Factors Affecting the Adoption of Faculty-Developed Academic Software: A Study of Five iCampus Projects

Instruction in higher education must adapt more rapidly to: changes in workforce needs, global issues, advances in disciplines, and resource constraints. The pace of such improvement depends on the speed with which new ideas and materials are adopted across institutions. In 1999 Microsoft pledged $25 million and staff support for iCampus, a seven-year MIT project to develop pioneering uses of educational technology. The TLT Group studied five iCampus projects in order to identify factors affecting institutionalization and widespread dissemination. Among the factors impeding adoption: lack of rewards and support for faculty to adopt innovations; faculty isolation; and a lack of attention to adoption issues among projects selected for funding. The study made recommendations for universities, foundations, government agencies and corporations: 1) continue making education more authentic, active, collaborative, and feedback-rich; 2) create demand to adopt ideas and materials from other sources by encouraging all faculty members to improve and document learning in their programs, year after year; 3) nurture coalitions for instructional improvement, across and within institutions; 4) create more effective higher education corporate alliances; and 5) improve institutional services to support faculty in educational design, software development, assessment methods, formative evaluation, and/or in sharing ideas with others who teach comparable courses

A brain-derived MeCP2 complex supports a role for MeCP2 in RNA processing

Mutations in MECP2 (methyl-CpG-binding protein 2) are linked to the severe postnatal neurodevelopmental disorder RTT (Rett syndrome). MeCP2 was originally characterized as a transcriptional repressor that preferentially bound methylated DNA; however, recent results indicate MeCP2 is a multifunctional protein. MeCP2 binding is now associated with certain expressed genes and involved in nuclear organization as well, indicating that its gene regulatory function is context-dependent. In addition, MeCP2 is proposed to regulate mRNA splicing and a mouse model for RTT shows aberrant mRNA splicing. To further understand MeCP2 and potential roles in RTT pathogenesis, we have employed a biochemical approach to identify the MeCP2 protein complexes present in the mammalian brain. We show that MeCP2 exists in at least four biochemically distinct pools in the brain and characterize one novel brain-derived MeCP2 complex that contains the splicing factor Prpf3 (pre-mRNA processing factor 3). MeCP2 directly interacts with Prpf3 in vitro and in vivo and many MECP2 RTT truncations disrupt the MeCP2-Prpf3 complex. In addition, MeCP2 and Prpf3 associate in vivo with mRNAs from genes known to be expressed when their promoters are associated with MeCP2. These results support a role for MeCP2 in mRNA biogenesis and suggest an additional mechanism for RTT pathophysiology

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

PurposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population.Materials and methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.ResultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease > 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.ConclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen

Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource

Genetic dissection of complex, polygenic trait variation is a key goal of medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, and an inability to identify variants that cumulatively explain the bulk of standing genetic variation in genome-wide association studies (GWAS). Thus, much of the heritability remains unexplained for most complex traits. Here we describe a novel, freely available resource for the Drosophila community consisting of two sets of recombinant inbred lines (RILs), each derived from an advanced generation cross between a different set of eight highly inbred, completely resequenced founders. The Drosophila Synthetic Population Resource (DSPR) has been designed to combine the high mapping resolution offered by multiple generations of recombination, with the high statistical power afforded by a linkage-based design. Here, we detail the properties of the mapping panel of >1600 genotyped RILs, and provide an empirical demonstration of the utility of the approach by genetically dissecting alcohol dehydrogenase (ADH) enzyme activity. We confirm that a large fraction of the variation in this classic quantitative trait is due to allelic variation at the Adh locus, and additionally identify several previously unknown modest-effect trans-acting QTL (quantitative trait loci). Using a unique property of multiparental linkage mapping designs, for each QTL we highlight a relatively small set of candidate causative variants for follow-up work. The DSPR represents an important step toward the ultimate goal of a complete understanding of the genetics of complex traits in the Drosophila model system.This work was supported by the following NIH R01 grants: RR024862 to S.J.M. and A.D.L., GM085260 to S.J.M., GM085251 to A.D.L., GM078338 to S.S., and GM074244 to K.W.B

Annual report for active IDOT wetland mitigation and hydrologic monitoring sites, September 1, 2014 through August 31, 2015

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US States’ Childhood Obesity Surveillance Practices and Recommendations for Improving Them, 2014–2015

Introduction: Routine collection, analysis, and reporting of data on child height, weight, and body mass index (BMI), particularly at the state and local levels, are needed to monitor the childhood obesity epidemic, plan intervention strategies, and evaluate the impact of interventions. Child BMI surveillance systems operated by the US government do not provide state or local data on children across a range of ages. The objective of this study was to describe the extent to which state governments conduct child BMI surveillance. Methods: From August through December 2014, we conducted a structured telephone survey with state government administrators to learn about state surveillance of child BMI. We also searched websites of state health and education agencies for information about state surveillance. Results: State agency administrators in 48 states and Washington, DC, completed telephone interviews (96% response rate). Based on our interviews and Internet research, we determined that 14 states collect child BMI data in a manner consistent with standard definitions of public health surveillance. Conclusion: The absence of child BMI surveillance systems in most states limits the ability of public health practitioners and policymakers to develop and evaluate responses to the childhood obesity epidemic. Greater investment in surveillance is needed to identify the most effective and cost-effective childhood obesity interventions

A faux hawk fullerene with PCBM-like properties

Reaction of C60, C6F5CF2I, and SnH(n-Bu)3 produced, among other unidentified fullerene derivatives, the two new compounds 1,9-C60(CF2C6F5)H (1) and 1,9-C60(cyclo-CF2(2-C6F4)) (2). The highest isolated yield of 1 was 35% based on C60. Depending on the reaction conditions, the relative amounts of 1 and 2 generated in situ were as high as 85% and 71%, respectively, based on HPLC peak integration and summing over all fullerene species present other than unreacted C60. Compound 1 is thermally stable in 1,2-dichlorobenzene (oDCB) at 160 °C but was rapidly converted to 2 upon addition of Sn2(n-Bu)6 at this temperature. In contrast, complete conversion of 1 to 2 occurred within minutes, or hours, at 25 °C in 90/10 (v/v) PhCN/C6D6 by addition of stoichiometric, or sub-stoichiometric, amounts of proton sponge (PS) or cobaltocene (CoCp2). DFT calculations indicate that when 1 is deprotonated, the anion C60(CF2C6F5)− can undergo facile intramolecular SNAr annulation to form 2 with concomitant loss of F−. To our knowledge this is the first observation of a fullerene-cage carbanion acting as an SNAr nucleophile towards an aromatic C–F bond. The gas-phase electron affinity (EA) of 2 was determined to be 2.805(10) eV by low-temperature PES, higher by 0.12(1) eV than the EA of C60 and higher by 0.18(1) eV than the EA of phenyl-C61-butyric acid methyl ester (PCBM). In contrast, the relative E1/2(0/−) values of 2 and C60, −0.01(1) and 0.00(1) V, respectively, are virtually the same (on this scale, and under the same conditions, the E1/2(0/−) of PCBM is −0.09 V). Time-resolved microwave conductivity charge-carrier yield × mobility values for organic photovoltaic active-layer-type blends of 2 and poly-3-hexylthiophene (P3HT) were comparable to those for equimolar blends of PCBM and P3HT. The structure of solvent-free crystals of 2 was determined by single-crystal X-ray diffraction. The number of nearest-neighbor fullerene–fullerene interactions with centroid⋯centroid (⊙⋯⊙) distances of ≤10.34 Å is significantly greater, and the average ⊙⋯⊙ distance is shorter, for 2 (10 nearest neighbors; ave. ⊙⋯⊙ distance = 10.09 Å) than for solvent-free crystals of PCBM (7 nearest neighbors; ave. ⊙⋯⊙ distance = 10.17 Å). Finally, the thermal stability of 2 was found to be far greater than that of PCBM

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru

© 2016 Public Library of Science. All Rights Reserved. Background: Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010–2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%–65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1–17.7). Conclusions/Significance: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics