Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes.

Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant (P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients' molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification

Thermal Infrared Observations of Asteroid (99942) Apophis with Herschel

The near-Earth asteroid (99942) Apophis is a potentially hazardous asteroid. We obtained far-infrared observations of this asteroid with the Herschel Space Observatory's PACS instrument at 70, 100, and 160 micron. These were taken at two epochs in January and March 2013 during a close Earth encounter. These first thermal measurements of Apophis were taken at similar phase angles before and after opposition. We performed a detailed thermophysical model analysis by using the spin and shape model recently derived from applying a 2-period Fourier series method to a large sample of well-calibrated photometric observations. We find that the tumbling asteroid Apophis has an elongated shape with a mean diameter of 375$^{+14}_{-10}$ m (of an equal volume sphere) and a geometric V-band albedo of 0.30$^{+0.05}_{-0.06}$. We find a thermal inertia in the range 250-800 Jm$^{-2}$s$^{-0.5}$K$^{-1}$ (best solution at 600 Jm$^{-2}$s$^{-0.5}$K$^{-1}$), which can be explained by a mixture of low conductivity fine regolith with larger rocks and boulders of high thermal inertia on the surface. The thermal inertia, and other similarities with (25143) Itokawa indicate that Apophis might also have a rubble-pile structure. If we combine the new size value with the assumption of an Itokawa-like density and porosity we estimate a mass between 4.4 and 6.2 10$^{10}$ kg which is more than 2-3 times larger than previous estimates. We expect that the newly derived properties will influence impact scenario studies and influence the long-term orbit predictions of Apophis.Comment: Accepted for publication in Astronomy & Astrophysics, 21 pages, 8 figures, 2 table

Clinician experiences on training and awareness of sexual orientation in NHS Talking Therapies Services for Anxiety and Depression

Previous research that explored sexual minority service users’ experiences of accessing NHS Talking Therapies for Anxiety and Depression Services highlighted the need for specific sexual orientation training. Inconsistent or lack of training may contribute to disparities in treatment outcomes between sexual minority service users and heterosexual service users. The aim of the study was to explore clinicians’ competencies working with sexual minority service users, their experiences of sexual orientation training, their view of current gaps intraining provision, and ways to improve training. Self-reported sexual orientation competency scales and open ended questions were used to address the aims of the study. Participants (n=83) included Psychological Wellbeing Practitioners (PWPs) and high-intensity CBT therapists (HITs). Responses on competency scales were analysed using Kruskal–Wallis tests and thematic analysis was used to analyse qualitative responses. Participants who identified as 25–29 years old had higher scores on the knowledge scale than 45+-year-olds.Bisexual participants also had higher scores on the knowledge subscale than heterosexual participants. Threeover-arching themes were identified: (a) training received on sexual minority issues by Talking Therapies clinicians, (b) clinicians’ experiences of accessing and receiving sexual minority training, and (c) perceived gaps in current sexual minority training and ways to improve training. Findings were linked to previous literature and recommendations to stakeholders are made throughout the Discussion section with the view of improving sexual orientation training

Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

Photochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS2a) or tetraphenylchlorin disulfonate (TPCS2a) and Bleomycin. Results from the use of 3D co-culture models demonstrate that a cancer cell line PCI30 and satellite glia were more sensitive to PCI than neurons and mixed glial cells, athough neurite length was affected. Neurons in culture survived PCI treatment under conditions sufficient to kill tumour cells, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology

South from Alaska: A Pilot aDNA Study of Genetic History on the Alaska Peninsula and the Eastern Aleutians

The Aleutian Islands were colonized, perhaps several times, from the Alaskan mainland. Earlier work documented transitions in the relative frequencies of mtDNA haplogroups over time, but little is known about potential source populations for prehistoric Aleut migrants. As part of a pilot investigation, we sequenced the mtDNA first hypervariable region (HVRI) in samples from two archaeological sites on the Alaska Peninsula (the Hot Springs site near Port Moller, Alaska; and samples from a cluster of sites in the Brooks River area near Katmai National Park and Preserve) and one site from Prince William Sound (Mink Island). The sequences revealed not only the mtDNA haplogroups typically found in both ancient and modern Aleut populations (A2 and D2) but also haplogroups B2 and D1 in the Brooks River samples and haplogroup D3 in one Mink Islander. These preliminary results suggest greater mtDNA diversity in prehistoric populations than previously observed and facilitate reconstruction of migration scenarios from the peninsula into the Aleutian archipelago in the past

Dye Sensitised Solar Cells: A Computational Approach

Dye sensitised solar cells (DSSCs) mimic charge excitation and transfer processes found in natural photosynthesis to directly convert sunlight into electricity. Combining easy assembly with relatively cheap materials they offer a potentially cost effective solution to our energy requirements. Numerous physical processes are at work within a DSSC and the underlying complexity of these competing processes has meant that, despite considerable research effort, advances in obtaining a viable device efficiency have stagnated. The aim of this thesis is to examine, by density functional theory calculations, some of the processes at work in DSSCs with the motivation being to provide insight that informs the design of more efficient devices by experimentalists. Our calculations study some of the key factors affecting device efficiency, in particular the interaction of binding moieties with titanium dioxide surfaces, the role intrinsic and extrinsic defects have in defining the properties of semiconductors, the molecular design of sensitising dyes and the effect this has on both dye-dye and dye-semiconductor interactions. Finally we implement and test the excited state formalism of time dependent density functional theory (TDDFT) within the linear scaling DFT code CONQUEST, allowing excited state properties of large systems to be examined computationally. Our approach propagates the density matrix in real time (RT-TDDFT), and finally we use our implementation to model the real time response of titanium dioxide clusters and dyes to external electric fields

Physical Properties of OSIRIS-REx Target Asteroid (101955) 1999 RQ36 derived from Herschel, ESO-VISIR and Spitzer observations

In September 2011, the Herschel Space Observatory performed an observation campaign with the PACS photometer observing the asteroid (101955) 1999 RQ36 in the far infrared. The Herschel observations were analysed, together with ESO VLT-VISIR and Spitzer-IRS data, by means of a thermophysical model in order to derive the physical properties of 1999 RQ36. We find the asteroid has an effective diameter in the range 480 to 511 m, a slightly elongated shape with a semi-major axis ratio of a/b=1.04, a geometric albedo of 0.045 +0.015/-0.012, and a retrograde rotation with a spin vector between -70 and -90 deg ecliptic latitude. The thermal emission at wavelengths below 12 micron -originating in the hot sub-solar region- shows that there may be large variations in roughness on the surface along the equatorial zone of 1999 RQ36, but further measurements are required for final proof. We determine that the asteroid has a disk-averaged thermal inertia of Gamma = 650 Jm-2s-0.5K-1 with a 3-sigma confidence range of 350 to 950 Jm-2s-0.5K-1, equivalent to what is observed for 25143 Itokawa and suggestive that 1999 RQ36 has a similar surface texture and may also be a rubble-pile in nature. The low albedo indicates that 1999 RQ36 very likely contains primitive volatile-rich material, consistent with its spectral type, and that it is an ideal target for the OSIRIS-REx sample return mission.Comment: Accepted for publication in Astronomy & Astrophysics, 9 pages, 7 figure

Mott transition in the π\pi-flux SU(44) Hubbard model on a square lattice

We employ the projector quantum Monte Carlo simulations to study the ground-state properties of the square-lattice SU(4) Hubbard model with a $\pi$ flux per plaquette. In the weak coupling regime, its ground state is in the gapless Dirac semi-metal phase. With increasing repulsive interaction, we show that, a Mott transition occurs from the semimetal to the valence bond solid, accompanied by the $Z_4$ discrete symmetry breaking. Our simulations demonstrate the existence of a second-order phase transition, which confirms the Ginzburg-Landau analysis. The phase transition point and the critical exponent $\eta$ are also estimated. To account for the effect of a $\pi$ flux on the ordering in the strong coupling regime, we analytically derive by the perturbation theory the ring-exchange term which describes the leading-order difference between the $\pi$-flux and zero-flux SU(4) Hubbard models.Comment: 8 pages, 9 figure