684 research outputs found
A New Approach to Developing Interactive Software Modules Through Graduate Education
Educational technology has attained significant importance as a mechanism for supporting experiential learning of science concepts. However, the growth of this mechanism is limited by the significant time and technical expertise needed to develop such products, particularly in specialized fields of science. We sought to test whether interactive, educational, online software modules can be developed effectively by students as a curriculum component of an advanced science course. We discuss a set of 15 such modules developed by Harvard University graduate students to demonstrate various concepts related to astronomy and physics. Their successful development of these modules demonstrates that online software tools for education and outreach on specialized topics can be produced while simultaneously fulfilling project-based learning objectives. We describe a set of technologies suitable for module development and present in detail four examples of modules developed by the students. We offer recommendations for incorporating educational software development within a graduate curriculum and conclude by discussing the relevance of this novel approach to new online learning environments like edX.Astronom
MI5 and the Cold War in South-East Asia: Examining the Performance of Security Intelligence Far East (SIFE), 1946-1963
From 1946–1963, MI5 operated a South-East Asian regional headquarters in Singapore: Security Intelligence Far East (SIFE). This article responds to growing interest in theatre-level intelligence organisation and the importance of intelligence to Britain’s Cold War and decolonisation by examining the performance of SIFE. On the organisational level, SIFE was strongest when it remained wedded to its charter functions and closely adhered to the priorities of its principal consumer: the Commissioner-General for South-East Asia. Its assessments were influential in shaping decision-makers’ understandings of key regional developments, although this did not always translate into public policy. Lastly, SIFE enjoyed success in developing lasting liaison relationships to cement British influence, but failed to utilise these to improve its intake of raw intelligence
Summary of Proposed Updates to the National Health Security Preparedness Index for 2015-2016
This report describes proposed updates in methodology and measures for the 2015-16 release of the National Health Security Preparedness Inde
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Rational optimization of tolC as a powerful dual selectable marker for genome engineering
Selection has been invaluable for genetic manipulation, although counter-selection has historically exhibited limited robustness and convenience. TolC, an outer membrane pore involved in transmembrane transport in E. coli, has been implemented as a selectable/counter-selectable marker, but counter-selection escape frequency using colicin E1 precludes using tolC for inefficient genetic manipulations and/or with large libraries. Here, we leveraged unbiased deep sequencing of 96 independent lineages exhibiting counter-selection escape to identify loss-of-function mutations, which offered mechanistic insight and guided strain engineering to reduce counter-selection escape frequency by ∼40-fold. We fundamentally improved the tolC counter-selection by supplementing a second agent, vancomycin, which reduces counter-selection escape by 425-fold, compared colicin E1 alone. Combining these improvements in a mismatch repair proficient strain reduced counter-selection escape frequency by 1.3E6-fold in total, making tolC counter-selection as effective as most selectable markers, and adding a valuable tool to the genome editing toolbox. These improvements permitted us to perform stable and continuous rounds of selection/counter-selection using tolC, enabling replacement of 10 alleles without requiring genotypic screening for the first time. Finally, we combined these advances to create an optimized E. coli strain for genome engineering that is ∼10-fold more efficient at achieving allelic diversity than previous best practices
Truthmakers and modality
This paper attempts to locate, within an actualist ontology, truthmakers for modal truths: truths of the form or . In section 1 I motivate the demand for substantial truthmakers for modal truths. In section 2 I criticise Armstrong’s account of truthmakers for modal truths. In section 3 I examine essentialism and defend an account of what makes essentialist attributions true, but I argue that this does not solve the problem of modal truth in general. In section 4 I discuss, and dismiss, a theistic account of the source of modal truth proposed by Alexander Pruss. In section 5 I offer a means of (dis)solving the problem
The Green Bank Ammonia Survey (GAS): First Results of NH3 mapping the Gould Belt
We present an overview of the first data release (DR1) and first-look science
from the Green Bank Ammonia Survey (GAS). GAS is a Large Program at the Green
Bank Telescope to map all Gould Belt star-forming regions with
mag visible from the northern hemisphere in emission from NH and other key
molecular tracers. This first release includes the data for four regions in
Gould Belt clouds: B18 in Taurus, NGC 1333 in Perseus, L1688 in Ophiuchus, and
Orion A North in Orion. We compare the NH emission to dust continuum
emission from Herschel, and find that the two tracers correspond closely.
NH is present in over 60\% of lines-of-sight with mag in
three of the four DR1 regions, in agreement with expectations from previous
observations. The sole exception is B18, where NH is detected toward ~ 40\%
of lines-of-sight with mag. Moreover, we find that the NH
emission is generally extended beyond the typical 0.1 pc length scales of dense
cores. We produce maps of the gas kinematics, temperature, and NH column
densities through forward modeling of the hyperfine structure of the NH
(1,1) and (2,2) lines. We show that the NH velocity dispersion,
, and gas kinetic temperature, , vary systematically between
the regions included in this release, with an increase in both the mean value
and spread of and with increasing star formation activity.
The data presented in this paper are publicly available.Comment: 33 pages, 27 figures, accepted to ApJS. Datasets are publicly
available: https://dataverse.harvard.edu/dataverse/GAS_DR
Droplets I: Pressure-Dominated Sub-0.1 pc Coherent Structures in L1688 and B18
We present the observation and analysis of newly discovered coherent
structures in the L1688 region of Ophiuchus and the B18 region of Taurus. Using
data from the Green Bank Ammonia Survey (GAS), we identify regions of high
density and near-constant, almost-thermal, velocity dispersion. Eighteen
coherent structures are revealed, twelve in L1688 and six in B18, each of which
shows a sharp "transition to coherence" in velocity dispersion around its
periphery. The identification of these structures provides a chance to study
the coherent structures in molecular clouds statistically. The identified
coherent structures have a typical radius of 0.04 pc and a typical mass of 0.4
Msun, generally smaller than previously known coherent cores identified by
Goodman et al. (1998), Caselli et al. (2002), and Pineda et al. (2010). We call
these structures "droplets." We find that unlike previously known coherent
cores, these structures are not virially bound by self-gravity and are instead
predominantly confined by ambient pressure. The droplets have density profiles
shallower than a critical Bonnor-Ebert sphere, and they have a velocity (VLSR)
distribution consistent with the dense gas motions traced by NH3 emission.
These results point to a potential formation mechanism through pressure
compression and turbulent processes in the dense gas. We present a comparison
with a magnetohydrodynamic simulation of a star-forming region, and we
speculate on the relationship of droplets with larger, gravitationally bound
coherent cores, as well as on the role that droplets and other coherent
structures play in the star formation process.Comment: Accepted by ApJ in April, 201
Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli
The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 “recalcitrant” AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes.United States. Department of Energy (DE-FG02-02ER63445
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Primis : design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis
BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with >= 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.Peer reviewe
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