Holistic interventions to trauma management for teachers following disaster: Expressive arts and Integrated Body-mind-spirit approaches

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Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.postprin

Recent developments of the Hierarchical Reference Theory of Fluids and its relation to the Renormalization Group

The Hierarchical Reference Theory (HRT) of fluids is a general framework for the description of phase transitions in microscopic models of classical and quantum statistical physics. The foundations of HRT are briefly reviewed in a self-consistent formulation which includes both the original sharp cut-off procedure and the smooth cut-off implementation, which has been recently investigated. The critical properties of HRT are summarized, together with the behavior of the theory at first order phase transitions. However, the emphasis of this presentation is on the close relationship between HRT and non perturbative renormalization group methods, as well as on recent generalizations of HRT to microscopic models of interest in soft matter and quantum many body physics.Comment: 17 pages, 5 figures. Review paper to appear in Molecular Physic

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Quantum Communication

Quantum communication, and indeed quantum information in general, has changed the way we think about quantum physics. In 1984 and 1991, the first protocol for quantum cryptography and the first application of quantum non-locality, respectively, attracted a diverse field of researchers in theoretical and experimental physics, mathematics and computer science. Since then we have seen a fundamental shift in how we understand information when it is encoded in quantum systems. We review the current state of research and future directions in this new field of science with special emphasis on quantum key distribution and quantum networks.Comment: Submitted version, 8 pg (2 cols) 5 fig

Evidence for phonon skew scattering in the spin Hall effect of platinum

\u3cp\u3eWe measure and analyze the effective spin Hall angle of platinum in the low-residual resistivity regime by second-harmonic measurements of the spin-orbit torques for a multilayer of Pt|Co|AlOx. An angular-dependent study of the torques allows us to extract the effective spin Hall angle responsible for the damping-like torque in the system. We observe a strikingly nonmonotonic and reproducible temperature dependence of the torques. This behavior is compatible with recent theoretical predictions which include both intrinsic and extrinsic (impurities and phonons) contributions to the spin Hall effect at finite temperatures.\u3c/p\u3

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

Experimental investigation into the kinetics of Falcon UF concentration: Implications for fluid dynamic-based modelling

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Centrifugal gravity separators, such as the Falcon UltraFine (UF) concentrator, are the most common gravity concentration techniques used for fine particles processing. Hence, understanding the kinetics and separation mechanisms at play within these separators is of paramount interest. Recent research yielded a predictive physical model for the Falcon UF which however does not explain some results obtained with industrial ores. The Falcon UF kinetics have been investigated through the processing of fine-grained ores from the Altenberg tin deposit (Germany), the Tabuaço tungsten deposit (Portugal), a synthetic iron ore as well as results from previous studies on kaolin residues. Results have shown an evolution of Falcon UF performance with time/feed mass in contradiction with the stationary separation hypothesis on which the physical model was based. In terms of Falcon UF separation timing, four phases can be distinguished. First, upon initial feeding of the bowl, particles are trapped or rejected depending on their settling velocity. It yields a relatively ineffective selection according to density so that only ultrafine particles are ejected from the bowl, resulting in the quick growth of the concentrate bed. When the bed reaches a critical size, recovery and enrichment continue to increase through selective resuspension phenomenon that favours the concentration of dense particles and the ejection of larger particles. This way, the bed builds up while the content of concentrate bed surface evolves until resuspension balances the stream of dense material reaching the bed and recovery drops. The evolution of partition curves over time confirmed the low recovery of ultrafine particles during the whole operation but also showed a decrease of coarse particles recovery with time. It suggests that the second separation mechanism is less sensible to particle size compared to the first one and that size even has a negative impact on recovery. Furthermore, erosion figures in furrows are observed in the concentrate bed which may play locally an active role in the separation. These observations suggest that two separation mechanisms are at play. Firstly, differential particles settling within the flowing film which is already accounted for in the existing physical model. Secondly, resuspension of particles from the concentrate bed by the action of a lift force acting preferentially on coarse particles deposited at the surface of the bed and resulting in the rejection of coarser and lower-density particles. The addition of a lift force component to the existing model is discussed and a resuspension criterion is proposed as a guidance of the physics involved in this second separation mechanism. Future developments will require a dynamic model which would need to integrate the evolution of the concentrate bed content over time.European Union Horizon 2020French National Research Agenc

Factors associated with completion of bowel cancer screening and the potential effects of simplifying the screening test algorithm

BACKGROUND: The primary colorectal cancer screening test in England is a guaiac faecal occult blood test (gFOBt). The NHS Bowel Cancer Screening Programme (BCSP) interprets tests on six samples on up to three test kits to determine a definitive positive or negative result. However, the test algorithm fails to achieve a definitive result for a significant number of participants because they do not comply with the programme requirements. This study identifies factors associated with failed compliance and modifications to the screening algorithm that will improve the clinical effectiveness of the screening programme. METHODS: The BCSP Southern Hub data for screening episodes started in 2006–2012 were analysed for participants aged 60–69 years. The variables included age, sex, level of deprivation, gFOBt results and clinical outcome. RESULTS: The data set included 1 409 335 screening episodes; 95.08% of participants had a definitively normal result on kit 1 (no positive spots). Among participants asked to complete a second or third gFOBt, 5.10% and 4.65%, respectively, failed to return a valid kit. Among participants referred for follow up, 13.80% did not comply. Older age was associated with compliance at repeat testing, but non-compliance at follow up. Increasing levels of deprivation were associated with non-compliance at repeat testing and follow up. Modelling a reduction in the threshold for immediate referral led to a small increase in completion of the screening pathway. CONCLUSIONS: Reducing the number of positive spots required on the first gFOBt kit for referral for follow-up and targeted measures to improve compliance with follow-up may improve completion of the screening pathway