Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic in vivo and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitored in vivo by diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.

Tumor necrosis factor-related apoptosis-inducing ligand in T cell development: Sensitivity of human thymocytes

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in various tumor cell lines, whereas most primary cells seem to be resistant. These observations have raised considerable interest in the use of TRAIL in tumor therapy. Yet little is known about the physiological function of TRAIL. This is particularly the case in the immune system, where TRAIL has been suggested by some to be involved in target cell killing and lymphocyte death. We have developed a panel of mAbs and soluble proteins to address the role of TRAIL in lymphocyte development. These studies demonstrate activation-induced sensitization of thymocytes to TRAIL-mediated apoptosis and expression of the apoptosis-inducing TRAIL receptors. However, with the use of several model systems, our subsequent experiments rule out the possibility that TRAIL plays a major role in antigen-induced deletion of thymocytes. In contrast to thymocytes, there is no up-regulation of TRAIL receptors in peripheral T cells on activation, which remain resistant to TRAIL. Thus, susceptibility to TRAIL-induced apoptosis is controlled differently by central and peripheral T cells.

T cell-specific FADD-deficient mice: FADD is required for early T cell development

FADD/Mort1, initially identified as a Fas-associated death-domain containing protein, functions as an adapter molecule in apoptosis initiated by Fas, tumor necrosis factor receptor-I, DR3, and TRAIL-receptors. However, FADD likely participates in additional signaling cascades. FADD-null mutations in mice are embryonic-lethal, and analysis of FADD−/− T cells from RAG-1−/− reconstituted chimeras has suggested a role for FADD in proliferation of mature T cells. Here, we report the generation of T cell-specific FADD-deficient mice via a conditional genomic rescue approach. We find that FADD-deficiency leads to inhibition of T cell development at the CD4−CD8− stage and a reduction in the number of mature T cells. The FADD mutation does not affect apoptosis or the proximal signaling events of the pre-T cell receptor; introduction of a T cell receptor transgene fails to rescue the mutant phenotype. These data suggest that FADD, through either a death-domain containing receptor or a novel receptor-independent mechanism, is required for the proliferative phase of early T cell development.

Solution to Darwin's dilemma: Discovery of the missing Precambrian record of life

In 1859, in On the Origin of Species, Darwin broached what he regarded to be the most vexing problem facing his theory of evolution—the lack of a rich fossil record predating the rise of shelly invertebrates that marks the beginning of the Cambrian Period of geologic time (≈550 million years ago), an “inexplicable” absence that could be “truly urged as a valid argument” against his all embracing synthesis. For more than 100 years, the “missing Precambrian history of life” stood out as one of the greatest unsolved mysteries in natural science. But in recent decades, understanding of life's history has changed markedly as the documented fossil record has been extended seven-fold to some 3,500 million years ago, an age more than three-quarters that of the planet itself. This long-sought solution to Darwin's dilemma was set in motion by a small vanguard of workers who blazed the trail in the 1950s and 1960s, just as their course was charted by a few pioneering pathfinders of the previous century, a history of bold pronouncements, dashed dreams, search, and final discovery.

Developing an Interdependent Relationship between Preservation and Recreation: Managing Mountain Bicycling in National Parks

Increasing demand from mountain bikers for greater access to riding in National Park Service (NPS) units is driving the need for park managers to seriously look at the impacts from and feasibility of permitting this recreational use. Currently, NPS units that permit mountain bicycling do not have formal mountain bicycling management plans. An analysis of recreational policies and existing research was conducted to identify criteria for effective mountain bicycling management strategies. Criteria were developed for trail selection, establishment, use, closures and rehabilitation. Criteria were also developed for user education, participatory planning and monitoring. This study shows that the NPS needs formal mountain bicycling management plans that focus on the preservation of natural and cultural resources and consider the appropriateness of proposed recreational uses.

Improving urban park design: A comparative and analytical study addressing resources available and components necessary to improve the environmental and economic sustainability of urban parks

Urban parks have long been valued for the environmental, social, and economic benefits they provide. Increasingly, parks are also being recognized as features important for sustainable city design. This Capstone Project will identify, compare, analyze, and discuss means for designing sustainable urban parks. Recommendations for designing sustainable urban parks, based on project results, include: 1) ensure park features will support high levels of human activity; 2) use gravel to construct park trails; 3) purchase playground structures made of recycled materials; 4) plant a high number of perennials in flowerbeds and other vegetated areas; 5) plant climate-appropriate plants in vegetated areas; 6) ensure parks have high levels of plant diversity; and 7) develop future studies further exploring sustainable park design.

Projeto – sustentabilidade e matemática

A disciplina matemática e o tema sustentabilidade podem ser muito bem trabalhados pelos docentes da área de exatas. Pois, saber quantificar, calcular e associar o consumo e o impacto ambiental através de dados numéricos é uma possibilidade que pode ser desenvolvida em sala de aula. Saber interpretar e construir gráficos de colunas são outras competências e habilidades presentes na ciência da matemática. Compreender conceitos, estratégias e situações matemáticas numéricas para aplicá-los a situações diversas no contexto das ciências, da tecnologia e da atividade cotidiana se faz necessário. E também, reconhecer, pela leitura de textos apropriados, a importância da Matemática na elaboração de proposta de intervenção solidária na realidade. Dessa forma, conhecer o ambiente em que vivemos, verificar a influência do homem na Natureza e quais ações deverão ser tomadas pensando nas futuras gerações é um despertar para o consumo consciente. O que acarreta como possibilidade o retorno à natureza de recursos utilizados de maneira correta. Conhecer uma conta de luz detalhada, aprender a calcular o consumo mensal de Kwh e diminuir o consumo de energia elétrica através da mudança de hábitos são exemplos cotidianos em que a matemática se faz presente. Relacionar a matemática ao estudo do meio ambiente proporciona através dos números mensurar os prejuízos e projetar soluções, torna a aprendizagem construtiva, podendo se constituir num comportamento cotidiano ou numa ação educativa para formar uma consciência ecológica dentro de indicadores reais. A aprendizagem se torna significativa quando relacionada ao cotidiano do aluno no sentido de mostrar o meio ambiente a que estão inseridos para que possam ser agentes transformadores, através da mudança de hábitos e principalmente desenvolvendo suas habilidades matemáticas. Sendo assim, o processo de ensino aprendizagem matemática-meio ambiente é realizado no sentido de oportunizar o conhecimento do mundo e domínio da natureza, com base nas linguagens matemáticas, criando-se condições de melhorar a capacidade de agir na sociedade, assumindo ações permanentes concentradas em um desenvolvimento sustentável para a continuidade da vida na Terra. Nesse diapasão, é possível desenvolver trabalhos pedagógicos “na trilha da matemática: do raciocínio ao meio-ambiente”. A resolução de situações problemas e assuntos referentes ao meio ambiente fazem com que os alunos tomem os cuidados necessários para com o meio ambiente, aos recursos por ele oferecidos e as consequências das ações errôneas causadas pelo homem.

THE DESIGN OF A POWER SYSTEM FOR A WIRELESS SENSOR NETWORK FOR LONG-TERM OPERATION

Wireless sensor networks (WSNs) have shown wide applicability to many fields including monitoring of environmental, civil, and industrial settings. WSNs however are resource constrained by many competing factors that span their hardware, software, and networking. One of the central resource constrains is the charge consumption of WSN nodes. With finite energy supplies, low charge consumption is needed to ensure long lifetimes and success of WSNs. This thesis details the design of a power system to support long-term operation of WSNs. The power system’s development occurs in parallel with a custom WSN from the Queen’s MEMS Lab (QML-WSN), with the goal of supporting a 1+ year lifetime without sacrificing functionality. The final power system design utilizes a TPS62740 DC-DC converter with AA alkaline batteries to efficiently supply the nodes while providing battery monitoring functionality and an expansion slot for future development. Testing tools for measuring current draw and charge consumption were created along with analysis and processing software. Through their use charge consumption of the power system was drastically lowered and issues in QML-WSN were identified and resolved including the proper shutdown of accelerometers, and incorrect microcontroller unit (MCU) power pin connection. Controlled current profiling revealed unexpected behaviour of nodes and detailed current-voltage relationships. These relationships were utilized with a lifetime projection model to estimate a lifetime between 521-551 days, depending on the mode of operation. The power system and QML-WSN were tested over a long term trial lasting 272+ days in an industrial testbed to monitor an air compressor pump. Environmental factors were found to influence the behaviour of nodes leading to increased charge consumption, while a node in an office setting was still operating at the conclusion of the trail. This agrees with the lifetime projection and gives a strong indication that a 1+ year lifetime is achievable. Additionally, a light-weight charge consumption model was developed which allows charge consumption information of nodes in a distributed WSN to be monitored. This model was tested in a laboratory setting demonstrating +95% accuracy for high packet reception rate WSNs across varying data rates, battery supply capacities, and runtimes up to full battery depletion.

Emergent Brazil and the Curse of the ‘Hen’s Flight’. CEPS Working Document No. 379, 27 February 2013

The ‘Emergent Brazil’ growth model is reaching its limits. Its main engines have been slowing significantly since the beginning of the global financial and economic crisis. Even its much-praised predictable macroeconomic policy has been eroded by political interference. Inflationary pressures are growing and GDP performance is anaemic. As ominous, Brazil cannot compensate for its domestic deficiencies with an export drive. Commodity exports are suffering with the world economic slow-down and the manufacturing industries’ competitiveness is in sharp decline. Brazil has put all its trade negotiation eggs into the South American and WTO baskets, and now its export market share is threatened by the Doha Round paralysis, the Latin American Alianza del Pacífico, and the US-led initiatives for a Trans-Pacific Partnership and a trade and investment agreement with the EU. Paradoxically, this alarming situation opens a window of opportunity. There is a mounting national consensus on the need to tackle head-on the country’s and its industries’ lack of competitiveness. That means finding a solution to the much-decried ‘Brazil Cost’ and stimulating private-sector investment. It also entails an aggressive trade-negotiating stance in order to secure better access to foreign markets and to foster more competition in the domestic one. The most promising near-term goal would be the conclusion of the EU–Mercosur trade talks. A scenario to overcome the paralysis of these negotiations could trail two parallel paths: bilateral EU–Brazil agreements on ‘anything but trade’ combined with a sequencing of the EU–Mercosur talks where each member of the South American bloc could adopt faster or slower liberalisation commitments and schedules.

Great Himalaya: Tourism and the dynamics of change in Nepal

Based on extensive field work and years of personal experience, the authors discuss the development of tourism in the Great Himalaya of Nepal from the early days of mountaineering to present-day trekking. Tourism and its potentials, drawbacks, and risks are illustrated with a focus on the Khumbu/Everest and Annapurna regions, the most popular mountain destinations in the country. The themes addressed include: growth and expansion of mountain tourism; employment and income generation; wealth, poverty, and livelihood as reflected in statistics and personal accounts by local people; the revival of trade with Tibet; tourism and the role of women; the crucial role played by institutions, policies and political stability; and environmental issues such as forest degradation, garbage management, and trail damage. With its numerous illustrations, text boxes and quotes, the book is intended for a broad readership of policy- and decision-makers in tourism and development, scholars, and tourists and mountaineers who take an interest in mountain development in the Great Himalaya and elsewhere.

The illustrated dictionary of gardening : a practical and scientific encyclopaedia of horticulture for gardeners and botanists /

"Reference to illustrations of plants other than those figured in this work" precedes text in each volume.

The works of Francis Parkman.

Each front accompanied by guard sheet with descriptive letterpress.

Fragments of a Plate with Engraved Designs

Glass, Islamic, Abbasid; 19/32 in.x 11 1/32 in.; glass, blown with applied trail, scratch-engraved

Private outdoor recreation businesses : horseback riding enterprises /

"Edited by Susan Hickey"--Acknowledgments.