36,848 research outputs found
Existential muck: Romantic borderlessness and dissolving dualisms in Schiller's die Räuber
The essay investigates Romantic tendencies in Schiller's inaugural drama, Die Räuber [The Robbers]. The play's overt discourse of dualism and exchange rests on a more viscous foundation of existential muck. Franz von Moor's "morastige Zirkel der menschlichen Bestimmung" [muckish cycle of human determination] is a cyclical solvent that engulfs the play's dualisms and dissolves opposition and exchange. Forms rise from the muck, taking on borders (dimensions, limits) and they descend back into the muck, becoming once more borderless. This may be the other side of an all-encompassing Freude [Joy], both originary and terminal, yet as "alle Menschen werden Brüder" [all people become brothers], we are reminded of what it means to be brothers in the Moor clan. As a belated product of the proto-Romanticism of the Sturm und Drang, Schiller's 1781 play is a specimen of retro-proto-Romanticism
Allergens, germs and asthma
Objective
To explore asthma pathogenesis using data from upper and lower airways.
Data Source
English-language papers on human asthma and nasal polyp subjects from 1990 onwards.
Study Selection
High-quality studies in established journals.
Results
The recognition of its inflammatory nature led to a quantum leap in the understanding and treatment of asthma, with lives saved by inhaled corticosteroids. Further work at genetic, molecular, histological and clinical levels has shown that asthma is polymorphic and rarely involves isolated Th2 bronchial inflammation.
Viral infections may act as an initiating event in children and adults, showing synergy with atopy. Chronic staphylococcal colonization of the mucosa may act as a promoter, as in atopic dermatitis. These two observations may be linked, with viruses providing an entry for bacteria into the mucosal epithelium.
Conclusions
Most asthma begins in the nose and involves allergy and infection: both viral and bacterial. The combination of atopy and infection suggests new possibilities for therapy
Effective of Passive Devices in Alleviation of Flow-induced oscillations of he nozzles of a Multi-Booster Launch vehicle
Wind tunnel tests to quantify the flow induced oscillations of nozzles of strap-on boosters of a typical launch vehicle
have been performed under jet-off conditions in the Mach number range 0.8 to 2.5. The effects of gymballing the nozzles on the steady and unsteady radial and tangential moments acting at the simulated position of gymbal actuators have been studied. The loads are seen to increase as the gymbal angle increases. The effectiveness of various load alleviating passive devices in reducing steady and unsteady loads was evaluated. The most effective device was found to be a semi-circular segment. The spectra of unsteady moments indicate that the loads alleviating devices do not significantly alter the magnitude as compared to that of the baseline data
Novel factors of Anopheles gambiae haemocyte immune response to Plasmodium berghei infection
Background Insect haemocytes mediate cellular immune responses (e.g., phagocytosis) and contribute to the synthesis of humoral immune factors. In previous work, a genome-wide molecular characterization of Anopheles gambiae circulating haemocytes was followed by functional gene characterization using cell-based RNAi screens. Assays were carried out to investigate the role of selected haemocyte-specific or enriched genes in phagocytosis of bacterial bio-particles, expression of the antimicrobial peptide cecropin1, and basal and induced expression of the mosquito complement factor LRIM1 (leucine-rich repeat immune gene I). Findings Here we studied the impact of a subset of genes (37 candidates) from the haemocyte-specific dsRNA collection on the development of Plasmodium in the mosquito by in vivo gene silencing. Our screening identifies 10 novel factors with a role in the mosquito response to Plasmodium. Analysis of in vivo screening phenotypes reveals a significant anti-correlation between the prevalence of oocysts and melanised ookinetes. Conclusions Among novel immune genes are putative pattern recognition proteins (leucine-rich repeat, fibrinogen-domain and R-type lectins), immune modulation and signalling proteins (LPS-induced tumor necrosis factor alpha factor, LITAF and CLIP proteases), and components of extracellular matrix such as laminin and collagen. Additional identified proteins such as the storage protein hexamerin and vesicular-type ATPase (V-ATPase) are associated for the first time with the mosquito response against Plasmodium
New approaches in detection and treatment of familial hypercholesterolemia
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that clinically leads to increased low density lipoprotein-cholesterol (LDL-C) levels. As a consequence, FH patients are at high risk for cardiovascular disease (CVD). Mutations are found in genes coding for the LDLR, apoB, and PCSK9, although FH cannot be ruled out in the absence of a mutation in one of these genes. It is pivotal to diagnose FH at an early age, since lipid lowering results in a decreased risk of cardiovascular complications especially if initiated early, but unfortunately FH is largely underdiagnosed. While a number of clinical criteria are available, identification of a pathogenic mutation in any of the three aforementioned genes is seen by many as a way to establish a definitive diagnosis of FH. It should be remembered that clinical treatment is based on LDL-C levels and not solely on presence or absence of genetic mutations as LDL-C is what drives risk. Traditionally, mutation detection has been done by means of dideoxy sequencing. However, novel molecular testing methods are gradually being introduced. These next generation sequencing-based methods are likely to be applied on broader scale once their efficacy and effect on cost are being established. Statins are the first-line therapy of choice for FH patients as they have been proven to reduce CVD risk across a range of conditions including hypercholesterolemia (though not specifically tested in FH). However, in a significant proportion of FH patients LDL-C goals are not met, despite the use of maximal statin doses and additional lipid-lowering therapies. This underlines the need for additional therapies, and inhibition of PCSK9 and CETP is among the most promising new therapeutic options. In this review, we aim to provide an overview of the latest information about the definition, diagnosis, screening, and current and novel therapies for F
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Oxygen targeting in preterm infants: a physiological interpretation.
Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare 'target SpO2 ranges'. In spite of this overlap, some of the studies did find significant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 <85 or >95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (<85% SpO2) and hyperoxemia (>95% SpO2)
B-cell Prolymphocytic Leukemia in a Young Male
B-cell prolymphocytic leukemia [B-PLL] is a neoplasm of B prolymphocytes affecting the peripheral blood, bone marrow and spleen. The principal disease characteristics are massive splenomegaly with absent or minimal peripheral lymphadenopathy and a rapidly rising lymphocyte count. Here, we report a case of B-PLL in a 42 year old male who had come for routine health check up
Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF
Injury to peripheral nerves results in the infiltration of immune cells, which remove axonal- and myelin-derived material. Schwann cells could play a key role in this process by regulating macrophage infiltration. We show here that medium conditioned by primary denervated Schwann cells or the Schwannoma cell line RN22 produces chemotactic activity for macrophages. The presence of blocking antibodies to macrophage chemoattractant protein-1 (MCP-1) or leukemia inhibitory factor (LIF) reduced this activity to similar to35 and 65% of control levels, respectively, and only 15% remained in the presence of both antibodies. The presence of chemotactic LIF in Schwann cell-conditioned medium was confirmed by using cells from lif-/- mice. Although interleukin-6 (IL-6) is not itself a chemotactic factor, we found that medium from il-6-/- nerves showed only 40% of the activity secreted by wild-type nerves. Furthermore, IL-6 rapidly induced LIF mRNA in primary Schwann cells, and LIF rapidly induced MCP-1 mRNA expression. Treatment of RN22 Schwannoma cells with IL-6 or LIF enhanced the secretion of the chemotactic activity of these cells.These observations show that Schwann cells attract macrophages by secreting MCP-1 and LIF. They also provide evidence for an autocrine-signaling cascade involving IL-6, LIF, and MCP-1, which amplifies the Schwann cell-derived chemotactic signals gradually, in agreement with the delayed entry of macrophages to injured nerves
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