The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

前开口无绷绳自举式钻机的结构和特点

阐述了前开口无绷绳自举式钻机的设计要求，分析了该钻机的结构特点。钻机的型式和基本参数符合SY／T5609—1999标准。各主要设备设计制造符合API相关规范及HSE的要求。该钻机可满足在钻井地域面积有限的情况下的使用要求，其特点及适用性时今后钻机的发展有一定的借鉴。     

Quality assessment of SRTM C- and X-band interferometric data: Implications for the retrieval of vegetation canopy height

The Shuttle Radar Topography Mission distinguished itself as the first near-global spaceborne mission to demonstrate direct sensitivity to vertical vegetation structure. Whether this sensitivity is viewed as exploitable signal or unwanted bias, a great deal of interest exists in retrieving vegetation canopy height information from the SRTM data. This study presents a comprehensive application-specific assessment of SRTM data quality, focusing on the characterization and mitigation of two primary sources of relative vertical error: uncompensated Shuttle mast motion and random phase noise. The assessment spans four test sites located in the upper Midwestern United States and examines the dependence of data quality on both frequency, i.e., C-band vs. X-band, and the number of acquired datatakes. The results indicate that the quality of SRTM data may be higher than previously thought. Novel mitigation strategies include a knowledge-based approach to sample averaging, which has the potential to reduce phase noise error by 43 to 80%. The strategies presented here are being implemented as part of an ongoing effort to produce regional- to continental-scale estimates of vegetation canopy height within the conterminous U.S.     

钻井井架力学性能分析

钻井井架作为钻机系统设备中的关键部分,其力学性能直接关系到整套钻机系统的安全生产。文章推导了常用于分析钻井井架力学性能的理论,即线性屈曲、几何非线性和双重非线性理论。提出同时用这三种理论对钻井井架进行综合比较分析,从而合理地预见井架力学性能的方法。以A形钻井井架为例,进行了详细的分析,得到了井架的失稳形式、极限承载、破坏特征及薄弱部位,为钻井井架的设计、优化与评定提供了参考。     

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

三边形桅杆风荷载谱模型试验研究

对三边形格构式桅杆进行了均匀流和两种紊流下的高频测力天平风洞试验,得到了顺风向、横风向和扭转向的气动力系数以及脉动风荷载谱。采用基于风速谱的数学模型对顺风向脉动风荷载谱进行拟合,验证了该经验公式在不同流场下的适用性。根据试验所得横风向和扭转向脉动风荷载功率谱曲线的特点,建立由紊流激励和旋涡脱落激励两部分组成的谱函数数学模型,最小二乘法拟合结果与风洞试验结果吻合良好。横风向脉动风荷载谱以紊流激励为主,紊流强度15%时旋涡脱落激励贡献仅占10%,扭转向脉动风荷载谱中旋涡脱落激励贡献明显增大,达到40%。     

5 nm Silver Nanoparticles Amplify Clinical Features of Atopic Dermatitis in Mice by Activating Mast Cells

The triggering effect of silver nanoparticles (NPs) on the induction of allergic reactions is evaluated, by studying the activation of mast cells and the clinical features of atopic dermatitis in a mouse model. Granule release is induced in RBL‐2H3 mast cells by 5 nm, but not 100 nm silver NPs. Increases in the levels of reactive oxygen species (hydrogen peroxide and mitochondrial superoxide) and intracellular Ca⁺⁺ in mast cells are induced by 5 nm silver NPs. In a mouse model of atopic dermatitis induced by a mite allergen, the skin lesions are more severe and appear earlier in mice treated simultaneously with 5 nm silver NPs and allergen compared with mice treated with allergen alone or 100 nm silver NPs and allergen. The histological findings reveal that number of tryptase‐positive mast cells and total IgE levels in the serum increase in mice treated with 5 nm silver NPs and allergen. The results in this study indicate that cotreatment with 5 nm silver NPs stimulates mast cell degranulation and induces earlier and more severe clinical alterations in allergy‐prone individuals.     

桅杆型光电探测系统总体可靠性分配与校核研究

对某桅杆型光电探测系统研制过程中的可靠性分析、分配与校核问题进行了研究。对载车型桅杆式光电系统总体的可靠性进行了合理分配,并对高架光电探测系统进行了半实物仿真成像试验,在满足0.01°探测精度的要求下对系统的可靠性进行了48h的不间断验证,得到系统最大方位误差0.008°的结果,认为本系统总体可靠性分配合理有效。