Adoptive T Cell Therapy for Metastatic Colorectal Cancer

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person\u27s life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer has been proved resistant to chemotherapy although little success has been achieved using a combination of 5-fluorouracil and levamisole. Survival rate decreases from 90% for primary tumors to 10% for distal metastasis of colorectal cancer (1). More attention has been attracted to immunotherapy against metastatic colon cancer, because of its potential for higher specificity and less side effect(4). Our main aim is to increase the eradication of metastatic colorectal cancer cells by optimizing immunotherapeutic approaches that have been well-underway. Guanylyl cyclase C (GCC) is a mucosal antigen expressed on apical surface of intestinal epithelial cells. It is a potential target for colorectal cancer immunotherapeutic approaches, because of its expression on \u3e95% of colorectal cancer cells and their maintenance through all the stages of colorectal cancer (5-9).This is because GCC is mainly expressed in the intestine so that its expression can be utilized to detect metastasis of colon cancer. The aim of this project is to develop an immunotherapy based on GCC-specific TCR transduced CD8 T cells to attack metastatic cancer cells. The initial step of this project is cloning out CD8 TCR specific to GCC. This can be done by T-hybridoma technology by which we fused T cells from mice immunized by GCC vaccine with fusion partner cells (BWZ/CD8)(10)

Neo-Malthusian Dilemma: Latin America and the Caribbean

Neo-malthusian dilemma manifests itself in a growing population of 500 million in 1998 and an additional net growth of 9 million people each year in Latin America and the Caribbean (LA & C) and low level of productivity resulting in poverty, a threat to sustainable development and prospects of continuing low level of the quality of life. To escape this dilemma it is necessary to reduce growth in the population while at the same time following the United Nations “Programme of Action” and the United Nations, The Economic Commission for Latin America and the Caribbean (ECLAC), “Social Equity and Changing Production Patterns: An Integrated Approach”. This paper examines the size of the population and its rate of growth and the contributing factors to these two, namely fertility, mortality and international migration. The population of Latin America and the Caribbean is large and is growing very significantly. Fertility is still high. Mortality is low, and the rate of natural increase is substantial in many countries. Emigration from outside the region is non-existent. Immigration exists but overall it is inconsequential, but for some individual countries it is important. There are some inter-regional migration. Internal migration is still important. Rural to urban migration is being superceded by urban to urban migration. The spatial distribution of the population is of great concern. Overall, densities are satisfactory. But the population is located in small areas of the national territory. Urbanization is a major aspect of the spatial distribution of the population. L A & C is a highly urbanized area. With few exceptions, the capital cities are primate cities. There are four mega cities of 10 million and more. Urbanization and the concentration of the population in a few small areas have many adverse effects for a sustainable development. Low level of productivity is seen in the low per capital income of less than $4000 for the region. Poverty is rampant throughout the countries. Food is scarce. Housing is inadequate and insufficient. Latin America and the Caribbean is classified as a middle income region. This may be true, but some countries are very poor, and there is much poverty in all countries

AN INSTRUMENTAL STUDY OF FIRE SERVICE LEADERS’ INFLUENCE ON FOLLOWERS’ WORKPLACE AEROBIC EXERCISE ACTIVITY

Sudden cardiac events resulting from the physical demands associated with fire suppression among individuals lacking adequate aerobic fitness are known concerns within the firefighting domain. The purpose of this research study was to explore fire service leaders\u27 perceived leadership behaviors that aided in followers\u27 performing workplace aerobic exercise activities (Creswell & Poth, 2018). Following within-case and cross-case analyses of interviewees\u27 data, five leadership themes emerged comprising four behaviors and one influence related to followers\u27 workplace aerobic exercise activities: role model, supportive, cooperative, visionary, and planned exercise regimen. In the present study, thematic findings indicated that fire service leaders\u27 role-modeling exercise and fitness behaviors exemplified the importance of performing workplace aerobic exercise activities among followers. In addition, supportive behaviors focused on interactive exchanges, job-related training, and team-building helped followers perform workplace aerobic exercise activities. Moreover, interviewees portrayed cooperative behaviors towards working out with followers, scaling exercises, and procuring fitness equipment promoted workplace aerobic exercise activities. Furthermore, interviewees described the use of visionary behaviors focused on thinking outside of the box and eliciting solutions to barriers limiting followers’ from performing workplace aerobic exercise activities. Equally important, interviewees identified that establishing a prescribed planned workout regimen influenced followers\u27 performance of workplace aerobic exercise activities. Therefore, the present study\u27s findings have practical implications for helping fire service leaders lessen followers\u27 cardiovascular disease-related events within the firefighting domain

Gender Transformative Philanthropy

As foundations and other philanthropic institutions assess where they can maximize the social return on their charitable investments, many are looking at issues of gender norms and gender equity. One program officer put it this way: "Our grantees and staff get race and class; some are even starting to get sexual orientation. What I want to know is -- what happened to gender? Where is the gender analysis?" Over two decades of research has now shown that challenging harmful codes of masculinity and femininity is a major key to improving outcomes in reproductive health and gender-based violence. Yet the field continues to mostly overlook gender norms. As the same time, studies have shown conclusively that having a strong gender analysis of the disparate impacts on women and men is crucial to increasing the effectiveness of civic engagement organizing. However, many non-profits in this space either ignore gender equity, or marginalize it as a "women's issue." As one experienced program officer put it, "Grantees need to see gender and race together. Gender impacts every issue they work on. But grantees are not being challenged to do innovative work around gender [in a way that parallels their work on race or class concerns]. This accessible overview will help program officers who want to integrate a stronger gender focus into their giving and their grantees' work and analysis

Physical characterization of long wear foundations

The current long wear face make-up products typically comprise of silicone resin or silicone film former and fillers to provide excellent attributes in sebum and sweat resistance to maintain the evenness of make-up for all day long. In order to evaluating the sebum and sweat resistance performance of the current marketed products such as Estee Lauder Double Wear (ELDW), Revlon ColorStay (RCS), and Lancôme Teint Idole Ultra (LTIU), we utilized the contact angle measurement to study the surface energy of the selected foundation films deposited on bio skin as well as the spreading and wetting of artificial sebum/sweat and water droplets on these films as shown in Fig 1. In addition, the tolerance of these foundations under sweat and sebum was evaluated by optical effect and the integrity of the films after exposing to sebum/sweat solutions directly for 8 hrs. The results from these measurements were found to be either dependent of the film former/resin structure and concentration or of the filler types which have strong influence to the performance of the foundations under sebum and sweat condition. In addition, the texture and sensory performance mapping of these long wear foundations were evaluated by rheology and tribology (Fig.2). The rheological behavior of these foundations will be discussed in term of the effect of solid contents and type of fillers used in the foundation formulations. Please click Additional Files below to see the full abstract

Vesicular dysfunction and the pathogenesis of Parkinson's disease: clues from genetic studies

Parkinson’s disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown aetiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson’s and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point towards synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients

Force Majeure: How Lessees Can Save Their Leases While the War on Fracking Rages on.

Abstract Forthcoming