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This study deals with the in-situ detection of volume fractions of melt in labradorite and basalt at 0.3 GPa pressure and temperatures ranging from 400–1500 °C. Methods used were frequency dependent electrical conductivity (EC) and energy dispersive X-ray diffraction (EDX). These techniques allowed melt fraction determination under in-situ pressure and temperature conditions, while optical analysis (SEM) was performed on quenched samples. EC allowed detecting melt frac- tions as low as 0.03 due to changes in dielectric properties. Increasing melt fractions caused the formerly isolated melt bubbles to interconnect along grain boundaries, thus increasing the bulk conductivity. Electrical conductivity thus provides a measure for both, the formation of melt (dielectric property) and the degree of interconnection of melt (bulk conductivity). Energy dispersive X-ray diffraction experiments (EDX) provided an additional measure for the volume fraction of melt. EDX diffraction data were used to calculate the volume fraction of melt on the basis of the peak to background ratio. In a final step the experimental data (SEM, EC, EDX) were compared with geometric models of melt distribution, namely the Archie-, cube-, tube-, Hashin-Shtrikman HS + and HS - model. The electrical "polarisability" data closely fit the HS + model, while bulk conductivity data were found to be less sensitive for melt fraction detection.
Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases
(2017)
ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss-of-function resulted in increased levels of H3K4me3, which co-precipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches.
This article analyzes how humanitarian and/or development organizations acting as intermediaries between scientists and vulnerable populations aim to make environmental changes visible while trying to meet local needs and demands for sustainable livelihoods. Based on an in-depth organizational case study in Southern Thailand, the research analyses the use of visualization tools to foster environmental knowledge and literacy while supporting both policymaking as well as citizen engagement. Drawing on insights from sociology of organizations, the study discusses the organizational reasons for the use of visualization tools, outlining the underlying coercive, mimetic and normative pressures that facilitate their proliferation in the context of environmental communication. The results show that both the participatory approach as well as the use of audiovisual and digital tools to communicate project goals and results have become indispensable and institutionalized tools in the organizational field of humanitarian and development aid. In this context, organizations have become intermediaries and translators between ‘climate risk’ scientists and ‘at risk’ people, thus, facilitating environmental communication. The results show that questions of trust and ownership of ideas play an important role in the context of livelihood related projects linked to climate change adaptation. In this context, not only does the style and content of communication, but also the relationship between the parties who communicate, have an impact upon the success or failure of managing options in climate change adaptation.
Enterprises demand universities not to limit education to theoretical knowledge, but instead, to prepare students for future challenges in the job. While demanding a focus on current technologies and practices appears reasonable, it contradicts academia’s general focus on sustainable knowledge. This “conflict-ofinterest” can be bridged through extra-curricular professional training. MOOCs are hyped as solution because they allow to simultaneously addressing masses of students. However, with the increasing number of learners, anonymity in education increases and first-level support decreases. Within the extracurricular online program erp4students we found that individual support is considered most relevant to successfully complete professional training.
"Bad usability equals no customer" – Mit diesem Zitat bringt Jakob Nielsen die große Bedeutung guter Usability auf den Punkt. Auch wenn Nielsen kommerzielle Unternehmen im Auge hat, so lässt sich auch für Bibliotheken die Relevanz ihres Webauftritts für den Kontakt zu ihren Benutzern oder potentiellen Benutzern nicht leugnen. In diesem Artikel soll dargestellt werden, wie Bibliotheken mit Hilfe von Usability-Tests die Schwächen ihres Webauftritts ermitteln können.
Do remittances and social assistance transfers have different impacts on household’s expenditure patterns? While two separate strands of literature have looked at how social assistance or remittances have been spent, few studies have compared them directly. Using data from a household survey conducted in Moldova in 2011, this paper assesses the impact both types of transfers have on household expenditure patterns. Contrary to the common assumption that money is fungible, we find that social assistance and remittances have different impacts on expenditure patterns (having controlled for potential endogeneity). In other words, where the income comes from can determine how it is spent. As such, different sources of income may have different poverty impacts. In our sample, the two types of transfers are received by different, but slightly overlapping population groups. The fact that the two transfers are spent in different ways means that, to some extent, social assistance and remittances are complements rather than substitutes.
Die Glücksforschung befasst sich primär mit einzelnen Konstrukten wie Arbeitszufriedenheit oder subjektivem Wohlbefinden. Allerdings fehlt ein zusammenhängendes Konzept, um die Erkenntnisse in der Praxis umzusetzen. Daher wird ein Bedürfnismodell vorgestellt, das sich nach ersten empirischen Untersuchungen als geeigneter Indikator für Wohlbefinden erweist. Außerdem lassen sich daraus konkrete Handlungsempfehlungen ableiten.
Die demografische Entwicklung spielt für Immobilieninvestoren eine große Rolle. Schließlich entscheidet die zukünftige Anzahl der Nutzer über die Nachfrage. Im Büroimmobilienmarkt ist daher vor allem die Anzahl der Bürobeschäftigten relevant, die sich wiederum aus dem Erwerbspersonenpotenzial ableitet. Auf Basis der Untersuchungen des Instituts der deutschen Wirtschaft zur Bürobeschäftigung und zur demografischen Entwicklung lassen sich die demografischen Perspektiven für den Büromarkt bis zum Jahr 2035 ableiten. Deutschlandweit ist nach einem kurzfristigen Anstieg mit einer Stagnation der Büronachfrage zu rechnen. In den Großstädten wird dagegen die Nachfrage weiter steigen. Vor allem in München und Berlin legt die Nachfrage kräftig zu, je nach Szenario zwischen 12 und 18 Prozent. In Düsseldorf, Hamburg und Frankfurt am Main liegen die Zuwächse dagegen zwischen 6 und 9 Prozent bis 2035. Im Vergleich zum Wohnungsmarkt sind die demografischen Perspektiven für den Büromarkt jedoch insgesamt schlechter, da die Anzahl der Erwerbspersonen langsamer wächst als die Gesamtbevölkerung. Zudem müssen bei langfristigen Betrachtungen auch mögliche Verschiebungen der Nachfrage, etwa durch die Digitalisierung, beachtet werden. Gerade in Kombination mit dem zunehmenden Fachkräftemangel können heutige Büroarbeitsplätze durch Verlagerungen ins Ausland oder durch Automatisierung wegfallen.
Maßgefertigte Abläufe
(2017)
A deployment of the Vehicle-2-Vehicle communication technology according to ETSI is in preparation in Europe. Currently, a policy for a necessary Public Key Infrastructure to enrol cryptographic keys and certificates for vehicles and infrastructure component is in discussion to enable an interoperable Vehicle-2-Vehicle communication. Vehicle-2-Vehicle communication means that vehicles periodically send Cooperative Awareness Messages. These messages contain the current geographic position, driving direction, speed, acceleration, and the current time of a vehicle. To protect privacy (location privacy, “speed privacy”) of vehicles and drivers ETSI provides a specific pseudonym concept. We show that the Vehicle-2-Vehicle communication can be misused by an attacker to plot a trace of sequent Cooperative Awareness Messages and to link this trace to a specific vehicle. Such a trace is non-disputable due to the cryptographic signing of the messages. So, the periodically sending of Cooperative Awareness Messages causes privacy problems even if the pseudonym concept is applied.
An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin) are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM) involve caveolae. We hypothesized that caveolin-1 (cav-1), a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra-and intrapulmonary bronchi in cav-1 deficient (cav-1-/-) and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD) treated and non-treated precision-cut lung slices (PCLS). The presence of caveolae was investigated by electron microscopy. Receptor subtypes driving 5-HT-responses were studied by RT-PCR and videomorphometry after pharmacological inhibition with ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a dose dependent contraction in all airway segments. A significantly higher Emax was observed in the caudal trachea. Although, caveolae abundancy was largely reduced in cav-1-/- mice, muscarine-induced airway contraction was maintained, albeit at diminished potency in the middle trachea, in the caudal trachea and in the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from cav-1-/- mice reduced cholinergic constriction by about 50%, indicating that cholesterol-rich plasma domains account for a substantial portion of the muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most prevalent subtypes in the airways. The 5-HT-induced-constriction in PCLS could be antagonized by ketanserin, a 5-HT2A receptor inhibitor. In conclusion, the role of cav-1, caveolae, and cholesterol-rich plasma domains in regulation of airway tone are highly agonist-specific and dependent on airway level. Cav-1 is indispensable for serotonergic contraction of extrapulmonary airways and modulates cholinergic constriction of the trachea and main bronchus. Thus, cav-1/caveolae shall be considered in settings such as bronchial hyperreactivity in common airway diseases and might provide an opportunity for modulation of the constrictor response.
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1 beta (IL-1 beta) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of alpha 7, alpha 9 and/or alpha 10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits alpha 9 and alpha 10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1 beta by acetylcholine (ACh), nicotine and PC depends on subunits alpha 7, alpha 9 and alpha 10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1 beta release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1 beta. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits alpha 9 and alpha 10, but only to a small degree on alpha 7. In Xenopus laevis oocytes heterologously expressing different combinations of human alpha 7, alpha 9 or alpha 10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits alpha 7, alpha 9 and alpha 10. For the metabotropic signaling of LPC and G-PC, nAChR subunits alpha 9 and alpha 10 are needed, whereas alpha 7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to regulate immune functions without perturbing canonical ion channel functions of nAChR.
Hydrogen sulfide stimulates CFTR in Xenopus oocytes by activation of the cAMP/PKA signalling axis
(2017)
Hydrogen sulfide (H2S) has been recognized as a signalling molecule which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H2S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiologically measured by microelectrode recordings. The H2S-forming sulphur salt Na2S as well as the slow-releasing H2S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes. Na2S had no effect on native, noninjected oocytes. The effect of Na2S was blocked by the CFTR inhibitor CFTR_inh172, the adenylyl cyclase inhibitor MDL 12330A, and the protein kinase A antagonist cAMPS-Rp. Na2S potentiated CFTR stimulation by forskolin, but not that by IBMX. Na2S enhanced CFTR stimulation by membranepermeable 8Br-cAMP under inhibition of adenylyl cyclase-mediated cAMP production by MDL 12330A. These data indicate that H2S activates CFTR in Xenopus oocytes by inhibiting phosphodiesterase activity and subsequent stimulation of CFTR by cAMP-dependent protein kinase A. In epithelia, an increased CFTR activity may correspond to a pro-secretory response to H2S which may be endogenously produced by the epithelium or H2S-generating microflora.
BACKGROUND
Given the unreliable self-report in patients with dementia, pain assessment should also rely on the observation of pain behaviors, such as facial expressions. Ideal observers should be well trained and should observe the patient continuously in order to pick up any pain-indicative behavior; which are requisitions beyond realistic possibilities of pain care. Therefore, the need for video-based pain detection systems has been repeatedly voiced. Such systems would allow for constant monitoring of pain behaviors and thereby allow for a timely adjustment of pain management in these fragile patients, who are often undertreated for pain.
METHODS
In this road map paper we describe an interdisciplinary approach to develop such a video-based pain detection system. The development starts with the selection of appropriate video material of people in pain as well as the development of technical methods to capture their faces. Furthermore, single facial motions are automatically extracted according to an international coding system. Computer algorithms are trained to detect the combination and timing of those motions, which are pain-indicative.
RESULTS/CONCLUSION
We hope to encourage colleagues to join forces and to inform end-users about an imminent solution of a pressing pain-care problem. For the near future, implementation of such systems can be foreseen to monitor immobile patients in intensive and postoperative care situations.
This work presents the analysis of data recorded by an eye tracking device in the course of evaluating a foveated rendering approach for head-mounted displays (HMDs). Foveated rendering methods adapt the image synthesis process to the user’s gaze and exploiting the human visual system’s limitations to increase rendering performance. Especially, foveated rendering has great potential when certain requirements have to be fulfilled, like low-latency rendering to cope with high display refresh rates. This is crucial for virtual reality (VR), as a high level of immersion, which can only be achieved with high rendering performance and also helps to reduce nausea, is an important factor in this field. We put things in context by first providing basic information about our rendering system, followed by a description of the user study and the collected data. This data stems from fixation tasks that subjects had to perform while being shown fly-through sequences of virtual scenes on an HMD. These fixation tasks consisted of a combination of various scenes and fixation modes. Besides static fixation targets, moving tar- gets on randomized paths as well as a free focus mode were tested. Using this data, we estimate the precision of the utilized eye tracker and analyze the participants’ accuracy in focusing the displayed fixation targets. Here, we also take a look at eccentricity-dependent quality ratings. Comparing this information with the users’ quality ratings given for the displayed sequences then reveals an interesting connection between fixation modes, fixation accuracy and quality ratings.
Wissenschaft trifft Praxis
(2017)
Advances in computer graphics enable us to create digital images of astonishing complexity and realism. However, processing resources are still a limiting factor. Hence, many costly but desirable aspects of realism are often not accounted for, including global illumination, accurate depth of field and motion blur, spectral effects, etc. especially in real‐time rendering. At the same time, there is a strong trend towards more pixels per display due to larger displays, higher pixel densities or larger fields of view. Further observable trends in current display technology include more bits per pixel (high dynamic range, wider color gamut/fidelity), increasing refresh rates (better motion depiction), and an increasing number of displayed views per pixel (stereo, multi‐view, all the way to holographic or lightfield displays). These developments cause significant unsolved technical challenges due to aspects such as limited compute power and bandwidth. Fortunately, the human visual system has certain limitations, which mean that providing the highest possible visual quality is not always necessary. In this report, we present the key research and models that exploit the limitations of perception to tackle visual quality and workload alike. Moreover, we present the open problems and promising future research targeting the question of how we can minimize the effort to compute and display only the necessary pixels while still offering a user full visual experience.
Human butyrylcholinesterase (BChE) is a glycoprotein capable of bioscavenging toxic compounds such as organophosphorus (OP) nerve agents. For commercial production of BChE, it is practical to synthesize BChE in non-human expression systems, such as plants or animals. However, the glycosylation profile in these systems is significantly different from the human glycosylation profile, which could result in changes in BChE's structure and function. From our investigation, we found that the glycan attached to ASN241 is both structurally and functionally important due to its close proximity to the BChE tetramerization domain and the active site gorge. To investigate the effects of populating glycosylation site ASN241, monomeric human BChE glycoforms were simulated with and without site ASN241 glycosylated. Our simulations indicate that the structure and function of human BChE are significantly affected by the absence of glycan 241.
This study contributes to the growing body of research concerning management consultancies by linking two previously disparate fields of study: (1) the examination of the effectiveness of consulting interventions and (2) the examination of the social processes that aim to create and legitimize the insights, knowledge and capabilities of management consultancies. We propose that consulting firms accumulate social authority in the course of pre-intervention discourse processes that is reflected in their reputation and celebrity. With respect to intervention, this social authority affects change recipients’ commitment to and compliance with the requirements of change implementation. We test the proposed relationships by conducting a measured variable path analysis of 117 change initiatives in German companies that were set up and implemented with the assistance of external consultancies. Our findings indicate that a consulting firm’s levels of both celebrity and reputation affect the change recipients’ commitment to proposed change strategies and thus, indirectly affect their behavioral compliance with the explicit requirements of change implementation.