189 research outputs found

    MIMO Passive Control Systems Are Not Necessarily Robust

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    Via several cases of study it is shown that a passive multivariable linear control system, contrary to its single input single output counterpart, may not be robust. Moreover, it is shown that lack of robustness can be exposed via the multivariable structure function

    TAp73 is a central transcriptional regulator of airway multiciliogenesis.

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    Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation

    Al<sub>2</sub>Pt für die Sauerstoffentwicklungsreaktion bei der Wasserspaltung: eine Strategie zur Erzeugung von Multifunktionalität in der Elektrokatalyse

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    Die Herstellung von Wasserstoff durch Wasserelektrolyse ist nur möglich, wenn wirksame und stabile Katalysatoren für die Sauerstoffentwicklungsreaktion (Oxygen Evolution Reaction, OER) verfügbar sind. Intermetallische Verbindungen mit genau definierter Kristallstruktur und elektronischen Eigenschaften sowie besonderer chemischer Bindung werden als Vorstufe für neue Werkstoffe vorgeschlagen, die interessante katalytische Eigenschaften aufweisen. Al2Pt kristallisiert im Anti‐Fluorit‐Kristallstrukturtyp und zeigt eine stark polare chemische Bindung. Platin ist hierbei katalytisch aktiv und wird auch unter den Bedingungen der Sauerstoffentwicklungsreaktion vergleichsweise wenig aus der Katalysatoroberfläche herausgelöst. Im Folgenden wird die unerwartete Leistungsfähigkeit einer Oberflächen‐Nanokomposit‐Architektur beschrieben, die aus der selbstorganisierten Umwandlung der intermetallischen Vorstufe Al2Pt resultiert. Hierbei wird insbesondere das Langzeitverhalten der katalytischen Aktivität und Stabilität unter den Bedingungen der Sauerstoffentwicklungsreaktion untersucht

    Neuropathology of 16p13.11 Deletion in Epilepsy

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    16p13.11 genomic copy number variants are implicated in several neuropsychiatric disorders, such as schizophrenia, autism, mental retardation, ADHD and epilepsy. The mechanisms leading to the diverse clinical manifestations of deletions and duplications at this locus are unknown. Most studies favour NDE1 as the leading disease-causing candidate gene at 16p13.11. In epilepsy at least, the deletion does not appear to unmask recessive-acting mutations in NDE1, with haploinsufficiency and genetic modifiers being prime candidate disease mechanisms. NDE1 encodes a protein critical to cell positioning during cortical development. As a first step, it is important to determine whether 16p13.11 copy number change translates to detectable brain structural alteration. We undertook detailed neuropathology on surgically resected brain tissue of two patients with intractable mesial temporal lobe epilepsy (MTLE), who had the same heterozygous NDE1-containing 800 kb 16p13.11 deletion, using routine histological stains and immunohistochemical markers against a range of layer-specific, white matter, neural precursor and migratory cell proteins, and NDE1 itself. Surgical temporal lobectomy samples from a MTLE case known not to have a deletion in NDE1 and three non-epilepsy cases were included as disease controls. We found that apart from a 3 mm hamartia in the temporal cortex of one MTLE case with NDE1 deletion and known hippocampal sclerosis in the other case, cortical lamination and cytoarchitecture were normal, with no differences between cases with deletion and disease controls. How 16p13.11 copy changes lead to a variety of brain diseases remains unclear, but at least in epilepsy, it would not seem to be through structural abnormality or dyslamination as judged by microscopy or immunohistochemistry. The need to integrate additional data with genetic findings to determine their significance will become more pressing as genetic technologies generate increasingly rich datasets. Detailed examination of brain tissue, where available, will be an important part of this process in neurogenetic disease specifically

    An international survey on the pragmatic management of epistaxis

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    Epistaxis is one of the most common ear, nose and throat emergencies. The management of epistaxis has evolved significantly in recent years, including the use of nasal cautery and packs. However, a correct treatment requires the knowledge of nasal anatomy, potential risks, and complications of treatment. Epistaxis is often a simple and readily treatable condition, even though a significant bleed may have potentially severe consequences. At present, there are very few guidelines concerning this topic. The current Survey explored the pragmatic approach in managing epistaxis. A questionnaire, including 7 practical questions has been used. The current International Survey on epistaxis management reported a relevant prevalence (21.7%), mainly during childhood and senescence, an important hospitalization rate (11.8%), the common use of anterior packing and electrocoagulation, and the popular prescription of a vitamin supplement and intranasal creams
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