Five Year Carbon Storage Analysis in the Gordon Natural Area

The Gordon Natural Area (GNA) serves as a natural laboratory for a range of class research projects. In a Geography Field Methods course led by Dr. Fritschle, students established five permanent carbon-study plots in 2008. Since then, students have returned to these plots to measure the carbon stock of standing trees in five plots located along a topographic gradient: floodplain, ridge-top, lower mid-slope, mid-slope and upper mid-slope. Using U.S. Forest Service established guidelines, all trees greater than 5 cm and up to 73 cm in diameter at breast height (DBH) were measured and identified within each 40 m circular plot. To ensure the same trees were measured each year, distance and azimuth from plot center were also collected. The woody species composition, forest structure, and carbon stock were compared between plots and across years using non-metric multidimensional scaling. While Tulip poplar (Liriodendron tulipfera) and American beech (Fagus grandifolia) remained the most single dominant overstory and understory species (respectively) through time, the analysis did suggest the forest is likely changing. Specifically, carbon stock appears to be declining; however no significant difference was established for data from one year to the next. This is further suggested by the paucity of understory trees compared to the overstory. Previous studies by students have found that these five plots are not statistically different from the rest of the Big Woods area in the GNA. More study is needed as these permanent plots do point to a potential decline in standing tree carbon stock in the GNA over the last five years. Given the importance of forests in mitigating the negative effects of climate change, this finding is especially of concern

Speciation leads to divergent methylmercury accumulation in sympatric whitefish

Central European lake whitefish (Coregonus spp.) colonized Swiss lakes following the last glacial retreat and have undergone rapid speciation and adaptive radiation. Up to six species have been shown to coexist in some lakes, and individual species occupy specific ecological niches and have distinct feeding and reproductive ecologies. We studied methylmercury (MeHg) accumulation in sympatric whitefish species from seven Swiss lakes to determine if ecological divergence has led to different rates of MeHg bioaccumulation. In four of seven lakes, sympatric species had distinctly different MeHg levels, which varied by up to a factor of two between species. Generally, species with greater MeHg levels were smaller in body size and planktivorous, and species with lower MeHg were larger and benthivorous. While modest disparities in trophic position between species might be expected a priori to explain the divergence in MeHg, δ15N of bulk tissue did not correlate with fish MeHg in five of seven lakes. Results of a nested ANCOVA analysis across all lakes indicated that only two factors (species, lake) explained substantial portions of the variance, with species accounting for more variance (52%) than inter-lake differences (32%). We suggest that differences in MeHg accumulation were likely caused by diverging metabolic traits between species, such as differences in energy partitioning between anabolism and catabolism, potentially interacting with species-specific prey resource utilization. These results indicate substantial variability in MeHg accumulation between closely related fish species, illustrating that ecological speciation in fish can lead to divergent MeHg accumulation pattern

Baker Center Journal of Applied Public Policy, Vol. I No. I

Welcome to the first issue of the Baker Center Journal of Applied Public Policy. Throughout my many years of service, I always have been impressed with the tremendous good that can be accomplished through the creation and implementation of sound public policy. I hope that, along the way, I have contributed to the body of policies that help our nation function in a strong, effective, compassionate, and prosperous fashion. As we launch this new Journal, under the auspices of the Howard H. Baker Jr. Center for Public Policy at the University of Tennnnessee, I wanted to briefly expand on some of the reasons I believe that this journal is necessary and why I believe that research on public policy is so vitally important. This Journal aims to discuss applied public policy. The goal is not to engage in theoretical discussions, though I believe those are important. Instead, we hope that the Baker Journal will focus on the most current issues that directly affect our nation and our world on the operational, or mechanical level. We intend to engage a wide variety of contributors. Scholars, of course, will be asked to write on critical topics of research. We also aim to include contributions from those who draft, approve and execute public policy at the local, state, and national levels. Additionally, at least one article in each issue will be reserved for the work of a university-level student. Our approach is varied, and I know that the result will be an intellectually sound and extraordinarily interesting presentation of experiences and ideas.I am especially pleased that so many University of Tennnnessee students are involved in the formulation and operation of the Journal. Our editorial board is comprised of some of the University of Tennnnessee’s most promising undergraduate, graduate, and law school students. With dedicated assistance and oversight from faculty and from the Baker Center, this board of extraordinarily intelligent and committed students has worked very hard to make this Journal a reality. The Center has also formed a national advisory panel for the Journal. I am a member of that panel, and I must note that I am grateful for the involvement and support of my colleagues who have agreed to serve with me: Ms. Emily Reynolds, former Secretary of the United States Senate; Congressman Bob Clement, former Tennnnessee Congressman; Mr. Glennnn Reynolds, noted author and professor of law at the University of Tennnnessee; Dr. Joseph Cooper, an accomplished professor of political science at Johns Hopkins University; and Mr. John Seigenthaler, distinguished journalist and founder and director of the First Amendment Center at Vanderbilt University. I believe it is critical that we think deeply about the issues that are confronting us today. Our representative system of governance is based on an informed citizenry and informed public servants. From international issues such as the war on terror and energy challenges to more local but equally important topics such as sustainable development and education, we must commit ourselves to understanding all challenges free of partisan rhetoric. Only then can we confront them together. It is my hope that this Journal will add to that understanding and will speak to many audiences. From the classroom to the boardroom, from city hall to the halls of our legislatures, I believe the work put forward in our journal will be useful for everyone who wants to be informed and engaged. It is an exciting undertaking, and I thank you for your support

Perspectives on Astrophysics Based on Atomic, Molecular, and Optical (AMO) Techniques

About two generations ago, a large part of AMO science was dominated by experimental high energy collision studies and perturbative theoretical methods. Since then, AMO science has undergone a transition and is now dominated by quantum, ultracold, and ultrafast studies. But in the process, the field has passed over the complexity that lies between these two extremes. Most of the Universe resides in this intermediate region. We put forward that the next frontier for AMO science is to explore the AMO complexity that describes most of the Cosmos.Comment: White paper submission to the Decadal Assessment and Outlook Report on Atomic, Molecular, and Optical (AMO) Science (AMO 2020

Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.This work was supported by National Science Foundation (NSF) Grant MCB0956027 and National Institutes of Health Grant R03 MH081231-01 from the Molecular Libraries Program (to A. W. N.); University of New Mexico Center for Molecular Discovery Molecular Libraries Probe Production Centers (UNMCMD MLPCN) National Institutes of Health Grants U54MH084690 and R01HL081062 (to L. A. S.); UNM National Center for Research Resources (NCRR) Grant 5P20RR016480 (to L. G. H.); National Institutes of Health Grant R21 CA170375-01 through the NCI (to A. W. N., L. G. H., and J. E. G.); National Institutes of Health Grants NS066429 and AI092130 (to T. B.); and University of Kansas Specialized Chemistry Center (KUSCC) MLPCN National Institutes of Health Grant U54HG005031 (to J. A.)

Germline EPHB2 Receptor Variants in Familial Colorectal Cancer

Familial clustering of colorectal cancer occurs in 15–20% of cases, however recognized cancer syndromes explain only a small fraction of this disease. Thus, the genetic basis for the majority of hereditary colorectal cancer remains unknown. EPHB2 has recently been implicated as a candidate tumor suppressor gene in colorectal cancer. The aim of this study was to evaluate the contribution of EPHB2 to hereditary colorectal cancer. We screened for germline EPHB2 sequence variants in 116 population-based familial colorectal cancer cases by DNA sequencing. We then estimated the population frequencies and characterized the biological activities of the EPHB2 variants identified. Three novel nonsynonymous missense alterations were detected. Two of these variants (A438T and G787R) result in significant residue changes, while the third leads to a conservative substitution in the carboxy-terminal SAM domain (V945I). The former two variants were found once in the 116 cases, while the V945I variant was present in 2 cases. Genotyping of additional patients with colorectal cancer and control subjects revealed that A438T and G787R represent rare EPHB2 alleles. In vitro functional studies show that the G787R substitution, located in the kinase domain, causes impaired receptor kinase activity and is therefore pathogenic, whereas the A438T variant retains its receptor function and likely represents a neutral polymorphism. Tumor tissue from the G787R variant case manifested loss of heterozygosity, with loss of the wild-type allele, supporting a tumor suppressor role for EPHB2 in rare colorectal cancer cases. Rare germline EPHB2 variants may contribute to a small fraction of hereditary colorectal cancer

Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921

PURPOSE Bosutinib is approved for adults with chronic myeloid leukemia (CML): 400 mg once daily in newly diagnosed (ND); 500 mg once daily in resistant/intolerant (R/I) patients. Bosutinib has a different tolerability profile than other tyrosine kinase inhibitors (TKIs) and potentially less impact on growth (preclinical data). The primary objective of this first-in-child trial was to determine the recommended phase II dose (RP2D) for pediatric R/I and ND patients. PATIENTS AND METHODS In the phase I part of this international, open-label trial (ClinicalTrials.gov identifier: NCT04258943), children age 1-18 years with R/I (per European LeukemiaNet 2013) Ph+ CML were enrolled using a 6 + 4 design, testing 300, 350, and 400 mg/m$^{2}$ once daily with food. The RP2D was the dose resulting in 0/6 or 1/10 dose-limiting toxicities (DLTs) during the first cycle and achieving adult target AUC levels for the respective indication. As ND participants were only enrolled in phase II, the ND RP2D was selected based on data from R/I patients. RESULTS Thirty patients were enrolled; 27 were evaluable for DLT: six at 300 mg/m$^{2}$, 11 at 350 mg/m$^{2}$ (one DLT), and 10 at 400 mg/m$^{2}$ (one DLT). The mean AUCs at 300 mg/m$^{2}$, 350 mg/m$^{2}$, and 400 mg/m$^{2}$ were 2.20 μg h/mL, 2.52 μg h/mL, and 2.66 μg h/mL, respectively. The most common adverse event was diarrhea (93%; ≥grade 3: 11%). Seven patients stopped because of intolerance and eight because of insufficient response. Complete cytogenetic and major molecular response to bosutinib appeared comparable with other published phase I/II trials with second-generation TKIs in children. CONCLUSION Bosutinib was safe and effective. The pediatric RP2D was 400 mg/m$^{2}$ once daily (max 600 mg/d) with food in R/I patients and 300 mg/m$^{2}$ once daily (max 500 mg/d) with food in ND patients, which achieved targeted exposures as per adult experience

Achieving a quantum smart workforce

Interest in building dedicated Quantum Information Science and Engineering (QISE) education programs has greatly expanded in recent years. These programs are inherently convergent, complex, often resource intensive and likely require collaboration with a broad variety of stakeholders. In order to address this combination of challenges, we have captured ideas from many members in the community. This manuscript not only addresses policy makers and funding agencies (both public and private and from the regional to the international level) but also contains needs identified by industry leaders and discusses the difficulties inherent in creating an inclusive QISE curriculum. We report on the status of eighteen post-secondary education programs in QISE and provide guidance for building new programs. Lastly, we encourage the development of a comprehensive strategic plan for quantum education and workforce development as a means to make the most of the ongoing substantial investments being made in QISE.Comment: 18 pages, 2 figures, 1 tabl