Study of Natural Killer Cells and Their Therapeutic Role in Pediatric Cancer

NK cells are known to play an important role in the natural defense against viral infections and tumor immune surveillance. Through complex interactions between NK cell receptors and target cell ligands, transformed or unhealthy cells are identified and rapidly eliminated. NK cells have been used for therapeutic purposes in pediatric oncology, for example by harnessing the mechanisms of NK cell surveillance in acute myeloid leukemia (AML) or intervention-augmented antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. However, the underlying cellular mechanisms in these processes are not fully understood. In my thesis research, I sought to gain a deeper understanding of the molecular and cellular changes within NK cells that occur in the tumor microenvironment and with immunotherapy. I discovered that NK cells have attenuated natural cytotoxicity in children with neuroblastoma that correlates with clinical tumor response to chemoimmunotherapy. Compared to age-matched reference data in healthy children, the studied patients had higher proportions of CD56bright NK cells, suggestive of immaturity of the NK cell compartment. Although preactivation with cytokines did not entirely overcome the hyporeactivity in patient NK cells, the therapeutic use of interleukin (IL)-2 or -15 significantly enhanced the natural cytotoxicity and ADCC of tested NK cells against neuroblastoma in vitro and in vivo and therefore warrants further investigation. To provide a suitable animal model for future studies of NK cell dysfunction and immunotherapy, I developed a humanize MISTRG neuroblastoma model. Human NK cells that arise in this model after hematopoietic progenitor cell transplantation were functionally intact and capable of suppressing neuroblastoma growth with chemoimmunotherapy in vivo. Despite the discovered molecular differences of NK cell subsets in these mice compared to patient NK cells, the humanized MISTRG neuroblastoma model is a valuable tool to study NK cell biology in neuroblastoma and test whether therapeutic interventions, such as cytokine supplementation, can overcome impaired NK cytotoxicity. Collectively, results from this work are important because they link the cellular capacity of a key effector cell involved in ADCC to antibody-mediated tumor shrinkage in the clinic, revealing potential mechanisms for therapy failure in patients who receive chemoimmunotherapy for neuroblastoma

Market returns to acquirers of substantial assets

Does poor post-acquisition performance characterise firms that make non-M&A acquisitions? We investigate the wealth effects of substantial asset acquisitions (i.e. acquisitions that cost over $10 million) on acquiring firms' shareholders. We find significant abnormal positive market reaction to asset acquisition announcements and, contrary to findings for firms undertaking M&As, the acquiring firms perform exceptionally well post-acquisition. Our findings are robust to the research method weaknesses common to many studies of long-term performance and we control for free-cash-flow as well. Our results contradict the hubris hypothesis of acquisitions and lend weight to the argument that the auction-style process that characterizes corporate takeover bids contributes to overpayment

Graphene oxide-based degradation of metaldehyde : effective oxidation through a modified Fenton's Process

A modified graphene oxide-based Fenton’s reaction has been investigated for the degradation of a challenging emerging contaminant which is not effectively removed in conventional water treatment. Metaldehyde, used as the challenge molecule in this study, is a common molluscicide that (like many highly soluble contaminants) has frequently breached European regulatory limits in surface waters. The new method involves graphene with higher hydrophilic characteristics (single-layer graphene oxide, SLGO) as a system that participates in a redox reaction with hydrogen peroxide and which can potentially stabilize the radical dotOH generated, which subsequently breaks down organic contaminants. The modified Fenton’s reaction has shown to be effective in degrading metaldehyde in natural waters (>92% removal), even at high contaminant concentrations (50 mg metaldehyde/L) and in the presence of high background organic matter and dissolved salts. The reaction is relatively pH insensitive. SLGO maintained its catalytic performance over 3 treatment cycles when immobilized. Its performance gradually decreased over time, reaching around 50% of starting performance on the 10th treatment cycle. X-ray photoelectron spectroscopy (XPS) analysis of modifications caused in SLGO by the oxidizing treatment indicated that the oxidation of Csingle bondC sp2 to carbonyl groups may be the cause of the decrease in performance. The proposed modified Fenton’s process has the potential to substitute traditional Fenton’s treatment although regeneration of the nanocarbon is required for its prolonged use

Graphene oxide-based degradation of metaldehyde: Effective oxidation through a modified Fenton’s process

A modified graphene oxide-based Fenton’s reaction has been investigated for the degradation of a challenging emerging contaminant which is not effectively removed in conventional water treatment. Metaldehyde, used as the challenge molecule in this study, is a common molluscicide that (like many highly soluble contaminants) has frequently breached European regulatory limits in surface waters. The new method involves graphene with higher hydrophilic characteristics (single-layer graphene oxide, SLGO) as a system that participates in a redox reaction with hydrogen peroxide and which can potentially stabilize theOH generated, which subsequently breaks down organic contaminants. The modified Fenton’s reaction has shown to be effective in degrading metaldehyde in natural waters (>92% removal), even at high contaminant concentrations (50mgmetaldehyde/L) and in the presence of high background organic matter and dissolved salts. The reaction is relatively pH insensitive. SLGO maintained its catalytic performance over 3 treatment cycles when immobilized. Its performance gradually decreased over time, reaching around 50% of starting performance on the 10th treatment cycle. X-ray photoelectron spectroscopy (XPS) analysis of modifications caused in SLGO by the oxidizing treatment indicated that the oxidation of CC sp2to carbonyl groups may be the cause of the decrease in performance. The proposed modified Fenton’s process has the potential to substitute traditional Fenton’s treatment although regeneration of the nanocarbon is required for its prolonged use

Urban morphology in the South: spontaneous and induced form

The paper is an urban morphology comparative study between four southern cities: São Paulo, Jakarta, Hanoi and Belo Horizonte, aiming to disclose common spatial outcomes of similar development processes, guided by positionality. Urban morphology was the tool used to read the distinct territories and territorial scales, through direct observation enabled by a joint fieldwork between the three researchers involved in the study. Therefore, the current research proposes a direct comparison of these elements, using fragments of four cities of diverse socio – politic and cultural backgrounds, but with similar industrialization and urbanization processes, aiming to reveal similarities between each city and its development; and the consequences of their urbanization process in a local scale.Peer Reviewe

The cyclin-dependent kinase inhibitor Orysa;KRP1 plays an important role in seed development of rice

Kip-related proteins (KRPs) play a major role in the regulation of the plant cell cycle. We report the identification of five putative rice (Oryza sativa) proteins that share characteristic motifs with previously described plant KRPs. To investigate the function of KRPs in rice development, we generated transgenic plants overexpressing the Orysa; KRP1 gene. Phenotypic analysis revealed that overexpressed KRP1 reduced cell production during leaf development. The reduced cell production in the leaf meristem was partly compensated by an increased cell size, demonstrating the existence of a compensatory mechanism in monocot species by which growth rate is less reduced than cell production, through cell expansion. Furthermore, Orysa; KRP1 overexpression dramatically reduced seed filling. Sectioning through the overexpressed KRP1 seeds showed that KRP overproduction disturbed the production of endosperm cells. The decrease in the number of fully formed seeds was accompanied by a drop in the endoreduplication of endosperm cells, pointing toward a role of KRP1 in connecting endocycle with endosperm development. Also, spatial and temporal transcript detection in developing seeds suggests that Orysa; KRP1 plays an important role in the exit from the mitotic cell cycle during rice grain formation

Medication Management Program Among Elderly at a Residential Facility

Abstract This quality improvement project aimed to address medication management-related issues at a residential facility. The project\u27s population was elderly residents who self- administered their medications. A root cause analysis and SWOT analysis identified multiple factors contributing to medication management errors, including lack of resident education, resident competency, and technology limitations. An intervention plan was developed and implemented in two phases. Phase 1 involved conducting medication reconciliation, assessing resident competency, and 1:1 educational sessions with the residents. Educational retention was assessed by using a pre-test and a post-test. Phase 2, to be implemented in the future, will address technology limitations, incorporate an electronic medical records (EMR) system, and provide ongoing staff education. Results from Phase 1 include 80% recalled new information while 20% showed no change after completion of the educational session and the pre/post-test; from those residents assessed with the Medi-Cog, 55% scored above 8 out of 10 while 45% scored below the cutoff score of 8, and last 100% of the Medication Administration Records (MAR) were reviewed. Although time constraints prevented Phase 2 interventions from being implemented, implementing an EMR system and a professional development plan for staff education are expected to contribute to further improvements in medication management at the residential facility. Continued monitoring and collaboration with the residents and staff are vital for sustained success