2018-2019 Open Access Publishing Fund
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Item Open Access Dehiscence and embolization of CorMatrix tricuspid valve replacement in the setting of infective endocarditis: A case report(2018-07-31) Tomdio, Anna N.; Moey, Melissa Y. Y.; Siddiqui, Irfan; Movahed, AssadItem Open Access Sensor selection to improve estimates of particulate matter concentration from a low-cost network(2018-09-08) Sousan, Sinan; Gray, Alyson; Zuidema, Christopher; Stebounova, Larissa; Thomas, Geb; Koehler, Kirsten; Peters, ThomasDeployment of low-cost sensors in the field is increasingly popular. However, each sensor requires on-site calibration to increase the accuracy of the measurements. We established a laboratory method, the Average Slope Method, to select sensors with similar response so that a single, on-site calibration for one sensor can be used for all other sensors. The laboratory method was performed with aerosolized salt. Based on linear regression, we calculated slopes for 100 particulate matter (PM) sensors, and 50% of the PM sensors fell within ±14% of the average slope. We then compared our Average Slope Method with an Individual Slope Method and concluded that our first method balanced convenience and precision for our application. Laboratory selection was tested in the field, where we deployed 40 PM sensors inside a heavy-manufacturing site at spatially optimal locations and performed a field calibration to calculate a slope for three PM sensors with a reference instrument at one location. The average slope was applied to all PM sensors for mass concentration calculations. The calculated percent differences in the field were similar to the laboratory results. Therefore, we established a method that reduces the time and cost associated with calibration of low-cost sensors in the field.Item Open Access Angioedema after thrombolysis with tissue plasminogen activator: An airway emergency.(2019-01-19) Rathbun, Kimberly M.Recombinant tissue plasminogen activator (rtPA), an enzyme that catalyzes the conversion of plasminogen to plasmin resulting in fibrinolysis, is used for the treatment of acute ischemic strokes. The use of this medication is not without complication. One complication of this therapy is angioedema. This complication can be life-threatening if not recognized quickly. However, the potential for the development of angioedema after rtPA administration is not widely known. This is a case of a 60-year-old man who suffered an acute ischemic stroke and was given rtPA. The patient subsequently developed rapidly progressing angioedema leading to airway compromise. The patient was intubated with some difficulty and the angioedema improved and the patient was able to be extubated the next day. Angioedema secondary to administration of rtPA is thought to be bradykinin mediated, but the exact mechanism is unknown. Treatment with FFP, Icatibant, Ecallantide or a C1-esterase inhibitor can be considered.Item Open Access N6-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progression(2018-07-27) Fry, Nate J.; Law, B. A.; Ilkayeva, O. R.; Holley, C. L.; Mansfield, Kyle D.; Carraway, Kristen R.The mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulatory processes including mRNA stability and translational efficiency. However, it is also imperative to correlate these processes with phenotypic outputs during cancer progression. Here we report that m6A levels are significantly decreased in genetically-defined immortalized and oncogenically-transformed human mammary epithelial cells (HMECs), as compared with their primary cell predecessor. Furthermore, the m6A methyltransferase (METTL3) is decreased and the demethylase (ALKBH5) is increased in the immortalized and transformed cell lines, providing a possible mechanism for this basal change in m6A levels. Although the immortalized and transformed cells showed lower m6A levels than their primary parental cell line, overexpression of METTL3 and METTL14, or ALKBH5 knockdown to increase m6A levels in transformed cells increased proliferation and migration. Remarkably, these treatments had little effect on the immortalized cells. Together, these results suggest that m6A modification may be downregulated in immortalized cells as a brake against malignant progression. Finally, we found that m6A levels in the immortalized and transformed cells increased in response to hypoxia without corresponding changes in METTL3, METTL14 or ALKBH5 expression, suggesting a novel pathway for regulation of m6A levels under stress.Item Open Access Emerging role of immune checkpoint blockade in pancreatic cancer(2018-11-07) Macherla, S.; Laks, S.; Naqash, Abdul R.; Bulumulle, Anushi; Zervos, E.; Muzaffar, MahvishImmune checkpoint blockade (ICB) with programmed cell death protein-1(PD-1)/programmed death ligand -1(PD-L1) antibodies has revolutionized the management of several cancers, especially non-small cell lung cancer, melanoma, urothelial, and renal cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with high morbidity and mortality. Based on available data, it's obvious that ICB has limited success in PDACs, which can be explained by the low immunogenicity and immunosuppressive tumor microenvironment of these tumors. In this review article, we focus on PD-L1 expression and microsatellite instability (MSI) in PDAC, and their roles as prognostic and predictive markers. We also discuss data supporting combination therapies to augment cancer immunity cycle. Combining anti-PD-1/PD-L1 agents with other modalities such as vaccines, chemotherapy, and radiation could potentially overcome resistance patterns and increase immune responsiveness in PDAC.Item Open Access TNM cancer staging: can it help develop a novel staging system for type 2 diabetes?(2018-11-28) Dar, Moahad S.; Beg, Sami A.Type 2 diabetes (DM2) constitutes 90%–95% of the diabetes cases and is increasing at an alarming rate in the world. The Centers for Disease Control and Prevention (CDC) estimates that more than 29 million people in the United States have diabetes, which often causes mortality from macrovascular complications and morbidity from microvascular complications. Despite these troubling facts, there is currently no widely accepted staging system for DM2 like there is for cancer. TNM oncologic staging has taken a complex condition like cancer and conveyed likelihood of survival in simple alpha-numeric terms that both patients and providers can understand. Oncology is now entering the era of precision medicine where cancer treatment is increasingly being tailored to each patient’s cancer. In contrast, DM2 lacks a staging system and remains a largely invisible disease even though it kills more Americans and costs more to treat than cancer. Is a comparable staging system for DM2 possible? We propose the Diabetes Staging System for DM2 that utilizes macrovascular events, microvascular complications, estimated glomerular filtration rate (GFR), and hemoglobin A1C to stage DM2. filtration rateItem Open Access Lack of complex type N-glycans lessens aberrant neuronal properties(2018-06) Hall, M. Kristen; Weidner, Douglas A.; Whitman, Austin A.; Schwalbe, Ruth A.Modifications in surface glycans attached to proteins via N-acetylglucosamine-β1-Nasparagine linkage have been linked to tumor development and progression. These modifications include complex N-glycans with high levels of branching, fucose and sialic acid residues. Previously, we silenced Mgat2 in neuroblastoma (NB) cells, which halted the conversion of hybrid type N-glycans to complex type, to generate a novel cell line, NB_1 (-Mgat2). By comparing the aberrant cell properties of the NB_1(-Mgat2) cell line to the parental cell line (NB_1), we investigated the impact of eliminating complex type N-glycans on NB cell behavior. Further, the N-glycosylation pathway in the NB_1(-Mgat2) cell line was rescued by transiently transfecting cells with Mgat2, thus creating the NB_1 (-/+Mgat2) cell line. Changes in the N-glycosylation pathway were verified by enhanced binding of E-PHA and L-PHA to proteins in the rescued cell line relative to those of the NB_1(-Mgat2) cell line. Also, western blotting of total membranes from the rescued cell line ectopically expressing a voltage-gated K+ channel (Kv3.1b) revealed that N-glycans of Kv3.1b were processed to complex type. By employment of various cell lines, we demonstrated that reduction of the complex type N-glycans diminished anchorage-independent cell growth, and enhanced cell-cell interactions. Two independent cell invasion assays showed that cell invasiveness was markedly lessened by lowering the levels of complex type N-glycans while cell mobility was only slightly modified. Neurites of NB cells were shortened by the absence of complex type N-glycans. Cell proliferation was reduced in NB cells with lowered levels of complex type N-glycans which resulted from hindered progression through G1+Go phases of the cell cycle. Overall, our results illustrate that reducing the ratio of complex to hybrid types of N-glycans diminishes aberrant NB cell behavior and thereby has a suppressive effect in cell proliferation, and cell dissociation and invasion phases of NB.Item Open Access The variability of song variability in zebra finch (Taeniopygia guttata) populations(2019-04-30) Balakrishnan, Christopher N.; Lansverk, Allison L.; Schroeder, Katie M.; London, Sarah E.; Griffith, Simon C.; Clayton, David F.Birdsong is a classic example of a learned social behaviour. Song behaviour is also influenced by genetic factors, and understanding the relative contributions of genetic and environmental influences remains a major goal. In this study, we take advantage of captive zebra finch populations to examine variation in a population-level song trait: song variability. Song variability is of particular interest in the context of individual recognition and in terms of the neuro-developmental mechanisms that generate song novelty. We find that the Australian zebra finch T. g. castanotis (TGC) maintains higher song diversity than the Timor zebra finch T. g. guttata (TGG) even after experimentally controlling for early life song exposure, suggesting a genetic basis to this trait. Although wild-derived TGC were intermediate in song variability between domesticated TGC populations and TGG, the difference between domesticated and wild TGC was not statistically significant. The observed variation in song behaviour among zebra finch populations represents a largely untapped opportunity for exploring the mechanisms of social behaviour.Item Open Access Item Open Access Risk Factors Associated with Physical and Mental Distress in People Who Report a Chronic Obstructive Pulmonary Disease (COPD) Diagnosis: Latent Class Analysis of 2016 Behavioral Risk Factor Surveillance System Data(2019-05-09) Stellefson, Michael; Paige, Samantha R.; Barry, Adam E.; Wang, Min Qi; Apperson, Avery; Health Education and PromotionItem Open Access Pgrmc1 Knockout Impairs Oocyte Maturation in Zebrafish(2018-09-24) Wu, Xin-Jun; Thomas, Peter; Zhu, YongRecent investigations suggest progestin receptor membrane component 1 (PGRMC1) associates with and transports a wide range of molecules such as heme, cytochromes P450, steroids with 21 carbons, membrane progestin receptor alpha (mPRα/Paqr7), epidermal growth factor receptor (EGFR), and insulin receptor. It is difficult to discriminate the true functions of PGRMC1 from the functions of its associated molecules using biochemical and pharmacological approaches. To determine the physiological function(s) of PGRMC1, we generated global knockouts for pgrmc1 (pgrmc1−/−) in zebrafish. We found a reduction in both spawning frequency and the number of embryos produced by female mutants. We also observed reduced sensitivity of fully-grown immature oocytes to a progestin hormone and a reduced number of oocytes undergone meiotic maturation both in vivo and in vitro in pgrmc1−/−. This reduced sensitivity to progestin corresponds well with significant reduced expression of mPRα, the receptor mainly responsible for mediating oocyte maturation and meiosis resumption in fish. The results provide in vivo and in vitro evidence for the physiological functions of Pgrmc1 in oocyte maturation and fertility, as well as a plausible molecular mechanism via regulation of mPRα, which in turn directly regulates oocyte maturation and affects fertility in zebrafish.Item Open Access Top-down pulses reduce prey population sizes and persistence(2018-06-19) Hamman, Elizabeth A.; McCoy, Michael W.; BiologyResource pulses are well documented and have important consequences for population dynamics relative to continuous inputs. However, pulses of top-down factors (e.g. predation) are less explored and appreciated in the ecological literature. Here, we use a simple differential equation population model to show how pulsed removals of individuals from a population alter population size relative to continuous dynamics. Pulsed removals result in lower equilibrium population sizes relative to continuous removals, and the differences are greatest at low population growth rates, high removal rates, and with large, infrequent pulses. Furthermore, the timing of the removal pulses (either stochastic or cyclic) affects population size. For example, cyclic removals are less likely than stochastic removals to result in population eradication, but when eradication occurs, the time until eradication is shorter for cyclic than with stochastic removals.Item Open Access Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog Dendrobates auratus(2019-04-18) Stuckert, Adam M. M.; Moore, Emily; Coyle, Kaitlin P.; Davison, Ian; MacManes, Matthew D.; Roberts, Reade; Summers, Kyle; BiologyAbstract Background Color and pattern phenotypes have clear implications for survival and reproduction in many species. However, the mechanisms that produce this coloration are still poorly characterized, especially at the genomic level. Here we have taken a transcriptomics-based approach to elucidate the underlying genetic mechanisms affecting color and pattern in a highly polytypic poison frog. We sequenced RNA from the skin from four different color morphs during the final stage of metamorphosis and assembled a de novo transcriptome. We then investigated differential gene expression, with an emphasis on examining candidate color genes from other taxa. Results Overall, we found differential expression of a suite of genes that control melanogenesis, melanocyte differentiation, and melanocyte proliferation (e.g., tyrp1, lef1, leo1, and mitf) as well as several differentially expressed genes involved in purine synthesis and iridophore development (e.g., arfgap1, arfgap2, airc, and gart). Conclusions Our results provide evidence that several gene networks known to affect color and pattern in vertebrates play a role in color and pattern variation in this species of poison frog.Item Open Access Innovative Controller Design for a 5MW Wind Turbine Blade(2018-06-29) Agarwala, Ranjeet; Chin, Robert; Technology SystemsThe development and evaluation of a nonlinear pitch controller for wind turbine blades and the design and modeling of an associated actuator and controller was examined. The pitch actuator and controller were modeled and analyzed using Pneumatically Actuated Muscles (PAMs) for actively pitching the wind turbine blade. PAMs are very light and have a high specific work and a good contraction ratio. Proportional Integral and Derivative (PID) controllers were envisaged for the wind turbine pitching system at the blade tip due to its routine usage in the wind turbine industry. Deployment of controllers enables effective pitch angle tracking for power abatement at various configurations. The controller was subjected to four pitch angle trajectory signals. PID controllers were tuned to achieve satisfactory performance when subjected to the test signal. Low pitch angle errors resulted in satisfactory blade pitch angle tracking. Deployment of these controllers enhances wind turbine performance and reliability. The data suggest that the pitch system and actuator that was modeled using PAMs and PID controllers is effective providing robust pitch angle trajectory tracking. The results suggest that the proposed design can be successfully integrated into the family of wind turbine blade pitch angle controller technologies.