Positive almost Dunford-Pettis operators and their duality

We study some properties of almost Dunford-Pettis operators and we characterize pairs of Banach lattices for which the adjoint of an almost Dunford-Pettis operator inherits the same property and look at conditions under which an operator is almost Dunford-Pettis whenever its adjoint is.

Positive association between nuclear Runx2 and oestrogen-progesterone receptor gene expression characterises a biological subtype of breast cancer

Purpose: The runt-related transcription factor, Runx2 may have an oncogenic role in mediating metastatic events in breast cancer, but whether Runx2 has a role in the early phases of breast cancer development is not clear. We examined the expression of Runx2 and its relationship with oestrogen receptor (ER) and progesterone receptor (PR) in breast cancer cell lines and tissues.

Adolescent men's attitudes and decision-making in relation to an unplanned pregnancy. Responses to an interactive video drama

This study confronts a gender bias in research on adolescent pregnancy by exploring adolescent men’s decisions relating to a hypothetical unplanned pregnancy. A cross-sectional survey was conducted with adolescent men (N = 360) aged between 14 and 18 years attending schools in the Republic of Ireland. The study, the first of its kind in Europe, extends the small body of evidence on adolescent men and pregnancy decision-making by developing and examining reactions to an interactive video drama used in a comparable study in Australia. In addition, we tested a more comprehensive range of sociological and psychological determinants of adolescent men’s decisions regarding an unplanned pregnancy. Results showed that adolescent men were more likely to choose to keep the baby in preference to abortion or adoption. Adolescent men’s choice to continue the pregnancy (keep or adopt) in preference to abortion was significantly associated with anticipated feelings of regret in relation to abortion, perceived positive attitudes of own mother to keeping the baby and a feeling that a part of them might want a baby. Religiosity was also shown to underlie adolescent men’s views on the perceived consequences of an abortion in their lives.

Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm

Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure. We studied 16 patients with JAK2-mutant (7 of 16) or JAK2 wild-type (9 of 16) AML after a JAK2-mutant MPN. Primary myelofibrosis or myelofibrotic transformation preceded all 7 JAK2-mutant but only 1 of 9 JAK2 wild-type AMLs (P = .001), implying that JAK2-mutant AML is preceded by mutation(s) that give rise to a "myelofibrosis" phenotype. Loss of the JAK2 mutation by mitotic recombination, gene conversion, or deletion was excluded in all wild-type AMLs. A search for additional mutations identified alterations of RUNX1, WT1, TP53, CBL, NRAS, and TET2, without significant differences between JAK2-mutant and wild-type leukemias. In 4 patients, mutations in TP53, CBL, or TET2 were present in JAK2 wild-type leukemic blasts but absent from the JAK2-mutant MPN. By contrast in a chronic-phase patient, clones harboring mutations in JAK2 or MPL represented the progeny of a shared TET2-mutant ancestral clone. These results indicate that different pathogenetic mechanisms underlie transformation to JAK2 wild-type and JAK2-mutant AML, show that TET2 mutations may be present in a clone distinct from that harboring a JAK2 mutation, and emphasize the clonal heterogeneity of the MPNs.

Comprehensive genomic screens identify a role for PLZF-RAR alpha as a positive regulator of cell proliferation via direct regulation of c-MYC

The t(11; 17)(q23;q21) translocation is associated with a retinoic acid (RA)-insensitive form of acute promyelocytic leukemia (APL), involving the production of reciprocal fusion proteins, promyelocytic leukemia zinc finger-retinoic acid receptor alpha (PLZF-RAR alpha) and RAR alpha-PLZF. Using a combination of chromatin immuno-precipitation promotor arrays (ChIP-chip) and gene expression profiling, we identify novel, direct target genes of PLZF-RAR alpha that tend to be repressed in APL compared with other myeloid leukemias, supporting the role of PLZF-RAR alpha as an aberrant repressor in APL. In primary murine hematopoietic progenitors, PLZF-RAR alpha promotes cell growth, and represses Dusp6 and Cdkn2d, while inducing c-Myc expression, consistent with its role in leukemogenesis. PLZF-RAR alpha binds to a region of the c-MYC promoter overlapping a functional PLZF site and antagonizes PLZF-mediated repression, suggesting that PLZF-RAR alpha may act as a dominant-negative version of PLZF by affecting the regulation of shared targets. RA induced the differentiation of PLZF-RAR alpha-transformed murine hematopoietic cells and reduced the frequency of clonogenic progenitors, concomitant with c-Myc down-regulation. Surviving RA-treated cells retained the ability to be replated and this was associated with sustained c-Myc expression and repression of Dusp6, suggesting a role for these genes in maintaining a self-renewal pathway triggered by PLZF-RAR alpha. (Blood. 2009; 114: 5499-5511)

Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. 'Molecular switches' were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents. Published by Elsevier Ltd.

Realising political equality: the European Court of Human Rights and positive obligations in a democracy'

The European Convention on Human Rights (ECHR) speaks of the importance of an “effective political democracy” in its Preamble, though it is only in Article 3 of Protocol 1 (P1-3) that we find a right to free elections. This paper discusses the role of “positive obligations” under P1-3. This paper outlines the positive obligations in P1-3 focusing on obligations where the state is required to do more than just change the law. This may mean providing resources or facilities, adopting regulatory frameworks or creating new institutions. The paper highlights specific positive obligations that need to be further developed in the jurisprudence of the European Court of Human Rights (ECtHR). Sometimes these can be developed by analogy with positive obligations recognised in other areas of ECtHR jurisprudence. However, beyond these cases, states should ensure that members of vulnerable and disadvantaged minorities are able to participate in the electoral process and should ensure that dominant political groups cannot abuse their political power to exclude other parties unfairly. This is necessary to realise equal political rights. The second section of this paper sketches some preliminary points about the Strasbourg institutions’ approach to P1-3. After that, the third section identifies circumstances where the ECtHR should apply a more intense scrutiny in P1-3 cases. The fourth, fifth and sixth sections look at positive obligations relating to the right to vote, the right to run for election and the regulation of political parties.