Is MOOC Madness Here To Stay? An Institutional Legitimacy Study Of Employers

This dissertation aims to assess the degree of human resource personnel\u27s acceptance of Massive Open Online Course (MOOC) providers. It is a critical part of understanding if MOOCs offer a viable and sustainable form of education because employer buy-in is essential to MOOCs\u27 success, according to many who have studied this online learning phenomenon. The sample for this study primarily was Society of Human Resource Management (SHRM) board and committee members located in metropolitan areas throughout the U.S, with 112 qualified participants. Participants were recruited through email and other online methods to take the survey. The survey had three sections, including demographic questions, a Likert-like section based on key MOOC characteristics, and a choice-based conjoint (CBC) exercise in which participants selected the most qualified job applicant from a pool of mock candidates--some with MOOC credentials. The results of this study reveal that participants, though largely unaware of MOOCs, are generally receptive to them once learning of their attributes. However, participants still prefer traditional education and work experience more than MOOCs when screening applicants--a finding uncovered during the simulation exercise. Despite this preference for traditional employment credentials, participants showed statistically significant preference for MOOCs when combined with traditional education. These results have implications for many higher education stakeholders, including employers, students, and higher education institutions

Mechanistic approaches for reactivation and elimination of latent HIV-1

Although HIV-1 can be adequately controlled by combination antiretroviral therapy (cART), it is still an incurable disease due in part to the latent reservoir that persists in resting CD4+ T cells (rCD4s). Latently infected rCD4s do not actively express HIV-1, allowing them to evade immune surveillance, but their ability to reinitiate viral expression maintains this barrier to a cure. Shock-and-kill, a prominent strategy for HIV-1 eradication, requires the reactivation of latent HIV-1 gene expression. Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we explore a strategy involving a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. We show that rapamycin downregulates markers of toxicity, including pro-inflammatory cytokine release and cellular proliferation, induced by potent T cell activating agents. Using an ex vivo assay for HIV-1 mRNA in rCD4s from infected individuals on antiretroviral therapy, we demonstrate that despite this immunomodulatory effect, rapamycin does not affect HIV-1 gene expression induced by T cell activation. In contrast the immunosuppressant cyclosporin, a calcineurin inhibitor, robustly inhibits HIV-1 reactivation. Importantly, cytotoxic T lymphocyte (CTL) recognition and killing of infected cells is also not impaired by rapamycin treatment. These findings are also being extended to HIV-positive individuals requiring solid organ transplant, which acts an in vivo immune activating stimulus without the need for additional intervention. A previous study has shown that a group of these patients who received rapamycin for immunosuppressive maintenance had lower levels of HIV-1 DNA in peripheral blood cells when compared with patients receiving a calcineurin inhibitor such as cyclosporin. This previous finding is in support of our findings, and suggests that rapamycin may allow for shock-and-kill in vivo. Here we compare pre- and post- transplant reservoir size using a novel assay, the quantitative viral induction assay (QVIA), and discuss the surprising result of an increase in the size of the HIV-1 latent reservoir post-transplant. Alternatively, compounds that may not elicit T cell activation phenotypes, and are not necessarily thought to act via any of the same pathways as T cell activation, may effectively stimulate HIV-1 transcription. Several latency reversing agents (LRAs) have activity in primary rCD4s isolated from patients on cART, including PKC agonists, HDAC inhibitors (HDACi), and bromodomain and extra-terminal (BET) bromodomain inhibitors. Of particular interest are HDACi, as there are several drugs in this class approved for clinical use. Although the activity of HDACi on HIV-1 expression is well documented; they act synergistically with other LRAs in primary cells and have high activity alone in several cell models for latency; these drugs have a broad scope of activities and their mechanism of action in this context is controversial. If a mechanism can be identified, a more targeted approach to reactivate latent HIV-1 may be developed. We therefore used a combination of gene expression and transcription factor array studies in the context of both primary and model cells to further understand how HDACi may be acting upon HIV-1 transcription. Using specific small molecule inhibitors we have identified a potential role for p21 in HDACi activity on latent HIV-1

Building and Maintaining LGBTQ+ Picture Book Collections

The LGBTQ+ community has had to continuously fight for their rights, including their right to be represented in the library. This toolkit provides instruction on how to develop and manage a library collection of LGBTQ+ children’s picture books. It is split into four sections that include a guide to evaluating materials, recommended picture books, a guide to fighting censorship, and a list of recommended resources

2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents

2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents

Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.Published versio

Stable pollination service in a generalist high Arctic community despite the warming climate

Insects provide key pollination services in most terrestrial biomes, but this service depends on a multistep interaction between insect and plant. An insect needs to visit a flower, receive pollen from the anthers, move to another conspecific flower, and finally deposit the pollen on a receptive stigma. Each of these steps may be affected by climate change, and focusing on only one of them (e.g., flower visitation) may miss important signals of change in service provision. In this study, we combine data on visitation, pollen transport, and single-visit pollen deposition to estimate functional outcomes in the high Arctic plant-pollinator network of Zackenberg, Northeast Greenland, a model system for global warming-associated impacts in pollination services. Over two decades of rapid climate warming, we sampled the network repeatedly: in 1996, 1997, 2010, 2011, and 2016. Although the flowering plant and insect communities and their interactions varied substantially between years, as expected based on highly variable Arctic weather, there was no detectable directional change in either the structure of flower-visitor networks or estimated pollen deposition. For flower-visitor networks compiled over a single week, species phenologies caused major within-year variation in network structure despite consistency across years. Weekly networks for the middle of the flowering season emerged as especially important because most pollination service can be expected to be provided by these large, highly nested networks. Our findings suggest that pollination ecosystem service in the high Arctic is remarkably resilient. This resilience may reflect the plasticity of Arctic biota as an adaptation to extreme and unpredictable weather. However, most pollination service was contributed by relatively few fly taxa (Diptera: Spilogona sanctipauli and Drymeia segnis [Muscidae] and species of Rhamphomyia [Empididae]). If these key pollinators are negatively affected by climate change, network structure and the pollination service that depends on it would be seriously compromised.Peer reviewe

Stable pollination service in a generalist high Arctic community despite the warming climate

Insects provide key pollination services in most terrestrial biomes, but this service depends on a multistep interaction between insect and plant. An insect needs to visit a flower, receive pollen from the anthers, move to another conspecific flower, and finally deposit the pollen on a receptive stigma. Each of these steps may be affected by climate change, and focusing on only one of them (e.g., flower visitation) may miss important signals of change in service provision. In this study, we combine data on visitation, pollen transport, and single-visit pollen deposition to estimate functional outcomes in the high Arctic plant-pollinator network of Zackenberg, Northeast Greenland, a model system for global warming–associated impacts in pollination services. Over two decades of rapid climate warming, we sampled the network repeatedly: in 1996, 1997, 2010, 2011, and 2016. Although the flowering plant and insect communities and their interactions varied substantially between years, as expected based on highly variable Arctic weather, there was no detectable directional change in either the structure of flower-visitor networks or estimated pollen deposition. For flower-visitor networks compiled over a single week, species phenologies caused major within-year variation in network structure despite consistency across years. Weekly networks for the middle of the flowering season emerged as especially important because most pollination service can be expected to be provided by these large, highly nested networks. Our findings suggest that pollination ecosystem service in the high Arctic is remarkably resilient. This resilience may reflect the plasticity of Arctic biota as an adaptation to extreme and unpredictable weather. However, most pollination service was contributed by relatively few fly taxa (Diptera: Spilogona sanctipauli and Drymeia segnis [Muscidae] and species of Rhamphomyia [Empididae]). If these key pollinators are negatively affected by climate change, network structure and the pollination service that depends on it would be seriously compromised