second treatment. Cumulative reductions from the two treatments and storage ranged from 0.5 to 1.5 log CFU/cm² (± 0.3 log CFU/cm²); the greatest reduction was observed when subprimals were treated with LA followed by vacuum packaged storage and another LA application. Nevertheless, there was no statistical significance among treatments for a particular combination of treatments in Study 2. These studies indicate that the individual antimicrobial treatments evaluated are marginally effective for reducing STEC populations on chilled beef subprimal cuts during fabrication. Although there does not seem to be a specific combination of treatment that is more effective than another, the overall bacterial reduction may be improved by combining treatments when the beef is stored under vacuum packaged conditions and retreated upon bag opening, as typical of mechanical tenderization operations.

The aim of this diploma thesis is to analyze the current situation of multimodal transport with a focus on the European Union, to describe the current concept of the Common Transport Policy and its main objectives and priorities for the future development. Further, to analyze the progress of the project Trans-European transport network with a focus on priority projects supporting the development of multimodal transport in the EU. One of the aims of this thesis is to outline the potential of the continental combined transport as an alternative option to multimodal transport and to focus on its current problems hampering the future prosperity of this new mode of transport.

The thesis discusses the issue of freight villages and the possible usage of European funds for their construction. The topic is very actual because by the current program period 2014-2020 has appeared change concerning the financial support of multimodal freight transportation. The aim of this thesis is to determine, whether from the production companies operating in the automotive industry exists demand for such a freight villages. Needed information has been obtained on the basis of in-depths inteviews of manufacturing companies located in the region Vysočina.

La promotion du transport ferroviaire de marchandises permet d'améliorer l'impact environnemental du transport de marchandises, à travers la réduction de la part modale de la route, qui est responsable d'environ un quart des émissions européennes de CO2. L'objet de cette thèse est d'analyser les flux de marchandises afin de proposer des solutions opérationnelles qui permettraient d'augmenter la part de marché du transport de fret ferroviaire, notamment grâce à une meilleure utilisation des terminaux intermodaux. La première partie de la thèse fournit une synthèse des principales modèles théoriques concernant l'analyse de la demande et de l'offre de transport de marchandises, afin d'analyser le lien entre activité économique et transport de marchandises. Une analyse détaillée des sources statistiques disponibles au niveau européen, national et régional, est aussi fournie. Dans la deuxième partie, une application au cas des chantiers de transbordement rail-route en France est présentée, et une comparaison avec d'autres pays européens est réalisée. L'objectif de cette analyse est d'estimer la demande potentielle de transport combiné, d'évaluer la productivité des terminaux intermodaux et d'étudier l'impact socio-économique et financier des investissements dans les terminaux intermodaux, en évaluant également la possibilité des nouveaux montages financiers (PPP). Les résultats de l'analyse montrent un large potentiel pour le transport combiné, en particulier en lien avec l'activité des ports maritimes, et une productivité faible dans les terminaux existants. En conséquence, cette analyse suggèrerait de concentrer les investissements sur un nombre limité de sites à haut potentiel, afin d'attirer des investissements privés et optimiser l'utilisation des fonds publics. Les implications politiques de cette analyse sont multiples : elles concernent d'abord le gestionnaire d'infrastructure et les opérateurs ferroviaires, qui doivent mieux planifier les investissements en fonction de la demande commerciale. Elles concernent aussi l'Etat et les collectivités locales, qui doivent optimiser l'utilisation des fonds publics en favorisant les localisations à haut potentiel.

碩士
元智大學
化學工程研究所
88
Leachate is a common liquid wastewater that is generated in a landfill site or municipal solid waste incinerator. Due to its complex characteristics and presence of many non-biodegradable substance, treatment of the landfill leachate has never been easy. The purpose of this work is to experimentally investigate several combined physical, chemical and biological methods for dealing with this particular type of wastewater. Chemical coagulation was adopted as a pretreatment of the raw landfill leachate. Test results have indicated that removal of suspended solids, color and some inorganic and/or organic compounds is quite good. The important operating variables of chemical coagulation included the initial pH, PAC/polymer ratio and the amount of PAC. Based on the test results, appropriate operating conditions of these variables were established for efficient operations. After chemical coagulation, the landfill leachate was treated by catalytic oxidation in a gas-induced reactor. In this chemical treatment, activated carbon fiber was employed, in conjunction with ozone, as a catalyst in oxidizing the recalcitrants in the wastewater. The test result of catalytic reaction was modeled using various kinetics, including first-order/multi-step, generalized and complex models. The models parameters were established by best fit of these models to the observed data. In the last of treatment train, sequencing batch reactor (SBR) was employed to further elevate the water quality of the landfill leachate to the discharge standards. The leachate after SBR treatment was clear with low COD below 100 ml/l. A Eckenfelder kinetics of completely mixed type was adopted to model the biological reaction of the SBR process and the parameters of the model were empirically identified.

This study explores the role of speaker and listener gaze in the production of recipient responses, often called backchannels or, in Japanese, aizuchi. Using elicited narrative audio/video data, speaker gaze and recipient response behaviours were first analyzed quantitatively. The results showed that majority of recipient responses are made while the speaker is gazing at the recipient. Next, a qualitative multimodal analysis was performed on a specific type of recipient response that occurred both during and without speaker gaze. The results showed that recipients make good use of the state of the speakers gaze to regulate the speakers talk and negotiate for a pause, a repair, or a turn at talk. These findings suggest that what are currently known as backchannels are only a small part of a much larger sequential multimodal system that is inseparable from the ongoing talk.
Japanese Language and Linguistics

Thesis (M.S.)--State University of New York at Buffalo, 2008.
Title from PDF title page (viewed on April 08, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Meyer, Anne E., Baier, Robert E. Includes bibliographical references.

The demand for proteins is rising and alternatives to animal-based proteins are necessary, either for nutritional or environmental reasons. Plant-based proteins appear as an alternative, however, their techno-functional properties need improvement. High-pressure processing (HPP) is a non-thermal technology that allows modifying proteins’ structure hence allowing to change several of their properties. Enzymes, such as microbial transglutaminase (MTG), can also modify the techno-functional properties of proteins, however, many globular proteins show low susceptibility to the action of this enzyme. HPP, being able to change protein conformation, may be a useful tool to increase the accessibility of proteins to the action of MTG. Nevertheless, HPP conditions need to be carefully optimized to avoid the expected decrease in enzymatic activity when subjected to pressure. Pressure inactivation of MTG under different HPP conditions (200 – 600 MPa; 20 – 40 °C; 10 – 30 min) was evaluated at different pH values. At least 20 % of MTG was inactivated when low pressures (< 300 MPa) were used at pH 4 and 5, whereas a higher pressure (above 400 MPa) was needed to obtain a similar inactivation at pH 6 or 7. MTG pressure-inactivation followed first-order kinetics under all tested conditions. Inactivation rate constants decreased with increasing pressure at constant temperature and pH 4, with a positive activation volume, while the opposite was verified for the other pH values. Both activation energy and volume were dependent on pH. Overall, MTG can be considered relatively resistant to pressure, particularly near its optimal pH. The influence of HPP (200 – 600 MPa; 5 – 15 min) was also evaluated, applied individually or in combination with MTG (up to 30 U·g-1), on selected properties of pea (PPI) and soy (SPI) protein isolates with concentrations between 1 and 9 % (w/v). For a protein concentration of 1 % (w/v), HPP increased the protein solubility of both isolates when applied individually. This effect was more pronounced for SPI, particularly at pH 7 and 8. Similarly, the protein surface hydrophobicity also increased with HPP for proteins from both sources, increasing, in general, with increasing pressure and holding time. On the contrary, the content of free sulfhydryl groups decreased with HPP for proteins from both sources. The effects of HPP on the emulsifying properties of the protein isolates, considering both the whole and soluble protein fractions, were dependent on pH and HPP conditions (pressure, holding time). HPP appeared to have minimal effects on the surface tension of both proteins and the general absence of negative effects on emulsifying activity results from HPP-induced protein aggregation effects. On the other hand, MTG individual treatments had no significant effects on the studied properties. For the other protein concentrations studied, HPP increased the solubility of proteins when there were at low initial concentrations, decreasing it when they were in the higher concentration range analysed. Regardless of the concentration, HPP decreased the content of free sulfhydryl groups for pea proteins, however, had the contrary effect on soy proteins. Comparably to the solubility, the surface hydrophobicity increased in low protein concentrations and the contrary was verified in high protein concentrations. MTG decreased solubility and increased the content of free sulfhydryl groups of both proteins. The enzyme decreased the surface hydrophobicity of soy proteins and of the pea proteins, but only when these were within the higher concentration range analysed. When combined, HPP and MTG appear to have antagonistic effects on the solubility and content of free sulfhydryl groups and synergistic effects on viscosity. The obtained results indicate that simultaneous HPP and MTG treatments can be used to modify the proteins’ structure and consequently tailor their techno-functional properties.
Verifica-se um crescente aumento da procura por proteínas para satisfazer as necessidades nutricionais da população a nível global, em particular de proteínas vegetais devido a preocupações nutricionais e ambientais. As proteínas de origem vegetal aparecem assim como uma alternativa vantajosa às proteínas de origem animal, no entanto, as suas propriedades tecno-funcionais precisam ser melhor conhecidas e otimizadas. O processamento de alta pressão (AP) é uma tecnologia não térmica que permite modificar a estrutura das proteínas, permitindo alterar várias das suas propriedades. Enzimas, como a transglutaminase microbiana (MTG), também podem modificar as propriedades tecno-funcionais das proteínas, no entanto, muitas proteínas globulares mostram baixa suscetibilidade à ação desta enzima. A AP, capaz de alterar a conformação de proteínas, pode ser uma ferramenta útil para aumentar a acessibilidade das proteínas à ação da MTG. No entanto, as condições de processamento precisam ser adequadamente otimizadas para evitar a diminuição da atividade enzimática quando sujeita a pressão. A inativação da MTG sob diferentes condições de pressão (200 – 600 MPa; 20 – 40 °C; 10 – 30 min) foi avaliada em diferentes valores de pH. Pelo menos 20% da MTG foi inativada quando foram usadas baixas pressões (< 300 MPa) a pH 4 e 5, enquanto foi necessária uma pressão acima de 400 MPa para obter uma inativação semelhante a pH 6 ou 7. A inativação por pressão da MTG seguiu uma cinética de primeira ordem em todas as condições testadas. As constantes cinéticas de inativação diminuíram com o aumento da pressão a uma temperatura constante a pH 4, com um volume de ativação positivo, enquanto o contrário foi verificado para os demais valores de pH. Tanto a energia de ativação quanto o volume de ativação foram dependentes do pH. No geral, a MTG pode ser considerada relativamente resistente à pressão, particularmente próximo do seu pH óptimo. Foi avaliada a influência da pressão (200 – 600 MPa; 5 – 15 min), aplicada individualmente ou em combinação com MTG (até 30 U·g-1), sobre propriedades selecionadas de proteínas de ervilha e soja com concentrações entre 1 e 9% (m/v). Para uma concentração de proteína de 1 % (m/v), a AP aumentou a solubilidade da proteína de ambos os isolados quando aplicada individualmente. Da mesma forma, a hidrofobicidade de superfície também aumentou com a AP nas proteínas de ambas as fontes, aumentando, em geral, com o aumento da pressão e do tempo. Pelo contrário, o conteúdo de grupos sulfidrilo livres diminuiu com a pressão nas proteínas de ambas as fontes. O efeito da AP nas propriedades emulsificantes das proteínas, considerando quer a fração total de proteína no isolado, quer a fração solúvel, foi dependente do pH e das condições de AP (pressão, tempo). A AP parece ter efeitos mínimos na tensão superficial de ambas as proteínas e a ausência geral de efeitos negativos na atividade emulsificante resulta dos efeitos de agregação de proteínas induzidas pela AP. Por outro lado, os tratamentos individuais de MTG não produziram efeitos sobre as propriedades estudadas. Para as demais concentrações de proteínas utilizadas, a AP aumentou a solubilidade de dispersões de baixa concentração, diminuindo-a nas mais altas. Independentemente da concentração, a AP diminuiu o conteúdo de grupos sulfidrilo livres para as proteínas de ervilha, no entanto, teve o efeito contrário para as proteínas de soja. Comparativamente à solubilidade, a hidrofobicidade de superfície aumentou para concentrações baixas de proteína e o contrário foi verificado para concentrações altas. A MTG diminuiu a solubilidade e aumentou o conteúdo de grupos sulfidrilo livres de ambas as as proteinas. A enzima diminuiu a hidrofobicidade de superfície de ambas as proteínas quando estas se encontravam em concentração relativamente elevada. Quando combinados, AP e MTG parecem ter efeitos antagonisticos na solubilidade e no conteúdo de grupos sulfidrilo livres e efeitos sinergisticos na viscosidade. Os resultados obtidos indicam que tratamentos simultâneos de AP e MTG podem ser usados para modificar a estrutura das proteínas e consequentemente adaptar suas propriedades tecno-funcionais.
Programa Doutoral em Ciência e Tecnologia Alimentar e Nutrição

Viscoelastic damping treatments, as passive damping control mechanism, have a wide application due to their high efficiency and reduced structural modification. The strong frequency and temperature dependency of these material’s properties, and the representation of the deformation pattern developed in the dissipative layer are key elements to the numerical simulation of such damping treatments. Free layer damping configurations provide a simple solution, but despite being characterized by an expeditious and simple application procedure, its efficiency is comparatively reduced and therefore are usually disregarded as valid solutions for critical structures. To increase the efficiency of these damping treatments, while maintaining the advantages of an application procedure based on a simple deposition of a single layer of material on the structure surface, a new configuration – Interlaced damping layer – is herein proposed and assessed. This new configuration takes advantage of the shear effect and border effect provided by a three-dimensional interlaced layering scheme combining one or several materials. The numerical and experimental results demonstrate the feasibility of this proposed and promising configuration, that can provide a valid replacement for constrained damping layers, which often require a time consume and laborious placement procedures, and in some cases, such those where the target component has a complex geometry, is even impracticable or severely damaged during the application.
Os tratamentos de amortecimento viscoelástico, como controlo passivo de vibrações, têm uma ampla aplicação devido à sua elevada eficiência e reduzida modificação estrutural. A forte dependência das propriedades destes materiais em relação à frequência e temperatura, e a representação do campo de deformações correspondente a essa camada dissipativa são aspetos fulcrais na modelação espacial de estruturas que apresentam estes tratamentos. Os tratamentos superficiais sem restrição proporcionam uma solução simples, porém mesmo caracterizados por simples e rápida aplicação, a sua eficiência é reduzida e por essa razão, são normalmente desconsiderados como solução de estruturas críticas. Com o intuito de aumentar a eficiência, mantendo as vantagens de um procedimento baseado na simples deposição de uma camada material sobre a superfície da estrutura, uma nova configuração - Tratamentos entrelaçados - é aqui proposta e analisada. Esta nova configuração beneficia do efeito de corte e fronteira proporcionado pela camada tridimensional entrelaçada, que combina um ou vários materiais. Os resultados numéricos e experimentais demonstram a viabilidade desta inovadora configuração, que pode proporcionar uma válida alternativa para os tratamentos superficiais com restrição. Estes são caracterizados por longos e laboriosos procedimentos de aplicação e, para geometrias complexas, podem ser impraticáveis ou sofrerem danos durante a sua aplicação.
Mestrado em Engenharia Mecânica

The demand for proteins is rising and alternatives to animal-based proteins are necessary, either for nutritional or environmental reasons. Plant-based proteins appear as an alternative, however, their techno-functional properties need improvement. High-pressure processing (HPP) is a non-thermal technology that allows modifying proteins’ structure hence allowing to change several of their properties. Enzymes, such as microbial transglutaminase (MTG), can also modify the techno-functional properties of proteins, however, many globular proteins show low susceptibility to the action of this enzyme. HPP, being able to change protein conformation, may be a useful tool to increase the accessibility of proteins to the action of MTG. Nevertheless, HPP conditions need to be carefully optimized to avoid the expected decrease in enzymatic activity when subjected to pressure. Pressure inactivation of MTG under different HPP conditions (200 – 600 MPa; 20 – 40 °C; 10 – 30 min) was evaluated at different pH values. At least 20 % of MTG was inactivated when low pressures (< 300 MPa) were used at pH 4 and 5, whereas a higher pressure (above 400 MPa) was needed to obtain a similar inactivation at pH 6 or 7. MTG pressure-inactivation followed first-order kinetics under all tested conditions. Inactivation rate constants decreased with increasing pressure at constant temperature and pH 4, with a positive activation volume, while the opposite was verified for the other pH values. Both activation energy and volume were dependent on pH. Overall, MTG can be considered relatively resistant to pressure, particularly near its optimal pH. The influence of HPP (200 – 600 MPa; 5 – 15 min) was also evaluated, applied individually or in combination with MTG (up to 30 U·g-1 ), on selected properties of pea (PPI) and soy (SPI) protein isolates with concentrations between 1 and 9 % (w/v). For a protein concentration of 1 % (w/v), HPP increased the protein solubility of both isolates when applied individually. This effect was more pronounced for SPI, particularly at pH 7 and 8. Similarly, the protein surface hydrophobicity also increased with HPP for proteins from both sources, increasing, in general, with increasing pressure and holding time. On the contrary, the content of free sulfhydryl groups decreased with HPP for proteins from both sources. The effects of HPP on the emulsifying properties of the protein isolates, considering both the whole and soluble protein fractions, were dependent on pH and HPP conditions (pressure, holding time). HPP appeared to have minimal effects on the surface tension of both proteins and the general absence of negative effects on emulsifying activity results from HPPinduced protein aggregation effects. On the other hand, MTG individual treatments had no significant effects on the studied properties. For the other protein concentrations studied, HPP increased the solubility of proteins when there were at low initial concentrations, decreasing it when they were in the higher concentration range analysed. Regardless of the concentration, HPP decreased the content of free sulfhydryl groups for pea proteins, however, had the contrary effect on soy proteins. Comparably to the solubility, the surface hydrophobicity increased in low protein concentrations and the contrary was verified in high protein concentrations. MTG decreased solubility and increased the content of free sulfhydryl groups of both proteins. The enzyme decreased the surface hydrophobicity of soy proteins and of the pea proteins, but only when these were within the higher concentration range analysed. When combined, HPP and MTG appear to have antagonistic effects on the solubility and content of free sulfhydryl groups and synergistic effects on viscosity. The obtained results indicate that simultaneous HPP and MTG treatments can be used to modify the proteins’ structure and consequently tailor their techno-functional properties.
Verifica-se um crescente aumento da procura por proteínas para satisfazer as necessidades nutricionais da população a nível global, em particular de proteínas vegetais devido a preocupações nutricionais e ambientais. As proteínas de origem vegetal aparecem assim como uma alternativa vantajosa às proteínas de origem animal, no entanto, as suas propriedades tecno-funcionais precisam ser melhor conhecidas e otimizadas. O processamento de alta pressão (AP) é uma tecnologia não térmica que permite modificar a estrutura das proteínas, permitindo alterar várias das suas propriedades. Enzimas, como a transglutaminase microbiana (MTG), também podem modificar as propriedades tecno-funcionais das proteínas, no entanto, muitas proteínas globulares mostram baixa suscetibilidade à ação desta enzima. A AP, capaz de alterar a conformação de proteínas, pode ser uma ferramenta útil para aumentar a acessibilidade das proteínas à ação da MTG. No entanto, as condições de processamento precisam ser adequadamente otimizadas para evitar a diminuição da atividade enzimática quando sujeita a pressão. A inativação da MTG sob diferentes condições de pressão (200 – 600 MPa; 20 – 40 °C; 10 – 30 min) foi avaliada em diferentes valores de pH. Pelo menos 20% da MTG foi inativada quando foram usadas baixas pressões (< 300 MPa) a pH 4 e 5, enquanto foi necessária uma pressão acima de 400 MPa para obter uma inativação semelhante a pH 6 ou 7. A inativação por pressão da MTG seguiu uma cinética de primeira ordem em todas as condições testadas. As constantes cinéticas de inativação diminuíram com o aumento da pressão a uma temperatura constante a pH 4, com um volume de ativação positivo, enquanto o contrário foi verificado para os demais valores de pH. Tanto a energia de ativação quanto o volume de ativação foram dependentes do pH. No geral, a MTG pode ser considerada relativamente resistente à pressão, particularmente próximo do seu pH óptimo. Foi avaliada a influência da pressão (200 – 600 MPa; 5 – 15 min), aplicada individualmente ou em combinação com MTG (até 30 U·g-1 ), sobre propriedades selecionadas de proteínas de ervilha e soja com concentrações entre 1 e 9% (m/v). Para uma concentração de proteína de 1 % (m/v), a AP aumentou a solubilidade da proteína de ambos os isolados quando aplicada individualmente. Da mesma forma, a hidrofobicidade de superfície também aumentou com a AP nas proteínas de ambas as fontes, aumentando, em geral, com o aumento da pressão e do tempo. Pelo contrário, o conteúdo de grupos sulfidrilo livres diminuiu com a pressão nas proteínas de ambas as fontes. O efeito da AP nas propriedades emulsificantes das proteínas, considerando quer a fração total de proteína no isolado, quer a fração solúvel, foi dependente do pH e das condições de AP (pressão, tempo). A AP parece ter efeitos mínimos na tensão superficial de ambas as proteínas e a ausência geral de efeitos negativos na atividade emulsificante resulta dos efeitos de agregação de proteínas induzidas pela AP. Por outro lado, os tratamentos individuais de MTG não produziram efeitos sobre as propriedades estudadas. Para as demais concentrações de proteínas utilizadas, a AP aumentou a solubilidade de dispersões de baixa concentração, diminuindo-a nas mais altas. Independentemente da concentração, a AP diminuiu o conteúdo de grupos sulfidrilo livres para as proteínas de ervilha, no entanto, teve o efeito contrário para as proteínas de soja. Comparativamente à solubilidade, a hidrofobicidade de superfície aumentou para concentrações baixas de proteína e o contrário foi verificado para concentrações altas. A MTG diminuiu a solubilidade e aumentou o conteúdo de grupos sulfidrilo livres de ambas as as proteinas. A enzima diminuiu a hidrofobicidade de superfície de ambas as proteínas quando estas se encontravam em concentração relativamente elevada. Quando combinados, AP e MTG parecem ter efeitos antagonisticos na solubilidade e no conteúdo de grupos sulfidrilo livres e efeitos sinergisticos na viscosidade. Os resultados obtidos indicam que tratamentos simultâneos de AP e MTG podem ser usados para modificar a estrutura das proteínas e consequentemente adaptar suas propriedades tecno-funcionais.
Programa Doutoral em Ciência e Tecnologia Alimentar e Nutrição

博士
國立臺灣大學
解剖學暨細胞生物學研究所
102
The combined ingestion of ketamine (Ket) and amphetamine (Amph) by drug-users has been rampant and produced more severe behavioral abnormality than each individual ingestion. Numerous studies illustrate the behavioral and neurochemical changes of polydrug administration; however, the interactive consequences of the two drugs are still unclear. In this study, young adult mice were intraperitoneally injected with saline, Amph (5 mg/kg), low Ket (LK, 10 mg/kg), high Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK). Single treatment or 7 repetitive treatments within 4 days were conducted. Animal behaviors, including locomotion, stereotypy and ataxia, were examined in a novel open field. Compared with saline, Amph, LK or HK treatment alone increased the levels of motor activities such as locomotion, stereotypy or ataxia of mice. At combined treatments, LK and HK differentially exacerbated Amph-induced locomotion and stereotypy. Notably, Amph-mediated potentiation in Ket-triggered ataxia were manifested after single or repeated drug treatments. After single treatment, the higher striatal dopamine levels of A, ALK and AHK groups correlated with their greater motor activities. The prolonged increase of dopamine in the motor cortex of ALK and AHK mice may associate with the longer duration of behavioral hyperactivity and greater peak score of locomotion; the greater dopamine level in the somatosensory cortex probably contributes to the more severe ataxia. For repetitive treatments, four hours after the final treatment, while the behavioral hyperactivities were ceased, considerable changes were still evident in the motor-related cortices, suggesting modulation to the DAergic system. Furthermore, a significant increase in the number of GAD67-positive puncta in the striatum and motor-related cortices were higher than respective saline controls after both single and repetitive treatments, suggesting a neural adaptive change in the GABAergic system. Our results demonstrate the first time the acute and receptive interplay between Amph and Ket in both behavioral and neurochemical aspects, and show neural adaptive changes in the GABAergic and DAergic systems.

碩士
國立彰化師範大學
生物學系
97
According to Department of Health, Executive Yuan, since in 1982, the malignant tumor has become the first of the ten leading causes of death in Taiwan. Among these cancers, lung cancer is the major cause of death, and also the highest number of women who died of cancer. In accordance with the definition of the World Health Organization (WHO), lung cancer can be divided into small cell lung cancer (patients of all lung cancer accounts for only 15%), as well as non-small cell lung cancer (all accounted for 85% of lung cancer patients). Curcumin has antioxidant, anti-inflammatory, anti-microbial and anti-cancer activities. However, its poor aqueous solubility, relatively low bioavailability and rapid elimination from the body, are the reasons that curcumin is unable to maximize its effectiveness in cancer therapy. Therefore, the synthesis of curcumin analogues or derivatives as well as the combination of curcumin and other drugs have been used to increase the biological activity of curcumin. This study used two non-small cell lung cancer cell lines-A549 (ERα-/ERβ+) and NCI-H460 (ERα+/ERβ+) as the experimental materials to analyze the effects of the organic compounds (total 10 families, 125 drugs) alone or combined with curcumin on lung cancer cell growth. The results of MTT assay showed that CH and 0- family have stronger cytotoxicity. However, CH-14 and 0-9 have the strongest DNA cleavage activity, but did not have cytotoxic activity against A549 and NCI-H460 cells. Furthermore, in the presence of curcumin, CH6, 7 and 10 exhibited cytotoxic activity against the A549 cell lines, but only CH 10 showed significant cytotoxic activity against NCI-H460, while the 0 family of the compound had no effect. In addition, in the presence of 17-β Estradiol (also known as E2), which can induce estrogen receptors (ERs) gene expression, the cytotoxicity of CH combined with curcumin would be inhibited. The results of reverse transcription-PCR analysis suggested that curcumin and organic compounds may affect the expression of estrogen receptor, therefore, led to more cell death.

Indiana University-Purdue University Indianapolis (IUPUI)
With the increasing availability of Electronic Health Records (EHRs) and advances in deep learning techniques, developing deep predictive models that use EHR data to solve healthcare problems has gained momentum in recent years. The majority of clinical predictive models benefit from structured data in EHR (e.g., lab measurements and medications). Still, learning clinical outcomes from all possible information sources is one of the main challenges when building predictive models. This work focuses mainly on two sources of information that have been underused by researchers; unstructured data (e.g., clinical notes) and a patient network. We propose a novel hybrid deep learning model, DeepNote-GNN, that integrates clinical notes information and patient network topological structure to improve 30-day hospital readmission prediction. DeepNote-GNN is a robust deep learning framework consisting of two modules: DeepNote and patient network. DeepNote extracts deep representations of clinical notes using a feature aggregation unit on top of a state-of-the-art Natural Language Processing (NLP) technique - BERT. By exploiting these deep representations, a patient network is built, and Graph Neural Network (GNN) is used to train the network for hospital readmission predictions. Performance evaluation on the MIMIC-III dataset demonstrates that DeepNote-GNN achieves superior results compared to the state-of-the-art baselines on the 30-day hospital readmission task. We extensively analyze the DeepNote-GNN model to illustrate the effectiveness and contribution of each component of it. The model analysis shows that patient network has a significant contribution to the overall performance, and DeepNote-GNN is robust and can consistently perform well on the 30-day readmission prediction task. To evaluate the generalization of DeepNote and patient network modules on new prediction tasks, we create a multimodal model and train it on structured and unstructured data of MIMIC-III dataset to predict patient mortality and Length of Stay (LOS). Our proposed multimodal model consists of four components: DeepNote, patient network, DeepTemporal, and score aggregation. While DeepNote keeps its functionality and extracts representations of clinical notes, we build a DeepTemporal module using a fully connected layer stacked on top of a one-layer Gated Recurrent Unit (GRU) to extract the deep representations of temporal signals. Independent to DeepTemporal, we extract feature vectors of temporal signals and use them to build a patient network. Finally, the DeepNote, DeepTemporal, and patient network scores are linearly aggregated to fit the multimodal model on downstream prediction tasks. Our results are very competitive to the baseline model. The multimodal model analysis reveals that unstructured text data better help to estimate predictions than temporal signals. Moreover, there is no limitation in applying a patient network on structured data. In comparison to other modules, the patient network makes a more significant contribution to prediction tasks. We believe that our efforts in this work have opened up a new study area that can be used to enhance the performance of clinical predictive models.