Dissertations / Theses on the topic 'Live box'

Reinforced Concrete Box Culverts (RCBCs) are an integral part of the national and international transportation infrastructure. The National Bridge Inventory Standards (NBIS) requires that all bridges, which include culverts with spans ≥ 20 ft. (6.1 m), be load rated for safe load carrying capacity in accordance with the AASHTO Manual for Bridge Evaluation (MBE). In Kentucky, the Transportation Cabinet manages more than 15,500 bridges, of which almost 1,400 are bridge size culverts. Of the 1241 bridge size RCBCs that were being evaluated in Kentucky between 2015 and 2018, 846 were 2-cell culverts (or 68%). The objective in this study is to evaluate 2-cell RCBCs using the finite element (FE) method and to propose dead load and live load demand equations that can be used to determine the capacity demand ratio (C/D) and the load rating. The results indicate that the maximum dead load forces (positive and negative moments, and shear) vary linearly with respect to an increase in fill height, while the variation is bi-linear for the maximum live load forces. The proposed equations are derived in terms of the clear span and fill height. The results also indicated that, for fill heights greater than 10 ft (3 m), the maximum live load positive bending moments are less than 10% of their dead load counterparts. The primary advantage of the proposed equations lies in their simple formulation when analyzing and designing 2-cell culverts, which in turn alleviates the need to conduct a detailed finite element analysis to determine the maximum forces in 2-cell RCBCs.

The Long Term Bridge Performance (LTBP) Program is a 20-year program initiated by the Federal Highway Administration to better understand the behavior of highway bridges as they deteriorate due to environmental variables and vehicle loads. Part of this program includes the periodic testing of selected bridges. The Lambert Road Bridge was subjected to nondestructive testing in the fall of 2009. Part of this testing included a live load test. This test involved driving two heavy trucks across the instrumented bridge on selected load paths. The bridge was instrumented with strain, displacement, and tilt sensors. This collected data was used to calibrate a finite element model. This finite element model was used to determine the theoretical live load distribution factors. Using the controlling distribution factor from the finite element model, the inventory and operating ratings of the bridge were determined. These load ratings were compared to those obtained from using the controlling distribution factor from the AASHTO LRFD Specifications. This thesis also examined how different parameters such as span length, girder spacing, parapets, skew, continuity, deck overhang, and deck thickness affect the distribution factors of box girder bridges. This was done by creating approximately 40 finite element models and comparing the results to those obtained by using the AASHTO LRFD Specifications.

Adjacent box beam bridges are economical bridge systems for accelerated bridge construction. The box beams are constructed at precast plants and are traditionally connected by a shear key filled with grout. This system is ideal for short spans with low clearance restrictions. However, due to the grout deteriorating and debonding from the precast concrete in the shear key, reflective cracking propogates through the deck allowing water and chemicals to leak down into the joints. This can lead to the prestressing steel inside the precast member and the transverse tie steel corroding. This necessitates the bridge being rehabilitated or replaced which shortens the life-span of the bridge system and negates the economical value it had to begin with. This research project aimed to design a rehabilitation plan for an adjacent box beam bridge with deteriorated joints using Very High Performance Concrete (VHPC). VHPC was chosen as an economical alternative to the proprietary Ultra High Performance Concrete (UHPC) and extensive material tests were performed. The results of the material testing of VHPC and grout revealed that VHPC had higher compressive and tensile strengths, a higher modulus of elasticity, gained strength faster, bonded better to precast concrete, was more durable over time, and shrank less than conventional grout. The results of this research project were applied to rehabilitate the Buffalo Branch Bridge and further testing will be completed to determine the effectiveness of the rehabilitation.
Master of Science

The scheduled replacement of the 8th North Bridge, in Salt Lake City, UT, presented a unique opportunity to test a pre-cast concrete deck, steel girder bridge. A live-load test was performed under the directions of Bridge Diagnostic Inc (BDI) and Utah State University. Six different load paths were chosen to be tested. The recorded data was used to calibrate a finite-element model of this superstructure, which was created using solid, shell, and frame elements. A comparison between the measured and finite-element response was performed and it was determined that the finite-element model replicated the measured results within 3.5% of the actual values. This model was later used to obtain theoretical live-load distribution factors, which were compared with the AASHTO LRFD Specifications estimations. The analysis was performed for the actual condition of the bridge and the original case of the bridge, which included sidewalks on both sides. The comparison showed that the code over predicted the behavior of the actual structure by 10%. For the original case, the code's estimation differed by as much as 45% of the theoretical values. Another opportunity was presented to test the behavior of a cast-in-place concrete box girder bridge in Joaquin County, CA. The Walnut Grove Bridge was tested by BDI at the request of Utah State University. The test was performed with six different load paths and the recorded data was used to calibrate a finite-element model of the structure. The bridge was modeled using shell elements and the supports were modeled using solid elements. The model was shown to replicate the actual behavior of the bridge to within 3% of the measured values. The calibrated model was then used to calculate the theoretical live-load distribution factors, which allowed a comparison of the results with the AASHTOO LRFD Specifications equations. This analysis was performed for the real conditions of the bridge and a second case where intermediate diaphragms were not included. It was determined that the code's equations estimated the behavior of the interior girder more accurately for the second model (within 10%) than the real model of the bridge (within 20%).

Includes abstract.|Includes bibliographical references.
Participation in social and educational environments is crucial for young people’s development, well-being and opportunities for leading a fulfilling and successful life. Many South African youngsters – and particularly street children – are often excluded from meaningful participation in their communities. This involves participation in social, educational, cultural, political and economic life. The family and the school are two important arenas where such participation can take place. In addition, these youngsters are confronted with unpredictable future life chances. Thus, they often find themselves in a disadvantaged position within society. In light of this observation, the theme of youth at risk has been much discussed in South Africa for the past three decades. This study focuses on a group of especially disadvantaged adolescents, who do not live in safe and nurturing family environments and who are excluded from formal education. I investigate whether ‘theories and practices of education’, featured in non-formal educational interventions, have an impact on the reproduction of disadvantage and risk among its students. My research focuses on the case of Learn to Live, a non-formal educational intervention that tries to counteract the disadvantages that especially disadvantaged youth in Cape Town face.My findings show that educators and students try to find a balance between, on the one hand, emphasising the uniqueness of students’ extremely disadvantaged situation and the need for a particular kind of education that results from it, and on the other hand, the desire to conform to mainstream ideas and mainstream adolescent life. In their attempts to find this balance, nearly all participants acknowledge that Learn to Live is a necessary stepping stone in students’ lives towards success and happiness. The educators believe that the school itself can contribute a lot to the students’ situation and emphasise their role of victims of their circumstances. The students, however, state that Learn to Live is merely there to give them a second chance. They do consider their own role in the schooling process and the path to success to be paramount. This is also reflected quite clearly in the students’ aspirations, their feelings of hope, and their looking to the future. The implications of these findings for Learn to Live include: building on students’ strengths, talents and resiliency by offering them an empowerment-based intervention, creating more opportunities where students can experience feelings of success and pride, and making use of testimonies of successful students.

In this Master's thesis a power line communication is shortly described and the scheme of the communication system is realized. The communication device is called NVMB. This abbreviation means Network Voice Message Box. It should be used for transfer of the voice message via power line. It enables its recording, playback and sending. A process of the scheme design is created, functionality of the device is realized and reviewed in the main part of the Master's thesis. The other chapter of the thesis is devoted to the software communication system.

Debido a la coyuntura actual causada por el COVID-19, surge en el consumidor una tendencia de optar por un estilo de vida más sano generando cambios en muchos aspectos dentro de su rutina habitual. Algunos de los cambios más importantes fueron realizar ejercicios en casa tras las restricciones impuestas por el gobierno y alimentarse de manera saludable dejando de lado aquellos productos que son perjudiciales para la salud. En consideración al aumento de esta tendencia es que se realizó la investigación para brindar un servicio que permita mejorar, promover y mantener un estilo de vida saludable. De esta manera, "Healthy Box" nace siendo una idea de negocio biosaludable y eficaz que busca ser el intermediario para las empresas del sector saludable, ofreciendo un servicio de delivery con variedad de productos, a hombres y mujeres de 18 a 45 años del NSE AB que quieran mantener o deseen iniciar un estilo de vida más saludable. Por otro lado, para comprobar la viabilidad y la intención de adquirir nuestro servicio, se realizaron diferentes experimentos. Después del análisis realizado se obtuvo que, con una inversión total de S/.79,427, en el primer año de operaciones, la utilidad neta será de -S/.29,651.66, para el segundo año de S/.153,989.26 y para el tercer año de S/.166,694.79. Finalmente, la inversión del proyecto puede ser recuperada en el tiempo establecido y se produjo un VAN S/.122,504.55, el cual demuestra la rentabilidad del negocio.
Due to the current situation caused by COVID-19, there is a trend among consumers to opt for a healthier lifestyle, generating changes in many aspects of their daily routine. Some of the most important changes were to exercise at home after the restrictions imposed by the government and to eat in a healthy way, leaving aside those products that are harmful to health. In consideration of the increase of this trend is that the research was conducted to provide a service to improve, promote and maintain a healthy lifestyle. Therefore, "Healthy Box" was born as a bio-healthy and effective business idea that seeks to be the intermediary for companies in the healthy sector, offering a delivery service with a variety of products to men and women from 18 to 45 years of age from the AB socioeconomic level who want to maintain or wish to start a healthier lifestyle. On the other hand, in order to test the feasibility and the intention to acquire our service, different experiments were carried out. The analysis showed that, with a total investment of S/. 79,427, in the first year of operations, the net profit will be -S/.29,651.66, for the second year S/.153,989.26 and for the third year S/.166,694.79. Finally, the project investment can be recovered in the established time and produced an NPV of S/.122,504.55, which demonstrates the profitability of the business.
Trabajo de investigación

Plasmodium falciparum, the deadliest strain of human malaria, affected 200 million people and resulted in several hundred thousand deaths in 2017 (World Health Organization, 2018). A better understanding of the mechanisms of P. falciparum gene regulation can open novel avenues for the development of much needed new drugs. A key step in eukaryotic gene regulation is the process of transcription, which is largely uncharacterized in Plasmodium. Bioinformatic analysis identified putatuve P. falciparum orthologues of RNA polymerase II general transcription factors (Bing, 2014; Milton, 2017), including a TATA box-binding-like protein, PfTLP. Bioinformatic analysis suggested that PfTLP is a TRF2-type TBP-like protein. However, PfTLP differs in several aspects from previously characterized TRF2-type proteins. These differences are thought to be Plasmodium specific adaptations to the parasite’s intricate life cycle and AT-rich genome. This study investigates two Plasmodium-specific features of PfTLP. Firstly, DNA binding by eukaryotic TATA-box binding protein (TBP) is mediated by four evolutionary conserved phenylalanine residues, two of which intercalate into the DNA. These residues are absent in previously characterized TRF2-type TLPs, and consistent with this, these proteins lack detectable DNA binding activity (Duttke et al., 2014). In contrast, PfTLP, a TRF2-type TLP, has DNA binding activity, and all four of the DNA binding phenylalanine residues are conserved (Bing, 2014; Milton, 2017). The importance of evolutionary conserved intercalating phenylalanine residues F60 and F283 was investigated by generating mutant PfTLP proteins, carrying alanine substitutions, and analysing their DNA-binding properties. The results suggest that while both phenylalanine residues are important for PfTLP DNA-binding, only F60 is critical for stabilization of PfTLP/DNA complexes. Secondly, PfTLP possesses two low-complexity or intrinsically disordered regions (LCR1 and 2), which are absent in TLPs from model eukaryotes. These regions are located at the same positions within the two quasi-symmetrical repeats of the TLP core structure and show a non-random compositional bias towards a limited set of amino acids. A growing body of evidence supports the idea that low complexity or intrinsically disordered proteins mediate liquid-liquid phase separation (LLPS) (Alberti et al., 2019; Brangwynne et al., 2009; Elbaum-Garfinkle et al., 2015; Nott et al., 2015). Bioinformatic analysis revealed that PfTLP LCRs are enriched in asparagine and lysine, and that these regions are well conserved throughout Plasmodium TLPs. PfTLP LCRs were fused to fluorescent proteins and the fusion proteins were functionally characterized in liquid-liquid phase separating assays. The results demonstrate that PfTLP LCR1 is capable of mediating LLPS, at least under certain conditions in vitro.

Beskrivning och analys av ett effektiviseringsprojekt på Sanminas fabrik i Örnsköldsvik. Projektet ska effektivisera BoM-hanteringsprocessen primärt genom tre förändringar. 1: Införa en BoM istället för flera. 2: Datorstöd istället för manuell hante-ring. 3: En konform hantering för alla projekt. Analysen av projektet grundas påLean-principer. Centrala begrepp som Lean och BoM beskrivs. En kvalitativ studiegenomförs med en fokusgrupp bestående av komponentingenjörer. Resultatet fråndenna ligger till grund för analysen. Ny metodik tolkas som effektivare än gammalmetodik på alla tre relevanta punkter. Ny metodik löser dock inte alla de bristersom finns i den gamla processen. Detta då de verktyg avsedda för interna processerinte har större inverkan på externa problem. Förändringarna tolkas som ett steg moten mer Lean BoM-hanteringsprocess. Fullständig analys kommer kunna genomförasnär ny metodik är implementerad. Diskussion kring tolkning av data och osäkerhet i analys av densamma. Detta då datan är kvalitativ.

The present thesis aims to develop an analogy between the methods for recognizing a black box group and the classification of the finite simple groups. We propose a uniform approach for recognizing simple groups of Lie type which can be viewed as the computational version of the classification of the finite simple groups. Similar to the inductive argument on centralizers of involutions which plays a crucial role in the classification project, our approach is based on a recursive construction of the centralizers of involutions in black box groups. We present an algorithm which constructs a long root SL_2(q)-subgroup in a finite simple group of Lie type of odd characteristic $p$ extended possibly by a p-group. Following this construction, we take the Aschbacher'
s ``Classical Involution Theorem'
'
as a model in the final recognition algorithm and we propose an algorithm which constructs all root SL_2(q)-subgroups corresponding to the nodes in the extended Dynkin diagram, that is, our approach is the construction of the the extended Curtis - Phan - Tits presentation of the finite simple groups of Lie type of odd characteristic which further yields the construction of all subsystem subgroups which can be read from the extended Dynkin diagram. In this thesis, we present this algorithm for the groups PSL_n(q) and PSU_n(q). We also present an algorithm which determines whether the p-core (or ``unipotent radical'
'
) O_p(G) of a black box group G is trivial or not where G/O_p(G) is a finite simple classical group of Lie type of odd characteristic p answering a well-known question of Babai and Shalev. The algorithms presented in this thesis have been implemented extensively in the computer algebra system GAP.

All kinds of products have economic, social and environmental impact throughout their entire life cycle. Today’s growing need for electronic devices contributes to the increasing problem within these fields.  The aim of this study is to investigate and determine the impact of a chosen Teracom Group product from a sustainability perspective and to develop recommendations regarding how to proceed, in order to reduce the impact of products. This study is mainly focusing on the environmental aspect of the concept of sustainability. A life cycle assessment (LCA) of a set-top box (STB) is conducted based on chosen indicators by using the software SimaPro. The goal of the assessment is to identify the phases within the life cycle with largest environmental impact and contribute to Teracom Group’s further sustainable work. 18 impact categories are included to express emissions and use of natural resources. The result clearly shows that the production phase has the largest environmental impact within categories such as terrestrial acidification, human toxicity, freshwater ecotoxicity, marine ecotoxicity, urban land occupation and metal resource depletion. The use phase affects the environment foremost within climate change, ozone depletion, terrestrial ecotoxicity, ionising radiation, agricultural land use, natural land transformation and water depletion. Transports and the waste scenario only have a small effect on certain categories. The experiences of this study are discussed, demonstrating the difficulty in making an LCA in the position of being at the company purchasing products, not at the company manufacturing them. The company has previously not focused enough on sustainability regarding products. An LCA performed by the supplier would be more reliable due to a better possibility of collecting accurate data. Communication and cooperation between the company and its suppliers are key solutions. Higher requirements during procurement should be put on the products, including demands on performed LCAs with clearly described references and methods, critically review by a third party.

Hepatocellular carcinoma (HCC)is one of the commonly diagnosed cancers in the world. Most patients have poor prognosis due to late detection of disease. Ankyrin repeat and suppressor of cytokine signaling box protein 4(ASB4), as a member of the ASB family, possesses two domains, ankyrin repeat (AR) and suppressor of cytokine signaling (SOCS)box, which are responsible for recruiting the target proteins for proteasomal degradation. Previous study has demonstrated high expression level of ASB4 in metastatic HCC cells, implicating the properties of ASB4 in cancer invasiveness. With this hypothesis, various experiments were performed in this research project to elucidate the functional roles of ASB4 in HCC cells. The aim of this study is to characterize the roles of ASB4 in HCC by manipulating its expression level in HCC cell lines through gene knockdown and over-expression. Altering the level of ASB4 in HCC cells resulted in no significant effects on the cell proliferation rates. However, ASB4 was demonstrated to promote migration and invasion properties of HCC cells, as suppression of its level led to slower migration and made cells less invasive. Opposite effects on cell migration and invasion were observed when ASB4 was ectopically expressed. Regarding the regulatory mechanism of ASB4, miR-200a was demonstrated to be a negative regulator for ASB4. In summary, ASB4 is probably involved in the migration and invasion properties of HCC cells, and also, being regulated by miR-200a.
published_or_final_version
Surgery
Master
Master of Philosophy

Thesis (M.S. in Mechanical Engineering) Naval Postgraduate School, September 1998.
"September 1998." Thesis advisor(s): Young S. Shin. Includes bibliographical references (p. 115-116). Also Available online.

Die rasionaal vir onderhawige studie was aan die hand van narratiewe navorsingsmetodes om insig en begrip te verwerf oor wat dit beteken om die moeder te wees van 'n seun met outisme. Ek (navorser) en die moeder (deelnemer) het verskeie data-inwinning-aktiwiteite aangewend, byvoorbeeld haar lewensverhaal, waarin ek en die moeder emosionele intelligensie komponente geïdentifiseer het met die verdere doel om haar belewinge van outisme te interpreteer. 'n Narratiewe navorsing-ontwerp, wat gebaseer is op interpretavistiese en konstruktivistiese paradigmata, kan dus die betekenisvolle emosies en ander belewinge van die moeder akkuraat interpreteer en kommunikeer oor wat dit beteken om 'n moeder te wees van 'n seun met outisme. In hierdie studie maak ek as navorser gebruik van 'n kwalitatiewe navorsingsbenadering met 'n narratiewe navorsings-ontwerp, waarin 'n multimetode benadering tot data-insameling aangewend word, met die doel om die belewinge van die moeder in die vorm van 'n lewensverhaal saam te vat. Die data-inwinning-strategieë wat aangewend is het gepoog om in-diepte, ryk en persoonlike verhaal-inhoude te genereer. Die volgende aktiwiteite is gebruik : 'n informele onderhoud, herinneringsboek (collages, staaltjies, lewenslyn en metafore), en 'n intellektuele bespreking van emosionele intelligensie. Die moeder het kollaboratief deelgeneem tydens die identifisering van emosionele intelligensie komponente in haar lewensverhaal. Dit was belangrik om deurlopend kollaboratiewe besprekinge met die moeder te skeduleer, aangesien haar insae met betrekking tot die wyse waarop die data georganiseer, geanaliseer en geïnterpreteer word verband hou met haar interpretasies van outisme en die verkenning van haar belewinge aan die hand van Bar-On (2003) se emosionele intelligensie komponente. Die betekenisvolle belewinge wat op grond van die moeder se verhaal-inhoude, in samehang met haar geïdentifiseerde emosionele intelligensie komponente, bespreek word, dui daarop dat die moeder 'n optimistiese, realistiese en intro-spektiewe uitkyk het met betrekking tot ouerskap en opvoeding. Dit kan as verantwoordbaar beskou word as ek as navorser dit stel dat die moeder begrip en insig demonstreer ten opsigte van die hindernis waarmee haar seun leef. Die moeder som haar belewing van outisme die beste op met die inspirerende aanhaling van Emily Pearl Kingsley: “Say goodbye to the child you wanted, or else your focus will never be with the child you have.”
ENGLISH : The rationale for this study was to gain a better understanding of what it means to be the mother of a child with autism, through the use of narrative research accounts. The mother (participant), and I (researcher) furthermore utilized the sources of collected data, such as her life story, to identify components of emotional intelligence with the purpose of additional interpretation. A narrative research design, firmly rooted in an interpretivist and constructivist paradigm, should therefore serve to accurately interpret the significant emotions and other lived-experiences that a mother attaches to living with a child that has been diagnosed with autism. A multi-method approach, directed by a qualitative research approach and a narrative research design, was followed in an attempt to capture the mother‘s experiences and life story. Data collection strategies employed to generate an in-depth, rich and personal life story consisted of the following activities: an informal interview, memory box (collages, anecdotes, life line, and methaphors) and an intellectual discussion regarding emotional intelligence. The mother also participated in a collaborative discussion to identify emotional intelligence components relevant to her life story. Further collaboration and discussion with the mother were required to ensure that the data were organised, analysed and interpreted according to the mother‘s lived-experiences of autism, along with her emotions that were identified on the basis of Bar-On‘s (2003) emotional intelligence components. The meaningful findings drawn from the mother‘s narratives (in relation to the identified emotional intelligence components) suggest that the mother demonstrates an optmistic, realistic and introspective view on parenting. It can be regarded as accountable for me as researcher to state that the mother displays an educated an comprehensive understanding of the disability with which her child is living. The mother perhaps best summarises her experiences of autism in the words of Emily Pearl Kingsley‘s inspirational words: “Say goodbye to the child you wanted, or else your focus will never be with the child you have.”
Dissertation (MEd)--University of Pretoria, 2010.
Educational Psychology
Unrestricted

Box turtle (Terrapene carolina) populations have been declining over the last several decades, and one major cause is increasing urbanization. As a result of habitat fragmentation, wildlife managers are frequently turning to new and alternative management strategies. Traditional box turtle management has included relocation, which has been met with limited success. This study aims to combine these strategies with another less-studied one: forcing turtles to overwinter on site by penning them in an outdoor enclosure. Two sets of juvenile box turtles were released at the Virginia Commonwealth University Rice Center: one penned on site in a pen for one year, the other allowed to move freely. Our objective was to compare a variety of factors between these two groups to see if penning was as effective as traditional approaches. Movement and location patterns were tracked using radio transmitters for two years and analyzed using GPS technology. Body condition and health status of all turtles were measured and compared over time as well. Finally, a life history model was developed to determine the effectiveness of management programs. While the penning treatment significantly reduced activity areas, it appears that all juvenile turtles had high site fidelity (87.5%) regardless of treatment. The eastern box turtle seems to be a prime candidate for penning used in conjunction with other management options.

Background and objectives: Nonalcoholic steatohepatitis (NASH), which is characterized by concurrent existence of hepatic steatosis and predominantly lobular necroinflammation, represents the more advanced stage in the spectrum of nonalcoholic fatty liver disease (NAFLD). NASH exhibits dramatically increased risk of progression to end-stage liver diseases than simple steatosis. Therefore, the progression of hepatic steatosis to steatohepatitis is the crucial step in the development of obesity-related NASH. Toll like receptor 4 (TLR4), a master regulator of innate immunity, is the principal receptor for endotoxin, which is a central mediator of liver inflammation associated with both alcoholic and nonalcoholic liver disease. However, due to a lack of suitable animal models which fully recapitulate the natural history of obesity-induced NASH, the precise pathophysiological function of TLR4 signaling in the development of this disease remains poorly understood. The objective of this study is to investigate the role of TLR4 in mediating inflammatory responses in obesity-induced NASH using both in vivo and ex vivo approaches, and to unveil cellular and molecular mechanisms responsible for TLR4 actions. Key findings: 1. To address the role of TLR4 in the pathogenesis of NASH, we crossed ApoEdeficient mice (ApoE-/-) with TLR4 mutant mice (TLR4-/-) to generate ApoE-/- /TLR4 wild type mice (ApoE-/-/TLR4-WT) and ApoE-/-/TLR4-/- mice. Noticeably, when fed with high fat high cholesterol (HFHC) diet, ApoE-/-/TLR4-WT mice developed the typical pathology of NASH (hepatic steatosis, lobular inflammation, and hepatocyte ballooning) in the context of obesity and metabolic syndrome, suggesting HFHC-fed ApoE-/- mice as a suitable animal model for NASH. 2. TLR4 inactivation protected ApoE-/- mice against HFHC diet-induced liver injury, as indicated by a significant improvement in liver histology, a a marked reduction in serum ALT activity, a dramatic repression of inflammatory infiltrates, as well as an obvious decrease in hepatic production of pro-inflammatory cytokines. 3. In ApoE-/-/TLR4-WT mice, TLR4 expression was selectively elevated in Kupffer cells in response to HFHC diet feeding. 4. The activation of XBP1, a transcription factor involved in endoplasmic reticulum stress, was markedly elevated in liver of ApoE-/-/TLR4-WT mice fed with HFHC diet, whereas this change was abrogated in HFHC diet-fed ApoE-/-/TLR4-/- mice. 5. In rat primary Kupffer cells, treatment with anti-oxidants blocked endotoxininduced activation of XBP1 and NF-κB, leading to decreased cytokine production. In addition, siRNA-mediated knockdown of XBP1 inhibited NF-κB activation and cytokine production resulted from the treatment with the TLR4 agonist LPS. 6. In ApoE-/-/TLR4-WT mice, adenovirus-mediated expression of dominant negative XBP1 had no obvious effect on HFHC diet-induced hepatic steatosis and ROS production, but markedly decreased lobular inflammation, NF-κB activation, cytokine production in the liver and significantly reduced serum levels of ALT. Conclusions: These findings support the role of TLR4 in Kupffer cells as a key player in mediating the progression of simple steatosis to NASH, by inducing ROS-dependent activation of XBP1. In light of the obligatory role of XBP1 in TLR4-induced liver inflammation and injury, therapeutic interventions that inhibit TLR4/XBP1 activation may represent a promising strategy for treatment of NASH.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy

BOD (Biochemical Oxygen Demand) is one of the important parameters in wastewater treatment technology,  it normally takes five days to get the result. Using MFC (Microbial Fuel Cell) to build up a small on-line system to measure BOD will reduce to operating time to 20 minutes. In this report, the MFC BOD on-line measurement was processed in order to test if this rapid way would work in practical usage. The experiment used secondary sedimentation sludge as the bacteria source on the MFC anode pattern with GGA (Glucose and Glutamic Acid solution) as an electron producer, and the 30 minutes voltage value changing curves was gotten by measuring the voltage. At the end the curve was analyzed and compared with the real BOD value in order to get the conclusion. The BOD on-line measurement is quite promising and efficient when multi-samples are needed to be tested.

Splicing of mRNA precursors (pre-mRNA) comprises a series of ATP-dependent steps, the first of which is the stable binding of U2 snRNP at the pre-mRNA branchpoint. The basis of ATP use in splicing is not well understood. Several yeast splicing factors belong to DEAD/H box family of RNA-dependent ATPase, and are implicated in dynamic RNA structure rearrangement during spliceosome assembly. In mammals, however, such information is conspicuously lacking. In fact, none of the known mammalian splicing factors has characteristics for ATP hydrolysis. In an attempt to identify mammalian splicing factors involved in ATP usage, we have developed a novel approach to identify and purify spliceosomal ATP binding proteins. Six spliceosomal ATP binding proteins were found, one of them, SAFp56, was purified and microsequenced, and found to be a DEAD box protein containing unique DECD motif instead of the canonical DEAD motif. During the course of this work, a new functional region in U2AF65, an essential splicing factor required for U2 snRNP entry into the spliceosome, was defined. This information was used to clone a human U2AF65 associated protein (UAP). UAP and SAFp56 are identical. We refer to this protein as hUAP56 (human 56 kDa U2AF65 associated protein). We present evidence that hUAP56 is an essential splicing factor required for the U2 snRNP binding to pre-mRNA. Interestingly, UAP56 is recruited to pre-mRNA in a polypyrimidine tract bound U2AF65-dependent fashion. This result underscores a new function of U2AF65, and provides the first description of how a specific DEAD box protein is directed to a pre-mRNA splicing signal, and/or, to the proximity of its substrate at a particular stage. Like an authentic DEAD box protein. hUAP56 has ATP binding, RNA-stimulated ATPase, as well as RNA binding activity. A particularly novel result is that the ATPase activity of UAP56 is stimulated by U2AF65. This observation strongly suggests the role of UAP56 in ATP dependent mechanism during U2 snRNP binding to the pre-mRNA branchpoint, and implies that UAP56 may function through a distinct mechanism. We identify yeast UAP (yUAP), a highly conserved S. cerevisiae homologue of hUAP56. yUAP is essential for viability, can be functionally substituted for by hUAP56, and like its human counterpart, is an essential pre-mRNA splicing factor required for spliceosome assembly. Furthermore, we show that yUAP is required for formation of the branchpoint dependent commitment complex, the precursor for U2 snRNP addition. Site-directed mutagenesis revealed that all DEAD box protein consensus motifs are required for yUAP function. Interestingly, a strain harboring a yUAP mutant in which the DECD sequence, characteristic of UAP members, was changed to canonical sequence, is inviable. Our results demonstrate that UAP is structurally and functionally conserved from yeast to man. In conjunction with previous studies, we conclude that at least two DEAD box proteins, Prp5p and yUAP, are required for the U2 snRNP-branchpoint interaction.

Dans les neuroblastomes, le gène N-MYC est amplifié dans 20-25 % des cas,associé à un mauvais pronostic. Au laboratoire, nous avions préalablement montré que la dérégulation de l'expression du gène TWIST1 était corrélée à celle de N-MYC dans les neuroblastomes agressifs de stade IV avec une amplification de N-MYC (Valsesia-Wittmann et al., 2004). Au cours de ma thèse, j'ai pu mettre en évidence que les gènes TWIST1 et TWIST2 étaient régulés positivement ou négativement de façon dose dépendante par les oncoprotéines Myc. De façon intéressante, le maintien de l'expression de TWIST1 est dépendant de l'expression des protéines Myc. Ces résultats suggèrent que la dérégulation et l'amplification des oncoprotéines Myc dans les neuroblastomes N-MYC Amplifiés pourraient permettre l'induction sélective et le maintien de l'expression de l'oncogène TWIST, agissant comme facteur de survie.

Denna studie belyser svårigheten för teknik och virtuell geografi att nå ut till mottagaren genom en kartläggning av e-postens geografi. För att skapa förståelse och fånga den osynliga processen bakom e-postens geografi  utgår uppsatsen dels från teorin Actor Network Theory (ANT) och dels från intervjuer.Under studiens gång uppstod ny förståelse för e-postens komplexitet och ledde fram till en reviderad syn. I början av uppsatsarbetet betraktades e-posten enbart utifrån sin funktion som aktant och intermediarie men i takt med att undersökningen fortgick framkom att den samtidigt, utöver dessa funktioner, fungerar e-posten som ett heterogent nätverk med betydelsefulla komponenter såsom aktörer och aktanter. Enligt uppsatsens konklusioner är e-postens trajektoria beroende av den strategi som producenten använder under skapandet av elektroniska meddelanden. Ett kontinuerligt arbete mellan producent och konsument krävs för att e-postens trajektoria ska upprätthållas och leda fram till att det elektroniska meddelande som löper igenom det virtuella nätverket når sitt syfte.

We summarize Chandra observations of the emission line profiles from 17 OB stars. The lines tend to be broad and unshifted. The forbidden/intercombination line ratios arising from Helium-like ions provide radial distance information for the X-ray emission sources, while the H-like to He-like line ratios provide X-ray temperatures, and thus also source temperature versus radius distributions. OB stars usually show power law differential emission measure distributions versus temperature. In models of bow shocks, we find a power law differential emission measure, a wide range of ion stages, and the bow shock flow around the clumps provides transverse velocities comparable to HWHM values. We find that the bow shock results for the line profile properties, consistent with the observations of X-ray line emission for a broad range of OB star properties.

As áreas de livre comércio – ALC – são zonas de benefícios tributários cujo principal objetivo é a promoção do desenvolvimento de regiões mais carentes. A área de livre comércio de Boa Vista, juntamente com a de Bonfim, foi a última a ser implantada, no ano de 2008, e seus impactos são analisados por meio de questionário aplicado a empresas de Boa Vista, com o objetivo de compreender seu grau de satisfação, os entraves e perspectivas da ALC-BV. Para tanto, foram entrevistadas 53 empresas, que representam 3,22% do universo de empresas de Boa Vista cadastradas e habilitadas na SUFRAMA, situação necessária para que as empresas tenham acesso aos benefícios da ALC. A análise da amostra apresenta que 69,81% dos entrevistados afirmam ter benefícios da ALC para sua empresa. Desses, a avaliação acerca dos incentivos mais significativos para a empresa, em ordem decrescente foi: PIS/COFINS, ICMS, IPI e Imposto de Importação. Dentre os principais entraves, os entrevistados destacaram: poucos incentivos da prefeitura e do governo; custo de transporte elevado; escassez de mão de obra especializada; ausência de porto alfandegado, dificuldade de desembaraço da fronteira com o estado do Amazonas, dentre outros. Acerca do grau de satisfação, a maioria indicou Média Satisfação (39,62%). Apesar disso, uma quantidade significativa dos entrevistados (28,30%) afirmou não ter obtido qualquer redução de preços dos produtos adquiridos. A resposta seguinte mais selecionada foi a de que os preços dos produtos adquiridos reduziram de 10,01 a 15% (26,42% das respostas). A pesquisa também indicou que grande parcela dos empresários não conhece os benéficos da ALC voltados à importação (45,28%) e desconhece benefícios a indústria (83,02%). Haja vista a perspectiva de crescimento e desenvolvimento, esses conceitos, bem como aspectos sobre impactos de desoneração fiscal, desigualdade regional no processo de desenvolvimento e dos ganhos do comércio internacional, dentre outros, são abordados nesse estudo.
The free trade areas are tax benefits institutes whose main objective is to promote the poor regions‟ development. The free trade area of Boa Vista, along with the Bonfim‟s, was the last to be deployed, in 2008, and its impacts are assessed through a questionnaire applied to companies of Boa Vista, in order to understand the satisfaction degree of businesses, barriers and perspectives of ALC of Boa Vista. For these reasons, we interviewed 53 companies, which represent 3.22% of the universe of companies registered and entitled Boa Vista in SUFRAMA, a situation necessary for companies to have access to the benefits of the ALC. The sample analysis shows that 69.81% of respondents say that their companies do have ALC‟s benefits. From this number, the assessment about the most significant incentives for the company, in descending order was: PIS/COFINS, ICMS, IPI and Import Tax. Among the main obstacles, respondents highlighted: few incentives for municipal and government; high shipping cost, shortage of skilled labor, lack of bonded port, difficulty in clearing the border with the state of Amazonas, among others. About the degree of satisfaction, the majority indicated satisfaction Average (39.62%). Nevertheless, most respondents (28.30%) said they had not obtained any reduction in prices of products purchased. The next most selected response was that the prices of purchased products reduced from 10.01 to 15% (26.42% of responses). The survey also indicated that a significant number of entrepreneurs do not know the benefits of targeted ALC imports (45.28%) and unknown benefits to industry (83.02%). Taking into account the perspective of growth and development, these concepts, as well as aspects of impacts of tax relief, regional disparities in development and the gains from international trade, among others, are addressed in this study.

L'objectif de mon travail de thèse a consisté à étudier la fonction chez le riz d'une famille de facteurs de transcription de type MADS box (OsMADS23, OsMADS25, OsMADS27, OsMADS57 et OsMADS61) homologues au clade AGL17-like d'Arabidopsis thaliana dans le développement du riz. Dans un premier temps, nous avons recherché les profils d'expression des différents gènes étudiés. Nous avons pu mettre en évidence que les gènes OsMADS23, OsMADS25 et OsMADS27 sont des gènes principalement exprimés dans la racine au niveau du cylindre central, OsMADS57 dans les parties aériennes et OsMADS61 au niveau des bases de tige. Nous avons pu également montrer que l'expression de ces gènes est différente en réponse aux stress salin et osmotique, aux hormones et au nitrate. Ceci suggère que ces gènes possèdent des fonctions distinctes et non redondantes.Mon travail s'est ensuite focalisé sur l'étude fonctionnelle du gène OsMADS25 dont l'expression est spécifiquement détectée dans le cylindre central des racines. Le mutant d'insertion Osmads25 présente un phénotype aérien caractérisé par une réduction drastique du nombre de talles, et un phénotype racinaire caractérisé par une diminution importante du nombre de racines adventives. Ce phénotype a pu être mimé par la création de lignées transgéniques sur-exprimant l'ADNc de OsMADS25 en fusion avec le motif dominant-répresseur de la transcription « EAR ». Ces résultats ainsi que la complémentation du mutant Osmads25 par surexpression de l'ADNc correspondant montre que OsMADS25 agit en tant qu'activateur est un régulateur positif du développement des méristèmes axillaires et de racines adventives chez le riz, agissant probablement des racines aux bases de tiges via une voie de signalisation systémique. Des études complémentaires de phénotypage du mutant au niveau histologique sont en cours afin de préciser le rôle joué par OsMADS25 sur l'initiation ou le développement des méristèmes axillaires. Des analyses de qRT-PCR dans les fonds mutant et sauvage ont montré que ce gène est impliqué dans le développement du riz via une voie de signalisation indépendante des strigolactones. En revanche, l'expression de facteurs de transcription comme OsNAC2 et MOC1, connus pour être impliqués dans le développement des talles ou de CRL1, un régulateur de l'initiation des primordia de racines adventives est atténuée chez les mutant Osmads25 suggérant qu'OsMADS25 pourrait, au moins en partie, directement ou indirectement réguler l'expression de ces gènes. Enfin, des analyses de transcriptome différentiel entre Osmads25 et le fond sauvage ont révélé l'inhibition de l'expression chez le mutant de 60 gènes dont neuf ont une fonction relative à des mécanismes de sécrétion, de transport d'auxine, ou de développement. De manière intéressante, l'un d'entre eux RCN4/Oscen4, appartient à une famille de protéines mobiles connues pour réguler l'activité des méristèmes et qui pourrait constituer un relais moléculaire systémique entre les racines et les bases de tiges permettant d'expliquer le phénotype contrôlé par OsMADS25
The aim of this work was to study AGL17-like clade MADS box transcription factors (OsMADS23, OsMADS25, OsMADS27 and OsMADS61) in rice development. First, we analyzed expression patterns of the different genes. We showed that OsMADS23, OsMADS25 and OsMADS27 are mainly expressed in the central cylinder of roots; OsMADS57 in aerial parts and OsMADS61 in stem base. Then, we showed that all these have a different response to osmotic and salt stresses, nitrate and hormone. This suggests that these genes have distinct and no redundant functions. My work focused on functional characterization of OsMADS25 which is specifically expressed in root stele. T-DNA mutant Osmads25 presents aerial phenotype characterized by drastic reduction of culm number; and also a root phenotype characterized by a strong decrease of adventitious root number. This phenotype was mimicked by the creation of transgenic lines overexpressing cDNA OsMADS25 in fusion with the “EAR” motif, which acts as a dominant repressor of transcription. These results added to mutant complementation by overexpression of corresponding cDNA show that OsMADS25 acts as an positive regulator of axillary meristem and nodal root development in rice; acting probably from root to stem base via a systemic pathway. Complementary studies as regards mutant microscopic phenotyping are in progress to precise the role acting by OsMADS25 on initiation or development of axillary buds. RT-qPCR analyses showed that this gene is involved in rice development by an strigolactones-independent pathway. On the other hand, expression if transcription factors as OsNAC2 and OsMOC1, known to be involved in tiller development, or as CRL1, regulator of adventitious root primordia initiation, are decreased in Osmads25; suggesting that OsMADS25 could directly or indirectly regulate expression of these genes. Eventually transcriptomic analyses between Osmads25 and WT revealed inhibition of expression of 60 genes which 9 have relative function to secretion mechanism, auxin transport or development. Interestingly, one of its, RCN4/Oscen4 belonging to mobile protein family known to regulate meristem activity and which could constitute a systemic molecular intermediary between root and stem base allowing to explain the controlled phenotype by OsMADS25

La Dystrophie Myotonique de type 1 (DM1) est cause par l'expansion anormale d'un triplet CTG dans la partie 3'UTR du gène DMPK, entrainant l'agrégation du transcrit mutant dans des inclusions ribonucléoprotéiques appelées foci. D'après plusieurs études structurales sur des courtes répétitions CUG, il a été proposé que les expansions CUG se replient en une structure en tige-boucle qui interfère avec l'activité de plusieurs facteurs lié au métabolisme de l'ARN et altère leur fonction cellulaire. Le facteur d'épissage muscleblind-like 1 (MBNL1) a été identifié par sa capacité à interagir avec les répétitions CUG. In vivo, ces répétitions entrainent la séquestration de cette protéine aboutissant en une déplétion nucléaire. Un autre facteur d'épissage, la CUG Binding protein (CUGBP1), est également impliqué dans la pathologie. Au lieu d'être séquestré par les répétitions, la stabilité protéique de CUGBP1 est augmentée dans les tissus DM1 entrainant un gain d'activité pour ce facteur. La séquestration de MBNL1 et la stabilisation de CUGBP1 résultent en la dérégulation de l'épissage alternatif de plusieurs transcrits musculaires et du cerveau et la réexpression d'isoformes protéiques fœtales dans les tissus adultes. Cependant, de récentes études suggèrent que d'autres facteurs ou voies de signalisation que celles faisant intervenir MBNL1 et CUGBP1 pourraient être impliquées dans la pathologie DM1.Le but de mon travail de thèse a été d'identifier de nouveaux facteurs ayant la capacité d'interagir avec les répétitions CUG. A l'aide d'une purification sur chromatographie d'affinité utilisant un ARN contenant 95 répétitions CUG comme appât, nous avons identifié l'ARN hélicase p68/DDX5. p68 fait partie de la famille des protéines DEAD-box, caractérisée par un core protéique conservé constitué de neufs domaines hautement conservés, dont le motif DEAD, à l'origine du nom de ces protéines. p68 est impliquée dans de nombreux aspects du métabolisme de l'ARN, dont la transcription, l'épissage, l'export, la traduction et la dégradation des ARN. Nous avons montré, que p68 colocalise avec les foci CUG dans un modèle cellulaire exprimant la partie 3'UTR du gène DMPK contenant de longues répétitions CTG. Nous avons identifié que p68 augmente l'interaction de MBNL1 sur les répétitions CUG et une structure secondaire particulière d'un élément régulateur de l'ARN pré-messager cardiac Troponin T (TNNT2), dont l'épissage est dérégulé dans la pathologie. L'insertion de mutations dans le core de l'hélicase de p68 abolit l'effet de p68 sur la fixation de MBNL1 ainsi que la colocalisation de p68 avec les expansions CUG in vivo, suggérant que le remodelage des structures secondaires ARN de manière ATP-dépendante par p68 facilite l'interaction de MBNL1. Nous trouvons également que la compétence de p68 pour réguler l'inclusion de l'exon alternatif 5 de TNNT2 dépend de l'intégrité des sites de fixation de MBNL1.Nous proposons que p68 agit comme un modificateur de l'activité de MBNL1 sur ces cibles d'épissage ainsi que sur les expansions CUG à l'origine de la pathologie.

The Eastern box turtle (Terrapene carolina carolina) is one of the most common reptiles in North America, but is soon to be threatened due to increased urbanization, disease, and the pet and food trades. In order to assist resource managers in choosing suitable sites for relocation studies, more information on the winter ecology of this species is necessary. We examined the temperature tolerance, microhabitat and degree of philopatry to hibernacula for juvenile and adult E. box turtles for two consecutive winters in Charles City Co, VA. The turtles were tracked via radio telemetry to record point locations during the active and inactive seasons. iButton data loggers were attached to each turtle to record temperature throughout winter. Vegetation data were collected and analyzed to determine if there are microhabitat differences between adult and juvenile turtles, and between occupied and random plots. Philopatry to wintering hibernacula was determined by measurements in the field and using ArcGIS. Adults had significantly higher minimum temperatures than juveniles during the first winter (P=0.027), but not during the second winter (P=0.327). Shrub and canopy cover were marginally higher for random plots than for occupied turtle hibernacula plots (P=0.066 and P=0.092, respectively); however there were no significant differences for any of the vegetation variables between adults and juveniles. Some of the turtles demonstrated site fidelity of their hibernacula. The temperature data from this study suggests that juveniles may have poorer hibernacula selection and therefore lower minimum temperatures compared with adults, but this was not seen in our second season suggesting that juvenile turtles may learn to choose better hibernacula or to dig deeper. The difference in findings for the two winters could be attributed to illness by several of the turtles the first winter, by increased maturity in the juveniles the second winter or by the significant difference in ambient temperature for the two winters (P=0.0001). Juveniles do not differ from adults in microhabitat selection, therefore resource managers may not need to plan differently for juveniles and adults in relocation studies. We also conclude that both age groups of T. c. carolina exhibit site fidelity of hibernacula.

Flavonoids are plant secondary metabolites that play diverse roles in plants and human health. These compounds in most part exist in the glucosylated form. Grapefruit accumulates high levels of glucosylated flavonoids. Plant secondary product glucosyltransferases (GTs) catalyze the glucosylation reaction, but due to low homology at both the nucleotide and amino acid sequence level of different GTs, it is not possible to ascribe function based on sequence only. The hypotheses that PGT clones 9 and 11 are plant secondary product GTs and are biochemically regulated were tested. PGT 9 has been cloned into Pichia pastoris using the pPICZA and pPICZAα vectors, expressed, enriched, and screened for GT activity with a variety of phenolic substrates. Initial screens show catechol, gentisic acid, vanillin, and p-hydroxylphenylacetic acid as potential substrates for the PGT 9 protein. PGT 11 has been successfully cloned into pPICZA for transformation into yeast, expression, and subsequent characterization.

We all want to live in a healthy community. Each of us has his or her own image of what such a community should look like. That image is shaped, in part, by our reaction to the communities in which we now live or used to live. However we often take for granted the elements of communities that enable and sometimes disable many of us to remain active in a community for a lifetime. For older residents, a lifelong community would include elements that help them to maintain independence and quality of life. The physical characteristics of a community often play a major role in facilitating our personal independence. In order to combat the growing challenges and health concerns facing the American lifestyle this research proposes a set of design guidelines that promote sustainable lifelong communities that are universally designed for people of all ages and levels of physical ability. The purpose of developing a set of universal design guidelines for lifelong communities is to alleviate many of the physical barriers and challenges that prevent some Americans from active involvement in the community. The methods employed to develop these guidelines were based on literature review and analysis. This research was incorporated into a new body of practical standards that was tested against a real life community in Decatur, Georgia. These standards were edited and revised to appropriately accommodate the necessary adaptations that were discovered during the evaluation phase. The resultant guidelines are presented with the intention of becoming a usable guide for planning agencies such as the Atlanta Regional Commission and other local and national community design facilitators.

Neste trabalho classificamos, a menos de isomorfismos, as álgebras de Bol de dimensão 2 sobre um corpo de característica 0. Também determinamos suas álgebras de Lie envolvente e, mostramos que existem álgebras de Bol não isomorfas cujas álgebras de Lie envolventes coorrespondentes são isomorfas. Calculamos os grupos algébricos (locais) correspondentes a cada uma das álgebras de Lie envolventes e provamos que todo loop de Bol analítico (algébrico) global de dimensão 2 sobre um corpo de característica 0 é um grupo. Exibimos exemplos de loops de Bol algébricos globais de dimensão n, para todo n > 2, e fornecemos uma condição necessária e suciente para a existência de um loop de Bol algébrico global quando a álgebra de Bol tem uma álgebra de Lie envolvente nilpotente de índice 2 sobre um corpo de característica diferente de 2.
In this work, we classify up to isomorphism, the Bol algebras of dimension 2 over a eld of characteristic 0. We also determine their enveloping Lie algebras and we exhibit two non-isomorphic Bol algebras which have isomorphic enveloping Lie algebras. We determine the (local) correspondent algebraic groups of each of those enveloping Lie algebras and we show that every global analytic (algebraic) Bol loop of dimension 2 over a eld of characteristic 0 is a group. We exhibit examples of non-nilpotent solvable algebraic Bol loops in dimension n for every n > 2, and we were able to give a necessary and sucient condition to decide if a local algebraic Bol loop is global when its enveloping Lie algebra is nilpotent of index 2 and char(F) 6= 2:

O objetivo deste estudo foi avaliar a dinâmica folicular ovariana, a concentração circulante de progesterona (P4) e a expressão hepática de genes (AKR1C4, AKR1D1, CYP3A4, CYP2C19, SRD5A1, SRD5A3) relacionados ao metabolismo de P4 durante protocolo de sincronização para IATF em novilhas Nelore (n = 16) e Holandesas (n = 16) submetidas a alto (ACMS) e baixo (BCMS) consumo de matéria seca/energia de acordo com o (NRC, 2001). O experimento foi realizado em arranjo fatorial 2 x 2 e delineamento cross-over. A dieta experimental foi fornecida por um período de 34 dias. Os animais foram pré-sincronizados com duas aplicações de cloprostenol sódico (500 µg,i.m. PGF2α, Sincrocio®, Ourofino Agronegócio), com intervalo de 12 dias (D -24 e D-12). Duas doses adicionais de PGF2α (18 e 12 h) foram administradas antes da inserção do dispositivo (D0). No D0, os animais receberam um dispositivo intravaginal de P4 (CIDR®, Zoetis, Brasil), 2 mg i.m. de benzoato de estradiol (BE, Sincrodiol®, Ourofino Agronegócio) e mais uma dose de PGF2α. Após 8 dias, o dispositivo de P4 foi retirado e 24 h após foi administrado i.m. 1 mg de BE. Foram realizados exames ultrassonográficos a cada 24h durante o período de permanência do dispositivo de P4, a cada 12h da retirada do dispositivo até a ovulação, e no D14 e D17 para mensurar o volume do corpo lúteo (CL). Foram realizadas coletas de sangue diárias do D0 ao D10. Uma única réplica foi realizada para biópsia hepática, que foi feita 48 h após a inserção de dispositivo de P4 (D2). Para os dados de dinâmica folicular e concentrações hormonais, os resultados foram analisados pelo PROC MIXED, e para os dados de expressão gênica pelo PROC GLIMMIX do SAS 9.3, e apresentados como média ± EPM. O número de folículos recrutados foi maior em novilhas Nelore que Holandesas (42,1 ± 3,4 vs. 23,5 ± 3,3, P < 0,001). Entretanto, não se verificou efeito da dieta no número de folículos recrutados (ACMS = 33,7 ± 3,3 vs. BCMS = 31,9 ± 3,3; P = 0,62). O diâmetro máximo do folículo dominante (mm) foi maior em novilhas Holandesas que novilhas Nelore (14,5 ± 0,4 vs. 13,0 ± 0,4, P = 0,009); e em animais com ACMS, que com BCMS (14,8 ± 0,4 vs. 12,7 ± 0,4; P = 0,0004). Ainda, novilhas Holandesas apresentaram maior volume do CL (mm3) que novilhas Nelore (6195 ± 427 vs. 3507 ± 461; P < 0,0001). Novilhas submetidas à BCMS apresentaram maior concentração plasmática de P4 ao longo do protocolo que novilhas submetidas à ACMS (P < 0,05), sendo isto mais evidente em novilhas Nelore (raça * dieta, P = 0,05). Novilhas Holandesas tiveram maior expressão de mRNA para SRD5A1, AKR1C4 e AKR1D1 (P < 0,05), que novilhas Nelore. Entretanto, a expressão de mRNA para CYP3A4 foi maior em novilhas Nelore que Holandesas (P < 0,0001). A expressão de mRNA para AKR1D1 foi maior em novilhas submetidas à ACMS comparada à BCMS (P = 0,004), e a expressão de mRNA para AKR1C4 foi maior em novilhas sob BCMS comparada à ACMS (P = 0,01). Os dados são indicativos de que pode existir característica inerente à raça e à dieta quanto à metabolização de P4, resposta folicular e modulação na expressão de genes envolvidos com a metabolização de P4 em fêmeas bovinas submetidas ao protocolo de sincronização da ovulação com dispositivo intravaginal de P4.
The objective of this study was to evaluate the circulating progesterone (P4) concentration, ovarian follicular dynamics, and liver-gene expression of genes (CYP2C19, CYP3A4, SRD5A1, SRD5A3, AKR1C4, AKR1D1) associated to P4 metabolism in Nelore (n = 16) and Holstein (n = 16) heifers, kept in high (HDM) or low (LDM) dry matter intake according NRC (2001) during a timed AI protocol. The experiment was performed in a cross-over factorial 2 x 2 design. The experimental diet was fed for a period of 34 days. Heifers were presynchronized with two prostaglandin treatments (500 µg,i.m. PGF2α, Sincrocio®, Ourofino Agronegócio) given 12 days apart (D-14 e D-12). Two further PGF2α treatments were also performed 18 and 12 h before device insertion (D0). At the beginning of the synchronization protocol (D0), all heifers received an intravaginal P4 device (CIDR®, Zoetis, Brazil), 2 mg i.m. of estradiol benzoate (BE, Sincrodiol®, Ourofino Agronegócio) and a PGF2α treatment. Eight days later, the P4 device was removed and 1 mg of BE was applied i.m. 24h later. Ultrasound exams took place at every 24h throughout the P4 device insertion period, at 12h intervals from device removal to ovulation, and again on D14 and D17 to measure corpus luteum (CL) volume. Daily blood sampling was performed from D0 to D10. A single liver biopsy was done 48 h after P4 device insertion (D2). The PROC MIXED procedure was used to analyze data from follicular dynamics and hormonal profiles, and gene expression records were analyzed by the PROC GLIMMIX of SAS 9.3. Results are presented as mean ± SEM. The number of recruited follicles was greater in Nelore than in Holstein heifers (42.1 ± 3.4 vs. 23.5 ± 3.3, P < 0.001). The diameter of the dominant follicle (mm) was greater in Holstein than in Nelore heifers (14.5 ± 0.4 vs. 13.0 ± 0.4, P = 0.009) and also for HDM heifers than for LDM (14.8 ± 0.4 vs. 12.7 ± 0.4; P = 0.0004). In addition, Holstein heifers had greater CL volume (mm3) than Nelore (6195 ± 427 vs. 3507 ± 461; P < 0.0001). Heifers submitted to BCMS have greater concentrations of P4 during the protocol that heifers submitted to ACMS (P < 0.05), and this is most evident in Nelore heifers (breed * diet, P < 0,05). Holstein heifers had greater mRNA expression of SRD5A1, AKR1C4 and AKR1D1 (P < 0.05) than Nelore heifers. The mRNA expression of the gene CYP3A4 was greater though in Nelore compared Holsteins (P < 0.0001). Furthermore, the mRNA expression of AKR1D1 was greater in heifers on HDM than in LDM (P = 0.004). In contrast, the mRNA expression of AKR1C4 was more expressed in heifers on LDM compared to HDM (P = 0.01). In conclusion, these results suggest that both cattle breed as well as level of dry matter intake can alter P4 metabolism, follicular dynamics and gene expression in heifers supplemented with exogenous P4 during synchronization programs.

Genetic Algorithms is a field of computer science that have many applications, ranging from teaching robots how to overcome a problem, to improving designs and optimizing solutions. Genetic Algorithms is a perfect tool for optimization of an AI’s thought process. In this thesis, I explore one way of how to make an AI-bot move through an area with obstacles and try to get to a goal somewhere on that playing field. Genetic Algorithms will be used to improve how the AI reacts when faced with obstacles and getting better at it with each generation. The thesis shows that it is possible to use Genetic Algorithms to optimize an AI at a specific task and a notion that the more resistance it encounters, the the better it gets.
Arbetet handlar om hur man kan använda Genetiska Algoritmer för att lära en AI att röra sig igenom ett område med hinder för att hitta ett mål.

Accelerated carbonation is a new C02 storage method under development as a  solutionfor climatechangecausedbyanthropogenicactivities.Inacceleratedcarbonationanalkalinesourcesuch as minerals or industrial resid ues react with carbon dioxide in a presence of slightly acidicsolution to produce stable solid carbonates. There are varieties of accelerated carbonation routes,which differ in process condition. The aim of this study was to evaluate  and  compare  the potential of a slurry route process and a wet route process for the carbonation of basicoxygenfurnace slag using the C02 emitted by a conventional natural gas power plant. For this pmpose alife cycle assessment (LCA) study was performed based on principles and guidelines provided byISO 14040:2006 and routines and data provided by the SimaPro V8 software  package.Thematerial and energy requirements for each of the steps involved in the carbonation process, i.e.pre-treatment of raw material, C02 compression, transportation, carbonation step, after-treatmentand landfill, were calculated and included in the LCA study. The slurry and wet route resulted innet C02 reduction of 87.4% and 72.3% respectively. However, a positive contribution to otherenvironmental issues was observed with the wet route  leading to higher  impact mainly due  tohigh heating requirement. An exception was the contribution of the slurry route  to  abioticresource depletion, which was higher for the slurry route due to high water  requirement.  Ageneral conclusion was that the electricity consumption is the  main  cause  ofenvironmentalissues. Sensitivity analyses showed that the environmental impacts are dependent on thetransp01iation distance and electricity source, while no dependence was observed with respect toconstruction of the carbonation plant.

Neuropathic pain is a serious health problem that greatly impairs quality of life. The International Association for the Study of Pain (IASP) defines neuropathic pain as `pain arising as a direct consequence of a lesion or disease affecting the nervous system'. It is important to note that with neuropathy the chronic pain is not a symptom of injury, but rather the pain is itself a disease process. Novel interactions between the nervous system and elements of the immune system may be key facets to a chronic disease state. One of particular note is the recent finding supporting an interaction between an immune response protein high mobility group box 1 (HMGB1) and Toll like receptor 4 (TLR4). HMGB1 is an endogenous ligand for TLR4 that influences the induction of cytokines in many non-neuronal cells. After tissue damage or injury, HMGB1 may function as a neuromodulatory cytokine and influence the production of pro-nociceptive mediators altering the state of sensory neurons. Very little is known about the HMGB1-TLR4 interaction in sensory neurons and whether chronic changes in endogenous HMGB1 signaling influence the establishment of neuropathic pain. This thesis aims to determine whether a physiologically relevant neuroimmune interaction involving endogenous HMGB1 and TLR4 in the dorsal root ganglia is altered following a tibial nerve injury model of neuropathic pain. I hypothesized that sensitization of sensory neurons following a peripheral nerve injury is dependent on endogenous HMGB1 and TLR4. The studies presented here demonstrate that HMGB1 undergoes subcellular redistribution from the nucleus to the cytoplasm in primary afferent neurons following peripheral nerve injury. Further, the presence of extracellular HMGB1 may directly contribute to peripheral sensitization and injury-induced tactile hyperalgesia. Though thought to be important as a pivotal receptor for HMGB1 activation, neuronal protein expression of TLR4 does not appear to influence the effects of HMGB1-dependent behavioral changes following peripheral nerve injury. Taken together, these findings suggest that extracellular HMGB1 may serve as an important endogenous cytokine that contributes to ongoing pain hypersensitivity in a rodent model of neuropathic pain.

[EN] Currently, there is a trend towards sustainability, especially in developed countries, where the concerns of society about environmental degradation and social problems have increased. Following this trend, the construction sector is one of the most influential sectors due to its high economic, environmental, and social impacts. At the same time, there is an increase in the demand for transport, which drives a need to develop and maintain the necessary infrastructure for this purpose. Taking all these factors into account, bridges become a key structure and therefore assessment of sustainability throughout their whole life-cycle is essential. The main objective of this thesis is to propose a methodology that allows assessment of the sustainability of a bridge under uncertain initial conditions (subjectivity of the decision-maker or variability of initial parameters) and optimization of the design to obtain a robust optimal bridge. To this end, an extensive bibliographic review of all the works that perform assessments of the sustainability of bridges through the valuation of criteria related to their main pillars (economic, environmental, or social) has been carried out. In this review, it has been observed that the most comprehensive way to evaluate the environmental and social pillars is through the use of life-cycle impact assessment methods. These methods allow sustainability assessment to be performed for the whole life-cycle of the bridge. This process provides valuable information to decision-makers for the assessment and selection of the most sustainable bridge. However, the decision-makers' subjective assessments of the relative importance of the criteria influence the final assessment of sustainability. For this reason, it is necessary to create a methodology that reduces the associated uncertainty and seeks robust solutions according to the opinion of decision-makers. In addition, for bridges, the design and decision-making are conditioned by the initially defined parameters. This leads to solutions that may be sensitive to small changes in these initial conditions. A robust optimal design makes it possible to obtain optimal solutions and structurally stable designs under variations of the initial conditions as well as sustainable designs that are not influenced by the preferences of the stakeholders who are part of the decision-making process. Thus, obtaining a robust optimal design becomes a probabilistic optimization process that has a high computational cost. For this reason, the use of metamodels has been integrated into the proposed methodology. Specifically, Latin hypercube sampling is used for the definition of the initial sample and a kriging model is used for the definition of the mathematical approximation. In this way, kriging-based heuristic optimization reduces the computational cost by more than 90% with respect to conventional heuristic optimization while obtaining very similar results. This thesis provides, first of all, an extensive bibliographic review of both the criteria used for the assessment of sustainability of bridges and the different methods of life-cycle impact assessment to obtain a complete profile of the environmental and social pillars. Subsequently, a methodology is defined for the full assessment of sustainability, using life-cycle impact assessment methods. Likewise, an approach is proposed that makes it possible to obtain structures with little influence from the structural parameters, as well as from the preferences of the different decision-makers regarding the sustainability criteria. The methodology provided in this thesis is applicable to any other type of structure.
[ES] Actualmente existe una tendencia hacia la sostenibilidad, especialmente en los países desarrollados donde la preocupación de la sociedad por el deterioro ambiental y los problemas sociales ha aumentado. Siguiendo esta tendencia, el sector de la construcción es uno de los sectores que mayor influencia tiene debido a su alto impacto económico, ambiental y social. Al mismo tiempo, existe un incremento en la demanda de transporte que provoca la necesidad de desarrollo y mantenimiento de las infraestructuras necesarias para tal fin. Con todo esto, los puentes se convierten en una estructura clave, y por tanto, la valoración de la sostenibilidad a lo largo de toda su vida es esencial. El objetivo principal de esta tesis es proponer una metodología que permita valorar la sostenibilidad de un puente bajo condiciones iniciales inciertas (subjetividad del decisor o variabilidad de parámetros iniciales) y optimizar el diseño para obtener puentes óptimos robustos. Para ello, se ha realizado una extensa revisión bibliográfica de todos los trabajos en los que se realiza un análisis de la sostenibilidad mediante la valoración de criterios relacionados con sus pilares principales (económico, medio ambiental o social). En esta revisión, se ha observado que la forma más completa de valorar los pilares medioambientales y sociales es mediante el uso de métodos de análisis de ciclo de vida. Estos métodos permiten llevar a cabo la valoración de la sostenibilidad durante todas las etapas de la vida de los puentes. Todo este procedimiento proporciona información muy valiosa a los decisores para la valoración y selección del puente más sostenible. No obstante, las valoraciones subjetivas de los decisores sobre la importancia de los criterios influyen en la evaluación final de la sostenibilidad. Por esta razón, es necesario crear una metodología que reduzca la incertidumbre asociada y busque soluciones robustas frente a las opiniones de los agentes implicados en la toma de decisiones. Además, el diseño y toma de decisiones en puentes está condicionado por los parámetros inicialmente definidos. Esto conduce a soluciones que pueden ser sensibles frente a pequeños cambios en dichas condiciones iniciales. El diseño óptimo robusto permite obtener diseños óptimos y estructuralmente estables frente a variaciones de las condiciones iniciales, y también diseños sostenibles y poco influenciables por las preferencias de los decisores que forman parte del proceso de toma de decisión. Así pues, el diseño óptimo robusto se convierte en un proceso de optimización probabilística que requiere un gran coste computacional. Por este motivo, el uso de metamodelos se ha integrado en la metodología propuesta. En concreto, se ha utilizado hipercubo latino para la definición de la muestra inicial y los modelos kriging para la definción de la aproximación matemática. De esta forma, la optimización heurística basada en kriging ha permitido reducir más de un 90% el coste computacional respecto a la optimización heurística conveniconal obteniendo resultados muy similares. Esta tesis proporciona en primer lugar, una amplia revisión bibliográfica, tanto de los criterios utilizados para la valoración de la sostenibilidad en puentes como de los diferentes métodos de análisis de ciclo de vida para obtener un perfil completo de los pilares ambientales y sociales. Posteriormente, se define una metodología para la valoración completa de la sostenibilidad, usando métodos de análisis de ciclo de vida. Asimismo, se propone un enfoque que permite obtener estructuras poco influenciables por los parámetros estructurales, así como por las preferencias de los diferentes decisores frente a los criterios sostenibles. La metodología proporcionada en esta tesis es aplicable a cualquier otro tipo de estructura.
[CA] Actualment existeix una tendència cap a la sostenibilitat, especialment en els països desenrotllats on la preocupació de la societat pel deteriori ambiental i els problemes socials ha augmentat. Seguint aquesta tendència, el sector de la construcció és un dels sectors que major influència té a causa del seu alt impacte econòmic, ambiental i social. Al mateix temps, existeix un increment en la demanda de transport que provoca la necessitat de desenrotll i manteniment de les infraestructures necessàries per a tal fi. En tot açò, els ponts es converteixen en una estructura clau, i per tant, la valoració de la sostenibilitat al llarg de tota la seua vida és essencial. L'objectiu principal d'aquesta tesi doctoral és proposar una metodologia que permeta valorar la sostenibilitat d'un pont baix condicions inicials incertes (subjectivitat del decisor o variabilitat dels paràmetres inicials) i optimitzar el disseny per a obtenir ponts òptims robusts. Per a això, s'ha realitzat una extensa revisió bibliogràfica de tots els treballs en els quals es realitza un anàlisis de la sostenibilitat mitjançant la valoració de criteris relacionats amb els seus pilars principals (econòmic, ambiental o social). En aquesta revisió s'ha observat que la forma més completa de valorar els pilars ambientals i socials és mitjançant l'ús de mètodes d'anàlisis de cicle de vida. Aquests mètodes permeten realitzar la valoració de la sostenibilitat al llarg de totes les etapes de la vida dels ponts. Tot aquest procediment proporciona informació molt valuosa als decisors per a la valoració i selecció del pont més sostenible. No obstant això, les valoracions subjectives dels decisors sobre la importància dels criteris influeixen en l'avaluació final de la sostenibilitat. Per aquesta raó, és necessari crear una metodologia que reduïsca la incertesa associada i busque solucions robustes enfront de les opinions dels agents implicats en la presa de decisions. A més, el disseny i la presa de decisions en ponts està condicionat pels paràmetres inicialment definits. Açò condueix a solucions que poden ser sensibles front a menuts canvis en les dites condicions inicials. El disseny òptim robust permet obtenir dissenys òptims i estructuralment estables front a variacions de les condicions inicials, i també dissenys sostenibles i poc influenciables per les preferències dels decisors que formen part del procés de presa de decisió. D'aquesta manera, el disseny òptim robust es converteix en un procés d'optimització probabilística que requereix un gran cost computacional. Per aquest motiu, l'ús de metamodels s'ha integrat en la metodologia proposta. En concret, s'ha utilitzat l'hipercub llatí per a la definició de la mostra inicial i els models kriging per a la definició de l'aproximació matemàtica. D'aquesta forma, l'optimització heurística basada en kriging ha permés reduir més d'un 90% el cost computacional respecte a l'optimització heurística convencional obtenint resultats molt similars. Aquesta tesi doctoral proporciona en primer lloc, una ampla revisió bibliogràfica, tant dels criteris utilitzats per a la valoració de la sostenibilitat en ponts com dels diferents mètodes d'anàlisis de cicle de vida per a obtenir un perfil complet dels pilars ambientals i socials. Posteriorment, es defineix una metodologia per a la valoració completa de la sostenibilitat, utilitzant mètodes d'anàlisis de cicle de vida. Així mateix, es proposa un enfocament que permet obtenir estructures poc influenciables pels paràmetres estructurals, així com per les preferències dels diferents decisors enfront dels criteris sostenibles. La metodologia proporcionada en aquesta tesi doctoral és aplicable a qualsevol altre tipus d'estructura. Nº de páginas:
I would like to acknowledge the economic support of the Spanish Ministry of Economy and Competitiveness, formerly called Spanish Ministry of Science and Innovation. This thesis has been possible thanks to the FPI fellowship and the financially support of BRIDLIFE (Research Project BIA2014-56574-R) and DIMALIFE (Project BIA2017-85098-R).
Penadés Plà, V. (2020). Life-cycle sustainability design of post-tensioned box-girder bridge obtained by metamodel-assisted optimization and decision-making under uncertainty [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/147480
TESIS

L’overdose au paracétamol est l’une des intoxications médicamenteuses la plus fréquente au monde, caractérisée par une atteinte hépatique dont l’issue peut être fatale. Les études réalisées sur ce phénomène ont montré que la phase initiale de la toxicité est induite par le métabolite actif du paracétamol, le N-acétyl-p-benzoquinone imine (NAPQI). Ce dernier, en l’absence de quantité suffisante de glutathion, s’accumulent dans la cellule et finit par se lier à d’autres protéines, principalement mitochondriales, formant alors des adduits. Cette liaison va altérer la fonction primaire des protéines et conduire, en cas d’overdose sévère, à la mort des hépatocytes. La mort cellulaire s’accompagne alors de la libération de composants cellulaire dont le rôle sera d’alerter le système immunitaire des lésions tissulaires. Ces composants prennent alors le nom d’«alarmines» ou de « damage-associated molecular patterns » (DAMPs). La protéine HMGB1 (High Mobility Group Box 1) fait partie de cette catégorie.Au cours de cette thèse nous nous sommes intéressés de plus près à la protéine HMGB1, à son origine ainsi qu’à son rôle dans l’amplification et la propagation des lésions hépatiques initialement induites par l’overdose au paracétamol. Nos travaux se sont d’abord portés sur l’étude de la protéine HMGB1 dans un modèle murin d’hépatite au paracétamol. Nos expériences nous permettent, d’une part, de confirmer que la libération d’HMGB1 est liée à la sévérité des lésions hépatiques et d’autre part, de démontrer que l’amplification et la propagation de ces lésions, dans les phases précoces de l’intoxication au paracétamol, peuvent se produire indépendamment des cellules immunitaires. Sur base de ces résultats, nous avons émis l’hypothèse de l’existence d’un dialogue entre la protéine HMGB1 et les hépatocytes plutôt que du dialogue, généralement décrit dans la littérature, entre la protéine HMGB1 et les cellules du système immunitaire Nos travaux se sont donc poursuivis, in vitro, sur une lignée cellulaire d’hépatocytes humains, les cellules HepaRG. Ces expériences nous ont permis, d’une part, de confirmer l’implication de la protéine HMGB1 dans l’hépatotoxicité au paracétamol et de mettre en évidence la capacité de cette protéine à provoquer, sans intermédiaire, la mort des cellules HepaRG. D’autre part, ces expériences nous permettent de suggérer la participation de la protéine HMGB1 dans la propagation et l’amplification de la mort des hépatocytes exposés au paracétamol par une voie de signalisation impliquant l’axe TLR4/TRIF/RIPK3. Finalement, l’inhibition de la protéine HMGB1 semblant être bénéfique, nous avons investigué la potentielle efficacité de l’administration d’une combinaison de N-acétylcystéine et de glycyrrhizine dans notre modèle murin. L’idée était de combiner une drogue qui agit sur l’accumulation du métabolite toxique et une seconde qui agit sur la phase de propagation du signal. Nos résultats, bien que préliminaires, ont démontré l’efficacité de cette combinaison à la fois sur la nécrose hépatique et sur la survie des souris. En conclusion, nos travaux confirment l’importance du rôle joué par la protéine HMGB1 dans l’hépatotoxicité induite par le paracétamol et nous permettent de mettre en évidence un nouveau mécanisme, impliquant la protéine HMGB1, qui pourrait contribuer à l’amplification et la propagation des lésions hépatiques induites par une overdose de paracétamol.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished

Nest box programs provide supplemental nest sites for American Kestrels, Falco sparverius. When the availability of nest sites is a limiting factor, the addition of nest boxes can increase local breeding populations. These programs also facilitate the collection of data on breeding kestrels. This study focuses on an American Kestrel (Falco sparverius) nest box trail along Interstate 26 in northeastern Tennessee during the breeding seasons of 1998, 1999, 2000, 2003, 2004, 2006, and 2009. Productivity measures and reproductive success of nesting birds are provided and compared to other programs. The data are analyzed across years and by box. Finally, a discussion of the habitat surrounding the most and least active boxes provides recommendations for increased efficiency of the program.