The Interview: Schnarking, Knob Jokes and the right to cause gross offence

Discussion of censorship and media freedom in the context of The Interview. A few weeks before the murderous attack by Islamic extremists on the satirical journal Charlie Hebdo, the Hollywood dream factory had its own encounter with would-be censors. The Interview (Evan Goldberg and Seth Rogen, 2014), as everyone with an interest in culture and current affairs cannot fail to be aware of by now, is a comedy in the “grossout” tradition exemplified by commercially successful movies such as Ted (Seth MacFarlane, 2012) and Bridesmaids (Paul Feig, 2011). Their humour is a combination of slapstick, physical comedy, and scatological jokes involving body fluids and the like— hence the “gross”. The best of them have been very funny, as well as bordering on the offensive (see Ted’s scene involving prostitutes, a foul-mouthed teddy bear and the entertainment value of someone taking a dump on the living room floor). They have often been controversial, as in the Farrelly brothers’ Me, Myself and Irene (2000), starring Jim Carrey as a schizophrenic police officer. At their most outrageous they have pushed the boundaries of political correctness to the limit.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

Helix-sheet interconversion in a synthetic pore lining peptide derived from a designed ion channel

We have designed a four-helix protein that is expected to tetramerize in the membrane to form an ion channel with a structurally well defined pore. A synthetic peptide corresponding to the channel lining helix facilitates ion transport across liposomal membranes and largely helical in membranes. Detailed circular dichroism studies of the peptide in methanol, water and methanal-water mixtures reveal that it is helical in methanol, beta-structured in 97.5% water and a combination of these two structures at intermediate compositions of methanol and water. A fluorescence resonance energy transfer study of the peptide shows that the peptide is monomeric in methanol but undergoes extensive anti-parallel aggregation in aqueous solution.

Oidiopsis (Erysiphaceae) on Euphorbia spp. in Australia and Vanuatu

One specimen of powdery mildew on Euphorbia cyathophora from Vanuatu and 11 specimens on E. cyathophora, E. dentata, E. heterophylla and E. leucocephala from Australia were studied. All were shown to represent the Oidiopsis anamorph of Leveillula taurica, which is described. This is the first record of Oidiopsis in Vanuatu. E. leucocephala is a new host record for this powdery mildew.

Effect of crop establishment methods and weed control treatments on weed management, and rice yield

Lower water availability coupled with labor shortage has resulted in the increasing inability of growers to cultivate puddled transplanted rice (PTR). A field study was conducted in the wet season of 2012 and dry season of 2013 to evaluate the performance of five rice establishment methods and four weed control treatments on weed management, and rice yield. Grass weeds were higher in dry-seeded rice (DSR) as compared to PTR and nonpuddled transplanted rice (NPTR). The highest total weed density (225-256plantsm-2) and total weed biomass (315-501gm-2) were recorded in DSR while the lowest (102-129plantsm-2 and 75-387gm-2) in PTR. Compared with the weedy plots, the treatment pretilachlor followed by fenoxaprop plus ethoxysulfuron plus 2,4-D provided excellent weed control. This treatment, however, had a poor performance in NPTR. In both seasons, herbicide efficacy was better in DSR and wet-seeded rice. PTR and DSR produced the maximum rice grain yields. The weed-free plots and herbicide treatments produced 84-614% and 58-504% higher rice grain yield, respectively, than the weedy plots in 2012, and a similar trend was observed in 2013.

Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion

Purpose: Testis specific heat-shock protein 70-2 (HSP70-2), a member of HSP70 chaperone family, is essential for the growth of spermatocytes and cancer cells. We investigated the association of HSP70-2 expression with clinical behaviour and progression of urothelial carcinoma of bladder. Experimental design: We assessed the HSP70-2 expression by RT-PCR and HSP70-2 protein expression by immunofluorescence, flow cytometry, immunohistochemistry and Western blotting in urothelial carcinoma patient specimens and HTB-1, UMUC-3, HTB-9, HTB-2 and normal human urothelial cell lines. Further, to investigate the role of HSP70-2 in bladder tumour development, HSP70-2 was silenced in the high-grade invasive HTB-1 and UMUC-3 cells. The malignant properties of urothelial carcinoma cells were examined using colony formation, migration assay, invasion assay in vitro and tumour growth in vivo. Results: Our RT-PCR analysis and immunohistochemistry analysis revealed that HSP70-2 was expressed in both moderate to well-differentiated and high-grade invasive urothelial carcinoma cell lines studied and not in normal human urothelial cells. In consistence with these results, HSP70-2 expression was also observed in superficially invasive (70%) and muscle-invasive (90%) patient's tumours. Furthermore, HSP70-2 knockdown significantly suppressed cellular motility and invasion ability. An in vivo xenograft study showed that inhibition of HSP70-2 significantly suppressed tumour growth. Conclusions: In conclusion, our data suggest that the HSP70-2 expression is associated with early spread and progression of urothelial carcinoma of bladder cancer and that HSP70-2 can be the potential therapeutic target for bladder urothelial carcinoma. (C) 2009 Elsevier Ltd. All rights reserved.

Additive Spanners and (alpha, beta)-Spanners

An (alpha, beta)-spanner of an unweighted graph G is a subgraph H that distorts distances in G up to a multiplicative factor of a and an additive term beta. It is well known that any graph contains a (multiplicative) (2k - 1, 0)-spanner of size O(n(1+1/k)) and an (additive) (1, 2)-spanner of size O(n(3/2)). However no other additive spanners are known to exist. In this article we develop a couple of new techniques for constructing (alpha, beta)-spanners. Our first result is an additive (1, 6)-spanner of size O(n(4/3)). The construction algorithm can be understood as an economical agent that assigns costs and values to paths in the graph, purchasing affordable paths and ignoring expensive ones, which are intuitively well approximated by paths already purchased. We show that this path buying algorithm can be parameterized in different ways to yield other sparseness-distortion tradeoffs. Our second result addresses the problem of which (alpha, beta)-spanners can be computed efficiently, ideally in linear time. We show that, for any k, a (k, k - 1)-spanner with size O(kn(1+1/k)) can be found in linear time, and, further, that in a distributed network the algorithm terminates in a constant number of rounds. Previous spanner constructions with similar performance had roughly twice the multiplicative distortion.

Embedded Thin Film Resistors on BCB by Low-Cost PWB Compatible Electroless Plating by Direct Foil Lamination Transfer Processes

Benzocyclobutene (BCB) has been proposed as a board level dielectric for advanced system-on-package (SOP) module primarily due to its attractive low-loss (for RF application) and thin film (for high density wiring) properties. Realization of embedded resistors on low loss benzocyclobutene (dielectric loss ~0.0008 at > 40 GHz) has been explored in this study. Two approaches, viz, foil transfer and electroless plating have been attempted for deposition of thin film resistors on benzocyclobutene (BCB). Ni-P alloys were plated using conventional electroless plating, and NiCr and NiCrAlSi foils were used for the foil transfer process. This paper reports NiP and NiWP electroless plated embedded resistors on BCB dielectric for the first time in the literature

Redox modification of Akt mediated by the dopaminergic neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt

Impairment of Akt phosphorylation, a critical survival signal, has been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. However, the mechanism underlying pAkt loss is unclear. In the current study, we demonstrate pAkt loss in ventral midbrain of mice treated with dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), when compared to ventral midbrain of control mice treated with vehicle alone. Thiol residues of the critical cysteines in Akt are oxidized to a greater degree in mice treated with MPTP, which is reflected as a 40% loss of reduced Akt. Association of oxidatively modified Akt with the phosphatase PP2A, which can lead to enhanced dephosphorylation of pAkt, was significantly stronger after MPTP treatment. Maintaining the protein thiol homeostasis by thiol antioxidants prevented loss of reduced Akt, decreased association with PP2A, and maintained pAkt levels. Overexpression of glutaredoxin, a protein disulfide oxidoreductase, in human primary neurons helped sustain reduced state of Akt and abolished MPP+-mediated pAkt loss. We demonstrate for the first time the selective loss of Akt activity, in vivo, due to oxidative modification of Akt and provide mechanistic insight into oxidative stress-induced down-regulation of cell survival pathway in mouse midbrain following exposure to MPTP.-Durgadoss, L., Nidadavolu, P., Khader Valli, R., Saeed, U., Mishra, M., Seth, P., Ravindranath, R. Redox modification of Akt mediated by the dopaminergic neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt. FASEB J. 26, 1473-1483 (2012). www.fasebj.org

Solvent-templated supramolecular isomerism in 2D coordination polymer constructed by (Ni2CoII)-Co-II nodes and dicyanamido spacers: drastic change in magnetic behaviours

Two heterometallic coordination polymers (CPs) have been prepared using (NiL)-L-II](2)Co-II (where H2L = N,N'-bis(salicylidene)-1,3-propanediamine) as nodes and dicyanamido spacers by varying the solvent for synthesis. Structural characterizations revealed that methanol assisted the formation of a two-dimensional (4,4) connected rhombic grid network of (NiL)(2)Co(NCNCN)2](infinity) (1a) whereas relatively less polar acetonitrile afforded a different superstructure {(NiL)(2)Co(NCNCN)(2)]center dot CH3CN}(infinity) (1b) with a two-dimensional (4,4) connected square grid network. The presence of acetonitrile molecules in the structure of 1b seems to change the spatial orientation of the terminal metalloligands NiL] from pseudo-eclipsed in 1a to staggered-like in 1b around the central Co(II). These structural changes in the nodes together with the conformationally flexible dicyanamido spacers, which are cis coordinated to the Co(II) in both trinuclear units, led to the differences in the final 2D network. Variable-temperature magnetic susceptibility measurements revealed that this supramolecular isomerism led to a drastic transition from spin-frustrated antiferromagnetism for 1a to a dominant ferromagnetic behaviour for 1b. The geometrical differences in Ni2Co coordination clusters (CCs) which are scalene triangular in 1a but nearly linear in 1b, are held responsible for the changes of the magnetic properties. The DFT calculations of exchange interactions between metal centres provide a clear evidence of the role played by the fundamental geometrical factors on the nature and magnitude of the magnetic coupling in these pseudo-polymorphic CPs.

Mycobacterium tuberculosis Inhibits RAB7 Recruitment to Selectively Modulate Autophagy Flux in Macrophages

Here we report a novel regulatory mechanism for autophagy-mediated degradation of Mycobacterium tuberculosis (Mtb) and specific strategy exploited by the virulent Mtb to evade it. We show while both avirulent (H37Ra) and virulent (H37Rv) mycobacteria could readily localize to autophagosomes, their maturation into autolysosomes (flux) was significantly inhibited by the latter strain. The inhibition of autophagy flux by the virulent strain was highly selective, as it did not perturb the basal autophagy flux in the macrophages. Selective inhibition of flux of Mtb-containing autophagosomes required virulence regulators PhoP and ESAT-6. We show that the maturation of Mtb-containing autophagosomes into autolysosomes required recruitment of the late endosome marker RAB7, forming the intermediate compartment amphisomes. Virulent Mtb selectively evaded their targeting to the amphisomes. Thus we report a crosstalk between autophagy and phagosome maturation pathway and highlight the adaptability of Mtb, manifested by selective regulation of autophagy flux.

Antiguo Oriente: Cuadernos del Centro de Estudios de Historia del Antiguo Oriente, 2005, n° 3 (número completo)

The first evangelization of the Mesopotamian regions in the Syriac tradition: the Acta Maris as a continuation of the Doctrina Addai / Ilaria Ramelli -- El culto a las tumbas de los ancestros en el Levante Mediterráneo / Jordi Vidal -- Identifiable and associated cordage. Examples from Berenike (Egyptian Red Sea Coast) / André Veldmeijer -- “Ordalías”, parentesco y estado en La contienda entre Horus y Seth / Marcelo Campagno -- Lamentos neosumerios por ciudades destruidas. Continuidad de un rito y un género del período protodinástico hasta el período seléucida / Santiago Rostom Maderna -- Reseñas bibliográficas

Descriptions of new fishes from Panama

The following preliminary descriptions are of new fishes obtained by the authors during their first season's work on the Biological Survey of the Canal Zone, the ichthyological work of which is being conducted cooperatively by the Field Museum of Natural History and the Smithsonian Institution. (2 page document)

New species of fishes from Panama

The fishes described in the following pages were collected by the authors in the fresh waters of Panama, while engaged in field work on the Biological Survey of the Canal Zone; the ichthyological work of which is being conducted cooperatively by the Smithsonian Institution, the Field Museum of Natural History and the Bureau of Fisheries. A complete account of all the fishes collected during the past two years on this survey is in the course of preparation. (Document contains 16 pages)

Analysis of SUMOylated proteins using SUMO-traps

6 p. [+ 7 p. Supplementary Information]