Non-linear unit root properties of stock prices : evidence from India, Pakistan and Sri Lanka.

This study applies a threshold autoregressive (TAR) model to monthly stock prices for three South Asian countries over the period from 1991:01 to 2009:09. Two main conclusions are drawn. Firstly, the results indicate that all the stock prices in this study exhibit non-linear behavior. Secondly, a partial unit root was found to be present in one of the regimes indicating that the stock prices are weak form efficiency, but not all the time

Microstructural parameter estimation in vivo using diffusion MRI and structured prior information.

Diffusion MRI has recently been used with detailed models to probe tissue microstructure. Much of this work has been performed ex vivo with powerful scanner hardware, to gain sensitivity to parameters such as axon radius. By contrast, performing microstructure imaging on clinical scanners is extremely challenging

Monitoring the Growth of an Orthotopic Tumour Xenograft Model: Multi-Modal Imaging Assessment with Benchtop MRI (1T), High-Field MRI (9.4T), Ultrasound and Bioluminescence

BACKGROUND: Research using orthotopic and transgenic models of cancer requires imaging methods to non-invasively quantify tumour burden. As the choice of appropriate imaging modality is wide-ranging, this study aimed to compare low-field (1T) magnetic resonance imaging (MRI), a novel and relatively low-cost system, against established preclinical techniques: bioluminescence imaging (BLI), ultrasound imaging (US), and high-field (9.4T) MRI. METHODS: A model of colorectal metastasis to the liver was established in eight mice, which were imaged with each modality over four weeks post-implantation. Tumour burden was assessed from manually segmented regions. RESULTS: All four imaging systems provided sufficient contrast to detect tumours in all of the mice after two weeks. No significant difference was detected between tumour doubling times estimated by low-field MRI, ultrasound imaging or high-field MRI. A strong correlation was measured between high-field MRI estimates of tumour burden and all the other modalities (p < 0.001, Pearson). CONCLUSION: These results suggest that both low-field MRI and ultrasound imaging are accurate modalities for characterising the growth of preclinical tumour models

Forestry and environmental conditions as determinants of pine marten Martes martes occurrence in Norway

The European pine marten Martes martes is often associated with late seral stage coniferous forest stands. Earlier research has indicated that this species may be nega tively influenced by clearcutting practices. However, the effects of current clearcutting methods on pine marten occurrence in conjunction with changing environmental conditions are not well known. In this study, we combined four complete years of nationwide data collected during a long-term camera trap (CT) monitoring program in Norway. We employed a multi-scale occupancy model to investigate the relationship of pine marten occurrence to clearcuts (regenerating stands ≤ 10 years old) and forests ≥ 120 years old. We also examined pine marten detection in relation to habitat features (i.e. dominant microsite characteristics) and to varying snow depths and temperatures. We found no relationship between pine marten occurrence and the proportions of old forest and clearcuts at the landscape scale. At the habitat-patch scale, pine marten occurrence was positively associated with the presence of old forest patches and terrain ruggedness, but not with clearcuts ≤ 100 m from sites. At CT sites near clearcuts, the detection probability was negatively correlated with snow depth. In contrast, pine marten occurrence was positively associated with snow depth at CT sites > 100 m from clearcuts. Furthermore, the detection probability increased with temperature and the presence of boulders at CT sites. Boulders may provide impor tant access points for foraging, and cover for resting and predator avoidance. While previous studies indicate that pine martens prefer older forest and avoid clearcuts, the current level and scale of clearcutting in Norway does not appear to influence its occurrence at the landscape scale.publishedVersio

Strong in-plane anisotropy in the electronic properties of doped transition metal dichalcogenides exhibited in W1−xNbxS2

We study the electronic properties of monolayer transition metal dichalcogenide materials subjected to aliovalent doping, using Nb-doped WS2 as an exemplar. Scanning transmission electron microscopy imaging of the as-grown samples reveals an anisotropic Nb dopant distribution, prompting an investigation of anisotropy in electronic properties. Through electronic structure calculations on supercells representative of observed structures, we confirm that local Nb-atom distributions are consistent with energetic considerations, although kinetic processes occurring during sample growth must be invoked to explain the overall symmetry-breaking. We perform effective bandstructure and conductivity calculations on realistic models of the material that demonstrate that a high level of anisotropy can be expected in electronic properties including conductivity. In-plane anisotropy of the conductivity is predicted to be as high as 5:1, which is higher than previously observed in any TMDC system in the [Mo,W][S,Se]2 class

Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases

Background: Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity.Methods: Eighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n = 40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end point was neurological progression-free survival (nPFS); hazard ratios (HRs) were calculated using Cox regression. All P values were two-sided.Results: Fifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to1.54; P = .84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P = .83). The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0% (placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of life differences were found.Conclusions: Our study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases compared to placebo. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.Up to 40% of patients with non-small cell lung cancer (NSCLC) develop brain metastases (BM), which are associated with poor outcome (median survival &lt;5 months) (1–3). Treatment options include whole-brain radiotherapy (WBRT) with or without corticosteroids. Modifying the radiation dose or fractionation or combining radiotherapy with radiosensitizers have not substantially improved prognosis (4–10). More than half of patients treated with WBRT ultimately die of progressive systemic disease (11–13).Erlotinib, an epidermal growth factor receptor (EGFR) pathway inhibitor, is currently approved as first-line treatment for advanced NSCLC patients harboring EGFR mutations, and, as maintenance, second-line or third-line treatments following chemotherapy (14–17). Pre-clinical data show that erlotinib enhances the inhibitory effect of ionizing radiation in lung cancer, and it crosses the blood-brain barrier, so it could be used to provide sufficient radiosensitizing and therapeutic level in the brain (18–22).To exploit the potential radiosensitizing properties, the direct effect on brain metastases, and systemic activity of erlotinib, we examined the role of erlotinib given concurrently with WBRT, then as maintenance

The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore

M11L, an antiapoptotic protein essential for the virulence of the myxoma poxvirus, is targeted to mitochondria and prevents the loss of mitochondrial membrane potential that accompanies cell death. In this study we show, using a cross-linking approach, that M11L physically associates with the mitochondrial peripheral benzodiazepine receptor (PBR) component of the permeability transition (PT) pore. Close association of M11L and the PBR is also indicated by fluorescence resonance energy transfer (FRET) analysis. Stable expression of M11L prevents the release of mitochondrial cytochrome c induced by staurosporine or protoporphyrin IX (PPIX), a ligand of the PBR. Transiently expressed M11L also prevents mitochondrial membrane potential loss induced by PPIX, or induced by staurosporine in combination with PK11195, another ligand of the PBR. Myxoma virus infection and the associated expression of early proteins, including M11L, protects cells from staurosporine- and Fas-mediated mitochondrial membrane potential loss and this effect is augmented by the presence of PBR. We conclude that M11L regulates the mitochondrial permeability transition pore complex, most likely by direct modulation of the PBR

Scalable magnet geometries enhance tumour targeting of magnetic nano-carriers

Targeted drug delivery systems aim to increase therapeutic effect within the target tissue or organ, while reducing off-target toxicity associated with systemic delivery. Magnetic drug targeting has been shown to be an effective strategy by manipulating therapeutics inside the body using a magnetic field and an iron oxide carrier. However, the effective targeting range of current magnets limits this method to small animal experiments or superficial parts of the human body. Here we produce clinically translatable magnet designs capable of increasing exposure of tissue to magnetic fields and field gradients, leading to increased carrier accumulation. The iron oxide nanoparticle capturing efficiency was first assessed in vitro using a simple vascular flow system. Secondly, accumulation of these particles, following magnetic targeting, was evaluated in vivo using a range of different magnet designs. We observed that our bespoke magnet produced a 4-fold increase in effective targeting depth when compared to a conventional 1 T disk magnet. Finally, we show that this magnet is readily scalable to human size proportions and has the potential to target 100 nm particles up to a depth of 7 cm at specific locations of human body

Investigating low-velocity fluid flow in tumours using convection-MRI

Several distinct fluid flow phenemena occur in solid tumours, including intravascular blood flow and interstitial convection. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we have developed a novel magnetic resonance imaging (MRI) technique named convection-MRI. It uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extra-vascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations and tumor xenograft models to investigate the technical feasibility of convection-MRI. We report a good correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma and show that convection-MRI can provide insights into the growth and response to vascular-targeting therapy in colorectal cancers