74 research outputs found
The Impact of Pre-K Programs on Student Achievement and Instructional Leadership in Rural Mississippi School Districts
In 2011, Mississippi continues to be the only state in the southern region without a single state-funded pre-k program (NIEER, 2007), and all preschool funds in the state are currently allotted to Head Start. Witte and Trowbridge (2004) warned that the combination of pre-k programs could be the reason for highly fragmented systems of state funding, policies, and regulations. The purpose of this mixed methods study was to investigate whether differences exist between preschool groups in three North Mississippi school districts and to determine the degree to which stakeholders in the programs practice instructional leadership. From a quantitative perspective, the STAR GE and STAR Est. ORF scores of 388 second graders were analyzed using a one-way ANOVA, and significant differences were found in academic achievement between all three groups of students who attended public school pre-k, Head Start, or no pre-k. From a qualitative perspective, the researcher folloa phenomenological approach to determine the degree to which 22 school instructional leaders collaborate to make decisions concerning their pre-k programs. The responses from four research questions indicate that traditional macro and micro-level roles of instructional leadership exist between administration and teachers, and collaboration between administrators and teachers dropped substantially after each program began. Trust and autonomy are strong and appreciated by the pre-k teachers, yet the teachers expressed a desire for ongoing collaboration with administration. Additionally, collaborative relationships need to be cultivated between public school programs and Head Start. Finally, several recommendations for further research and practice are suggested
The impact of baryons on the direct detection of dark matter
The spatial and velocity distributions of dark matter particles in the Milky
Way Halo affect the signals expected to be observed in searches for dark
matter. Results from direct detection experiments are often analyzed assuming a
simple isothermal distribution of dark matter, the Standard Halo Model (SHM).
Yet there has been skepticism regarding the validity of this simple model due
to the complicated gravitational collapse and merger history of actual
galaxies. In this paper we compare the SHM to the results of cosmological
hydrodynamical simulations of galaxy formation to investigate whether or not
the SHM is a good representation of the true WIMP distribution in the analysis
of direct detection data. We examine two Milky Way-like galaxies from the
MaGICC cosmological simulations (a) with dark matter only and (b) with baryonic
physics included. The inclusion of baryons drives the shape of the DM halo to
become more spherical and makes the velocity distribution of dark matter
particles less anisotropic especially at large heliocentric velocities, thereby
making the SHM a better fit. We also note that we do not find a significant
disk-like rotating dark matter component in either of the two galaxy halos with
baryons that we examine, suggesting that dark disks are not a generic
prediction of cosmological hydrodynamical simulations. We conclude that in the
Solar neighborhood, the SHM is in fact a good approximation to the true dark
matter distribution in these cosmological simulations (with baryons) which are
reasonable representations of the Milky Way, and hence can also be used for the
purpose of dark matter direct detection calculations.Comment: Minor changes to match JCAP version. 21 pages, 9 figure
Systematic problems with using dark matter simulations to model stellar halos
The limits of available computing power have forced models for the structure of stellar halos to adopt one or both of the following simplifying assumptions: (1) stellar mass can be "painted" onto dark matter (DM) particles in progenitor satellites; (2) pure DM simulations that do not form a luminous galaxy can be used. We estimate the magnitude of the systematic errors introduced by these assumptions using a controlled set of stellar halo models where we independently vary whether we look at star particles or painted DM particles, and whether we use a simulation in which a baryonic disk galaxy forms or a matching pure DM simulation that does not form a baryonic disk. We find that the "painting" simplification reduces the halo concentration and internal structure, predominantly because painted DM particles have different kinematics from star particles even when both are buried deep in the potential well of the satellite. The simplification of using pure DM simulations reduces the concentration further, but increases the internal structure, and results in a more prolate stellar halo. These differences can be a factor of 1.5-7 in concentration (as measured by the half-mass radius) and 2-7 in internal density structure. Given this level of systematic uncertainty, one should be wary of overinterpreting differences between observations and the current generation of stellar halo models based on DM-only simulations when such differences are less than an order of magnitude
Consequences of cosmic microwave background-regulated star formation
It has been hypothesized that the cosmic microwave background (CMB) provides
a temperature floor for collapsing protostars that can regulate the process of
star formation and result in a top-heavy initial mass function at high
metallicity and high redshift. We examine whether this hypothesis has any
testable observational consequences. First we determine, using a set of
hydrodynamic galaxy formation simulations, that the CMB temperature floor would
have influenced the majority of stars formed at redshifts between z=3 and 6,
and probably even to higher redshift. Five signatures of CMB-regulated star
formation are: (1) a higher supernova rate than currently predicted at high
redshift; (2) a systematic discrepancy between direct and indirect measurements
of the high redshift star formation rate; (3) a lack of surviving globular
clusters that formed at high metallicity and high redshift; (4) a more rapid
rise in the metallicity of cosmic gas than is predicted by current simulations;
and (5) an enhancement in the abundances of alpha elements such as O and Mg at
metallicities -2 < [Fe/H] < -0.5. Observations are not presently able to either
confirm or rule out the presence of these signatures. However, if correct, the
top-heavy IMF of high-redshift high-metallicity globular clusters could provide
an explanation for the observed bimodality of their metallicity distribution.Comment: ApJ in press, 10 pages, emulateap
Halo orbits in cosmological disk galaxies : tracers of information history
We analyze the orbits of stars and dark matter particles in the halo of a disk galaxy formed in a cosmological hydrodynamical simulation. The halo is oblate within the inner ∼20 kpc and triaxial beyond this radius. About 43% of orbits are short axis tubes—the rest belong to orbit families that characterize triaxial potentials (boxes, long-axis tubes and chaotic orbits), but their shapes are close to axisymmetric. We find no evidence that the self-consistent distribution function of the nearly oblate inner halo is comprised primarily of axisymmetric short-axis tube orbits. Orbits of all families and both types of particles are highly eccentric, with mean eccentricity �0.6. We find that randomly selected samples of halo stars show no substructure in “integrals of motion” space. However, individual accretion events can clearly be identified in plots of metallicity versus formation time. Dynamically young tidal debris is found primarily on a single type of orbit. However, stars associated with older satellites become chaotically mixed during the formation process (possibly due to scattering by the central bulge and disk, and baryonic processes), and appear on all four types of orbits. We find that the tidal debris in cosmological hydrodynamical simulations experiences significantly more chaotic evolution than in collisionless simulations, making it much harder to identify individual progenitors using phase space coordinates alone. However, by combining information on stellar ages and chemical abundances with the orbital properties of halo stars in the underlying self-consistent potential, the identification of progenitors is likely to be possible
Supersymmetric dS/CFT
We put forward new explicit realisations of dS/CFT that relate
supersymmetric Euclidean vector models with reversed spin-statistics in three
dimensions to specific supersymmetric Vasiliev theories in four-dimensional de
Sitter space. The partition function of the free supersymmetric vector model
deformed by a range of low spin deformations that preserve supersymmetry
appears to specify a well-defined wave function with asymptotic de Sitter
boundary conditions in the bulk. In particular we find the wave function is
globally peaked at undeformed de Sitter space, with a low amplitude for strong
deformations. This suggests that supersymmetric de Sitter space is stable in
higher-spin gravity and in particular free from ghosts. We speculate this is a
limiting case of the de Sitter realizations in exotic string theories.Comment: V2: references and comments added, typos corrected, version published
in JHEP; 27 pages, 3 figures, 1 tabl
Oncogenic ERBB3 Mutations in Human Cancers
SummaryThe human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ∼11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression in vivo
Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples
<p>Abstract</p> <p>Background</p> <p>Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome.</p> <p>Methods</p> <p>We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays.</p> <p>Results</p> <p>Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%.</p> <p>We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the <it>SLC45A3-ELK4 </it>e4-e2 TIC to <it>ERG</it>-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines.</p> <p>Conclusions</p> <p>Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as <it>MSMB-NCOA4</it>, may play functional roles in cancer.</p
Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness
Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases
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