Pressure element of constant logarithmic stiffness for temperature compensated altimeter

The usual type of altimeter contains a pressure element, the deflections of which are approximately proportional to pressure changes. An evenly divided altitude scale is secured by using a mechanism between the pressure element and pointer which gives the required motion of the pointer. A temperature-compensated altimeter was constructed at the Bureau of Standards for the Bureau of Aeronautics of the Navy Department which contained a manually operated device for controlling the multiplication of the mechanism to the extent necessary for temperature compensation. The introduction of this device made it difficult to adjust the multiplying mechanism to fit an evenly divided altitude scale. To meet this difficulty a pressure element was designed and constructed which gave deflections which were proportional to altitude; that is, to the logarithm of the pressure. The element consisted of a metal bellows of the sylphon type coupled to an internal helical spring which was designed so as to have a variable number of active coils. This report presents a description of and laboratory data relating to the special pressure element for the altimeter. In addition equations which apply generally to springs and pressure elements of constant logarithmic stiffness are developed, including the deflection and the spacing between the coils in terms of the constants of the helical spring and pressure elements. (author

House dust mite induced allergic airway disease is attenuated in CD11ccreIL-4Rα−/l°x mice

Abstract The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα−/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα−/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge. In the OVA/alum model, CD11ccreIL-4Rα−/lox mice had similar airway hyperreactivity, eosinophil infiltration, Th2-type cytokine production and mucus hypersecretion to littermate controls. When alum was omitted during sensitization, CD11ccreIL-4Rα−/lox mice had similar airway hyperreactivity and mucus secretion but reduced Th2-type cytokine production and eosinophils, suggesting alum overrides the requirement for IL-4Rα signaling on CD11c+ cells in enhancing Th2-type responses. In the house dust mite model, CD11ccreIL-4Rα−/lox mice showed similar mucus secretion, but reduced Th2 responses, eosinophils, neutrophils and airway hyperreactivity, unlike previously tested LysMcreIL-4Rα−/lox mice, which lack IL-4Rα on alveolar macrophages but not on dendritic cells. Therefore, our results indicate that IL-4Rα signaling on dendritic cells promotes allergen-induced Th2 responses and eosinophil infiltration into the lung

Comparative trial with highly purified natural ACTH, synthetic ACTH 1—24 peptide and synthetic ACTH 1—39 peptide

Peer Reviewe

Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice.

We recently demonstrated that statins mediate protection against intracellular pathogens, Mycobacterium tuberculosis and Listeria monocytogenes in mice. Here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by Leishmania major (LV39). In an ear infection model, topical application of simvastatin directly on established lesions significantly reduced severity of the disease reflected by ear lesion size and ulceration. The host protective effect was further accompanied by decreased parasite burden in the ear and draining lymph nodes in both BALB/c and C57BL/6 mice. Pre-treatment of these mice on a low-fat cholesterol diet and systemic simvastatin also reduced footpad swelling, as well as parasite burdens and ulceration/necrosis in the more robust footpad infection model, demonstrating the prophylactic potential of simvastatin for cutaneous leishmaniasis. Mechanistically, following L. major infection, simvastatin-treated primary macrophages responded with significantly reduced cholesterol levels and increased production of hydrogen peroxide. Furthermore, simvastatin-treated macrophages displayed enhanced phagosome maturation, as revealed by increased LAMP-3 expression in fluorescent microscopy and Western blot analysis. These findings demonstrate that simvastatin treatment enhances host protection against L. major by increasing macrophage phagosome maturation and killing effector functions

IL-13 Signals Independent of IL-4 Receptor-Alpha Chain to Drive Ovalbumin-Induced Dermatitis

Atopic dermatitis (AD) is an allergic skin condition that can result from intrinsic genetic factors or repetitive occupational damage. Disruption of the skin barrier leads to sensitization to allergens followed by local inflammation (Leung et al., 2004, Pigatto et al., 1992). Strong evidence has shown that the T helper-2 (Th2) cytokine, IL-13, is the dominant disease-causing factor in the pathogenesis of AD in mice (Nieuwenhuizen et al., 2009, Sivaprasad et al., 2010, Tazawa et al., 2004). Hence, it is possible that patients with AD would benefit from treatments specifically targeting IL-13 signaling pathways. However, current treatment strategies are limited to broader therapies, such as emollients, topical glucocorticoids, and calcineurin inhibitors (Beck et al., 2014, De Benedetto et al., 2012, Gittler et al., 2012). A recent study by Beck et al. (2014), which used the monoclonal antibody dupilumab to block IL-4 receptor-alpha (IL-4Rα) signaling, showed promise in targeting specific immunological pathways. Until recently, IL-13 was thought to signal only through the IL-4Rα/IL-13Rα1 complex; however, recent data suggest that IL-13 may also signal via IL-13Rα2, previously known as a decoy receptor. In AD, the signaling pathway of IL-13 remains to be defined. In this study we addressed this problem by using a combination of IL-4Rα–deficient mice that lacked or overexpressed IL-13 to determine if IL-13 can signal independently of the IL-4Rα chain to mediate AD. Our results may have potential implications for therapeutic strategies, such as using IL-4Rα–antagonists to treat the disease.National Research Foundation (South Africa

eredeti vigjáték 3 felvonásban - irta Tóth Kálmán

Debreceni Nemzeti Színház. Szerdán Április 11-kén 1866. Szathmáry Károly, a pesti nemzeti szinház volt tagja, mint vendég. Szakál Rózsa, szerződött tag első fellépteDebreceni Egyetem Egyetemi és Nemzeti Könyvtá

IL-4Rα Signaling in Keratinocytes and Early IL-4 Production Are Dispensable for Generating a Curative T Helper 1 Response in Leishmania major-Infected C57BL/6 Mice.

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major