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Weltentwicklungspolitik – Aufgabe kompetenter und demokratisch legitimierter Globaler Staatlichkeit
(2010)
Usable Security und Privacy
(2010)
Wesch D, Miranda P, Afonso-Oramas D, Althaus M, Castro-Hernandez J, Dominguez J, Morty RE, Clauss W, Gonzalez-Hernandez T, Alvarez de la Rosa D, Giraldez T. The neuronalspecific SGK1.1 kinase regulates delta-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling. Am J Physiol Cell Physiol 299: C779-C790, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00184.2010.-The delta-subunit of the epithelial Na+ channel (ENaC) is expressed in neurons of the human and monkey central nervous system and forms voltage-independent, amiloride-sensitive Na+ channels when expressed in heterologous systems. It has been proposed that delta-ENaC could affect neuronal excitability and participate in the transduction of ischemic signals during hypoxia or inflammation. The regulation of delta-ENaC activity is poorly understood. ENaC channels in kidney epithelial cells are regulated by the serum-and glucocorticoid-induced kinase 1 (SGK1). Recently, a new isoform of this kinase (SGK1.1) has been described in the central nervous system. Here we show that delta-ENaC isoforms and SGK1.1 are coexpressed in pyramidal neurons of the human and monkey (Macaca fascicularis) cerebral cortex. Coexpression of delta beta gamma-ENaC and SGK1.1 in Xenopus oocytes increases amiloride-sensitive current and channel plasma membrane abundance. The kinase also exerts its effect when delta-subunits are expressed alone, indicating that the process is not dependent on accessory subunits or the presence of PY motifs in the channel. Furthermore, SGK1.1 action depends on its enzymatic activity and binding to phosphatidylinositol(4,5)-bisphosphate. Physiological or pharmacological activation of phospholipase C abrogates SGK1.1 interaction with the plasma membrane and modulation of delta-ENaC. Our data support a physiological role for SGK1.1 in the regulation of delta-ENaC through a pathway that differs from the classical one and suggest that the kinase could serve as an integrator of different signaling pathways converging on the channel.
One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors.
Environment monitoring using multiple observation cameras is increasingly popular. Different techniques exist to visualize the incoming video streams, but only few evaluations are available to find the best suitable one for a given task and context. This article compares three techniques for browsing video feeds from cameras that are located around the user in an unstructured manner. The techniques allow mobile users to gain extra information about the surroundings, the objects and the actors in the environment by observing a site from different perspectives. The techniques relate local and remote cameras topologically, via a tunnel, or via bird's eye viewpoint. Their common goal is to enhance spatial awareness of the viewer, without relying on a model or previous knowledge of the environment. We introduce several factors of spatial awareness inherent to multi-camera systems, and present a comparative evaluation of the proposed techniques with respect to spatial understanding and workload.
The aim of the study was to develop a method for fast and reliable diagnosis of peroxisomal diseases and to facilitate differential diagnosis of cholestatic hepatopathy. For the quantification of bile acids and their conjugates as well as C(27) precursors di- and trihydroxycholestanoic acid (DHCA, THCA), in small pediatric blood samples we combined HPLC separation on a reverse-phase C18 column with ESI-MS/MS analysis in the negative ion mode. Analysis was done with good precision (CV 3,7%-11.1%) and sufficient sensitivity (LOQ: 11-91 nmol/L) without derivatization. Complete analysis of 17 free and conjugated bile acids from dried blood spots and 10 microL serum samples, respectively, was performed within 12 min. Measurement of conjugated primary bile acids plus DHCA and THCA as well as ursodeoxycholic acid was done in 4.5 min. In blood spots of healthy newborns, conjugated primary bile acids were found in the range of 0.01 to 2.01 micromol/L. Concentrations of C(27) precursors were below the detection limit in normal controls. DHCA and THCA were specifically elevated in cases of peroxysomal defects and one Zellweger patient.
When entering a password (or other secrets) the typed input is most commonly masked, i.e. the characters are hidden behind bullets or asterisks. This, however, complicates the input and highly decreases the user's confident causing several issues such as login failure attempts. On the other hand, password masking is an important security requirement for a lot of applications and contexts to prevent a third person to read the password. Thus, simply dropping password masking is not feasible in general. A common solution provides the user with the choice of toggling password masking on and off, but due to distinct defaults (in dependency of the application and context) this is rather complex and confusing. Enhanced password visualization technologies beyond the simple masking of passwords can provide more sophisticated solutions from both a usability and security perspective. In this paper, available password visualization technologies are presented and discussed. Furthermore a novel password visualization approach is introduced, the TransparentMask, which provides unique properties in comparison to the existing schemes. Amongst these are the ability to detect mistakes while typing and being able to localize and correct the typo within a certain range. Finally, a security analysis of the TransparentMask shows that the protection level given by a certain password length is slightly decreased in comparison to the fully masked approach.