Search results for "ADAM"
showing 10 items of 372 documents
Strategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution
2021
For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor α (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a n…
Dimeric Capsules Formed by Tetra-CMPO Derivatives of (Thia)Calix[4]arenes
2010
Thiacalix[4]arene 2, calix[4]arene 3 a and its tetraether fixed in the cone conformation 3 b form homo- and heterodimeric capsules in apolar solvents, which are held together by a seam of NH⋅⋅⋅O=P hydrogen bonds between carbamoylmethyl phospine oxide functions attached to their wide rim. Their internal volume of ∼370 A3 requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes (1H- and 31P-time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (ΔG=42.5 and 49.7 kJ mol−1 for 3 a and 3 b) than that f…
A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura
2020
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by inhibitory autoantibodies against ADAMTS13 protein. Until recently, the combination of plasma exchange (PEX) and immunosuppression has been the standard front-line treatment in this disorder. However, aTTP-related mortality, refractoriness, and relapse are still a matter of concern. Areas covered: The better understanding of the pathophysiological mechanisms of aTTP has allowed substantial improvements in the diagnosis and treatment of this disease. Recently, the novel anti-VWF nanobody caplacizumab has been approved for acute episodes of aTTP. Caplacizumab is capable to block the adh…
COVID-19 as a Potential Trigger for Immune Thrombotic Thrombocytopenic Purpura and Reason for an Unusual Treatment: A Case Report
2021
AbstractImmune thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder characterized by severely reduced activity of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to autoantibodies. This leads to the development of pathogenic multimers of VWF, causing a thrombotic microangiopathy with decreased number of platelets, hemolysis, and life-threatening tissue ischemia of mostly brain, heart, and kidneys. Standard treatment of iTTP involves daily plasma exchange to remove ultra large multimers of VWF, inhibitors, substituting ADAMTS13, and the accompaniment of an immunosuppressive …
Polysemy and Search for Meaning in Dea Loher’s Adam Geist
2018
En el presente trabajo se analizan tanto el desmoronamiento del sentido como la búsqueda subsiguiente de este en relación con el protagonista de la obra teatral de la dramaturga alemana Dea Loher, Adam Geist (1998). Al desmoronarse el sentido, la realidad del protagonista deviene indeterminable y polisémica. El personaje adopta una variedad de identidades para contraponerse a esta nueva realidad. La lógica espacio-temporal se destruye y, a causa de ello, se genera una expansión espacial y una compresión temporal a las que debe adaptarse el protagonista.
Improved Switching Strategy for Selective Harmonic Elimination in DC-AC Signal Generation via Pulse-Width Modulation
2013
Published version of an article in the journal: Abstract and Applied Analysis. Also available from the publisher at: http://dx.doi.org/10.1155/2013/870904 Open Access We present an advanced design methodology for pulse-width-modulated (PWM) DC-AC signal generation. Using design methods based on the Walsh transform, AC sinusoidal signals can be approximated by suitable PWM signals. For different AC amplitudes, the switching instants of the PWM signals can be efficiently computed by using appropriate systems of explicit linear equations. However, the equation systems provided by conventional implementations of this approach are typically only valid for a restricted interval of AC amplitudes a…
Recensione a: «Devotionis munus». La cultura e l’opera di Adamo di Brema, a cura di R. Scarcia - F. Stok, Pisa 2010, in «Mediaeval Sophia» 11 (gennai…
2012
Si tratta di una recensione al vol. «Devotionis munus». La cultura e l’opera di Adamo di Brema, a cura di R. Scarcia e F. Stok, pubblicato a Pisa nel 2010, e contenente gli atti di un Convegno dedicato allo scrittore mediolatino Adamo di Brema, autore dei «Gesta Hammaburgensis Ecclesiae».
Pharmacologic Inhibition of ADAM10 Attenuates Brain Tissue Loss, Axonal Injury and Pro-inflammatory Gene Expression Following Traumatic Brain Injury …
2021
The α-secretase A disintegrin and metalloprotease 10 (ADAM10) regulates various physiological and pathophysiological processes. Despite its broad functional implications during development, plasticity, and disease, no pharmacological approaches to inhibit ADAM10 in acute brain injury have been reported. Here, we examined the effects of the ADAM10 inhibitor GI254023X on the neurological and histopathological outcome after experimental traumatic brain injury (TBI). C57BL/6N mice were subjected to the controlled cortical impact (CCI) model of TBI or sham procedure and received GI254023X or vehicle during the acute phase of injury (n = 40, 100 mg/kg, 25% DMSO, 0.1 M Na2CO3, intraperitoneal, 30 …
« Mouvement est nécessité » Pour une relation au monde du mouvement et de la musique
2021
Starting from a stationary state in order to feed a process, the idea of movement in music can affect both the sound material and the listening (the Hoerspiel...), both the view (musical theater) and the ancillary disciplines (dance or maping-video)... Based on examples taken in the 20th and 21st centuries (Debussy, Berg, Webern, Stravinsky, Stockhausen, Kagel, Ferrari, La Monte Young, Xenakis, Adams, De Chizy, De Mey, Trapani?), musicological study ultimately deduces that the metaphor of movement is for man an experience considered fundamental to his particular relationship to the world.
Hermenéutica crítica desde la facticidad de la experiencia
2008
Se intenta mostrar, primero, el sentido de la hermeéutica transcendental de K.O.Apel para transformar por vía herméneutica la fi losofía kantiana y también su conexión con el giro hermenéutico, tanto nietzscheano como gadameriano en una razón experiencial.