“The most brutal immigration regime in the developed world”: International Media Responses to Australia’s Asylum-Seeker Policy

Despite intense media coverage of Australia’s asylum-seeker policy, there is minimal attention to structures and processes that influence international media perspectives. This article explores international media responses to Australia’s policy using a mixed-method approach. Our research focused on twenty-five articles from international media outlets surrounding the 2014 “riots” at Manus Island Regional Processing Centre. Three major themes (political relationships, domestic policy and practice, and treatment of asylum-seekers) highlight some key trends in international media representations of this event as an example. We discuss the implications of such findings for the production, representation, and reception of international media stories.Malgré une couverture médiatique intense de la politique australienne concernant les chercheurs d’asile, il y a très peu d’attention portée aux structures et processus qui influencent les perspectives médiatiques internationales. Cet article étudie les réactions de la part des médias internationaux concernant la politique australienne en utilisant une approche à méthodologie mixte. Nos recherches se sont portées sur 25 articles émanant de diffuseurs de médias internationaux autour des «émeutes» de 2014 au Manus Island Regional Processing Centre (centre de traitement régional pour l’immigration de l’île de Manus). Trois thèmes principaux (Relations politiques, Politique interne et pratiques, et Traitement des chercheurs d’asile) mettent en valeur des tendances clés dans la représentation de la part des médias internationaux de cet évènement particulier en tant qu’exemple. Nous abordons une discussion des implications de ces recherches pour la production, la représentation et la réception des actualités médiatiques internationales

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Semileptonic decay constants of octet baryons in the chiral quark-soliton model

Based on the recent study of the magnetic moments and axial constants within the framework of the chiral quark-soliton model, we investigate the baryon semileptonic decay constants $(f_1,f_2)$ and $(g_1, g_2)$. Employing the relations between the diagonal transition matrix elements and off-diagonal ones in the vector and axial-vector channels, we obtain the ratios of baryon semileptonic decay constants $f_2/f_1$ and $g_1/f_1$. The $F/D$ ratio is also discussed and found that the value predicted by the present model naturally lies between that of the Skyrme model and that of the nonrelativistic quark model. The singlet axial constant $g^{(0)}_A$ can be expressed in terms of the $F/D$ ratio and $g^{(3)}_A$ in the present model and turns out to be small. The results are compared with available experimental data and found to be in good agreement with them. In addition, the induced pseudotensor coupling constants $g_2/f_1$ are calculated, the SU(3) symmetry breaking being considered. The results indicate that the effect of SU(3) symmetry breaking might play an important role for some decay modes in hyperon semileptonic decay.Comment: 16 pages, RevTeX is used. No figure. Accepted for publication in Phys. Rev.

A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis:a protocol for the CLEAR clinical trial

Background: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. Methods: This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care-the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: Adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. Discussion: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. Trial registration: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). Sponsor: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: V3.0 Final_14052018

The Transcriptionally Active Amyloid Precursor Protein (APP) Intracellular Domain Is Preferentially Produced from the 695 Isoform of APP in a β-Secretase-dependent Pathway*♦

Amyloidogenic processing of the amyloid precursor protein (APP) by β- and γ-secretases generates several biologically active products, including amyloid-β (Aβ) and the APP intracellular domain (AICD). AICD regulates transcription of several neuronal genes, especially the Aβ-degrading enzyme, neprilysin (NEP). APP exists in several alternatively spliced isoforms, APP695, APP751, and APP770. We have examined whether each isoform can contribute to AICD generation and hence up-regulation of NEP expression. Using SH-SY5Y neuronal cells stably expressing each of the APP isoforms, we observed that only APP695 up-regulated nuclear AICD levels (9-fold) and NEP expression (6-fold). Increased NEP expression was abolished by a β- or γ-secretase inhibitor but not an α-secretase inhibitor. This correlated with a marked increase in both Aβ1–40 and Aβ1–42 in APP695 cells as compared with APP751 or APP770 cells. Similar phenomena were observed in Neuro2a but not HEK293 cells. SH-SY5Y cells expressing the Swedish mutant of APP695 also showed an increase in Aβ levels and NEP expression as compared with wild-type APP695 cells. Chromatin immunoprecipitation revealed that AICD was associated with the NEP promoter in APP695, Neuro2a, and APPSwe cells but not APP751 nor APP770 cells where AICD was replaced by histone deacetylase 1 (HDAC1). AICD occupancy of the NEP promoter was replaced by HDAC1 after treatment of the APP695 cells with a β- but not an α-secretase inhibitor. The increased AICD and NEP levels were significantly reduced in cholesterol-depleted APP695 cells. In conclusion, Aβ and functional AICD appear to be preferentially synthesized through β-secretase action on APP695