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Using P‐wave seismograms, we trained a seismic source classifier using a Convolutional Neural Network. We trained for three classes: earthquake P‐wave, underground nuclear explosion (UNE) P‐wave, and noise. With the current absence of nuclear testing by countries that have signed the Comprehensive Test Ban Treaty, high quality seismic data from UNEs is limited. Even with limited training data, our model can accurately characterize most events recorded at regional and teleseismic distances, finding over 95% signals in the validation set. We applied the model on holdout datasets of the North Korean test explosions to evaluate the performance on unique region and station‐source pairs, with promising results. Additionally, we tested on the Source Physics Experiment events to investigate the potential for chemical explosions to act as a surrogate for nuclear explosions. We anticipate that machine‐learning models like our classifier system can have broad application for other seismic signals including volcanic and non‐volcanic tremor, anomalous earthquakes, ice‐quakes or landslide‐quakes. Plain Language Summary: We train a global seismic event classifier using machine learning on underground nuclear test explosion seismic data. Our classifier model can successfully discriminate (with over 95% accuracy) between underground nuclear explosion, earthquake, and noise signals from stations both regionally and far‐field. Since this model was trained on a relatively small data set (for machine learning applications) we expect that similar methods can be applied to event or discrimination of other unique seismic sources like those from volcanoes, landslides, or glaciers. Key Points: We successfully discriminate underground nuclear explosions with a Convolutional Neural network (CNN) trained on P‐wave seismogramsRobust global seismic event discrimination is possible with machine learning trained on regional and teleseismic dataA CNN trained with historical nuclear explosion data can be applied with high accuracy to other regions, like the six Democratic People's Republic of Korea's test explosions [ABSTRACT FROM AUTHOR]

The author reflects on the political culture of rural areas in the U.S. He discusses the problems occurring in Columbus County, North Carolina and the lack of policy intervention in the county. He argues that the evidence of separation of these rural areas from the modern society, such as poverty and local oligarchy, are the effects of political and economic integration. He also tackles the assumption by liberal Democrats that they cannot build political power or win elections in these rural areas.

The article examines the relationship between African American land tenure in North Carolina and disaster relief policy in the U.S. Topics discussed include the origins of the challenges facing land ownership and heir property in the African American community, difficulties facing African American heir property owners in seeking disaster relief in the state, and the tendency of state policies to devalue the property owned by African Americans in North Carolina such as redlining.

X ray photoelectron diffraction (XPD) patterns of polar zinc oxide (ZnO) surfaces were investigated experimentally using hard x rays and monochromatized Cr Kα radiation and theoretically using a cluster model approach and a dynamical Bloch wave approach. We focused on photoelectrons emitted from the Zn 2p3/2 and O 1s orbitals in the analysis. The obtained XPD patterns for the (0001) and (000[formula]) surfaces of a ZnO single crystal were distinct for a given emitter and polarity. Polarity determination of c-axis-textured polycrystalline ZnO thin films was also achieved with the concept of XPD, even though the in-plane orientation of the columnar ZnO grains was random. [ABSTRACT FROM AUTHOR]

Steam thermal cracking is an established technology for the production of light olefins, such as ethylene and propylene. The shift to lighter, ethane-based feeds means that propylene production from steam crackers will be lower than the corresponding ethylene production. Therefore, alternative technologies have to be developed to produce more propylene to make up for the shortfall from steam cracking. This review looks at the steam catalytic cracking technology, which combines both catalytic cracking and steam cracking to maximize the production of light olefins. This review looks at the effect of catalyst and technology applied in fluid catalytic cracking reactors to enhance light olefins production. The influence of reaction conditions and the reaction mechanism are also presented. The graphical abstract shows the feed and steam being fed into the FCC unit from which light olefins and gasoline are produced as the desired products. [ABSTRACT FROM AUTHOR]

Arterial inflammation is a hallmark of atherosclerosis, and appropriate management of this inflammation represents a major unmet therapeutic need for cardiovascular disease patients. Here, we review the diverse contributions of immune cells to atherosclerosis, the mechanisms of immune cell activation in this context, and the cytokine circuits that underlie disease progression. We discuss the recent application of these insights in the form of immunotherapy to treat cardiovascular disease and highlight how studies on the cardiovascular co-morbidity that arises in autoimmunity might reveal additional roles for cytokines in atherosclerosis. Currently, data point to interleukin-1β (IL-1β), tumor necrosis factor (TNF), and IL-17 as cytokines that, at least in some settings, are effective targets to reduce cardiovascular disease progression. The appropriate management of arterial inflammation, a hallmark of atherosclerosis, represents an unmet therapeutic need for cardiovascular disease patients. Randolph et al. review the cytokine circuits that underlie the diverse contributions of immune cells to atherosclerosis and discuss the recent application of these insights in the form immunotherapy to treat cardiovascular disease. [ABSTRACT FROM AUTHOR]

Macrophages represent one of the most numerous and diverse leukocyte types in the body. Furthermore, they are important regulators and promoters of many cardiovascular disease programs. Their functions range from sensing pathogens to digesting cell debris, modulating inflammation, and producing key cytokines and other regulatory factors throughout the body. Macrophage research has undergone a renaissance in recent years, which has propelled a newfound interest in their heterogeneity as well as a new understanding of ontological differences in their development. In addition, recent technological advances such as single-cell mass-cytometry by time-of-flight have enabled phenotype and functional analyses of individual immune myeloid cells, including macrophages, at unprecedented resolution. In this Part 1 of a 4-part review series covering the macrophage in cardiovascular disease, we focus on the basic principles of macrophage development, heterogeneity, phenotype, tissue-specific differentiation, and functionality as a basis to understand their role in cardiovascular disease. [ABSTRACT FROM AUTHOR]

The prism graph is the planar dual of $$K_5 \backslash e$$ . Kingan and Lemos (Graphs Comb 30:1479-1497, ) proved a decomposition theorem for the class of binary matroids with no prism minor. In this paper, we present a different proof using fundamental graphs and blocking sequences. [ABSTRACT FROM AUTHOR]

This essay discusses Spike Lee's 2008 World War II filmMiracle at St. Annaas both a response to the myth of national unity in Frank Capra's 1942 documentaryPrelude to Warand a reminder of the campaign for “Double Victory” launched that same year by thePittsburgh Courier. [ABSTRACT FROM PUBLISHER]

Abstract: The effect of crystalline polarity on the microstructure of gallium-doped zinc oxide (GZO) deposited using magnetron sputtering onto glass substrates was investigated. X-ray photoelectron spectroscopy was used to determine the crystalline polarity of c-axis textured GZO films. Grains whose radii were more than 1μm grew abnormally in 0.2mol% doped GZO when the film was thicker than ~1μm, and the radius of the grains was much smaller than 100nm in the heavily (i.e., 4mol%) doped GZO, regardless of the film thickness. Such abnormal growth of the grains in the 0.2mol% doped GZO films coincided with a change in the crystalline polarity: the surfaces of unusually large GZO grains were terminated with the (000 ) face, and those of normal GZO grains were terminated with the (0001) face. The results indicated that polarity flipping is a very important event for controlling the texture of doped zinc oxide films. [Copyright &y& Elsevier]

T cell migration toward sites of antigen exposure is mediated by G protein signaling and is a key function in the development of immune responses. Regulators of G protein signaling (RGS) proteins modulate G protein signaling; however, their role in the regulation of adaptive immune responses has not been thoroughly explored. Herein we demonstrated abundant expression of the Gi/Gq-specific RGS3 in activated T cells, and that diminished RGS3 expression in a T cell thymoma increased cytokine-induced migration. To examine the role of endogenous RGS3 in vivo, mice deficient in the RGS domain (RGS3ΔRGS) were generated and tested in an experimental model of asthma. Compared with littermate controls, the inflammation in the RGS3ΔRGS mice was characterized by increased T cell numbers and the striking development of perivascular lymphoid structures. Surprisingly, while innate inflammatory cells were also increased in the lungs of RGS3ΔRGS mice, eosinophil numbers and Th2 cytokine production were equivalent to control mice. In contrast, T cell numbers in the draining lymph nodes (dLN) were reduced in the RGS3ΔRGS, demonstrating a redistribution of T cells from the dLN to the lungs via increased RGS3ΔRGS T cell migration. Together these novel findings show a nonredundant role for endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model of inflammation. [ABSTRACT FROM AUTHOR]

Atopic asthma is a chronic inflammatory disease of the lungs generally marked by excessive Th2 inflammation. The role of allergen-specific IgG in asthma is still controversial; however, a receptor of IgG-immune complexes (IgG-ICs), FcγRIII, has been shown to promote Th2 responses through an unknown mechanism. Herein, we demonstrate that allergen-specific IgG-ICs, formed upon reexposure to allergen, promoted Th2 responses in two different models of IC-mediated inflammation that were independent of a preformed T cell memory response. Development of Th2-type airway inflammation was shown to be both FcγRIII and TLR4 dependent, and T cells were necessary and sufficient for this process to occur, even in the absence of type 2 innate lymphoid cells. We sought to identify downstream targets of FcγRIII signaling that could contribute to this process and demonstrated that bone marrow-derived DCs, alveolar macrophages, and respiratory DCs significantly upregulated IL-33 when activated through FcγRIII and TLR4. Importantly, IC-induced Th2 inflammation was dependent on the ST2/IL-33 pathway. Our results suggest that allergen-specific IgG can enhance secondary responses by ligating FcγRIII on antigen-presenting cells to augment development of Th2-mediated responses in the lungs via an IL-33-dependent mechanism. [ABSTRACT FROM AUTHOR]

Atopic asthma is a chronic inflammatory disease of the lungs generally marked by excessive Th2 inflammation. The role of allergen-specific IgG in asthma is still controversial; however, a receptor of IgG-immune complexes (IgG-ICs), FcγRIII, has been shown to promote Th2 responses through an unknown mechanism. Herein, we demonstrate that allergen-specific IgG-ICs, formed upon reexposure to allergen, promoted Th2 responses in two different models of IC-mediated inflammation that were independent of a preformed T cell memory response. Development of Th2-type airway inflammation was shown to be both FcγRIII and TLR4 dependent, and T cells were necessary and sufficient for this process to occur, even in the absence of type 2 innate lymphoid cells. We sought to identify downstream targets of FcγRIII signaling that could contribute to this process and demonstrated that bone marrow-derived DCs, alveolar macrophages, and respiratory DCs significantly upregulated IL-33 when activated through FcγRIII and TLR4. Importantly, IC-induced Th2 inflammation was dependent on the ST2/IL-33 pathway. Our results suggest that allergen-specific IgG can enhance secondary responses by ligating FcγRIII on antigen-presenting cells to augment development of Th2- mediated responses in the lungs via an IL-33-dependent mechanism. [ABSTRACT FROM AUTHOR]

In both human asthmatics and animal models of allergy, allergen-specific IgG can contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an important role for IgG and Fc-gamma receptor (FcγR) signaling on antigen presenting cells (APC) for the induction of airway inflammation. These studies suggest a positive feedback loop between IgG produced by the adaptive B cell response and FcγR signaling on innate immune cells. Studies of IgG and FcγRs in humans with asthma or allergic lung disease have been more controversial. Some reports have identified associations between allergen-specific IgG and severity of allergic responses, while other studies have found associations of IgG subclass IgG4 with allergic tolerance. In this paper, we review the literature to help define the nature of IgG and FcγR signaling on innate immune cells and how it contributes to the development of allergic immune responses. [ABSTRACT FROM AUTHOR]

Abstract: The surface structure of a single-crystal ZnO wafer was studied by angle-resolved x-ray photoelectron spectroscopy (ARXPS) using synchrotron radiation. As a result, well-defined x-ray photoelectron diffraction (XPD) patterns were obtained for the (0001) and (000) polar surfaces using the photoemission from the Zn 2p3/2 and O 1s core levels. The XPD patterns were indexed assuming forward scattering of photoelectrons by neighboring ions. Further, the XPD patterns for the (0001) and (000) surfaces were different from each other, indicating the possibility for using the XPD technique for polarity determination. [Copyright &y& Elsevier]

Abstract: Thin gold films can be strengthened by the incorporation, during reactive sputtering, of nanosized dispersions of monoclinic zirconia. Micron-thick films containing ∼2vol.% zirconia particles having a particle size of 1–3nm are found to have an indentation hardness of 3.8GPa after annealing for 60h at 500°C in air. Sputtered gold films of the same thickness and annealed under the same conditions had a hardness of 2.3GPa. The nanoparticles of zirconia resist coarsening with no change in diameter between deposition and after 60h at 500°C. They also suppress grain growth of the gold grains. The electrical resistivity of the strengthened gold films was 4.5μΩcm, about 55% higher than gold films. The temperature coefficient of resistivity was unaffected. [Copyright &y& Elsevier]

In the most common method of fresco painting, a unique integration of paint and plaster allows for frescos to acquire great durability and permanence. As the plaster or layers of fresco walls deteriorate over time, frescos become vulnerable to serious damage. In order to prevent such damage without harming frescos, non-destructive techniques must be used to analyze and determine areas of structure delamination. In the past, different non-destructive methods have been studied. However, many require expensive equipment. The main scope of this work is the evaluation of the effectiveness of non-invasive detection of fresco delamination via thermography, a comparatively inexpensive technique. In non-invasive active infrared thermography, thermal images are captured of a fresco before, during, and after a heating or cooling process. A defect beneath the surface acts as an insulative pocket, which in turn entraps heat and decreases the rate of heat diffusion. The accumulation of heat results in a defective region being abnormally hotter than a non-defective region, which causes a greater change in temperature throughout a heating or cooling process. Therefore, the analysis of the temperature change highlights defects location and entity beneath the surface. This technique was used and validated with two constructed surrogates, one with a known defect and one without a defect. The thermal analysis of the surrogates was performed via MATLAB®. Additionally, simulations of heating and cooling processes on modeled surrogates were generated in COMSOL® Multiphysics. The results of these simulations assessed the MATLAB® analysis and the use of non-invasive thermography as a tool to detect fresco delaminations. This method was then implemented on frescos within the Senate Reception Room of the United States Capitol Building. [ABSTRACT FROM AUTHOR]

Round goby Neogobius melanostomus – a small, benthic fish native to Eurasia – was first introduced to North America in the 1980s through ballast water of cargo ships. In 1990, the Round goby was first discovered in the Laurentian Great Lakes Basin and rapidly spread through all Great Lakes from 1993 to 1998. The Round goby is an aggressive, prolific, and efficient egg predator that subsequently displaced native fishes from their preferred habitats and resources in the Great Lakes, where they are well established and abundant. From Lake Michigan, Round goby moved south into the Chicago Area Waterway System in 1993 and slowly progressed down the Illinois Waterway to the Mississippi River from 2004 to 2019, where less is known about their abundance, establishment, and impact. The goal of this study was to gain a comprehensive understanding of the first large river invasion by Round goby in the Mississippi River Basin by leveraging Round goby capture data from 2019 to 2022 on all pools of the Illinois Waterway. We describe their current distribution, relative abundance (i.e., catch-per-unit-effort), frequency of occurrence, and establishment (i.e., presence of young-of-year and adults) status throughout the Illinois Waterway. Results show that catch-per-unit-effort, frequency of occurrence, and the proportion of sites where multiple life stages are present are considerably higher in the upstream pools relative to more downstream pools of the Illinois Waterway. Our data support that the Round goby has established self-sustaining populations in the Chicago Area Waterway System, the upper Illinois River (i.e. Dresden Island Pool downstream through Starved Rock Pool), and a portion of the lower Illinois River (i.e. Peoria Pool downstream through Alton Pool) of the Illinois Waterway. In the lower Illinois River, Round gobies appear to only be established in Peoria Pool, with captures occurring infrequently in La Grange Pool, and no Round gobies being captured in Alton Pool. [ABSTRACT FROM AUTHOR]

The polar surfaces of wurtzite-type zinc oxide (ZnO) were characterized by x-ray photoemission spectroscopy to identify the origin of the polarity dependence of the valence band spectra. A characteristic sub-peak always appeared in the valence band spectra of the (0001) face regardless of the surface preparation conditions. It also appeared in the valence band spectra of the (10[formula]2) face, but only when the photoelectron take-off angle was parallel to the c-axis of ZnO. Our analysis demonstrates that this take-off angle dependency originates not from the surface state, photoelectron diffraction, or the presence of surfactants but from the crystal polarity. [ABSTRACT FROM AUTHOR]

Fatigue testing is critical in order to establish the service life of load‐bearing components and structures. The extensive time associated with full fatigue spectrum testing can lead to prohibitive costs. A significant need exists for a fatigue load spectrum editing methodology, based on the mechanics of fatigue, that produces load spectra that can replicate service damage in laboratory testing and can lead to compressed testing times and reduced costs. In this work, a wavelet genetic (WAVEGEN) algorithm is developed to edit fatigue loading spectra using wavelet analysis to greatly reduce the length of a spectrum while retaining the same damage accumulation characteristics. In addition, an optimization protocol using a genetic algorithm is included within this process to automatically select the best wavelet editing parameters. The algorithm is designed to identify the most suitable wavelet type, filter, and level to optimally edit a given fatigue spectrum and ensure equivalence between edited and unedited spectra from a damage perspective. The algorithm was applied to two well‐known aircraft fatigue spectra: Fighter Aircraft Loading Standard for Fatigue evaluation (FALSTAFF) and Transport Wing Standard (TWIST). The proposed approach has demonstrated that both spectra can be compressed significantly even while ensuring equivalence from a damage perspective. Highlights: A wavelet genetic (WAVEGEN) algorithm has been developed to edit fatigue loading spectra.The algorithm optimizes wavelet parameters while ensuring damage equivalence.The algorithm's efficacy is demonstrated with two well‐known fatigue spectra. [ABSTRACT FROM AUTHOR]

The structures and properties of zinc oxide thin films deposited by radio-frequency magnetron sputtering were investigated for different substrate biases applied during deposition. The electrical bias determined the crystalline polarity of a nominally undoped film on an amorphous substrate: films with a (0001) surface and a ([formula]) surface were produced under positive and negative biases, respectively. Moreover, the polarity of the films was determined at an early stage of the deposition and could not be reversed by switching the substrate bias. [ABSTRACT FROM AUTHOR]

Abstract: The 5-HT2C receptor is one of 14 different serotonin (5-HT) receptors that control neural function and behavior. Here, we present the entire sequence of a zebrafish 5-HT2C receptor cDNA including the 3′ untranslated region and the previously unknown 5′ untranslated region. The cloned 5-HT2C receptor gene is located on chromosome 7, is approximately 202kbp long, and contains six exons. The coding region of the gene is 1557bp long and flanked by a 504bp 5′ UTR and a 1474bp 3′ UTR. The deduced protein sequence of 518 amino acids aligns with orthologs of other vertebrates and is 54% identical to the human and mouse 5-HT2C receptor protein sequences. The region of the cDNA that encodes the 2nd cytoplasmic loop of the protein shows a 66% identity with vertebrate orthologs and clearly identifies the gene as a 5-HT2C receptor gene. Coupling sites for beta-arrestin and calmodulin are conserved in zebrafish. In-situ hybridization shows that the receptor is expressed in the brain and spinal cord including areas such as the olfactory bulb, the dorsal thalamus, the posterior tuberculum, the hypothalamus and the medulla oblongata. Reverse Transcriptase-PCR experiments indicate that the receptor gene can also be active in other tissues such as skin, ovaries, and axial muscle of adult zebrafish. Expression of the 5-HT2C receptor during ontogeny was found as early as 2.5hpf. Five edited adenines in the region of the human, rat and mouse mRNA that encodes the 2nd cytoplasmic loop are conserved in the zebrafish transcript. However, RNA editing was not detected in the zebrafish. The results characterize the zebrafish 5-HT2C receptor gene and gene expression pattern for the first time. The similarities to mammalian 5-HT2C receptor genes suggest the use of zebrafish for the study of 5-HT2C receptor function in behavior, development and drug discovery. [Copyright &y& Elsevier]

Atherosclerotic lesions progress through the continued recruitment of circulating blood monocytes that differentiate into macrophages within plaque. Lesion-associated macrophages are the primary immune cells present in plaque, where they take up cholesterol and store lipids in the form of small droplets resulting in a unique morphology termed foam cell. Recent scientific advances have used single-cell gene expression profiling, live-cell imaging, and fate mapping approaches to describe macrophage and monocyte contributions to pro- or anti-inflammatory mechanisms, in addition to functions of motility and proliferation within lesions. Yet, many questions regarding tissue-specific regulation of monocyte-to-macrophage differentiation and the contribution of recruited monocytes at stages of atherosclerotic disease progression remain unknown. In this review, we highlight recent advances regarding the role of monocyte and macrophage dynamics in atherosclerotic disease and identify gaps in knowledge that we hope will allow for advancing therapeutic treatment or prevention strategies for cardiovascular disease. [ABSTRACT FROM AUTHOR]

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells' inflammatory phenotype may impact obesity and its complications. [ABSTRACT FROM AUTHOR]

The success of B cell depletion therapies and identification of leptomeningeal ectopic lymphoid tissue (ELT) in patients with multiple sclerosis (MS) has renewed interest in the antibodyindependent pathogenic functions of B cells during neuroinflammation. The timing and location of B cell antigen presentation during MS and its animal model experimental autoimmune encephalomyelitis (EAE) remain undefined. Using a new EAE system that incorporates temporal regulation of MHCII expression by myelin-specific B cells, we observed the rapid formation of large B cell clusters in the spinal cord subarachnoid space. Neutrophils preceded the accumulation of meningeal B cell clusters, and inhibition of CXCR2-mediated granulocyte trafficking to the central nervous system reduced pathogenic B cell clusters and disease severity. Further, B cell-restricted very late antigen-4 (VLA-4) deficiency abrogated EAE dependent on B cell antigen presentation. Together, our findings demonstrate that neutrophils coordinate VLA-4-dependent B cell accumulation within the meninges during neuroinflammation, a key early step in the formation of ELT observed in MS. [ABSTRACT FROM AUTHOR]

Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7-/- mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs. [ABSTRACT FROM AUTHOR]

Crystalline-polarity-dependent electronic structures of gallium nitride (GaN) were studied by photoemission spectroscopy (PES) using soft and hard x-rays with different linear polarizations. A peak located near the valence band (VB) maximum was enhanced for a (0001) surface compared with that for a (0001) surface regardless of photon energy. Comparison of the VB density of states obtained by ab-initio calculations with the observed VB-PES spectra indicates that the crystalline-polarity dependence is associated with the Ga 4p and N 2p states. The most plausible origin of the crystalline-polarity-dependent VB feature is based on the photoemission phenomena of electrons in the pz -orbitals due to spontaneous electric polarization along the c-axis of GaN. [ABSTRACT FROM AUTHOR]

Myofibroblast differentiation induced by transforming growth factor-β (TGF-β) is characterized by the expression of smooth muscle α-actin (SMA) and extracellular matrix proteins. We and others have previously shown that these changes are regulated by protein kinase A (PKA). Adrenomedullin (ADM) is a vasodilator peptide that activates cAMP/PKA signaling through the calcitonin-receptor-like receptor (CRLR) and receptoractivity- modifying proteins (RAMP). In this study, we found that recombinant ADM had little effect on cAMP/PKA in quiescent human pulmonary fibroblasts, whereas it induced a profound activation of cAMP/PKA signaling in differentiated (by TGF-β) myofibroblasts. In contrast, the prostacyclin agonist iloprost was equally effective at activating PKA in both quiescent fibroblasts and differentiated myofibroblasts. TGF-β stimulated a profound expression of CRLR with a time course that mirrored the increased PKA responses to ADM. The TGF-β receptor kinase inhibitor SB431542 abolished expression of CRLR and attenuated the PKA responses of cells to ADM but not to iloprost. CRLR expression was also dramatically increased in lungs from bleomycin-treated mice. Functionally, ADM did not affect initial differentiation of quiescent fibroblasts in response to TGF-β but significantly attenuated the expression of SMA, collagen- 1, and fibronectin in pre-differentiated myofibroblasts, which was accompanied by decreased contractility of myofibroblasts. Finally, sensitization of ADM signaling by transgenic overexpression of RAMP2 in myofibroblasts resulted in enhanced survival and reduced pulmonary fibrosis in the bleomycin model of the disease. In conclusion, differentiated pulmonary myofibroblasts gain responsiveness to ADM via increased CRLR expression, suggesting the possibility of using ADM for targeting pathological myofibroblasts without affecting normal fibroblasts. [ABSTRACT FROM AUTHOR]

CD4-unhelped CD8+ T cells are functionally defective T cells primed in the absence of CD4+ T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8+ T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-stimulation through NKG2D during priming paradoxically rescues memory, but not effector, CD8+ T cell responses. NKG2D-mediated rescue is characterized by reversal of elevated transcription factor T-box expressed in T cells (T-bet) expression and recovery of interleukin-2 and interferon-? production and cytolytic responses. Rescue is abrogated in CD8+ T cells lacking NKG2D. Augmented co-stimulation through NKG2D confers a high rate of survival to mice lacking CD4+ T cells in a CD4-dependent influenza model and rescues HIV-specific CD8+ T cell responses from CD4-deficient HIV-positive donors. These findings demonstrate that augmented co-stimulation through NKG2D is effective in rescuing CD4-unhelped CD8+ T cells from their pathophysiological fate and may provide therapeutic benefits. [ABSTRACT FROM AUTHOR]

Abstract: The crystalline polarity of undoped and impurity-doped ZnO films grown on SiO2 glass substrates was investigated with the goal of achieving polarity-selective growth of ZnO films on non-crystalline substrates. We first demonstrated that hard X-ray photoelectron spectroscopy (HX-PES) is an appropriate method for determining the crystalline polarity of ZnO. We then characterized the ZnO films grown by pulsed laser deposition using HX-PES. The resulting films deposited with a 1mol% Al-doped ZnO target had the (0001) surface, whereas films grown with nominally undoped, 0.1mol% Al-doped, 1mol%Ga-doped, and 1mol% In-doped ZnO targets had the (000) surface. Since a clear polarity change due to Al-doping was seen at the ZnO/glass structure, we conclude that the essential parameter governing the polarity of the ZnO films is unlikely lattice matching (alignment of the lattice on the atomic scale) at the heterointerface between the ZnO films and substrates. [Copyright &y& Elsevier]

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS-/- and ICOSL-/- mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS-/- or ICOSL-/- mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS-/- EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS-/- CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS-/- mice were infected with influenza virus. ICOS-/- mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells. [ABSTRACT FROM AUTHOR]

Cardiac myocytes have multiple cell autonomous mechanisms that facilitate stabilization and repair of damaged sarcolemmal membranes following myocardial injury. Dysferlin is a protein which facilitates membrane repair by promoting membrane resealing. Although prior studies have shown that dysferlin-deficient (Dysf−/−) mouse hearts have an impaired recovery from acute ischemia/reperfusion (I/R) injury ex vivo, the role of dysferlin in mediating the recovery from myocardial injury in vivo is unknown. Here we show that Dysf−/− mice develop adverse LV remodeling following I/R injury secondary to the collateral damage from sustained myocardial inflammation within the infarct zone. Backcrossing Dysf−/− mice with mice lacking signaling through the Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein (Tirap−/−), attenuated inflammation and abrogated adverse LV remodeling following I/R injury. Subsequent studies using Poloxamer 188 (P188), a membrane resealing reagent, demonstrated that P188 did not attenuate inflammation nor prevent adverse LV remodeling in Dysf−/− mice following I/R injury. Viewed together these studies reveal a previously unappreciated role for the importance of membrane sealing and the resolution of inflammation following myocardial injury. [ABSTRACT FROM AUTHOR]

Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6+ macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1 + stromal cells reduced the frequency of GATA6+ macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1 + mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages. • Large cavity macrophages (LCMs) reside in peritoneal, pleural, and pericardial spaces • LCMs express the retinoic-acid-responsive transcription factor GATA6 • Wt1 + stromal cells generate retinoic acid and maintain LCM GATA6 expression • Genetic ablation of Wt1 + stroma elicits loss of LCM across cavity spaces Buechler et al. show that large cavity macrophages (LCMs), which rely on the retinoic-acid-responsive transcription factor GATA6, are found in all visceral cavity spaces. Wt1+ mesothelial and fibroblastic stromal cells maintain the LCM transcriptome in part via the generation of retinoic acid and are required for LCM homeostasis in vivo. [ABSTRACT FROM AUTHOR]

Acute rejection, a common complication of lung transplantation, may promote obliterative bronchiolitis leading to graft failure in lung transplant recipients. During acute rejection episodes, CD8+ T cells can contribute to lung epithelial injury but the mechanisms promoting and controlling CD8-mediated injury in the lung are not well understood. To study the mechanisms regulating CD8+ T cell–mediated lung rejection, we used a transgenic model in which adoptively transferred ovalbumin (OVA)-specific cytotoxic T lymphocytes (CTL) induce lung injury in mice expressing an ovalbumin transgene in the small airway epithelium of the lungs (CC10-OVA mice). The lung pathology is similar to findings in humans with acute lung transplant. In the presence of an intact immune response the inflammation resolves by day 30. Using CC10-OVA.RAG-/- mice, we found that CD4+ T cells and ICOS+/+ T cells were required for protection against lethal lung injury, while neutrophil depletion was not protective. In addition, CD4+Foxp3 + ICOS+ T cells were enriched in the lungs of animals surviving lung injury and ICOS+/+ Tregs promoted survival in animals that received ICOS-/- T cells. Direct comparison of ICOS-/- Tregs to ICOS+/+ Tregs found defects in vitro but no differences in the ability of ICOS-/- Tregs to protect from lethal lung injury. These data suggest that ICOS affects Treg development but is not necessarily required for Treg effector function. [ABSTRACT FROM AUTHOR]