1-Naphthyl- and mesityltellurium(IV,II) derivatives of small bite chelating organic ligands: effect of steric bulk and intramolecular secondary bonding interaction on molecular geometry and supramolecular association

The synthesis and characterization of unsymmetric diorganotellurium compounds containing a sterically demanding I-naphthyl or
mesitylligand and a small bite chelating organic ligand capable of 1,4-Te···N(O) intramolecular interaction is described. The reaction
of ArTeCl₃ (Ar = I-C_lOH₇, Np; 2,4,6-Me<sub>3b>C₆H_2' Mes) with (SB)HgCI [SB = the Schiff base, 2-(4,4'-N0<sub>2b>C₆H_{4b>CH=NC6H3-Me)] or a methyl ketone (RCOCH3) afforded the corresponding dichlorides (SB)ArTeCI2 (Ar = Np, 1Aa; Mes, 1Ba) or (RCOCH2)ArTeCl2 (Ar = Np; R = Ph (2Aa), Me (3Aa), Np (4Aa); Ar = Mes, R = Ph (2Ba)). Reduction of 1Aa and 1Ba by Na2S205 readily gave the tellurides (SB)ArTe (Ar = Np (1A), Mes, (1B) but that of dichlorides derived from methylketones was complicated due to partial decomposition to tellurium powder and diarylditelluride (Ar2Te2), resulting in poor yields of the corresponding tellurides 2A, 2B and 3A. Oxidation of the isolated tellurides with S02b>Cl2, Br2 and I2 yielded the corresponding dihalides. All the synthesized compounds have been characterized with the help of IR, ¹H, ^l3C, and ¹²⁵Te NMR and in the case of 2Aa, and 2Ba by X-ray crystallography. Appearance of only one ¹²⁵Te signal indicated that the unsymmetric derivatives were stable to disproportionation to symmetric species. Intramolecular 1,4-Te· . ·0 secondary bonding interactions (SBIs) are exhibited in the crystal structures of both the tellurium(IV) dichlorides, 2Aa, and 2Ba. Steric repulsion of the mesityl group in the latter dominates over lone pair-bond pair repulsion, resulting in significant widening of the equatorial C-Te-C angle. This appears to be responsible for the lack of Te· . ·CI involved supramolecular associations in the crystal structure of 2Ba.}

Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer

Background: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC.

Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m2 dose every three weeks

Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%.

<b>Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma

Background In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs).

Methods Eligible patients received daily temozolomide (50 mg/m2) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially “drugable” mutations in patients entering recurrent MG clinical trials.

Results Among glioblastoma patients, median age was 56 y; median Karnofsky Performance Score (KPS) was 80; 62% of patients had been treated for ≥2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1).

<b>Conclusions In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG.

The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats.

Aims/hypothesis: Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3prime-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet to be reported in skeletal muscle. Methods: Lean and obese Zucker rats were randomly assigned to one of three treatment groups: (i) control, (ii) insulin-stimulated or (iii) acute, exhaustive exercise. Hind limb skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl measured.  Results:   Insulin receptor phosphorylation was increased 12-fold after insulin stimulation (p<0.0001) in lean rats and threefold in obese rats. Acute exercise had no effect on IR tyrosine phosphorylation. Similar results were found for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after insulin treatment (p<0.001). <b>Conclusions/interpretation: We also found that c-Cbl associating protein expression is relatively low in skeletal muscle of Zucker rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin-resistant Zucker rats (p<0.05), but the physiological relevance is not clear. We conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs from that previously reported in adipocytes.

Beryllium (II) complexes of the klaui tripodal ligand cyclopentadienyltris (diethylphosphito-P) cobaltate(-)

The interactions of the beryllium(II) ion with the cyclopentadienyltris(diethylphosphito-P)cobaltate monoanion, L^-, have been investigated, in aqueous solution, by synthetic methods, potentiometry, ESMS, and ¹H, ³¹P, and ⁹Be NMR spectroscopy. L^- has been found able to displace either two or three water molecules in the beryllium(II) coordination sphere, to form mononuclear, dinuclear, and trinuclear derivatives, in which the metal ion is pseudotetrahedrally coordinated. The species [BeL(H₂O)]⁺ and [Be₂L₂(μ-OH)]⁺ have been identified in solution while complexes of formula BeL₂ and [Be₃L₄](ClO₄)₂ have been isolated as solid materials. The species [BeL(OPPh₂)]⁺, closely related to [BeL(H₂O)]⁺, has been characterized in acetone solution and isolated as tetraphenylborate salt. The structure of the unusual trimeric complex [Be₃L₄]²⁺ has been elucidated by an unprecedented 2D ⁹Be-³¹P NMR correlation spectrum showing the presence of a single central beryllium nucleus and two equivalent terminal beryllium nuclei. The three beryllium centers are held together by four cobaltate ligands, which display two different bonding modes: two ligands are terminally linked with all the three oxygen donors to one terminal beryllium, and the other two bridge two metal centers, sharing the oxygen donors between central and terminal beryllium atoms.

Continuity and change at C.B.C. : an ethnography of a Catholic Brothers School in Australian society

This thesis is an ethnographic investigation of a Catholic Brothers school, Christian Brothers College (C.B.C.), in the provincial city of Newburyport, Australia* The study explores the traditions and historical purposes of education at the independent, religious school, and examines the manner in which these have changed or are changing. All names, including the name of the school and the city, have been altered to preserve anonymity. The opening section discusses the emergence of the theoretical problem of the dialectic of change and continuity in the ongoing activity of C.B.C. actors. This is followed by an argument that an understanding of such activity requires an ethnographic perspective. Such a perspective, however, must not overlook the organisational and structural constraints within which participants operate. Hence, a critical ethnography, which takes account of both the agency of human actors and the structures which influence their activity, is advocated as the most suitable approach for understanding continuity and change within a complex organisation in its social context. This argument is followed by an ethnographic account of Christian Brothers College, which focuses on the perceptions and activities of teachers and administrators, Individual chapters deal with the Christian Brothers Order and its educational mission at C.B.C.; the nature of religious education at the school; the administration of the school; approaches to control and discipline; the curriculum and evaluation of pupils; and the relationship between C.B.C. and the wider Newburyport community. The concluding section integrates an analysis of continuity and change at C.B.C. with a discussion of theoretical perspectives on reproduction and transformation. The thesis concludes that, although change has occurred in many ways, an institutionalised image of C.B.C. as 'Brothers’ school'persists and impedes the formation of more democratic authority relations, curriculum, and evaluation. The potential for such change, however, is seen most strongly in the ongoing reform of religious education.

Migrant Houses in the village Zavoj, Republic of Macedonia, 1988-2010

The focus of this data is on the transformation of the village Zavoj in the Republic of Macedonia, due to emigration from the village, recorded through the architectural changes to the houses in the village. The village had become by default a place for the accommodation of elderly people who did not want to join their offspring abroad in the cities of immigration, or in the fringe suburbs of nearby towns.

The data documents the ‘material history’ of the houses, and constitutes a longitudinal research project tracing the transformation of the architectural fabric of the village since 1988. It includes visual documentation such as photographs and drawings, and includes the houses as HOUSE-STATES as follows:

House-Traditional: Vernacular architecture still in use and maintained as a dwelling.
House-Construction: Buildings that are still being constructed, the house as ongoing construction site.
House-Fragment: An eMigrant house-fragment is juxtaposed with the vernacular dwelling. Typical and affordable techniques of single brick cavity and reinforced concrete structure are evident in the new fragment.
House-Closed: Many new houses have only one door and one window, height, size and volume are minimal; and are closed a lot of the time.
House-Ruin: Vernacular traditional dwellings that are deteriorating. Traditional vernacular dwellings are rarely renovated, reconstructed or repaired.

The data is complemented by several field-work methods including participant observation, interviews, documentation of the village as a totality, recording of oral histories and myths, festivities, and archival statistical research about the vicinity.

This dataset comprises photographic documentation, sketch/drawing documentation, digital interview recordings, and interview notes.

Alcohol sponsorship of community football clubs : the current situation

Issue addressed: There is accumulating evidence supporting a link between alcohol industry sponsorship and alcohol-related problems in both community and elite-level sports. Little is known, however, about the current status of such sponsorship, particularly of community sport. This study aimed to assess associations between alcohol industry sponsorship and different community football clubs in Australia.

Methods: The study involved 101 community football clubs across New South Wales, Australia. One representative from each club took part in a cross-sectional telephone survey designed to assess club (football code, number of players, socioeconomic and geographic descriptors) and alcohol industry sponsorship (money, equipment, free alcohol or discounted alcohol) characteristics. Chi-square analysis was used to test associations between club characteristics, and: i) any alcohol industry sponsorship; and ii) type of sponsorship.

Results: Eighty-eight per cent of clubs reported receiving sponsorship from the alcohol industry, and most clubs (82%) were sponsored by a licensed premises. There were no significant associations between club characteristics and source of alcohol industry sponsorship. However, small clubs were found to be significantly more likely to receive free or discounted alcohol sponsorship than larger clubs (p=0.05).

<b>Conclusions: This exploratory study suggests a significant presence of alcohol industry sponsorship among community football clubs in Australia.