Leading, Learning, and Leadership Support

Offers a framework for improving learning-focused leadership through the use of data and evidence, reallocation of resources, redefined roles and responsibilities, assessment of leadership performance, better governance, and a focus on high schools

Learning-Focused Leadership and Leadership Support: Meaning and Practice in Urban Systems

Synthesizes three reports on what good education leadership means and how it can best be supported, including the role of the school leader and the transformation of central district offices to focus more on improving instruction. Outlines key practices

Shaping electron wave functions in a carbon nanotube with a parallel magnetic field

A magnetic field, through its vector potential, usually causes measurable changes in the electron wave function only in the direction transverse to the field. Here we demonstrate experimentally and theoretically that in carbon nanotube quantum dots, combining cylindrical topology and bipartite hexagonal lattice, a magnetic field along the nanotube axis impacts also the longitudinal profile of the electronic states. With the high (up to 17T) magnetic fields in our experiment the wave functions can be tuned all the way from "half-wave resonator" shape, with nodes at both ends, to "quarter-wave resonator" shape, with an antinode at one end. This in turn causes a distinct dependence of the conductance on the magnetic field. Our results demonstrate a new strategy for the control of wave functions using magnetic fields in quantum systems with nontrivial lattice and topology.Comment: 5 figure

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells

MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34&lt;sup&gt;+&lt;/sup&gt;38&lt;sup&gt;lo&lt;/sup&gt;) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells &lt;i&gt;in vitro&lt;/i&gt;. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34&lt;sup&gt;+&lt;/sup&gt; cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

An fMRI investigation of the effects of attempted naming on word retrieval in aphasia

In healthy controls, picture naming performance can be facilitated by a single prior exposure to the same picture ("priming"). This priming phenomenon is utilized in the treatment of aphasia, which often includes repeated picture naming as part of a therapeutic task. The current study sought to determine whether single and/or multiple exposures facilitate subsequent naming in aphasia and whether such facilitatory effects act through normal priming mechanisms. A functional magnetic resonance imaging paradigm was employed to explore the beneficial effects of attempted naming in two individuals with aphasia and a control group. The timing and number of prior exposures was manipulated, with investigation of both short-term effects (single prior exposure over a period of minutes) and long-term effects (multiple presentations over a period of days). Following attempted naming, both short-term and long-term facilitated items showed improvement for controls, while only the long-term condition showed benefits at a behavioral level for the participants with aphasia. At a neural level, effects of long-term facilitation were noted in the left precuneus for one participant with aphasia, a result also identified for the equivalent contrast in controls. It appears that multiple attempts are required to improve naming performance in the presence of anomia and that for some individuals with aphasia the source of facilitation may be similar to unimpaired mechanisms engaged outside the language network

Analysis of model rotor blade pressures during parallel interaction with twin vortices

This paper presents and provides analysis of unsteady surface pressures measured on a model rotor blade as the blade experienced near parallel blade vortex interaction with a twin vortex system. To provide a basis for analysis, the vortex system was characterized by hot-wire measurements made in the interaction plane but in the absence of the rotor. The unsteady pressure response resulting from a single vortex interaction is then presented to provide a frame of reference for the twin vortex results. A series of twin vortex interaction cases are then presented and analyzed. It is shown that the unsteady blade pressures and forces are very sensitive to the inclination angle and separation distance of the vortex pair. When the vortex cores lie almost parallel to the blade chord, the interaction is characterized by a two-stage response associated with the sequential passage of the two cores. Conversely, when the cores lie on a plane that is almost perpendicular to the blade chord, the response is similar to that of a single vortex interaction. In all cases, the normal force response is consistent with the distribution of vertical velocity in the flow field of the vortex system. The pitching moment response, on the other hand, depends on the localized suction associated with the vortex cores as they traverse the blade chord

Massive Type II in Double Field Theory

We provide an extension of the recently constructed double field theory formulation of the low-energy limits of type II strings, in which the RR fields can depend simultaneously on the 10-dimensional space-time coordinates and linearly on the dual winding coordinates. For the special case that only the RR one-form of type IIA carries such a dependence, we obtain the massive deformation of type IIA supergravity due to Romans. For T-dual configurations we obtain a `massive' but non-covariant formulation of type IIB, in which the 10-dimensional diffeomorphism symmetry is deformed by the mass parameter.Comment: 21 page