Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.

Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC

Coordination Dependence of Hyperfine Fields of 5sp Impurities on Ni Surfaces

We present first-principles calculations of the magnetic hyperfine fields H of 5sp impurities on the (001), (111), and (110) surfaces of Ni. We examine the dependence of H on the coordination number by placing the impurity in the surfaces, on top of them at the adatom positions, and in the bulk. We find a strong coordination dependence of H, different and characteristic for each impurity. The behavior is explained in terms of the on-site s-p hybridization as the symmetry is reduced at the surface. Our results are in agreement with recent experimental findings.Comment: 4 pages, 3 figure

The Unified Model of Active Galactic Nuclei: II. Evolutionary Connection

(Abbreviated) We assemble a sample composed of 243 nearby Seyfert galaxies with redshifts $z\le 0.05$ to test the unification scheme. The sample contains 94 BLS1s, 44 NLS1s, 36 X-ray absorbed HBLR S2s, 42 X-ray absorbed non-HBLR S2s and 27 X-ray unabsorbed Seyfert 2s (unabsorbed non-HBLR S2s and HBLR S2s). We find that: 1) NLS1s have less massive black hole masses than BLS1s; 2) HBLRS2s have the same mass distribution of the black holes with BLS1s; 3) the absorbed non-HBLR S2s have less massive black holes than HBLR S2s; 4) unabsorbed non-HBLR S2s have the most massive black holes. We thus have a queue of black hole masses from small to large: narrow to broad line Seyfert galaxies, providing new evidence for the evolutionary sequence of Seyfert galaxies. We find that the opening angles of the torus in NLS1s and absorbed non-HBLR S2s are significantly smaller than that in BLS1s and HBLR S2s. The growth of the black holes and increases of the opening angles of the tori determine the various appearances of Seyfert galaxies. We also find that the unabsorbed Seyfert 2 galaxies could be caused by low gas-to-dust ratios in the present sample. This indicates that the star formation histories could be different in the unabsorbed from in absorbed Seyfert 2 galaxies, showing evidence for suppressed star formation by black hole activities. We outline a new unification scheme based on the orientation hypothesis: Seyfert galaxies can be unified by including growth of black holes, Eddington ratios, changing opening angles of tori and gas-to-dust ratios in the tori. Seyfert galaxies are tending to finally evolve to unabsorbed non-HBLR Seyfert 2 galaxies, in which the black holes are accreting with low accretion rates and both the broad line region and dusty torus disappear.Comment: ApJ, vol 661 (2007), in pres

Operational Challenges in Diagnosing Multi-Drug Resistant TB and Initiating Treatment in Andhra Pradesh, India

Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services

Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels

Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA −158 G/A, rs266882) in ARE1 of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case–control analysis of 500 white cases and 676 age- and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR=1.21, 95% confidence intervals (CI): 0.88–1.67) or prostate cancer-specific survival (RR=0.94, 95%CI: 0.56–1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null

On measurement of top polarization as a probe of ttˉt \bar t production mechanisms at the LHC

In this note we demonstrate the use of top polarization in the study of $t \bar t$ resonances at the LHC, in the possible case where the dynamics implies a non-zero top polarization. As a probe of top polarization we construct an asymmetry in the decay-lepton azimuthal angle distribution (corresponding to the sign of $\cos\phi_\ell$) in the laboratory. The asymmetry is non-vanishing even for a symmetric collider like the LHC, where a positive $z$ axis is not uniquely defined. The angular distribution of the leptons has the advantage of being a faithful top-spin analyzer, unaffected by possible anomalous $tbW$ couplings, to linear order. We study, for purposes of demonstration, the case of a $Z'$ as might exist in the little Higgs models. We identify kinematic cuts which ensure that our asymmetry reflects the polarization in sign and magnitude. We investigate possibilities at the LHC with two energy options: $\sqrt{s} = 14$ TeV and $\sqrt{s} = 7$ TeV, as well as at the Tevatron. At the LHC the model predicts net top quark polarization of the order of a few per cent for $M_{Z'} \simeq 1200$ GeV, being as high as $10$ for a smaller mass of the $Z'$ of $700$ GeV and for the largest allowed coupling in the model, the values being higher for the $7$ TeV option. These polarizations translate to a deviation from the standard-model value of azimuthal asymmetry of up to about $4$ ($7$) for $14$ ($7$) TeV LHC, whereas for the Tevatron, values as high as $12$ are attained. For the $14$ TeV LHC with an integrated luminosity of 10 fb$^{-1}$, these numbers translate into a $3 \sigma$ sensitivity over a large part of the range $500 \lesssim M_{Z'} \lesssim 1500$ GeV.Comment: 28 page, LaTeX, requires JHEP style file, 12 figures. Typos corrected and references adde

Effects of uniaxial strain in LaMnO_3

The effects of uniaxial strain on the structural, orbital, optical, and magnetic properties of LaMnO_3 are calculated using a general elastic energy expression, along with a tight-binding parameterization of the band theory. Tensile uniaxial strain of the order of 2 % (i.e., of the order of magnitude of those induced in thin films by lattice mismatch with substrates) is found to lead to changes in the magnetic ground state, leading to dramatic changes in the band structure and optical conductivity spectrum. The magnetostriction effect associated with the Neel transition of bulk(unstrained) LaMnO_3 is also determined. Due to the Jahn-Teller coupling, the uniform tetragonal distortion mode is softer in LaMnO_3 than in doped cubic manganates. Reasons why the observed (\pi \pi 0) orbital ordering is favored over a (\pi \pi \pi) periodicity are discussed.Comment: 9 figures, submitted in Phys. Rev.

Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship