Policy Barriers to School Improvement: What's Real and What's Imagined?

Some of the most promising reforms are happening where school leaders are thinking differently about how to get the strongest student outcomes from the limited resources available. But even principals who use their autonomy to aggressively reallocate resources say that persistent district, state, and federal barriers prohibit them from doing more.What are these barriers? What do they block principals from doing? Is there a way around them?CRPE researchers probed these questions with principals in three states (NH, CT, MD). These principals cited numerous district, state, and federal barriers standing in the way of school improvement. The barriers, 128 in all, fell into three categories: 1) barriers to instructional innovations, 2) barriers to allocating resources differently, and 3) barriers to improving teacher quality.Upon investigation, researchers found that principals have far more authority than they think. Only 31% of the barriers cited were "real" -- immovable statutes, policies, or managerial directives that bring the threat of real consequences if broken.The report recommends educating principals on the authority they already possess, to help them find workarounds to onerous rules. The report also outlines a number of specific state and district policy changes to grant schools the autonomy they need to improve student outcomes

Method for ambiguity resolution in range-Doppler measurements

A method for resolving range and Doppler target ambiguities when the target has substantial range or has a high relative velocity in which a first signal is generated and a second signal is also generated which is coherent with the first signal but at a slightly different frequency such that there exists a difference in frequency between these two signals of Delta f(sub t). The first and second signals are converted into a dual-frequency pulsed signal, amplified, and the dual-frequency pulsed signal is transmitted towards a target. A reflected dual-frequency signal is received from the target, amplified, and changed to an intermediate dual-frequency signal. The intermediate dual-frequency signal is amplified, with extracting of a shifted difference frequency Delta f(sub r) from the amplified intermediate dual-frequency signal done by a nonlinear detector. The final step is generating two quadrature signals from the difference frequency Delta f(sub t) and the shifted difference frequency Delta f(sub r) and processing the two quadrature signals to determine range and Doppler information of the target

Comptonization and QPO Origins in Accreting Neutron Star Systems

We develop a simple, time-dependent Comptonization model to probe the origins of spectral variability in accreting neutron star systems. In the model, soft ``seed photons'' are injected into a corona of hot electrons, where they are Compton upscattered before escaping as hard X-rays. The model describes how the hard X-ray spectrum varies when the properties of either the soft photon source or the Comptonizing medium undergo small oscillations. Observations of the resulting spectral modulations can determine whether the variability is due to (i) oscillations in the injection of seed photons, (ii) oscillations in the coronal electron density, or (iii) oscillations in the coronal energy dissipation rate. Identifying the origin of spectral variability should help clarify how the corona operates and its relation to the accretion disk. It will also help in finding the mechanisms underlying the various quasi-periodic oscillations (QPO) observed in the X-ray outputs of many accreting neutron star and black hole systems. As a sample application of our model, we analyze a kilohertz QPO observed in the atoll source 4U~1608-52. We find that the QPO is driven predominantly by an oscillation in the electron density of the Comptonizing gas.Comment: Submitted to MNRAS, 22 pages in latex using AASTeX macros, 5 Postscript figure

DGR mutagenic transposition occurs via hypermutagenic reverse transcription primed by nicked template RNA.

Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed by an adenine residue in TR RNA and is dependent on the DGR-encoded reverse transcriptase (bRT) and accessory variability determinant (Avd ), but is VR-independent. We also find that the catalytic center of bRT plays an essential role in site-specific cleavage of TR RNA for cDNA priming. Adenine-specific mutagenesis occurs during reverse transcription and does not involve dUTP incorporation, indicating it results from bRT-catalyzed misincorporation of standard deoxyribonucleotides. In vivo assays show that this hybrid RNA-cDNA molecule is required for mutagenic transposition, revealing a unique mechanism of DNA hypervariation for microbial adaptation

Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities.

BackgroundThe phosphatidylinositol 3-kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co-alterations serving as potential resistance/attenuation mechanisms.MethodsConsecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment-certified laboratory using comprehensive genomic profiling performed by next-generation sequencing (315 genes). The co-alterations evaluated included the Erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, RAS, MET proto-oncogene tyrosine kinase (MET), and mitogen-activated protein kinase kinase (MAP2K) genes as well as tumor protein 53 (TP53), estrogen receptor 1 (ESR1), and androgen receptor (AR).ResultsAlterations in any of 18 PI3K-pathway associated genes were identified in 44% of 60,991 tumors. Although single base and insertions/deletions (indels) were the most frequent alterations, copy number changes and rearrangements were identified in 11% and 0.9% of patients, respectively. Overall, the most frequently altered genes were PIK3 catalytic subunit α (PIK3CA) (13%), phosphatase and tensin homolog (PTEN) (9%), and serine/threonine kinase 11 (STK11) (5%). Tumor types that frequently harbored at least 1 PI3K alteration were uterine (77%), cervical (62%), anal (59%), and breast (58%) cancers. Alterations also were discerned frequently in tumors with carcinosarcoma (89%) and squamous cell carcinoma (62%) histologies. Tumors with a greater likelihood of co-occurring PI3K pathway and MAPK pathway alterations included colorectal cancers (odds ratio [OR], 1.64; P < .001), mesotheliomas (OR, 2.67; P = .024), anal cancers (OR, 1.98; P = .03), and nonsquamous head and neck cancers (OR, 2.03; P = .019). The co-occurrence of ESR1 and/or AR alterations with PI3K alterations was statistically significant in bladder, colorectal, uterine, prostate, and unknown primary cancers.ConclusionsComprehensive genomic profiling reveals altered PI3K-related genes in 44% of solid malignancies, including rare disease and histology types. The frequency of alterations and the co-occurrence of resistance pathways vary by tumor type, directly affecting opportunities for targeted therapy