Evaluating force field accuracy with long-time simulations of a tryptophan zipper peptide

We have combined a custom implementation of the fast multiple-time-stepping LN integrator with parallel tempering to explore folding properties of small peptides in implicit solvent on the time scale of microseconds. We applied this algorithm to the synthetic {\beta}-hairpin trpzip2 and one of its sequence variants W2W9. Each simulation consisted of over 12 {\mu}s of aggregated virtual time. Several measures of folding behavior showed convergence, allowing comparison with experimental equilibrium properties. Our simulations suggest that the electrostatic interaction of tryptophan sidechains is responsible for much of the stability of the native fold. We conclude that the ff99 force field combined with ff96 {\phi} and {\psi} dihedral energies and implicit solvent can reproduce plausible folding behavior in both trpzip2 and W2W9.Comment: 10 pages, 11 figures, submitted to the Journal of Chemical Physics on June 28, 201

Simulated LM static reflectivity data, for site P-2-6

Simulated lunar module static reflectivity data for site P-2-

Teacher Attitudes Toward Personalized Learning Plans

The aim of this research was to analyze Vermont K-8 teachers’ attitudes toward student personalized learning plans with respect to the independent variable of years of personalized learning plans implementation. This was an important study because personalization has become the new trend in Vermont education. The purpose of this study was to bridge a gap in the literature and research surrounding teacher attitudes toward personalized learning plan implementation. Personalized learning plans were being used as a pathway to high school graduation. Determining the attitudes of teachers toward this initiative seemed reasonable given the upswing of this recent trend in education. Over 150 Vermont teachers participated in this study, ranging geographically over more than twenty supervisory unions. The teachers range in personalized learning plans implementation of one year of experience to five or more years of experience. The Personalized Learning Environment Attitude Scale (PLEAS) instrument was used to collect the data. The voluntary teachers were given a link to the 27-question, five-minute online survey. A causal-comparative research design was used in this study with the one-way between-subjects analysis of variance (ANOVA) as the tool of analysis. There was no statistical significance found; rather, the study found largely favorable attitudes toward personalized learning plans. It is recommended that more research be conducted around the effectiveness of personalized learning plans and the solicitation of teacher input of such research

LM radar reflectivity simulation Final report

Ultrasonic simulation of lunar module radar reflectivit

Altitude dependent radar return statistics

Effect of decreasing altitude on statistics of radar backscatter from random rough surfac

Is the Yb2Ti2O7 pyrochlore a quantum spin ice?

We use numerical linked cluster (NLC) expansions to compute the specific heat, C(T), and entropy, S(T), of a quantum spin ice model of Yb2Ti2O7 using anisotropic exchange interactions recently determined from inelastic neutron scattering measurements and find good agreement with experimental calorimetric data. In the perturbative weak quantum regime, this model has a ferrimagnetic ordered ground state, with two peaks in C(T): a Schottky anomaly signalling the paramagnetic to spin ice crossover followed at lower temperature by a sharp peak accompanying a first order phase transition to the ferrimagnetic state. We suggest that the two C(T) features observed in Yb2Ti2O7 are associated with the same physics. Spin excitations in this regime consist of weakly confined spinon-antispinon pairs. We suggest that conventional ground state with exotic quantum dynamics will prove a prevalent characteristic of many real quantum spin ice materials.Comment: 8 pages (two-column), 9 figure

Simulated Cytoskeletal Collapse via Tau Degradation

We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimer's disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundle falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse.Comment: 11 pages, 9 figure

The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.We thank Ludovic Vallier for constitutive Nanog-EpiSC, Gabrielle Brons for 129S2 EpiSC, Prim Singh for H3K9me3 antibody, Maria Elena Torres Padilla for TALE-mClover and luciferase plasmids, Wellcome Trust Sanger Institute for pCyL43 plasmid and Andras Nagy for PB-TET and rtTA plasmids. We are grateful to David Oxley and Judith Webster Novo et al. for mass spectrometry support, Simon Walker for imaging support and Anne Segonds- Pichon for statistical advice. We thank Wolf Reik and Jon Houseley for comments on the manuscript and members of Wolf Reik’s group for helpful discussions. P.J.R.-G. is supported by the Wellcome Trust [WT093736], BBSRC [M022285] and the European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]. The work was also supported with funds from the Canadian Institutes of Health Research to J.E. [Team Grant EPS-129129] and D.P.B.-J. D.P.B-J. holds the Canada Research Chair in Molecular and Cellular Imaging. I.C. is supported by the MRC

Understanding transmission and control of Cystic Echinococcosis and other taeniid infections in the Falkland Islands

Cystic echinococcosis, caused by the larval form of the cestode parasite Echinococcus granulosus, has been identified as an important public health risk in the Falkland Islands since the early 1940s. This prompted the instigation of an intensive control scheme in the mid-1960s, comprised of regular dosing of domestic dogs with the anthelmintic praziquantel and education of local people about safe disposal of potentially infected offal. This scheme has remained in place to the current day and is generally considered to be a successful programme– resulting in a reduction in the prevalence of infection in sheep has reduced from >50% in the 1950s to less than 1 % now and there has not been a case of human hydatid disease for more than 20 years. However, concerns remain that hydatid cysts are still identified in a small number of sheep at slaughter (0.004% in 2017) and occurring every year subsequently suggesting transmission is still occurring. This is also supported by the observation that sheep continue to be infected at higher levels with the (non-zoonotic) cestode Taenia hydatigena, also transmitted by dogs. In 2010, all dogs on the Falkland Islands were tested by Copro-PCR, resulting in eight dogs (1.4%) testing positive. The dog population was tested again in 2012, where there were no cases but when tested in 2014 by Coproantigen testing, six (1.04%) were positive for E. granulosus coproantigens. This project used questionnaires, coproantigen and coproPCR analysis, abattoir data surveillance, DNA sequencing, environmental sample analysis and mathematical modelling to study Echinococcus granulosus and other taeniids endemic in the Falklands and investigate how their continued transmission can occur in the face of the prolonged intensive control programme. A questionnaire survey identified possible methods of disposal of offal that in a previous study, were associated with canine coproantigen positivity. The entire dog population was analysed via coproantigen techniques in 2018, and four (0.68%) dogs were coproantigen positive, though none of these were confirmed by PCR. From 2018 to 2020, five cases of CE were identified in sheep at the Sand Bay abattoir in the Falklands (0.01%), with one of the cases coming from a positive farm in 2018. There were two cases from farms with positive dogs in 2010 and one from a farm with a positive dog in 2014. To investigate environmental contamination on farms and potentially identify historical dog infections, soil samples taken from kennel sites were analysed for the presence of coproantigens, with five farms having positive results, one farm matching with a positive dog in 2018. To identify key processes fuelling the transmission of E. granulosus in the Falklands, a mechanically informed compartmental model was created, estimating the basic reproduction number (R0) for the parasite, and identifying scenarios where this estimate increased above one suggesting continued transmission could occur. Seven scenarios where lapses in control measures could result in the R0 estimate increasing above one and continued transmission of E. granulosus could occur. The results of this project show clear evidence of dogs still being involved in the transmission of taeniid parasites in the Falklands, with key areas of the eradication programme such as the inadequate disposal of offal and dogs gaining access to offal allowing the transmission cycle to be completed and transmission of E. granulosus and other taeniids to occur. Rectifying these lapses in control measures and focussing control and surveillance to a more localised control approach will help strengthen the control programme and move the Falklands closer towards the complete eradication of Cystic Echinococcosis