7,355 research outputs found

    Investigation of phase separation within the generalized Lin-Taylor model for a binary liquid mixture of large hexagonal and small triangular particles

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    The generalized Lin-Taylor model defined on the hexagonal lattice is used to investigate the phase separation in an asymmetric binary liquid mixture consisting of large A (hexagons) and small B (triangles) particles. By considering interaction energies between A-A and A-B pairs of particles that occupy nearest-neighbour cells of the hexagonal lattice, we have derived an exact solution for the considered model system having established a mapping correspondence with the two-dimensional Ising model on its dual triangular lattice. Altogether, six different types of coexistence curves including those with reentrant miscibility regions (i.e. closed-loop coexistence curves) were found in dependence on the relative strength between both coupling constants.Comment: 8 pages, 4 figures, presented at 7th Liblice conference on the Statistical Mechanics of Liquids to be held in Lednice on June 11-16, 200

    Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis

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    Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration

    Targeting co-stimulatory molecules in autoimmune disease

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    Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, in which efforts have focused in particular on cytotoxic T lymphocyte antigen 4 (CTLA4) and PD1, both of which are members of the CD28 family. In autoimmunity, these same pathways can be targeted to opposite effect: to curb the over-exuberant immune response. The CTLA4 checkpoint serves as an exemplar, whereby CTLA4 activity is blocked by antibodies in cancer immunotherapy and augmented by the provision of soluble CTLA4 in autoimmunity. Here, we review the targeting of co-stimulatory molecules in autoimmune diseases, focusing in particular on agents directed at members of the CD28 or tumour necrosis factor receptor families. We present the state of the art in co-stimulatory blockade approaches, including rational combinations of immune inhibitory agents, and discuss the future opportunities and challenges in this field

    The James Clerk Maxwell telescope dense gas survey of the Perseus molecular cloud

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    This is the final version of the article. Available from the publisher via the DOI in this record.We present the results of a large-scale survey of the very dense (n > 106 cm-3) gas in the Perseus molecular cloud using HCO+ and HCN (J = 4 → 3) transitions. We have used this emission to trace the structure and kinematics of gas found in pre- and protostellar cores, as well as in outflows. We compare the HCO+/HCN data, highlighting regions where there is a marked discrepancy in the spectra of the two emission lines. We use the HCO+ to identify positively protostellar outflows and their driving sources, and present a statistical analysis of the outflow properties that we derive from this tracer. We find that the relations we calculate between the HCO+ outflow driving force and the Menv and Lbol of the driving source are comparable to those obtained from similar outflow analyses using 12CO, indicating that the two molecules give reliable estimates of outflow properties. We also compare the HCO+ and the HCN in the outflows, and find that the HCN traces only the most energetic outflows, the majority of which are driven by young Class 0 sources. We analyse the abundances of HCN and HCO+ in the particular case of the IRAS 2A outflows, and find that the HCN is much more enhanced than the HCO+ in the outflow lobes. We suggest that this is indicative of shock enhancement of HCN along the length of the outflow; this process is not so evident for HCO+, which is largely confined to the outflow base. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.SLW-S and JH are funded by the Science and Technology Facilities Council of the UK. The James Clerk Maxwell Telescope is operated by the Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the National Research Council of Canada and (until 2013 March 31) the Netherlands Organisation for Scientific Researc

    Mapping Epileptic Networks Using Simultaneous Intracranial EEG-fMRI

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    Background: Potentially curative epilepsy surgery can be offered if a single, discrete epileptogenic zone (EZ) can be identified. For individuals in whom there is no clear concordance between clinical localization, scalp EEG, and imaging data, intracranial EEG (icEEG) may be needed to confirm a predefined hypothesis regarding irritative zone (IZ), seizure onset zone (SOZ), and EZ prior to surgery. However, icEEG has limited spatial sampling and may fail to reveal the full extent of epileptogenic network if predefined hypothesis is not correct. Simultaneous icEEG-fMRI has been safely acquired in humans and allows exploration of neuronal activity at the whole-brain level related to interictal epileptiform discharges (IED) captured intracranially. Methods: We report icEEG-fMRI in eight patients with refractory focal epilepsy who had resective surgery and good postsurgical outcome. Surgical resection volume in seizure-free patients post-surgically reflects confirmed identification of the EZ. IEDs on icEEG were classified according to their topographic distribution and localization (Focal, Regional, Widespread, and Non-contiguous). We also divided IEDs by their location within the surgical resection volume [primary IZ (IZ1) IED] or outside [secondary IZ (IZ2) IED]. The distribution of fMRI blood oxygen level-dependent (BOLD) changes associated with individual IED classes were assessed over the whole brain using a general linear model. The concordance of resulting BOLD map was evaluated by comparing localization of BOLD clusters with surgical resection volume. Additionally, we compared the concordance of BOLD maps and presence of BOLD clusters in remote brain areas: precuneus, cuneus, cingulate, medial frontal, and thalamus for different IED classes. Results: A total of 38 different topographic IED classes were identified across the 8 patients: Focal (22) and non-focal (16, Regional = 9, Widespread = 2, Non-contiguous = 5). Twenty-nine IEDs originated from IZ1 and 9 from IZ2. All IED classes were associated with BOLD changes. BOLD maps were concordant with the surgical resection volume for 27/38 (71%) IED classes, showing statistical global maximum BOLD cluster or another cluster in the surgical resection volume. The concordance of BOLD maps with surgical resection volume was greater (p < 0.05) for non-focal (87.5%, 14/16) as compared to Focal (59%, 13/22) IED classes. Additionally, BOLD clusters in remote cortical and deep brain areas were present in 84% (32/38) of BOLD maps, more commonly (15/16; 93%) for non-focal IED-related BOLD maps. Conclusions: Simultaneous icEEG-fMRI can reveal BOLD changes at the whole-brain level for a wide range of IEDs on icEEG. BOLD clusters within surgical resection volume and remote brain areas were more commonly seen for non-focal IED classes, suggesting that a wider hemodynamic network is at play
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