A New Perspective for Science Inservice: Problem Solving Demonstration Classrooms

Project: Problem Solving in the Model Classroom was begun one year before the Governor\u27s II Conference as a cooperative effort between the University of Iowa and a number of Iowa school districts. The Dwight D. Eisenhower funded program was intended to develop model classrooms that used problem solving with math/science, Science/Technology /Society (STS) or technology as effective classroom practice. The project has become an integration of inservice strategies, demonstration classrooms and reform initiatives that improve science education in Iowa. At the Governor\u27s II Conference, we recognized that future model classrooms could benefit from our experience, specifically our rationale, development of district autonomy, demonstration classroom inservice structure and future extensions

Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes

Pancreatic ductal adenocarcinomas (PDACs) are hypovascular, but overexpress pro-angiogenic factors and exhibit regions of microvasculature. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we previously reported that ~12% of PDACs have an angiogenesis gene signature with increased expression of multiple pro-angiogenic genes. By analyzing the recently expanded TCGA dataset, we now report that this signature is present in ~35% of PDACs but that it is mostly distinct from an angiogenesis signature present in pancreatic neuroendocrine tumors (PNETs). These PDACs exhibit a transcriptome that reflects active TGF-β signaling, and up-regulation of several pro-inflammatory genes, and many members of JAK signaling pathways. Moreover, expression of SMAD4 and HDAC9 correlates with endothelial cell abundance in PDAC tissues. Concomitantly targeting the TGF-β type I receptor (TβRI) kinase with SB505124 and JAK1-2 with ruxolitinib suppresses JAK1 phosphorylation and blocks proliferative cross-talk between human pancreatic cancer cells (PCCs) and human endothelial cells (ECs), and these anti-proliferative effects were mimicked by JAK1 silencing in ECs. By contrast, either inhibitor alone does not suppress their enhanced proliferation in 3D co-cultures. These findings suggest that targeting both TGF-β and JAK1 signaling could be explored therapeutically in the 35% of PDAC patients whose cancers exhibit an angiogenesis gene signature

Population Dynamics of Long-tailed Ducks Breeding on the Yukon-Kuskokwim Delta, Alaska

Population estimates for long-tailed ducks in North America have declined by nearly 50% over the past 30 years. Life history and population dynamics of this species are difficult to ascertain, because the birds nest at low densities across a broad range of habitat types. Between 1991 and 2004, we collected information on productivity and survival of long-tailed ducks at three locations on the Yukon-Kuskokwim Delta. Clutch size averaged 7.1 eggs, and nesting success averaged 30%. Duckling survival to 30 days old averaged 10% but was highly variable among years, ranging from 0% to 25%. Apparent annual survival of adult females based on mark-recapture of nesting females was estimated at 74%. We combined these estimates of survival and productivity into a matrix-based population model, which predicted an annual population decline of 19%. Elasticities indicated that population growth rate (?) was most sensitive to changes in adult female survival. Further, the relatively high sensitivity of ? to duckling survival suggests that low duckling survival may be a bottleneck to productivity in some years. These data represent the first attempt to synthesize a population model for this species. Although our analyses were hampered by the small sample sizes inherent in studying a dispersed nesting species, our model provides a basis for management actions and can be enhanced as additional data become available.Les estimations de populations d’hareldes kakawis en Amérique du Nord ont chuté de près de 50 pour cent ces 30 dernières années. Le cycle biologique et la dynamique des populations de cette espèce sont difficiles à établir car ces oiseaux nichent moyennant de faibles densités dans une vaste gamme d’habitats. De 1991 à 2004, nous avons recueilli des données sur la productivité et la survie des hareldes kakawis à trois emplacements du delta Yukon-Kuskokwim. Les couvées atteignaient 7,1 oeufs en moyenne, tandis que le succès de reproduction s’établissait généralement à 30 pour cent. En moyenne, 10 pour cent des jeunes canards survivaient jusqu’à l’âge de 30 jours, mais ce taux variait beaucoup d’une année à l’autre, allant de 0 pour cent à 25 pour cent. Annuellement, d’après la méthode par marquage et recapture des femelles nidificatrices, la survie apparente des femelles adultes était évaluée à 74 pour cent. Nous avons combiné ces estimations de survie et de productivité dans un modèle de population matriciel, ce qui a permis de prédire un déclin de population annuel de 19 pour cent. Selon les élasticités, le taux de croissance de la population (?) était plus sensible aux changements dans le cas de la survie des femelles adultes. Par ailleurs, la sensibilité relativement élevée du ? par rapport à la survie des jeunes canards laisse croire que le faible taux de survie des jeunes canards pourrait présenter une embûche en matière de productivité d’ici quelques années. Ces données représentent la première tentative de synthèse d’un modèle de population pour cette espèce. Bien que nos analyses aient été gênées par la petite taille des échantillons inhérente à l’étude d’espèces de nidification dispersées, notre modèle fournit un fondement permettant d’aboutir à des mesures de gestion en plus de présenter la possibilité d’être amélioré au fur et à mesure que des données supplémentaires sont disponibles

Rare BANF1 Alleles and Relatively Frequent EMD Alleles Including `Healthy Lipid' Emerin p.D149H in the ExAC Cohort

Emerin (EMD) and barrier to autointegration factor 1 (BANF1) each bind A-type lamins (LMNA) as fundamental components of nuclear lamina structure. Mutations in LMNA, EMD and BANF1 are genetically linked to many tissue-specific disorders including Emery-Dreifuss muscular dystrophy and cardiomyopathy (LMNA, EMD), lipodystrophy, insulin resistance and type 2 diabetes (LMNA) and progeria (LMNA, BANF1). To explore human genetic variation in these genes, we analyzed EMD and BANF1 alleles in the Exome Aggregation Consortium (ExAC) cohort of 60,706 unrelated individuals. We identified 13 rare heterozygous BANF1 missense variants (p.T2S, p.H7Y, p.D9N, p.S22R, p.G25E, p.D55N, p.D57Y, p.L63P, p.N70T, p.K72R, p.R75W, p.R75Q, p.G79R), and one homozygous variant (p.D9H). Several variants are known (p.G25E) or predicted (e.g., p.D9H, p.D9N, p.L63P) to perturb BANF1 and warrant further study. Analysis of EMD revealed two previously identified variants associated with adult-onset cardiomyopathy (p.K37del, p.E35K) and one deemed `benign' in an Emery-Dreifuss patient (p.D149H). Interestingly p.D149H was the most frequent emerin variant in ExAC, identified in 58 individuals (overall allele frequency 0.06645%), of whom 55 were East Asian (allele frequency 0.8297%). Furthermore, p.D149H associated with four `healthy' traits: reduced triglycerides (-0.336; p = 0.0368), reduced waist circumference (-0.321; p = 0.0486), reduced cholesterol (-0.572; p = 0.000346) and reduced LDL cholesterol (-0.599; p = 0.000272). These traits are distinct from LMNA-associated metabolic disorders and provide the first insight that emerin influences metabolism. We also identified one novel in-frame deletion (p.F39del) and 62 novel emerin missense variants, many of which were relatively frequent and potentially disruptive including p.N91S and p.S143F (0.041% and -0.034% of non-Finnish Europeans, respectively), p.G156S (-0.39% of Africans), p.R204G (-0.18% of Latinx), p.R207P (-0.08% of South Asians) and p.R221L (-0.15% of Latinx). Many novel BANF1 variants are predicted to disrupt dimerization or binding to DNA, histones, emerin or A-type lamins. Many novel emerin variants are predicted to disrupt emerin filament dynamics or binding to BANF1, HDAC3, A-type lamins or other partners. These new human variants provide a foundational resource for future studies to test the molecular mechanisms of BANF1 and emerin function, and to understand the link between emerin variant p.D149H and a `healthy' lipid profile

American black bear den-site selection and characteristics in an urban environment

Selection of den sites is a crucial aspect of American black bear (Ursus americanus) life history. High-quality dens provide thermal insulation, protection from disturbance, suitable environment for parturition and cub development, and proximity to available forage upon emergence. Black bears are increasingly coexisting with people in human-dominated landscapes; however, little is known about whether urban environments influence characteristics of dens and den site selection. Our objective was to determine the effect of housing density (a proxy for human activity and availability of anthropogenic resources) on selection of den sites in years of good and poor natural forage.We additionally compared size, shape, and location of dens of males and females to describe den characteristics and explorewhether differences existed between males and females. We revisited 34 den locations detected during a 6-year (2005–2010) urban black bear study in Aspen, Colorado, USA, and measured den entrance and den volume. We fit a conditional logistic regression model using a resource selection function framework to determine the importance of housing density and other landscape variables (elevation, slope, aspect, and vegetation type) associated with den site selection. Slope was the best predictor of den site selection and there was no relationship between den selection and housing density, indicating that black bears were neither avoiding nor seeking urban areas for denning. Dens were smaller for females (x =3.30m3, SE = 1.94, n = 22) than for males (x = 7.56 m3, SE = 3.31, n = 8), supporting the idea that females have greater constraints in den characteristics, possibly related to cub development and security from predation or because females generally are smaller than males

TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis

Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1-2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1-2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature

Connecting Those That Care: Designing for Transitioning, Talking, Belonging and Escaping

This is the author accepted manuscript. The final version is available from ACM via the DOI in this record.Care provision in many nations increasingly relies on the work of informal, or non-professional, carers. Often these carers experience substantial disruptions and reductions to their own sociality, weakened social support networks and, ultimately, a heightened risk of social isolation. We describe a qualitative study, comprised of interviews, design workshops and probes, that investigated the social and community support practices of carers. Our findings highlight issues related to becoming and recognising being a carer, and feelings of being ignored by, and isolated from, others. We also note the benefits that sharing between carers can bring, and routes to coping and relaxing from the burdens of care. We conclude with design considerations for facilitating new forms of digitally mediated support that connect those that care, emphasising design qualities related to transitioning, talking, belonging and escaping

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition