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Abstract Human cerebellum consists of high density and complexity of neurons. Thus, it is challenging to differentiate cerebellar-like organoids with similar cellular markers and function to the human brain. Our previous study showed that the combination of retinoic acid (RA), Wingless/integrated (Wnt) activator, and Sonic Hedgehog (SHH) activator promotes cerebellar differentiation from human induced pluripotent stem cells (hiPSCs). This study examined phenotypic, metabolic, and biogenesis in early cerebellar development. Cerebellum spheroids were differentiated from human iPSK3 cells. During day 7–14, RA and Wnt activator CHIR99021 were used and SHH activator purmorphamine (PMR) was added later to promote ventralization. Gene expressionmore »for early cerebellar layer markers, metabolism, and extracellular vesicle (EV) biogenesis were characterized. Zinc-induced neurotoxicity was investigated as a proof-of-concept of neurotoxicity study. Flow cytometry results showed that there was no significant difference in NEPH3, PTF1A, OLIG2, and MATH1 protein expression between RCP (RA-CHIR-PMR) versus the control condition. However, the expression of cerebellar genes for the molecular layer ( BHLE22 ), the granule cell layer ( GABRB2 , PAX6 , TMEM266 , KCNIP4 ), the Bergmann glial cells ( QK1 , DAO ), and the Purkinje cell layer ( ARHGEF33 , KIT , MX1 , MYH10 , PPP1R17 , SCGN ) was significantly higher in the RCP condition than the control. The shift in metabolic pathways toward glycolysis was observed for RCP condition. The EV biogenesis marker expression was retained. Mild zinc-induced neurotoxicity may exist when zinc exposure exceeds 1.0 µM. RCP treatment can promote specific cerebellar-like differentiation from hiPSCs indicated by gene expression of early cerebellar markers and regionally enriched genes. The higher cerebellar marker expression is accompanied by the elevated glycolysis with the retained EV biogenesis. This study should advance the understanding of biomarkers during early cerebellar development for cerebellum organoid engineering and neurotoxicity study.« less
Free, publicly-accessible full text available December 1, 2023
Milev, Sandra; Goodwin, David G.; Sattar, Siamak; Tatar, Jovan(
, Construction building materials)
This study assesses physical and chemical properties of fiber reinforced polymer (FRP) composite materials aged in Alaska’s subarctic climate. Carbon FRP (CFRP) and glass FRP (GFRP) samples were collected in 2019 from the exterior and interior of Ted Stevens International Airport (TSIA, retrofitted in 2008) and McKinley Tower (MKT, retrofitted in 2004). Differential scanning calorimetry (DSC) was used to measure glass transition temperature (Tg) and physical aging, FTIR and Raman spectroscopy were used to investigate potential chemical degradation and degree of cure, and scanning electron microscopy (SEM) to evaluate cross-sectional microstructure, respectively. The results indicate that exposure to the subarcticmore »climate had minimal effect on the composites’ and chemical properties. The variability in fiber content at MKT and thermal properties at TSIA suggest there were likely some inconsistencies in the FRP installation that may affect load-carrying capacity. Furthermore, some microcracks were observed in the FRP retrofits which may have resulted from a combination of poor fiber impregnation and thermal cycling.« less
Free, publicly-accessible full text available July 18, 2023
Olin, Agnes B; Banas, Neil S; Johns, David G; Heath, Michael R; Wright, Peter J; Nager, Ruedi G(
, ICES Journal of Marine Science)
Dolgov, Andrey
(Ed.)
Abstract The phenology, distribution, and size composition of plankton communities are changing rapidly in response to warming. This may lead to shifts in the prey fields of planktivorous fish, which play a key role in transferring energy up marine food chains. Here, we use 60 + years of Continuous Plankton Recorder data to explore temporal trends in key taxa and community traits in the prey field of planktivorous lesser sandeels (Ammodytes marinus) in the North Sea, the Faroes and southern Iceland. We found marked spatial variation in the prey field, with Calanus copepods generally being much more common in the northern partmore »of the study area. In the western North Sea, the estimated amount of available energy in the prey field has decreased by more than 50% since the 1960s. This decrease was accompanied by declining abundances of small copepods, and shifts in the timing of peak annual prey abundances. Further, the estimated average prey community body size has increased in several of the locations considered. Overall, our results point to the importance of regional studies of prey fields, and caution against inferring ecological consequences based only on large-scale trends in key taxa or mean community traits.« less
Free, publicly-accessible full text available June 11, 2023
Rosenblum, Erica; Stroeve, Julienne; Gille, Sarah T.; Lique, Camille; Fajber, Robert; Tremblay, L. Bruno; Galley, Ryan; Loureiro, Thiago; Barber, David G.; Lukovich, Jennifer V.(
, Journal of Physical Oceanography)
Abstract The Arctic seasonal halocline impacts the exchange of heat, energy, and nutrients between the surface and the deeper ocean, and it is changing in response to Arctic sea ice melt over the past several decades. Here, we assess seasonal halocline formation in 1975 and 2006–12 by comparing daily, May–September, salinity profiles collected in the Canada Basin under sea ice. We evaluate differences between the two time periods using a one-dimensional (1D) bulk model to quantify differences in freshwater input and vertical mixing. The 1D metrics indicate that two separate factors contribute similarly to stronger stratification in 2006–12 relative tomore »1975: 1) larger surface freshwater input and 2) less vertical mixing of that freshwater. The larger freshwater input is mainly important in August–September, consistent with a longer melt season in recent years. The reduced vertical mixing is mainly important from June until mid-August, when similar levels of freshwater input in 1975 and 2006–12 are mixed over a different depth range, resulting in different stratification. These results imply that decadal changes to ice–ocean dynamics, in addition to freshwater input, significantly contribute to the stronger seasonal stratification in 2006–12 relative to 1975. These findings highlight the need for near-surface process studies to elucidate the impact of lateral processes and ice–ocean momentum exchange on vertical mixing. Moreover, the results may provide insight for improving the representation of decadal changes to Arctic upper-ocean stratification in climate models that do not capture decadal changes to vertical mixing.« less
Free, publicly-accessible full text available July 1, 2023
Gupta, Anupam; Harris, David G.; Lee, Euiwoong; Li, Jason(
, Journal of the ACM)
In the k -cut problem, we want to find the lowest-weight set of edges whose deletion breaks a given (multi)graph into k connected components. Algorithms of Karger and Stein can solve this in roughly O ( n 2k ) time. However, lower bounds from conjectures about the k -clique problem imply that Ω ( n (1- o (1)) k ) time is likely needed. Recent results of Gupta, Lee, and Li have given new algorithms for general k -cut in n 1.98k + O(1) time, as well as specialized algorithms with better performance for certain classes of graphs (e.g., formore »small integer edge weights). In this work, we resolve the problem for general graphs. We show that the Contraction Algorithm of Karger outputs any fixed k -cut of weight α λ k with probability Ω k ( n - α k ), where λ k denotes the minimum k -cut weight. This also gives an extremal bound of O k ( n k ) on the number of minimum k -cuts and an algorithm to compute λ k with roughly n k polylog( n ) runtime. Both are tight up to lower-order factors, with the algorithmic lower bound assuming hardness of max-weight k -clique. The first main ingredient in our result is an extremal bound on the number of cuts of weight less than 2 λ k / k , using the Sunflower lemma. The second ingredient is a fine-grained analysis of how the graph shrinks—and how the average degree evolves—in the Karger process.« less
Free, publicly-accessible full text available February 28, 2023
