72 research outputs found
The Development and Validation of a System for the Knowledge-Based Tutoring of Special Education Rules and Regulations
Research indicates that school officials fail to identify a relatively high proportion of school-aged children with behavioral or emotional handicaps. As a result, these children may not be receiving the special education services to which they are entitled. Multidisciplinary team members may be failing to identify these children because they lack understanding of special education rules and regulations. The purpose of this project was to combine the technologies of expert systems and mastery-based instruction to develop an inservice and preservice training program capable of producing mastery-level performance of the skills required to identify children with behavioral or emotional handicaps. Borg and Gall\u27s ( 983) research and development cycle provided the model for developing, testing, and revising the program.
Prototype evaluations and large-scale field tests revealed that the program met its performance and user satisfaction objectives when administered under conditions of independent administration. However, a failure on the use and part of remote remote administrators to comply with prescribed program administration procedures allowed an unacceptable number of subjects to end training without completing all computer exercises. Attention to administration procedures contributed to the success of the project in meeting its performance and user satisfaction objectives in the final operational field test.
The positive findings of the project have implications on two levels. First, the findings are important for the positive effect they may have on the lives of children. Decision-making errors on the part of multidisciplinary team members can be costly to children with behavioral or emotional handicaps, as well as to other children. The evidence obtained in this project suggests that multidisciplinary team members can be trained to accurately identify children with behavioral or emotional handicaps.
On another, and perhaps more important, level, the findings have implications for the design of effective inservice and preservice training programs. The application of innovative technologies to inservice and preservice training problems does not necessarily result in the development of products capable of producing mastery-level decision-making performance. The positive results achieved in the present project suggest that those seeking to apply innovative technologies to inservice and preservice training problems take into account basic instructional design principles
Revisiting Event Horizon Finders
Event horizons are the defining physical features of black hole spacetimes,
and are of considerable interest in studying black hole dynamics. Here, we
reconsider three techniques to localise event horizons in numerical spacetimes:
integrating geodesics, integrating a surface, and integrating a level-set of
surfaces over a volume. We implement the first two techniques and find that
straightforward integration of geodesics backward in time to be most robust. We
find that the exponential rate of approach of a null surface towards the event
horizon of a spinning black hole equals the surface gravity of the black hole.
In head-on mergers we are able to track quasi-normal ringing of the merged
black hole through seven oscillations, covering a dynamic range of about 10^5.
Both at late times (when the final black hole has settled down) and at early
times (before the merger), the apparent horizon is found to be an excellent
approximation of the event horizon. In the head-on binary black hole merger,
only {\em some} of the future null generators of the horizon are found to start
from past null infinity; the others approach the event horizons of the
individual black holes at times far before merger.Comment: 30 pages, 15 figures, revision
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses
Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project
The Numerical INJection Analysis (NINJA) project is a collaborative effort
between members of the numerical relativity and gravitational-wave data
analysis communities. The purpose of NINJA is to study the sensitivity of
existing gravitational-wave search algorithms using numerically generated
waveforms and to foster closer collaboration between the numerical relativity
and data analysis communities. We describe the results of the first NINJA
analysis which focused on gravitational waveforms from binary black hole
coalescence. Ten numerical relativity groups contributed numerical data which
were used to generate a set of gravitational-wave signals. These signals were
injected into a simulated data set, designed to mimic the response of the
Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this
data using search and parameter-estimation pipelines. Matched filter
algorithms, un-modelled-burst searches and Bayesian parameter-estimation and
model-selection algorithms were applied to the data. We report the efficiency
of these search methods in detecting the numerical waveforms and measuring
their parameters. We describe preliminary comparisons between the different
search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ
Status of black-hole-binary simulations for gravitational-wave detection
It is now possible to theoretically calculate the gravitational-wave signal
from the inspiral, merger and ringdown of a black-hole-binary system. The late
inspiral, merger and ringdown can be calculated in full general relativity
using numerical methods. The numerical waveforms can then be either stitched to
inspiral waveforms predicted by approximation techniques (in particular
post-Newtonian calculations) that start at an arbitrarily low frequency, or
used to calibrate free parameters in analytic models of the full waveforms. In
this review I summarize the status of numerical-relativity (NR) waveforms that
include at least ten cycles of the dominant mode of the GW signal before
merger, which should be long enough to produce accurate, complete waveforms for
GW observations.Comment: 22 pages, 6 figures, Version to be published in CQG, NRDA 2008
Special Issu
A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: Functional characterisation and signatures of selection
Although cytochrome P450 (CYP450) enzymes are frequently up-regulated in mosquitoes resistant to insecticides, no regulatory motifs driving these expression differences with relevance to wild populations have been identified. Transposable elements (TEs) are often enriched upstream of those CYP450s involved in insecticide resistance, leading to the assumption that they contribute regulatory motifs that directly underlie the resistance phenotype. A partial CuRE1 (Culex Repetitive Element 1) transposable element is found directly upstream of CYP9M10, a cytochrome P450 implicated previously in larval resistance to permethrin in the ISOP450 strain of Cx. quinquefasciatus, but is absent from the equivalent genomic region of a susceptible strain. Via expression of CYP9M10 in E.coli we have now demonstrated time- and NADPH-dependant permethrin metabolism, prerequisites for confirmation of a role in metabolic resistance, and through qPCR shown that CYP9M10 is >20-fold over-expressed in ISOP450 compared to a susceptible strain. In a fluorescent reporter assay the region upstream of CYP9M10 from ISOP450 drove 10x expression compared to the equivalent region (lacking CuRE1) from the susceptible strain. Close correspondence with the
gene expression fold-change implicates the upstream region including CuRE1 as a cis-regulatory
element involved in resistance. Only a single CuRE1 bearing allele, identical to the CuRE1 bearing
allele in the resistant strain, is found throughout Sub-Saharan Africa, in contrast to the diversity encountered in non-CuRE1 alleles. This suggests a single origin and subsequent spread due to selective advantage. CuRE1 is detectable using a simple diagnostic. When applied to Cx.
quinquefasciatus larvae from Ghana we have demonstrated a significant association with permethrin resistance in multiple field sites (mean Odds Ratio = 3.86) suggesting this marker has relevance to natural populations of vector mosquitoes. However, when CuRE1 was excised from the allele used in the reporter assay through fusion PCR, expression was unaffected, indicating that the TE has no direct role in resistance and hence that CuRE1 is acting only as a marker of an as yet unidentified regulatory motif in the association analysis. This suggests that a re-evaluation of the assumption that TEs contribute regulatory motifs involved in gene expression may be necessary
Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga \u3ci\u3eNannochloropsis oceanica\u3c/i\u3e CCMP1779
Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogendepleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica–specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing academic community focused on this genus
Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections
γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections
Response to correspondence on Reproducibility of CRISPR-Cas9 Methods for Generation of Conditional Mouse Alleles: A Multi-Center Evaluation
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