“How Can We Avoid a Columbia?”

American universities were unprepared for the explosion of student protests on their campuses in the mid-1960s. Consequently, trustees of many leading universities appointed their industrial relations professors—the National War Labor Board vets and their protégés—as their new presidents, chancellors, and top deans. Clark Kerr botched the job at the University of California at Berkeley, but the Labor Board vets were more successful elsewhere. They not only mediated conflicts on their campuses but designed conflict-resolution systems that remain in place at universities and colleges throughout the nation. Their systems drew on the models they created with unions and management in the 1940s. This chapter explains the development by focusing on Robben Fleming at the University of Michigan, John McConnell at the University of New Hampshire, and John Dunlop at Harvard University.

Numerical Model of a Vertical-Axis Cross-Flow Tidal Turbine

An array of close-packed contra-rotating cross-flow vertical-axis tidal rotors, a concept developed to maximize the fraction of flow passage swept, has potential advantages for hydrokinetic power generation. To predict the commercial feasibility of such rotors in large-scale application, a numerical model of a vertical-axis turbine (VAT) with a torque-controlled system is developed using an actuator line model (ALM). The open-source OpenFOAM computational fluid dynamics (CFD) code is first coupled with this ALM model, and efficiently parallelized to examine the characteristics of turbulent flow behind a vertical axis tidal turbine. The numerical model is validated against previous experimental measurements from a 1:6 scale physical model of a three-bladed reference vertical axis tidal turbine at the University of New Hampshire (UNH-RM2). Satisfactory overall agreement is obtained between numerical predictions and measured data on performance and near-wake characteristics, validating the numerical model. Details of the model setup and discussions on its output/results are included in the paper.

GDF1 Regulation of Ceramide Metabolism Restores Effective Hematopoiesis in Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a clonal hematopoietic disorder characterized by ineffective hematopoiesis, cytopenias, and an increased risk of transformation to acute myeloid leukemia. New studies are urgently needed to understand the underlying processes that govern MDS and related bone marrow failure disorders and to develop better therapeutic modalities. Sphingolipids are an extensive classification of lipids which play prominent roles in cellular signaling in addition to being essential components of membranes. The most well studied sphingolipid is ceramide, which serves as a hypothetical center of sphingolipid metabolism. Ceramide is an important cellular signal that can lead to apoptosis. Overall ceramide biology is significant because novel metabolic routes that persist in MDS may be exploited for therapeutic development. Interestingly, the gene encoding ceramide synthase 1 is encoded from a bicistronic transcript that also encodes for GDF1. Little is known about the roles of GDF1 outside of cardiac development. However, GDF1 is in the TGF-beta superfamily of which many members have been attributed roles in stem cell biology. Therefore, a better understanding of the role of GDF1 and its regulation of ceramide metabolism and hematopoiesis may lead to better treatment approaches for MDS and other bone marrow failure syndromes. The current study tested an overarching hypothesis that GDF1 regulates SMAD and STAT signaling to promote ceramide generation and restore effective myelopoiesis in MDS. Initially, the expression of GDF1 was evaluated in hematopoietic cells isolated from transgenic murine models of MDS (Nup98-HoxD13; Srsf2P95H-mutant) as well as myeloproliferation (Flt3ITD). Interestingly, GDF1 expression was greatest in the bone marrow of MDS models. This was significant because we recently reported that nanoliposomal ceramide (Lip-C6), which delivers a bioactive ceramide analog, exerts unique therapeutic efficacy towards acute myeloid leukemia arising out of MDS (Barth et. al. Blood Advances 2019). Lip-C6 is a ceramide-based therapy that currently is in a clinical trial for solid tumor malignancies (ClinicalTrials.gov identifier: NCT02834611). Next, treatment of transgenic MDS mice with either recombinant GDF1 or Lip-C6 was shown to stimulate the expansion of erythroid progenitors. This was concomitant with a decrease in immature myeloid cells, which was revealed to be due to granulo-monocytopoietic differentiation. Mechanistic studies subsequently revealed that GDF1 increased SMAD2/3 phosphorylation while simultaneously down regulating STAT3 (Y705) phosphorylation, both in a TGF-beta receptor 1-dependent fashion. This dual effect was unique to GDF1, whereas TGF-beta or GDF3 only recapitulated individual the effects on SMAD2/3 and STAT3 signaling, respectively. Finally, STAT3 binding sites were identified in the promoter region of the ceramide detoxifying enzyme glucosylceramide synthase. This is important because glucosylceramide synthase expression was shown to be downregulated by recombinant GDF1 treatment. Therefore, GDF1-mediated downregulation of STAT3-dependent glucosylceramide synthase expression provides a mechanistic link where GDF1 can augment intracellular ceramide levels. Overall, this study enhances our understanding of a fundamental hematopoietic process where GDF1 regulates ceramide metabolism and myelopoiesis. This is impactful because the effects of GDF1, which are unique from other related factors including TGF-beta and GDF3, are due to a novel mechanism of action that both upregulates SMAD2/3 signaling while downregulating STAT3 signaling. More so, this study demonstrated that GDF1, and/or ceramide, can exert an anti-MDS therapeutic role by restoring normal aspects of myelopoiesis. This work was funded by NIH/NCI K22 CA190674 (B.M.B.) and University of New Hampshire COBRE Pilot Project Grant NIH/NIGMS P20 GM113131 (B.M.B.). The authors acknowledge US Provisional Patent 62/602,437, issued to B.M.B. and the University of New Hampshire. Disclosures Barth: University of New Hampshire: Patents & Royalties: US Provisional Patent 62/602,437; NIH (NCI and NIGMS): Research Funding. Loughran:Bioniz: Membership on an entity's Board of Directors or advisory committees; Keystone Nano: Membership on an entity's Board of Directors or advisory committees.

GDF1 Is a Regulator of Sphingolipid Metabolism in Acute Myeloid Leukemia

BACKGROUND: Mutations to epigenetic and spliceosome regulators frequently occur in acute myeloid leukemia (AML) and contribute to the underlying pathobiology of the disease. In addition, recent studies have sought to improve the anti-AML efficacy of sphingolipid-based therapeutics by identifying the underlying mechanisms responsible for dysfunctional sphingolipid metabolism. Sphingolipids are an extensive classification of lipids that play profound roles in membrane structure as well as regulation of cellular function and fate. Ceramide, as the hydrophobic moiety of sphingolipids, serves as the hypothetical center of sphingolipid metabolism. It regulates cellular stress responses and apoptosis, whereas many of its metabolites regulate opposing processes such as proliferation and survival. Growth/differentiation factor 1 (GDF1) is a TGF-beta superfamily member, of which other members have been attributed roles in stem cell biology and hematopoiesis. Mutations in GDF1 have been found to be associated with congenital cardiovascular malformations, yet little is known about the role of GDF1 outside of cardiac development. GDF1 is encoded from a bicistronic gene that also encodes for ceramide synthase 1 (CERS1), which is responsible for generating the C18:0 species of ceramide. Recently, an anti-AML role was attributed to CERS1 in FLT3-ITD-mutated AML (Dany et. al. Blood 2016). However, a potential role for GDF1 was not evaluated in this study. Intriguingly, in preliminary work using FLT3ITD transgenic mice we observed an inverse correlation between the expression of GDF1 and UGCG which encodes for the ceramide detoxifying enzyme glucosylceramide synthase. Therefore, our present study tested the hypothesis that GDF1, encoded from the bicistronic CERS1-GDF1 gene, exerts anti-AML efficacy by downregulating ceramide neutralization and promoting stem cell differentiation METHODS & RESULTS: Studies were carried out using AML cell lines as well as primary cells harvested from transgenic murine models of myelodysplastic syndrome (MDS) and AML (FLT3ITD, Nup98-HoxD13, Srsf2P95H-mutant, Tet2-deficient, Asxl1-deficient, and Tert-deficient). The expression of GDF1 was evaluated by real time qPCR in hematopoietic cells isolated from these models of MDS and AML. GDF1 expression was greatest in Srsf2P95H-mutant (MDS) samples, which corresponded to enhanced sensitivity to ceramide-based therapies. We had recently reported this MDS-specific sensitivity for nanoliposomal ceramide (Barth et. al. Blood Advances 2019), which is a ceramide-based therapy currently in a clinical trial for solid tumor malignancies (ClinicalTrials.gov identifier: NCT02834611). Next, cell lines and models were treated with recombinant GDF1. Real time qPCR revealed that GDF1 treatment downregulated the expression of the genes in the ceramide neutralization pathway including UGCG. In addition, flow cytometry was used to show that GDF1 treatment promoted hematopoietic stem cell differentiation. Lastly, C57BL/6J mice engrafted with C1498 AML cells was used to show that GDF1 enhanced the therapeutic efficacy of cytarabine and nanoliposomal ceramide. CONCLUSIONS: Overall, this study provided evidence for differential expression of GDF1 in subtypes of MDS and AML and showed that GDF1 can regulate sphingolipid metabolism by downregulating ceramide neutralization. Importantly, we have demonstrated that GDF1 exerts anti-AML efficacy in combination with either standard care therapy or ceramide-based therapy. Therefore, GDF1-elevating strategies are well-positioned as novel therapeutic approaches for the treatment of AML and related myeloid hematological disorders. This work was funded by NIH/NCI K22 CA190674 (B.M.B.) and University of New Hampshire COBRE Pilot Project Grant NIH/NIGMS P20 GM113131 (B.M.B.). The authors acknowledge US Provisional Patent 62/602,437, issued to B.M.B. and the University of New Hampshire. Disclosures Loughran: Bioniz: Membership on an entity's Board of Directors or advisory committees; Keystone Nano: Membership on an entity's Board of Directors or advisory committees. Barth:University of New Hampshire: Patents & Royalties: US Provisional Patent 62/602,437; NIH (NCI and NIGMS): Research Funding.

Open-Source Computational Fluid Dynamics in Engineering Education

Computational Fluid Dynamics (CFD) is widely used in industry but is not discussed sufficiently in undergraduate engineering education. In some cases, CFD is studied only from a mathematical perspective, focusing on computational partial differential equations, and in some cases it is introduced as a black-box tool. A hybrid CFD class was developed for undergraduate and graduate students at the University of New Hampshire, which combines the two approaches. The students are exposed to the mathematics and physics behind CFD, and they also utilize OpenFOAM — an open source CFD package — to work on practical problems. Since the code is open-source, the students are able to see and modify it. Although OpenFOAM is challenging due to the minimum graphical user interface, the code-base environment forces the students to learn what the code is doing. Sample assignments and project submissions from the students are presented in the paper.

Thanks and Welcome!

It is with saddened heart that I announce the retirement of Dr. Nancy Richeson, PhD, CTRS, FDRT as Editorin- Chief of the American Journal of Recreation Therapy (AJRT). . .As with many transitions, change can be unsettling. Fortunately for the American Journal of Recreation Therapy and the field, I am pleased to welcome Dr. Allison Wilder, PhD, CTRS/L as our new Editor-in-Chief. Dr. Wilder is Associate Professor and Faculty Fellow at the Center on Aging and Community Living in the Department of Recreation Management and Policy at the University of New Hampshire—College of Health and Human Services.

Corals in the Anthropocene

Peter F. Sale is a marine ecologist. He has been a faculty member at the University of Sydney, Australia; the University of New Hampshire, USA; and the University of Windsor, Canada, where he is currently professor emeritus. His research in Hawai‘i, Australia, the Caribbean, and the Middle East has focused primarily on reef fish ecology and on the management of coral reefs. In his 2011 book ...