Project Lead the Way and Deeper Learning: An Evaluation Study

For the past several decades governmental, educational, and philanthropic entities have endeavored to respond to the national STEM gap directing tremendous amounts of resources in response. During this time a specific STEM intervention, Project Lead the Way, a K12 program with a purpose to address the STEM gap, has spread across the country. This study investigates whether Project Lead the Way is delivering on its promise. Project Lead the Way exhibits many of the characteristics recommended by leading experts to reform traditional education into one that stresses deeper learning and the acquisition of 21st Century Skills. The central question of this study was to determine whether exposure to Project Lead the Way curriculum does indeed lead to deeper learning as evidenced through the acquisition of 21st Century Skills, specifically problem solving, critical thinking, and creativity. Further, are the recommendations of researchers who intend to more fully integrate deeper learning into the fabric of high school coursework validated by the effects of a program that follow those recommendations. The results suggest that the answer is maybe to both questions

Aspects Of Deregulated Glucose Metabolism In Liver And Kidney Cancer

Deregulated glucose metabolism is a critical component of cancer growth and survival, as is clinically evident by FDG-PET imaging of enhanced glucose uptake in tumors. However, the efficacy of direct pharmacological intervention of glycolysis, a critical biochemical pathway that catabolizes glucose, has yet to be realized. As an alternative approach, we explored the potential therapeutic value of two physiological pathways that oppose glucose catabolism in either liver or kidney cancer: gluconeogenesis and glycogen synthesis, respectively. In liver cancer, I hypothesized that gluconeogenesis could be stimulated by glucagon signaling to antagonize glycolysis and reduce tumor cell growth. Upon supraphysiologic overexpression of the glucagon receptor, GCGR, glucagon treatment of the liver cancer cell line, SNU398, reproducibly decreased cell viability, but without transcriptionally inducing gluconeogenic gene expression, regardless of the epigenetic landscape. In kidney cancer, we hypothesized that disrupting glycogen breakdown could prevent release of glucose under stress conditions and inhibit tumor cell proliferation. Through genetic knockout of key enzymes and carbon-13 labeling, we observed that glycogen metabolism does not affect tumor growth, despite metabolic utilization of glycogen-derived glucose in culture conditions without glucose. In conclusion, we describe context-specific approaches to targeting glucose metabolism in cancer that warrant further investigation

Auxin and tryptophan homeostasis are facilitated by the ISS1/VAS1 aromatic aminotransferase in arabidopsis

Indole-3-acetic acid (IAA) plays a critical role in regulating numerous aspects of plant growth and development. While there is much genetic support for tryptophan-dependent (Trp-D) IAA synthesis pathways, there is little genetic evidence for tryptophan-independent (Trp-I) IAA synthesis pathways. Using Arabidopsis, we identified two mutant alleles of ISS1 ( I: ndole S: evere S: ensitive) that display indole-dependent IAA overproduction phenotypes including leaf epinasty and adventitious rooting. Stable isotope labeling showed that iss1, but not WT, uses primarily Trp-I IAA synthesis when grown on indole-supplemented medium. In contrast, both iss1 and WT use primarily Trp-D IAA synthesis when grown on unsupplemented medium. iss1 seedlings produce 8-fold higher levels of IAA when grown on indole and surprisingly have a 174-fold increase in Trp. These findings indicate that the iss1 mutant's increase in Trp-I IAA synthesis is due to a loss of Trp catabolism. ISS1 was identified as At1g80360, a predicted aromatic aminotransferase, and in vitro and in vivo analysis confirmed this activity. At1g80360 was previously shown to primarily carry out the conversion of indole-3-pyruvic acid to Trp as an IAA homeostatic mechanism in young seedlings. Our results suggest that in addition to this activity, in more mature plants ISS1 has a role in Trp catabolism and possibly in the metabolism of other aromatic amino acids. We postulate that this loss of Trp catabolism impacts the use of Trp-D and/or Trp-I IAA synthesis pathways.T32 AR059033 - NIAMS NIH HH

A proposed computer vision model for running gait assessment

Running gait assessment is critical in performance optimization and injury prevention. Traditional approaches to running gait assessment are inhibited by unnatural running environments (e.g., indoor lab), varied assessor (i.e., subjective experience) and high costs with traditional reference standard equipment. Thus, development of valid, reproduceable and low-cost approaches are key. Use of wearables such as inertial measurement units have shown promise but despite their flexible use in any environment and reduced cost, they often retain complexities such as connectivity to mobile platforms and stringent attachment protocols. Here, we propose a non-wearable camera-based approach to running gait assessment, focusing on identification of initial contact events within a runner's stride. We investigated different artificial intelligence and object tracking approaches to determine the optimal methodology. A cohort of 40 healthy runners were video recorded (240FPS, multi-angle) during 2-minute running bouts on a treadmill. Validation of the proposed approach is obtained from comparison to manually labelled videos. The computing vision approach can accurately identify initial contact events (ICC(2,1) = 0.902)

Heterogeneous nickel isotope compositions of the terrestrial mantle – Part 2: Mafic lithologies

We report stable Ni isotope compositions (δ⁶⁰/⁵⁸Ni, relative to SRM986) for mafic lavas with a range of -0.16 ‰ to +0.20 ‰ (n=44), similar to that of peridotite samples. Ocean island basalts (OIB) have been analysed from Iceland (n=6), the Azores (n=3), the Galápagos Islands (n=2), and Lōʻihi, Hawaii (n=1). Samples from Iceland (average δ⁶⁰/⁵⁸Ni = +0.13±0.16‰, 2s, n=7) display the greatest range in Ni isotope compositions from a single OIB location in this work, of +0.01 ‰ to +0.23 ‰. Samples from the Azores (average δ⁶⁰/⁵⁸Ni = -0.10±0.10 ‰, 2s) and Galápagos (average δ⁶⁰/⁵⁸Ni = -0.01±0.04 ‰, 2s) are generally isotopically lighter. The single Lōʻihi sample has a δ⁶⁰/⁵⁸Ni of +0.17 ‰. The lightest analysed bulk rock δ⁶⁰/⁵⁸Ni in this work, -0.16 ‰, is from the Azores island, Pico. Enriched mid ocean ridge basalts (E-MORB), which have (La/Sm)_N>1, are isotopically lighter than normal type MORB (N-MORB), as shown by data from the Mid Atlantic Ridge (n=9) and East Pacific Rise (n=3). All E-MORB average δ60/58Ni = +0.00±0.06 ‰ (2s, n=7), whereas N-MORB average δ60/58Ni = +0.14±0.10 ‰ (2s, n=5). A suite of 15 mafic samples from the Cameroon Line, comprising lithologies ranging from nephelinites to hypersthene-normative basalts, have Ni isotope compositions that are identical within analytical uncertainty (average δ⁶⁰/⁵⁸Ni = +0.08±0.06 ‰, 2s). Similarly, MORB samples display no relationship between δ⁶⁰/⁵⁸Ni and geochemical indicators of degree of partial melting or fractional crystallisation. Host lavas for two previously analysed ultramafic xenolith suites have δ⁶⁰/⁵⁸Ni identical to the average δ⁶⁰/⁵⁸Ni of their respective xenolith suites. This is consistent with previously published evidence from peridotites and komatiites that Ni isotopes are not greatly fractionated by melting. Therefore, mafic rocks may preserve the δ⁶⁰/⁵⁸Ni of their mantle source. Sampling a greater volume of mantle, their average Ni isotope composition +0.07±0.17 ‰ (2s, n=44) may also be a better representation of the Bulk Silicate Earth (BSE), than estimates based purely on peridotites. The δ⁶⁰/⁵⁸Ni of MORB co-varies with La/Sm, Rb/Sr, europium anomaly (Eu/Eu*), and K₂O/(K₂O+Na₂O). The relationships between these parameters and δ⁶⁰/⁵⁸Ni are consistent with mixing between two model endmembers. One could be depleted MORB or depleted MORB mantle (DMM) with a relatively heavy Ni isotope composition; the other a more enriched endmember that has isotopically lighter δ⁶⁰/⁵⁸Ni. The link between lighter δ⁶⁰/⁵⁸Ni and enriched lithologies in the mantle is further supported by published evidence of light Ni isotope compositions associated with some pyroxenite xenoliths. However, the curvature of the apparent mixing arrays defined by basalts is hard to reconcile with admixing of geochemically enriched but isotopically fractionated oceanic crustal lithologies. High [Ni] enriched magmas such as kimberlites may be a closer match to the enriched endmember. However, this needs further study

Heterogeneous nickel isotopic compositions in the terrestrial mantle – Part 1: Ultramafic lithologies

High precision nickel stable isotopic compositions (δ⁶⁰/⁵⁸Ni) are reported for 22 peridotite xenoliths from the USA (Kilbourne Hole, New Mexico), Tanzania, and Cameroon. For a subset of these, δ⁶⁰/⁵⁸Ni is also reported for their constituent mineral separates (olivine, orthopyroxene, clinopyroxene, and spinel). Bulk peridotites show significant heterogeneity in Ni isotopic composition, ranging from +0.02‰ to +0.26‰. Unmetasomatised fertile peridotites from three localities, define an average δ⁶⁰/⁵⁸Ni of +0.19±0.09‰ (n = 18). This value is comparable to previous estimates for the δ⁶⁰/⁵⁸Ni of the bulk silicate earth (BSE), but is unlikely to be representative, given observed heterogeneity, presented here and elsewhere. Samples with reaction rims and interstitial glass (interpreted as petrographic indications of minor metasomatism) were excluded from this average; their Ni isotopic compositions extend to lighter values, spanning nearly the entire range observed in peridotite worldwide. Dunites (n = 2) are lighter in δ⁶⁰/⁵⁸Ni than lherzolites and harzburgites from the same location, and pyroxenites (n = 5) range from +0.16‰ to as light as −0.38‰. The δ⁶⁰/⁵⁸Ni in the Kilbourne Hole xenoliths correlate negatively with bulk-rock Fe concentration and positively with ¹⁴³Nd/¹⁴⁴Nd, providing evidence that light δ⁶⁰/⁵⁸Ni is associated with mantle fertility and enrichment. The trend between δ⁶⁰/⁵⁸Ni and Fe concentration in bulk rocks appears to be global, replicated across the peridotites in this work from other localities, and in literature data. The inter-mineral fractionations are small; the maximum difference between heaviest and lightest phase is 0.12‰. This provides evidence that bulk rock δ⁶⁰/⁵⁸Nii variation does not result from differences in modal mineralogy, fractional crystallization or degrees of partial melting. The δ⁶⁰/⁵⁸Ni fractionation appears to be an equilibrium effect and usually is in the decreasing order spinel > olivine = orthopyroxene > clinopyroxene. However, the fractionation between clinopyroxene and orthopyroxene varies in magnitude and sign, and is correlated with pyroxene Si/Fe positively, and Fe/Mg negatively. The magnitude of inter-pyroxene fractionation also correlates with other pyroxene compositional ratios (e.g. La/Sm_clinopyroxene); as well as bulk rock δ⁶⁰/⁵⁸Ni, and [U]. These data provide evidence that Ni isotopes fractionate at the bulk rock and mineral scale in response to mantle enrichment processes, possibly related to recycling of isotopically light subducted components

Enhancing free-living fall risk assessment: Contextualising mobility based IMU data

Fall risk assessment needs contemporary approaches based on habitual data. Currently, inertial measurement unit (IMU) based wearables are used to inform free-living spatio-temporal gait characteristics to inform mobility assessment. Typically, a fluctuation of those characteristics will infer an increased fall risk. However, current approaches with IMU’s remains limited as there are no contextual data to comprehensively determine if underlying mechanistic (intrinsic) or envi-ronmental (extrinsic) factors impact mobility and therefore fall risk. Here, a case study is used to explore and discuss how contemporary video-based wearables could be used to supplement arising mobility-based IMU gait data to better inform habitual fall risk assessment. A single stroke survivor was recruited, and he conducted a series of mobility tasks in a lab and beyond while wearing video-based glasses and a single IMU. The latter generated topical gait characteristics that were discussed according to current research practices. Although current IMU-based approaches are beginning to provide habitual data they remain limited. Given the plethora of extrinsic factors that may influence mobility-based gait there is a need to corroborate IMU’s with video data to comprehensively inform fall risk assessment. Use of artificial intelligence (AI) based computer vision approaches could drastically aid the processing of video data in a timely and ethical manner. Many off-the-shelf AI tools exist to aid this current need and provide a means to automate con-textual analysis to better inform mobility from IMU gait data for an individualized and con-temporary approach to habitual fall risk assessment

The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes.

BACKGROUND: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. METHODS: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. RESULTS: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 x 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. CONCLUSION: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

fMRI Response During Figural Memory Task Performance in College Drinkers [pre-print]

Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding. Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). Results: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed: 1) greater BOLD response during correct encoding in right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; 2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and 3) less bilateral insula response during correct recognition (clusters \u3e10,233ul, p Conclusions: This is the first investigation of the neural substrates of figural memory among heavy drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers

Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.

BACKGROUND: The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). RESULTS: We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. CONCLUSION: We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are