Judging the impact of leadership-development activities on school practice

The nature and effectiveness of professional-development activities should be judged in a way that takes account of both the achievement of intended outcomes and the unintended consequences that may result. Our research project set out to create a robust approach that school staff members could use to assess the impact of professional-development programs on leadership and management practice without being constrained in this judgment by the stated aims of the program. In the process, we identified a number of factors and requirements relevant to a wider audience than that concerned with the development of leadership and management in England. Such an assessment has to rest upon a clear understanding of educational leadership,a clearly articulated model of practice, and a clear model of potential forms of impact. Such foundations, suitably adapted to the subject being addressed, are appropriate for assessing all teacher professional development

Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition

Several molecular subtypes of cancer are highly dependent on splicing for cell survival. There is a general interest in the therapeutic targeting of splicing by small molecules. E7107, a first-in-class spliceosome inhibitor, showed strong growth inhibitory activities against a large variety of human cancer xenografts. Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous hematologic malignancy, with approximately 90% of cases being TP53 wild-type at diagnosis. An increasing number of studies are evaluating alternative targeted agents in CLL, including MDM2–p53 binding antagonists. In this study, we report the effect of splicing modulation on key proteins in the p53 signalling pathway, an important cell death pathway in B cells. Splicing modulation by E7107 treatment reduced full-length MDM2 production due to exon skipping, generating a consequent reciprocal p53 increase in TP53WT cells. It was especially noteworthy that a novel p21WAF1 isoform with compromised cyclin-dependent kinase inhibitory activity was produced due to intron retention. E7107 synergized with the MDM2 inhibitor RG7388, via dual MDM2 inhibition; by E7107 at the transcript level and by RG7388 at the protein level, producing greater p53 stabilisation and apoptosis. This study provides evidence for a synergistic MDM2 and spliceosome inhibitor combination as a novel approach to treat CLL and potentially other haematological malignancies

Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli

The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with less changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: 1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation, and 2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog

Growth methods of c-axis oriented MgB2 thin films by pulsed laser deposition

High quality MgB2 thin films have been obtained by pulsed laser deposition both on MgO and on Al2O3 substrates using different methods. In the standard two-step procedure, an amorphous precursor layer is deposited at room temperature starting both from stoichiometric target and from boron target: after this first step, it is annealed in magnesium atmosphere in order to crystallize the superconducting phase. The so obtained films show a strong c-axis orientation, evidenced by XRD analysis, a critical temperature up to 38 K and very high critical fields along the basal planes, up to 22T at 15K. Also an in situ one step technique for the realization of superconducting MgB2 thin films has been developed. In this case, the presence of an argon buffer gas during deposition is crucial and we observe a strong dependence of the quality of the deposited film on the background gas pressure. The influence of the Ar atmosphere has been confirmed by time and space-resolved spectroscopy measurements on the emission spectrum of the plume. The Ar pressure modifies strongly the plasma kinetics by promoting excitation and ionization of the plume species, especially of the most volatile Mg atoms, increasing their internal energy.Comment: Paper presented at Boromag Workshop, Genoa 17-19 June 2002, in press on SUS

Emission Lines from Companion Galaxies of QSOs

Anticipating new spectroscopic studies of quasar companions, we calculate expected emission line spectra for the companion galaxies. Under the assumption of isotropic photoionizing radiation, we predict equivalent widths for Halpha, Hbeta, [O III], [O II], [Ne III], and Mg II lines. We consider 6 quasars, two of which (PKS 2135-14 and PKS 2349-014) have very close companions with projected separation < 4 h^{-1} kpc. For these companions the calculated emission lines should be easily observable, with W_lambda > 20 AA for the [O III], [O II], and Halpha lines. Presence of strong emission lines from the companions occupying only a tiny solid angle would suggest that 1) quasar radiation is isotropic; 2) companion galaxies have measurable amount of gas, which can be assessed using the photoionization models; 3) host galaxies, if present, have been depleted of gas or do not interact with the companions.Comment: 20 pages, 4 figures. ApJ 491, in pres

Detectability of Terrestrial Planets in Multi-Planet Systems: Preliminary Report

We ask if Earth-like planets (terrestrial mass and habitable-zone orbit) can be detected in multi-planet systems, using astrometric and radial velocity observations. We report here the preliminary results of double-blind calculations designed to answer this question.Comment: 10 pages, 0 figure

Particulate polycyclic aromatic hydrocarbon spatial variability and aging in Mexico City

International audienceAs part of the Megacities Initiative: Local and Global Research Observations (MILAGRO) study in the Mexico City Metropolitan Area in March 2006, we measured particulate polycyclic aromatic hydrocarbons (PAHs) and other gaseous species and particulate properties at six locations throughout the city. The measurements were intended to support the following objectives: to describe spatial and temporal patterns in PAH concentrations, to gain insight into sources and transformations of PAHs, and to quantify the relationships between PAHs and other pollutants. Total particulate PAHs at the Instituto Mexicano del Petróleo (T0 supersite) located near downtown averaged 50 ng m?3, and aerosol active surface area averaged 80 mm2 m?3. PAHs were also measured on board the Aerodyne Mobile Laboratory, which visited six sites encompassing a mixture of different land uses and a range of ages of air parcels transported from the city core. Weak intersite correlations suggest that local sources are important and variable and that exposure to PAHs cannot be represented by a single regional-scale value. The relationships between PAHs and other pollutants suggest that a variety of sources and ages of particles are present. Among carbon monoxide, nitrogen oxides (NOx), and carbon dioxide, particulate PAHs are most strongly correlated with NOx. Mexico City's PAH-to-black carbon mass ratio of 0.01 is similar to that found on a freeway loop in the Los Angeles area and approximately 8?30 times higher than that found in other cities. Ratios also indicate that primary combustion particles are rapidly coated by secondary aerosol in Mexico City. If so, the lifetime of PAHs may be prolonged if the coating protects them against photodegradation or heterogeneous reactions

Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow.

To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging.Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled ≥2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes.CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021).CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals