Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1–1 μM) by comparatively low dose of 405 nm light (3.6 J cm−2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin

Increased non-homologous end joining makes DNA-PK a promising target for therapeutic intervention in uveal melanoma

Uveal melanoma (UM) is the most common primary intraocular tumour in adults, with a mean survival of six months following metastasis. The survival rates have not improved in over 30 years. This study has shown that sister chromatid exchange (SCE) is low in UM which is likely due to a reduced expression of FANCD2. As FANCD2 can function to suppress non-homologous end joining (NHEJ), this study therefore investigated NHEJ in UM. The activation of the catalytic subunit of the NHEJ pathway protein DNA-dependent protein kinase (DNA-PK) was measured by analysing the foci formation and the ligation efficiency by NHEJ determined using a plasmid-based end-joining assay. Using small-interfering RNA (siRNA) knock-down, and chemical inhibitors of DNA-PK, the survival of primary UM cultures and two cell lines were determined. To assess the homologous recombination capacity in response to the inhibition of DNA-PK, a SCE analysis was performed. In addition, to support the findings, the messenger RNA (mRNA) expression of genes associated with NHEJ was analysed using the Cancer Genome Atlas (TCGA)-UM RNAseq data (n = 79). The NHEJ activity and DNA-PKcs activation was upregulated in UM and the inhibition of DNA-PK selectively induced apoptosis and sensitized to ionising radiation and inter-strand cross-linking agents. The inhibition of the NHEJ protein DNA-PK is lethal to UM, indicating a potentially effective therapeutic option, either alone or as a sensitizer for other treatments

Deception and self-awareness

This paper presents a study conducted for the Shades of Grey EPSRC research project (EP/H02302X/1), which aims to develop a suite of interventions for identifying terrorist activities. The study investigated the body movements demonstrated by participants while waiting to be interviewed, in one of two conditions: preparing to lie or preparing to tell the truth. The effect of self-awareness was also investigated, with half of the participants sitting in front of a full length mirror during the waiting period. The other half faced a blank wall. A significant interaction was found for the duration of hand/arm movements between the deception and self-awareness conditions (F=4.335, df=1;76, p<0.05). Without a mirror, participants expecting to lie spent less time moving their hands than those expecting to tell the truth; the opposite was seen in the presence of a mirror. This finding indicates a new research area worth further investigation

Late Solitary Extraocular Recurrence from Previously Resected Iris Melanoma.

Purpose To report on cases of late extraocular relapse of previously resected iris melanoma, without concurrent intraocular recurrence. Design Retrospective case series. Methods A retrospective chart review of 4 patients diagnosed with late subconjunctival relapse of previously resected iris melanoma. Results Three females and one male underwent iris tumour resection and presented to our service with suspicious conjunctival lesions at a median of 22 years later (mean: 21). None showed intraocular relapse. Treatment of the conjunctival tumours included excisional biopsy (n=4) followed by cryotherapy (n=3) and/or brachytherapy (n=3). In all cases, histopathology confirmed malignant melanoma, with no intraepithelial component or associated melanosis. Genetic sequencing (n=3) showed wildtype BRAF and NRAS in all. GNA11 mutation was found in 1 case. On array CGH (n=3), gain of 6p was found in 2 cases and gain of 8 in 2. Overall, findings were strongly suggestive of a diagnosis of late extraocular relapse from previously resected iris melanoma. In a median of 2.5 years (mean: 7.7) from the subconjunctival relapse, no further episodes of intra/extraocular recurrence were recorded, and all patients were free from distant metastasis. Conclusions Patients undergoing iris melanoma resection are at risk of developing late solitary extraocular relapse even over 30 years after surgery. In the absence of an intraocular component, diagnosis may be challenging, as tumours mimic a primary conjunctival lesion. Management by excisional biopsy followed by adjuvant therapy was successful, and histopathology and genetic analysis supported a diagnosis of extraocular uveal tumour spread rather than a primary conjunctival tumour

"Author! Author!" : Shakespeare and biography

Original article can be found at: http://www.informaworld.com/smpp/title~content=t714579626~db=all Copyright Informa / Taylor &amp; Francis Group. DOI: 10.1080/17450910902764454Since 1996, not a year has passed without the publication of at least one Shakespeare biography. Yet for many years the place of the author in the practice of understanding literary works has been problematized, and even on occasions eliminated. Criticism reads the “works”, and may or may not refer to an author whose “life” contributed to their meaning. Biography seeks the author in the works, the personality that precedes the works and gives them their characteristic shape and meaning. But the form of literary biography addresses the unusual kind of “life” that puts itself into “works”, and this is particularly challenging where the “works” predominate massively over the salient facts of the “life”. This essay surveys the current terrain of Shakespeare biography, and considers the key questions raised by the medium: can we know anything of Shakespeare's “personality” from the facts of his life and the survival of his works? What is the status of the kind of speculation that inevitably plays a part in biographical reconstruction? Are biographers in the end telling us as much about themselves as they tell us about Shakespeare?Peer reviewe

On the Deformation of Dendrites During Directional Solidification of a Nickel-Based Superalloy

Abstract: Synchrotron X-ray imaging has been used to examine in situ the deformation of dendrites that takes place during the solidification of a nickel-based superalloy. By combining absorption and diffraction contrast imaging, deformation events could be classified by their localization and permanence. In particular, a deformation mechanism arising from thermal contraction in a temperature gradient was elucidated through digital image correlation. It was concluded that this mechanism may explain the small misorientations typically observed in single crystal castings

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter