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  • General cognitive ability (or general intelligence; g) has been widely recognized to influence a broad array of cognitive abilities of both humans and mice. Working memory has also become recognized as a strong predictor of g in both humans and mice. Recent evidence suggests that a component of working memory, selective attention, is responsible for the relationship between working memory and g. In three experiments, we test a hypothesis that emerges from human behavioral studies which suggests that attentional disengagement, a component of selective attention, critically mediates its relationship with g, and therefore should be most strongly predictive of general cognitive performance. Experiments 1 and 2 both assess the factor loadings of selective disengagement tasks on a general cognitive factor derived from larger batteries of cognitive tests and finds that selective disengagement loads more highly than any other measures that place less explicit demands on disengagement. In experiment 3 we demonstrate how groups with known differences in cognitive abilities (young vs. old mice) differ significantly on measures of attentional disengagement. Our results provide support for the hypothesis that disengagement acts as the latent variable that determines intelligence.
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  • Like most cemeteries, the grounds of Laurel Hill are mostly covered by two things: grave markers and grass. Although landscaping is necessary to keep the grave markers clean, visible, and accessible, modern landscaping methods can potentially cause damage to Laurel Hill‘s hundred-year-old grave markers. This thesis looks at the methods used by groundskeepers at Laurel Hill and suggests changes that could be made to better protect and preserve the site. My investigation concentrates on grave markers installed during the Victorian period, between 1837 and 1901. I considered any and all modern-day landscaping equipment used by Laurel Hill‘s groundskeepers, including lawnmowers, pesticides, the removal of plants by hand, and especially string trimmers. Following my research, this thesis recommends that financial resources be reallocated to hire landscapers that specialize in cemetery maintenance. Further, this thesis recommends that additional study be conducted, and a master plan commissioned.
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  • Readmission within 30 days of hospital discharge and avoidable emergency room visits have been shown to result in substantial costs and increased risk to patients. Evolving payment models under the ACA are focused on reducing unnecessary costs and decreasing short-term readmissions and will eliminate or reduce payment for 30-day readmissions after treatment for specified conditions and procedures. Evolving communications technology can help providers and patients to exchange critical patient data in the vulnerable post-discharge period and can encourage a shift to shared responsibility and collaboration between patients and providers. However, many providers are not prepared to collect, analyze, or respond to PGHD in their existing workflows, to make it actionable at the point of care, and to establish best practices for the use of PGHD. This study considers the patient’s outcomes of readmission and/or emergency department use in relation to the use of conversational artificial intelligence in the form of chatbots to gather structured PGHD which is integrated directly into the patient’s EHR and into usual provider workflow, making it available in real time for the provider for use in treatment decisions. Additionally, the study describes characteristics of patients elect or decline to participate in the use of chatbots and their preferences for how they receive and send messages. This study may provide valuable insight into developing optimal models of chatbot use for PGHD sharing and for the establishment of best practices for future implementations of this emerging technology.
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  • Global mean temperatures have risen above pre-industrial temperatures resulting in a sea level rose 0.3 – 0.4m between 1901-2010 in the Mid-Atlantic (Kopp et al., 2016) and causing increasingly frequent and intense storms (Trenberth, 2011). These changes in environmental factors are linked to changes in vegetation communities in coastal marsh and adjacent maritime forest. This vegetation change is evident in the appearance of standing dead trees among tidal salt marsh vegetation known as “Ghost Forests”. This study investigates this transition of maritime forest to tidal saltwater marsh observed in New Jersey, USA. The spatial location of the salt marsh-upland forest edge was mapped using historical aerial photography and the rates of edge migration were measured at eight sites in New Jersey, USA. This study also reviews the present state of knowledge of the geographic scope and potential mechanisms behind forest edge migration along the eastern seaboard of the United States and investigates. The results were compared to data gathered on several of the identified mechanisms to determine the potential role each mechanism may be playing in the forest edge migration. Using aerial photography between 1940 and 2015 at intervals ranging from ten to two years, this study demonstrates that forest dieback is occurring at the forest- coastal marsh interface and that salt marsh is expanding into this transition zone. The rates of forest edge migration observed at the 8 sites varied geographically and across the 75 year time period. This variation in forest edge migration rate is likely due to a combination of mechanisms that vary between sites, some as direct mechanisms and others as modulators. The driving mechanisms of migration of the forest edge are likely sea level rise induced changes in groundwater and increased severity of storm surges, as these mechanisms directly affect the soil properties of the ecosystem. These mechanisms are ultimately controlled by climate change induced changes in SLR and storm intensity, but are moderated by other physical phenomena such as changes in tidal flooding and human land use alterations.
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  • Recent discoveries in both investigating and modulating cells have enriched our understanding and knowledge about cellular behavior, signaling pathways as well as molecular mechanisms. In addition, tremendous advances in nanomaterials, especially nanomaterial-based optical probes, have enabled scientists to not only study various molecular, cellular, cell-environment interactions at the nanoscale level, but also interrogate, perturb as well as manipulate biological behaviors at different scale functionally and therapeutically. As a result, nanotechnology-based optical investigation and manipulation at the biological and neural interfaces have gained great research interests and attentions for the purpose of understanding studying physiological mechanisms, identifying pathogenic pathways, and developing enhanced treatments of devastating diseases.In the introductory chapter, the discussion is focused on recent advances of nano-optical probe-based cellular sensing and manipulations. Firstly, the nanoprobe-based optical sensing of cellular environments is elaborated, followed by detailed discussion on applications in cellular activities investigation. Finally, light-mediated nanoparticle-based cellular manipulations and behavior controls is discussed. To better investigate and further regulate the complex biological processes, near infrared (NIR) could be an ideal stimulus for modulating the spatiotemporal dynamics of signals in living cells and organisms with high resolution. Subsequently, initial work on the development of NIR-responsive lanthanide-doped nanomaterials with orthogonal emissions for dynamic photo-switching reaction control is presented. Two studies utilizing NIR-responsive nanomaterials for small molecule release monitoring and neurotransmitter imaging are stated. These works represent the sensing aspects of photo-responsive nanomaterials probing at the cancer and neural interfaces. Two proof-of-concept studies on NIR-mediated stem cell behaviors control is incorporated in the later chapters. Lastly, in the final chapter, recent works on biodegradable dendritic peptide nanoparticle platform for regenerative medicine and cancer therapeutic applications are discussed. Moreover, the translational journey and perspectives of the dendritic peptide nanoparticle system for next-generation pancreatic cancer therapy are presented.
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  • Unique functions of living organisms in nature inspire a broad spectrum of engineering systems. Since biological living systems are often composed of multiple soft active materials with micro-scale three-dimensional (3D) structures, fundamental understanding on soft active materials and development of micro 3D manufacturing techniques are essential for effective implementations of their characteristics and functionalities. Hydrogels are soft polymeric materials that undergo volumetric changes upon solvent absorption. Some hydrogels exhibit such changes in response to external environmental conditions, such as temperature, pH, light, magnetic field, electric field, and chemical triggers, which are referred to as stimuli-responsive hydrogels. They have played an important role in a variety of applications, such as soft robotics, soft electronics, and biomedical engineering. Despite the growing attention to stimuli-responsive hydrogels and their diverse applications, manufacturing techniques for stimuli-responsive hydrogels have been limited to simple two-dimensional (2D) fabrication methods which restrict full utilization of their unique material behavior.This dissertation focuses on the development and application of a high-resolution multi-material 3D digital fabrication technology, multi-material projection micro-stereolithography (MM-PuSL), in order to engineer stimuli-responsive hydrogels into 3D multi-functional soft active devices. Specifically, it consists of development of MM-PuSL, studies of fundamental physics for various stimuli-responsive hydrogels, including electroactive hydrogels, thermo-responsive hydrogels, and photo-active hydrogels, micro 3D printing of stimuli-responsive hydrogels, and development of multi-functional soft active devices, such as soft robots actuated by temperature changes or electric fields, and light-driven camouflage skin.
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  • Dioxins and dioxin-like compounds are highly toxic, ubiquitous polycyclic aromatic hydrocarbons with important environmental and human health impacts. Dioxins are listed among the most relevant environmental organic pollutants due to their high persistence and extreme lipophilicity. In recent years, a number of bacterial strains have been isolated and identified for their diverse metabolic capabilities to grow on and metabolize a broad range of environmentally recalcitrant compounds including, dibenzo-p-dioxin and dibenzofuran. Among these strains Sphingomonas wittichii RW1 has been one of the most effective dioxin degraders studied so far. RW1 is of great interest for its diverse metabolic activities and unusual genome structure. The complete genome sequence of RW1 reveals that this strain contains one chromosome and two circular megaplasmids referred to as pSWIT01 and pSWIT02. Many of the important catabolic genes that are involved in dibenzofuran and dibenzo-p-dioxin degradation are located on the small megaplasmid pSWIT02; particularly genes encoding the initial dioxygenase system DxnA1A2, a ferredoxin Fdx3, and a reductase RedA2. This unusual dioxygenase system initiates the oxygenolytic attack of dibenzofuran and dibenzo-p-dioxin in an angular fashion. Here we report the first physiological identification of the important proteins that together function as the initial dibenzofuran and dibenzo-p-dioxin dioxygenase enzyme in RW1. Knock out mutagenesis showed that two reductases RedA1 and RedA2 and two ferredoxins Fdx1 and Fdx3 are interchangeable where either RedA1/RedA2 in combination with Fdx1/Fdx3 can function as an electron donor to the terminal oxygenase. The knockout mutants were also screened on substrates other than dibenzofuran and dibenzo-p-dioxin such as salicylate and benzoate. We discovered that the reductase RedA2 is involved in supplying electrons to the salicylate oxygenase since deletion of the redA2 gene blocked the growth of RW1 on salicylate. Interestingly, single knockout mutants of redA1 and redA2 had no effect on RW1's ability to grow on benzoate while a double knockout mutant resulted in the loss of the ability to grow on benzoate. In addition, we constructed stable and unstable cloning vectors for sphingomonads based on the Sphingobium yanoikuyae B1 pKG2 plasmid and the Sphingomonas wittichii RW1 pSWIT02 plasmid. Stable vectors included the rep and par plasmid regions for replication and partitioning while unstable vectors included only the rep region. The stable vector pSEZ_RW1RP was used to cure RW1 of pSWIT02 by plasmid incompatibility. The cured strain RW1c was no longer able to grow on dibenzo-p-dioxin or dibenzofuran. A complementation test with the broad host range plasmid pRK415 carrying the initial dioxygenase system allows RW1c to grow on both dibenzo-p-dioxin and dibenzofuran. These results demonstrate that the only major role that pSWIT02 plays in the degradation of dibenzo-p-dioxin and dibenzofuran is to supply the initial dioxygenase responsible for the first step in the catabolic pathway.
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  • The interaction between cognate T and B cells decides the progression of an immune response to a pathogen or self-antigen. Of the multiple signals that synchronize to fine-tune this union, the binding of CD40 on the surface of B cells to CD40L expressed on CD4 T cells is of paramount importance. Ligation of CD40 on antigen-experienced B cells is associated with the initiation and development of germinal centers (GCs) resulting in the subsequent generation of high affinity antibodies and B cell memory. Post-transcriptional regulation of CD40L has been implicated in regulating the activation dependent expression of this protein. Our lab has previously shown a polypyrimidine tract binding protein complex binds to the 3’ UTR of the CD40L mRNA and that the deletion of a PTBP1 binding stability element in the same results in a significant decrease in the half-life of the CD40L transcript and subsequently the surface expression at later stages of activation in vitro. To understand the biological basis for activation-induced posttranscriptional regulation of CD40L, a mouse was engineered with a deletion of two segments in the PTBP1 stability element that provide stability to the transcript and termed CD40LΔ5 (data not shown, work done by K. Voskoboynik and J. La Porta). Notably, splenic CD4 cells from the CD40LΔ5 mouse showed decreased CD40L expression at later stages following ex vivo activation. It has been well established that CD40L knock-out mice are unable to surmount an adequate immune response when subject to antigen challenge. The question we asked was whether the activation-induced pathway of CD40L mRNA stability was required to achieve an optimal immune response. It has been shown that GC B cells constantly shuttle between the T follicular (Tfh) rich, light zone (LZ) and the dark zone (DZ) where they undergo somatic hypermutation. B cells rely on interactions with the Tfh cells to provide direction as to how to evolve to optimize the immune response. We hypothesized that this interaction would be disrupted in CD40LΔ5 mice and subsequently result in the Tfh cells being unable to provide durable support to the B cells to develop into functioning antibody factories.To test our hypothesis, we assessed the immune response in CD40LΔ5 and wild type mice in response to a T dependent antigen, NP-KLH. We observed significantly reduced levels of antigen-specific antibodies in the mutant mice when compared to the wild type by ELISA. On evaluating whether this decreased antibody generation was subsequent to a reduced number of plasma cells (by ELISPOT), we found that there was indeed a decrease in the number of NP-KLH specific clones of plasma cells in the CD40LΔ5 mice. The splenic sections from WT and mutant mice revealed that the mutant mice were able to produce GCs in contrast to the CD40L knock out mice, but these GCs were much less organized with scattered GL7 (marker of GC B cells) positive cells when compared to the wildtype where distinct GL7 positive cores were surrounded by IgD positive rings. This data suggested that the CD40LΔ5 is allowing for seeding and initiation of GCs, but at subsequent stages, deregulated CD40L results in less effective development of the immune response.Based on phenotypic and genotypic evaluation we conclude that the CD40LΔ5 mice have reduced number of organized GCs and in turn lower levels of antibody secreting plasma cells and consequently lower titers of antibodies from isotypes IgG1, IgG2b, IgG2c, and IgM against NP. We also found decreased affinity maturation in the CD40LΔ5 mice, but the SHM rate was similar to that of the wild type. In addition, the alteration in CD40L mRNA stability alters the development of the memory B cell and long-term plasma cell populations. When we looked at differentially expressed genes by RNAseq, several genes associated with proliferation were down regulated in the CD40LΔ5 mice. On the contrary, genes linked to apoptosis were upregulated in the CD40LΔ5. We were able to confirm this pattern by flow cytometry on GC B cells. The sum total of our data strongly supports a major role for the posttranscriptional pathway of CD40L mRNA stabilization for regulating expression and ensuring the timely availability of CD40L on Tfh cells to signal activated B cells to produce a robust humoral response.
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