The Influence of Organization Culture on Aviation Safety – A Case Study of a United States Navy FA-18 Landing Mishap

Aviation safety has improved dramatically in the last 50 years as evidenced by declining mishap rates. Improvements in aviation safety have come about primarily through work on two fronts; mechanical improvements (aircraft and its support systems) and human improvements (human interface, training and process interaction). Safety improvements on the hardware side of aviation have come relatively quickly and continuously, paralleling advances in engineering and science. Today’s aircraft have become extremely reliable machines with redundancy built into every system. Unfortunately, while the overall aviation mishap rate has declined, the percentage of accidents attributed to “human error” has steadily increased. Strides in the human or software side of aviation safety have not kept pace with the mechanical or hardware advances. Most think of “human error” in terms of the individual, be it pilot, controller, or mechanic. A less obvious aspect is the organizational responsibility to aviation safety. Why is one airline or squadron able to maintain a perfect safety record with the same machines and personnel available to other less successful organizations? This thesis will examine a Judge Advocate General (JAG) Investigation (written and conducted by the author) of a Landing Mishap involving a Navy FA-18 Hornet. The mishap is significant because a key causal factor was poor organizational climate. The analysis of real-world mistakes and lessons learned in a “high risk” organization will aid in identifying the warning signs of a failing organization and assist in producing some practical solutions towards improving the safety of any aviation organization

Lifting the Mood on Treating Fragile X

Only a decade ago, it was believed that a genetic diagnosis of intellectual disability and autism offered little in the way of hope for a medical treatment to lessen the burden on the affected individuals and their families. However, recent research aimed at understanding the cellular and molecular mechanisms that underlie the pathogenesis of ASD has ushered in a new era of targeted treatment strategies. Studies in fragile X syndrome (FXS) have been at the forefront of this revolution, and they are forging a path that could define future approaches to the treatment of ASD

Validation Studies of the ATLAS Pixel Detector Control System

The ATLAS pixel detector consists of 1744 identical silicon pixel modules arranged in three barrel layers providing coverage for the central region, and three disk layers on either side of the primary interaction point providing coverage of the forward regions. Once deployed into the experiment, the detector will employ optical data transfer, with the requisite powering being provided by a complex system of commercial and custom-made power supplies. However, during normal performance and production tests in the laboratory, only single modules are operated and electrical readout is used. In addition, standard laboratory power supplies are used. In contrast to these normal tests, the data discussed here was obtained from a multi-module assembly which was powered and read out using production items: the optical data path, the final design power supply system using close to final services, and the Detector Control System (DCS). To demonstrate the functionality of the pixel detector system a stepwise transition was made from the normal laboratory readout and power supply systems to the ones foreseen for the experiment, with validation of the data obtained at each transition.Comment: 8 pages, 8 figures, proceedings for the Pixel2005 worksho

A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency

SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walkup et al., 2016). For example, the ratio to PSD-95 of Transmembrane AMPA-Receptor-associated Proteins (TARPs), which mediate binding of AMPA-type glutamate receptors to PSD-95, was increased in young Syngap1+/- mice. Here we show that only females and not males show a highly significant correlation between an increase in TARP and a decrease in synGAP in the PSDs of Syngap1+/- rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency

NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease

The NMDA receptor is a Ca 2+-permeant glutamate receptor which plays key roles in health and disease. Canonical NMDARs contain two GluN2 subunits, of which 2A and 2B are predominant in the forebrain. Moreover, the relative contribution of 2A vs. 2B is controlled both developmentally and in an activity-dependent manner. The GluN2 subtype influences the biophysical properties of the receptor through difference in their N-terminal extracellular domain and transmembrane regions, but they also have large cytoplasmic Carboxyl (C)-terminal domains (CTDs) which have diverged substantially during evolution. While the CTD identity does not influence NMDAR subunit specific channel properties, it determines the nature of CTD-associated signalling molecules and has been implicated in mediating the control of subunit composition (2A vs. 2B) at the synapse. Historically, much of the research into the differential function of GluN2 CTDs has been conducted in vitro by over-expressing mutant subunits, but more recently, the generation of knock-in (KI) mouse models have allowed CTD function to be probed in vivo and in ex vivo systems without heterologous expression of GluN2 mutants. In some instances, findings involving KI mice have been in disagreement with models that were proposed based on earlier approaches. This review will examine the current research with the aim of addressing these controversies and how methodology may contribute to differences between studies. We will also discuss the outstanding questions regarding the role of GluN2 CTD sequences in regulating NMDAR subunit composition, as well as their relevance to neurodegenerative disease and neurodevelopmental disorders. </p

FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis

Synaptic vesicle (SV) recycling is essential for the maintenance of neurotransmission, with a number of neurodevelopmental disorders linked to defects in this process. Fragile X syndrome (FXS) results from a loss of fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. Hyperexcitability of neuronal circuits is a key feature of FXS, therefore we investigated whether SV recycling was affected by the absence of FMRP during increased neuronal activity. We revealed that primary neuronal cultures from male Fmr1 knock-out (KO) rats display a specific defect in activity-dependent bulk endocytosis (ADBE). ADBE is dominant during intense neuronal activity, and this defect resulted in an inability of Fmr1 KO neurons to sustain SV recycling during trains of high-frequency stimulation. Using a molecular replacement strategy, we also revealed that a human FMRP mutant that cannot bind BK channels failed to correct ADBE dysfunction in KO neurons, however this dysfunction was corrected by BK channel agonists. Therefore, FMRP performs a key role in sustaining neurotransmitter release via selective control of ADBE, suggesting intervention via this endocytosis mode may correct the hyperexcitability observed in FXS. SIGNIFICANCE STATEMENT Loss of fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), however whether its loss has a direct role in neurotransmitter release remains a matter of debate. We demonstrate that neurons lacking FMRP display a specific defect in a mechanism that sustains neurotransmitter release during intense neuronal firing, called activity-dependent bulk endocytosis (ADBE). This discovery provides key insights into mechanisms of brain communication that occur because of loss of FMRP function. Importantly it also reveals ADBE as a potential therapeutic target to correct the circuit hyperexcitability observed in FXS

Virtual and augmented reality. TAB-Fokus

VR and AR technologies have progressed to the point where an increased diffusion into different fields of application takes place. The use of VR requires specific hardware, whereas many AR applications can be used with smartphones or tablets. In addition to consumer markets, industrial fields of application are also increasingly being tapped. While German research makes a decisive contribution to VR and AR development, German industry has difficulty exploiting VR and AR. The use of VR implies legal and ethical issues that are still largely unresolved

New Space – new dynamics in space exploration. TAB-Fokus

New Space refers to dynamics of innovation in space exploration that are driven by the private sector. New business areas are emerging due to an easier access to and use of space. Around the world, there are different approaches to encourage the development of New Space companies. In this context, national space agencies play a central role. The German space and New Space ecosystem is considered an innovation driver and technology developer for European space exploration. In international comparison, however, its competitiveness is less pronounced. A lack of venture capital, unclear regulatory framework conditions and insufficient transfer of technologies and data to non-space industries hinder growth in the space industry through New Space players. New financing instruments, a national space law as well as the consideration of the specific dynamics and requirements of space companies in political strategies might strengthen the New Space sector and the space industry in Germany

Epilepsy-related CDKL5 deficiency slows synaptic vesicle endocytosis in central nerve terminals

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe early-onset epileptic encephalopathy resulting mainly from de novo mutations in the X-linked CDKL5 gene. To determine whether loss of presynaptic CDKL5 function contributes to CDD, we examined synaptic vesicle (SV) recycling in primary hippocampal neurons generated from Cdkl5 knockout rat males. Using a genetically encoded reporter, we revealed that CDKL5 is selectively required for efficient SV endocytosis. We showed that CDKL5 kinase activity is both necessary and sufficient for optimal SV endocytosis, since kinase-inactive mutations failed to correct endocytosis in Cdkl5 knockout neurons, whereas the isolated CDKL5 kinase domain fully restored SV endocytosis kinetics. Finally, we demonstrated that CDKL5-mediated phosphorylation of amphiphysin 1, a putative presynaptic target, is not required for CDKL5-dependent control of SV endocytosis. Overall, our findings reveal a key presynaptic role for CDKL5 kinase activity and enhance our insight into how its dysfunction may culminate in CDD. SIGNIFICANCE STATEMENT Loss of cyclin-dependent kinase like 5 (CDKL5) function is a leading cause of monogenic childhood epileptic encephalopathy. However, information regarding its biological role is scarce. In this study, we reveal a selective presynaptic role for CDKL5 in synaptic vesicle endocytosis and that its protein kinase activity is both necessary and sufficient for this role. The isolated protein kinase domain is sufficient to correct this loss of function, which may facilitate future gene therapy strategies if presynaptic dysfunction is proven to be central to the disorder. It also reveals that a CDKL5-specific substrate is located at the presynapse, the phosphorylation of which is required for optimal SV endocytosis. </p

Big Social Data – die gesellschaftspolitische Dimension von Prognose- und Ratingalgorithmen

Das Thema Big Social Data umfasst technologische Ansätze zur Sammlung, Verknüpfung und Auswertung personenbezogener und semantisch reichhaltiger Daten sowie daran geknüpfte Verwertungszusammenhänge. Die Bedeutung von Big Social Data für die Wirtschaft des 21. Jahrhunderts ist eng mit dem prägenden Einfluss von Firmen wie Google oder Facebook verknüpft, deren Geschäftsmodelle im Wesentlichen auf der umfassenden Erhebung und kommerziellen Verwertung von Nutzerdaten basieren. Dabei werden möglichst viele der Spuren und Informationen, die Nutzer digitaler Dienste und Plattformen im Internet hinterlassen, gesammelt und zu individuellen oder Gruppenprofilen verdichtet. Diese bilden die Grundlage für eine möglichst gezielte Aufmerksamkeitssteuerung oder die Vorhersage individueller Verhaltens- und Entscheidungsmuster, die beispielsweise für die Platzierung personalisierter Werbung genutzt werden können. Ein vergleichsweise neues Phänomen bildet die Übertragung dieser Funktionsprinzipien und Technologien auf Gesellschaftsbereiche, in denen die umfassende Sammlung und Auswertung personenbezogener Daten durch Ratingund Vorhersagealgorithmen – noch stärker, als dies in kommerziellen Zusammenhängen der Fall sein kann – mit individueller Überwachung und Verhaltenskontrolle in Verbindung gebracht wird. Die strukturierte Analyse persönlicher Daten, die im Kontext von Finanztransaktionen, Mobilitätsverhalten oder sozialen Netzwerken erhoben werden, kann sich direkt auf Handlungsmöglichkeiten und Lebensumstände der Nutzer auswirken. Beispiele, wie die Pläne zur Einführung eines flächendeckenden Sozialkreditsystems in der Volksrepublik China oder die durch Software beeinflusste Bemessung von Haftstrafen bei einigen US-amerikanischen Gerichten, belegen bereits heute die gesellschaftliche Tragweite dieser Entwicklungen. Existieren im internationalen Kontext also bereits Anwendungen, in denen der Einsatz von Rating- und Vorhersagealgorithmen unter Nutzung von Big Social Data zu einer digitalen Stigmatisierung Einzelner führen kann, ist deren sozialpolitische Brisanz in Deutschland aktuell noch eher gering. Dennoch lassen sich beispielsweise im Kontext von Kreditvergaben oder der Personalisierung politischer Inhalte (Nachrichten, Werbung etc.) in sozialen Netzwerken bereits erste Implikationen für die hiesige Bevölkerung beobachten. Inwiefern daraus resultierende gesellschaftliche Risiken auch in Deutschland an Bedeutung gewinnen werden, wird entscheidend durch das Geschäftsgebaren der auf Datenerhebung, -auswertung und -handel spezialisierten Unternehmen beeinflusst. Eine staatliche Regulierung scheint gegebenenfalls geboten, um mögliche negative Effekte von Big Social Data zu begrenzen