Fostering Student Agency to Build a Whole Child, Whole School, Whole Community Approach

In this practitioner perspective, we explore the concept of student agency through the implementation of a student government association in a laboratory middle school. Interviews with a social studies teacher and her students offer perspectives of the impact of student voice and choice for student experiences. We describe three major lessons learned through this implementation process: students learn to have healthy conflict and cooperative skills; students learn the appropriate processes to enact change in a democratic society; and students learn to conduct service for their peers, school, and community

Cruise Missile Integrated Air Defense System Penetration: Modeling the S-400 System

This research determines improved flight-path routes that make maximum utilization of terrain-masking opportunities, and defending radar and missile system equipment performance and launch timing constraints, in order to avoid radar detection and tracking, and to mitigate subsequent missile shoot-down risks. The problem is formulated as one of constrained optimization in three dimensions. Advantageous solutions are identified using the A* Algorithm in conjunction with detailed equipment performance and constraint calculations and high-resolution digital terrain elevation maps. Topographical features in digital terrain are exploited by the algorithm to avoid radar detection and tracking. The model includes provisions for all-aspect/all-frequency radar cross section variations, radar horizon masking, and specific factors relevant to the TLAM BGM-109 cruise missile and the Russian S-400 long-range and Pantsir point-defense IADS systems. Research conclusions indicate that intelligent exploitation of modeled system technical and performance capabilities and limitations yields improved survivability in conjunction with, and supplementing, terrain masking

DNA repair glycosylases with a [4Fe–4S] cluster: A redox cofactor for DNA-mediated charge transport?

The [4Fe–4S] cluster is ubiquitous to a class of base excision repair enzymes in organisms ranging from bacteria to man and was first considered as a structural element, owing to its redox stability under physiological conditions. When studied bound to DNA, two of these repair proteins (MutY and Endonuclease III from Escherichia coli) display DNA-dependent reversible electron transfer with characteristics typical of high potential iron proteins. These results have inspired a reexamination of the role of the [4Fe–4S] cluster in this class of enzymes. Might the [4Fe–4S] cluster be used as a redox cofactor to search for damaged sites using DNA-mediated charge transport, a process well known to be highly sensitive to lesions and mismatched bases? Described here are experiments demonstrating the utility of DNA-mediated charge transport in characterizing these DNA-binding metalloproteins, as well as efforts to elucidate this new function for DNA as an electronic signaling medium among the proteins

Biological contexts for DNA charge transport chemistry

Many experiments have now shown that double helical DNA can serve as a conduit for efficient charge transport (CT) reactions over long distances in vitro. These results prompt the consideration of biological roles for DNA-mediated CT. DNA CT has been demonstrated to occur in biologically relevant environments such as within the mitochondria and nuclei of HeLa cells as well as in isolated nucleosomes. In mitochondria, DNA damage that results from CT is funneled to a crucial regulatory element. Thus, DNA CT provides a strategy to funnel damage to particular sites in the genome. DNA CT might also be important in long-range signaling to DNA-bound proteins. Both DNA repair proteins, containing Fe-S clusters, and the transcription factor, p53, which is regulated through thiol-disulfide switches, can be oxidized from a distance through DNA-mediated CT. These observations highlight a means through which oxidative stress may be chemically signaled in the genome over long distances through CT from guanine radicals to DNA-bound proteins. Moreover, DNA-mediated CT may also play a role in signaling among DNA-binding proteins, as has been proposed as a mechanism for how DNA repair glycosylases more efficiently detect lesions inside the cell

Direct Electrochemistry of Endonuclease III in the Presence and Absence of DNA

The electrochemistry of the base excision repair enzyme Endonuclease III (Endo III) in the presence and absence of DNA has been examined on highly oriented pyrolytic graphite (HOPG). At the surface modified with pyrenated DNA, a reversible signal is observed at 20 mV versus NHE for the [4Fe−4S]^(3+/2+) couple of Endo III, similar to Au. Without DNA modification, oxidative and reductive signals for the [4Fe−4S] cluster of Endo III are found on bare HOPG, allowing a direct comparison between DNA-bound and free redox potentials. These data indicate a shift of approximately −200 mV in the 3+/2+ couple upon binding of Endo III to DNA. This potential shift reflects a difference in affinity for DNA of more than 3 orders of magnitude between the oxidized 3+ and reduced 2+ protein and provides quantitative support for our model utilizing DNA-mediated charge transport to redistribute base excision repair enzymes in the vicinity of damaged DNA

An Unusual Combination of Neurological Manifestations and Sudden Vision Loss in a Child with Familial Hyperphosphatemic Tumoral Calcinosis

Hyperphosphatemia in the absence of renal failure is an unusual occurrence, particularly in children, but is a common primary feature of familial hyperphosphatemic tumor calcinosis. We report a child with hyperphosphatemia who presented with multiple episodes of neurologic dysfunction involving lower motor neuron facial nerve palsy along with sequential visual loss. He also had an episode of stroke. There was an extensive metastatic calcification of soft tissue and vasculature. Hyperphosphatemia with normal serum alkaline phosphatase, calcium, parathyroid hormone, and renal function was noted. He was managed with hemodialysis and sevelamer (3 months) without much success in reducing serum phosphate level, requiring continuous ambulatory peritoneal dialysis (3 years). Intact fibroblast growth factor 23 (FGF23) was undetectable, with C-terminal FGF23 fragments significantly elevated (2575 RU/ml, normal A (p.N162K) mutation in FGF23 exon 3, confirming the diagnoses of primary FGF23 deficiency, the first case to be reported from India

Among the Authentic Audience: Young Adults’ Perceptions and Responses to Youth as Scientists

Thesis advisor: George M. BarnettLifelong science learning is important for making informed decisions on science topics, and there is a need to engage broader and more diverse audiences with science. One opportunity for engagement occurs when students share science topics with a public audience. Research indicates this interaction can have benefits for students, but little is known about the impact it may have on audience members’ thoughts about science. Youth are different from typical sources of science information, and may elicit different reactions. This dissertation examines the impact youth sources may have on adults’ perceptions of and responses to science topics. Young adults (N = 399) were randomly assigned to one of two scenarios. Both scenarios stated two individuals would describe research they had done about local air quality on the news. One scenario identified the individuals as local high school students, and the other as research scientists from a local institution. Dependent variables included perceptions of the warmth and competence of the presenters, expectations of the quality of the information they would share, willingness to take action based on that information, and general trust in scientists. A subset of participants (N=22) was selected for cognitive interviews and asked to explain the thoughts that influenced their survey responses. Results showed multiple reactions to the scenario. Three groups were identified in the perceptions data: one expressed trust in the presenters, one expressed skepticism, and one based their perceptions on personal experiences doing science. Participants said intertwined thoughts about trust in scientists and assumptions about the presenters’ intentions influenced perceptions, with an overall assumption that youth would have good intentions while adults might not. Participants did not appear to separate their expectations of the information from the people who would share it. However, their willingness to take action was related to the action, not the presenter or information. Findings suggest youth may be an avenue for engaging individuals who have lower trust in typical science information sources. Implications for science education and communication are discussed.Thesis (PhD) — Boston College, 2017.Submitted to: Boston College. Lynch School of Education.Discipline: Teacher Education, Special Education, Curriculum and Instruction

Protein-DNA charge transport: Redox activation of a DNA repair protein by guanine radical

DNA charge transport (CT) chemistry provides a route to carry out oxidative DNA damage from a distance in a reaction that is sensitive to DNA mismatches and lesions. Here, DNA-mediated CT also leads to oxidation of a DNA-bound base excision repair enzyme, MutY. DNA-bound Ru(III), generated through a flash/quench technique, is found to promote oxidation of the [4Fe-4S](2+) cluster of MutY to [4Fe-4S](3+) and its decomposition product [3Fe-4S](1+). Flash/quench experiments monitored by EPR spectroscopy reveal spectra with g = 2.08, 2.06, and 2.02, characteristic of the oxidized clusters. Transient absorption spectra of poly(dGC) and [Ru(phen)(2)dppz](3+) (dppz = dipyridophenazine), generated in situ, show an absorption characteristic of the guanine radical that is depleted in the presence of MutY with formation instead of a long-lived species with an absorption at 405 nm; we attribute this absorption also to formation of the oxidized [4Fe-4S](3+) and [3Fe4S](1+) clusters. In ruthenium-tethered DNA assemblies, oxidative damage to the 5'-G of a 5'-GG-3' doublet is generated from a distance but this irreversible damage is inhibited by MutY and instead EPR experiments reveal cluster oxidation. With ruthenium-tethered assemblies containing duplex versus single-stranded regions, MutY oxidation is found to be mediated by the DNA duplex, with guanine radical as an intermediate oxidant; guanine radical formation facilitates MutY oxidation. A model is proposed for the redox activation of DNA repair proteins through DNA CT, with guanine radicals, the first product under oxidative stress, in oxidizing the DNA-bound repair proteins, providing the signal to stimulate DNA repair

IS AGRICULTURAL RESEARCH STILL A PUBLIC GOOD?

The nature of public agricultural research changed in 1980 when the Bayh-Dole Act allowed universities to retain title to inventions that were created with Federal funds, and the court case Diamond v. Chakrabarty allowed patenting of living tissue and eventually other bio-engineered products. In 1997, over 2,300 new licenses and options were executed on academic life-sciences property. This raises the questions agricultural research still be a public good? This paper is a critical first step in understanding how increasingly private ownership of intellectual property affects the agribusiness environment and the evolving role of public agricultural research institutions. The innovative step in this paper is the development of a formal economic model which represents the role of applied biotech research in the agricultural life sciences. The model is built around neo-Schumpeterian ideas of endogenous innovation and growth. The most salient implications for the role of the public sector are(1)The private sector underinvests in applied R&D activity. (2) Concentration in the large-firm, life-science R&D industry increases over time. (3) The life-science revolution is reducing the number of markets, in the short run. This reduction in the number of niche markets diminishes the role of the public sector. (4) There is a role for the public sector in conducting R&D in niche markets. (5) In the long run, the life-science revolution may also create new niche markets. (6) There is a role for the public sector in the provision of basic research which increases the productivity of applied R&D.Research and Development/Tech Change/Emerging Technologies,

Nicotinamide treatment in a murine model of familial tumoral calcinosis reduces serum Fgf23 and raises heart calcium

Mutations in the GALNT3 gene result in familial tumoral calcinosis, characterized by persistent hyperphosphatemia and ectopic calcific masses in soft tissues. Since calcific masses often recur after surgical removal, a more permanent solution to the problem is required. Nicotinamide is reported to lower serum phosphate by decreasing sodium-dependent phosphate co-transporters in the gut and kidney. However, its effectiveness in tumoral calcinosis remains unknown. In this study, we investigated nicotinamide as a potential therapy for tumoral calcinosis, using a murine model of the disease-Galnt3 knockout mice. Initially, five different doses of nicotinamide were given to normal heterozygous mice intraperitoneally or orally. Treatment had no effect on serum phosphate levels, but serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23), decreased in a dose-dependent manner. Subsequently, high-dose nicotinamide (40mM) was tested in Galnt3 knockout mice fed a high phosphate diet. The radiographic data pre- and post-treatment showed that nicotinamide did not reverse the calcification. However, the treatment retarded calcification growth after 4weeks, while in the untreated animals, calcifications increased in size. The therapy did not affect serum phosphate levels, but intact Fgf23 decreased in the treated mice. The treated mice also had increased calcium in the heart. In summary, nicotinamide did not alter serum phosphate levels, likely due to compensatory decrease in Fgf23 to counteract the phosphate lowering effect of nicotinamide. Although increased calcium accumulation in the heart is a concern, the therapy appears to slow down the progression of ectopic calcifications