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- Enzyme activity (2)
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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.
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.
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.
What are the processes behind efforts for more sustainable mountain destinations in the German Alps and what are the views of different tourism stakeholders on these processes? The research deals both with threats pushing the agenda of sustainable development (such as climate change and depletion of resources), indicators of sustainable tourism (to measure the scope of change), as well as cross-border cooperation and stakeholder engagement in the German Alps. The data was collected through 30 interviews with individuals dealing with tourism development and sustainable tourism development in the German Alps. The findings suggest that a holistic approach and collection and dissemination of data and knowledge on sustainability are the basis for developing sustainable mountain tourism. Implementation and monitoring should focus on specific flagship sustainable tourism products, as well as on a destination in a broader sense and the sustainable tourism market. Three themes emerged as important for implementation of sustainable tourism in the German Alps: indicators of sustainable tourism, cross-border cooperation and stakeholder engagement.
In order to achieve the highest possible performance, the ray traversal and intersection routines at the core of every high-performance ray tracer are usually hand-coded, heavily optimized, and implemented separately for each hardware platform—even though they share most of their algorithmic core. The results are implementations that heavily mix algorithmic aspects with hardware and implementation details, making the code non-portable and difficult to change and maintain.
In this paper, we present a new approach that offers the ability to define in a functional language a set of conceptual, high-level language abstractions that are optimized away by a special compiler in order to maximize performance. Using this abstraction mechanism we separate a generic ray traversal and intersection algorithm from its low-level aspects that are specific to the target hardware. We demonstrate that our code is not only significantly more flexible, simpler to write, and more concise but also that the compiled results perform as well as state-of-the-art implementations on any of the tested CPU and GPU platforms.
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.
3D Printers as Sociable Technologies: Taking Appropriation Infrastructures to the Internet of Things
(2017)
Maßgefertigte Abläufe
(2017)
In silico Epitope Mapping of Glucose-6-Phosphate Isomerase: A Rheumatoid Arthritis Autoantigen
(2017)
Rheumatoid arthritis-like symptoms can be initiated experimentally in naive K/BxN mice by simultaneously administering the two monoclonal antibodies 11H3 and 46H9. Both antibodies specifically recognize Glucose-6-Phosphate Isomerase (GPI), a known auto antigen in RA patients. Amino acid sequences of the Fv parts of the antibodies were determined by translating the respective hybridoma DNA sequences and served for threedimensional structure modeling of the paratope regions. In silico docking of both Fv antibody structure models to the X-ray structures of the homodimeric murine GPI as well as to the homodimeric human GPI predicted the murine epitope of the 11H3 antibodies to comprise partial amino acid sequences QRVRSGDWKGYTGKS (aa134-148) and AAKDPSAVAK (aa232-241), generating an assembled (conformational) epitope. The 11H3 epitope on human GPI encompasses the matching partial amino acid sequences QRVRSGDWKGYTGKT (aa134-148) and AAKDPSAVAK (aa232-241). The epitope of the 46H9 antibody was determined to consist of the partial murine GPI amino acid sequence RKELQAAGKSPEDLEK (aa446-461) and the human GPI amino acid sequence RKELQAAGKSPEDLER (aa446-461), respectively, resembling consecutive (linear) epitopes. The predicted epitopes were verified by mass spectrometric epitope mapping using synthetic epitope peptides. Peptide QRVRSGDWKGYTGKS[GSMSGS] AAKDPSAAK included a small spacer sequence in between the epitope sequences, mimicking the assembled epitope for the 11H3 antibody. The peptide RKELQAAGKSPEDLEK represented the consecutive epitope for the 46H9 antibody. The determined B-cell epitopes of GPI and their interactions with the monoclonal antibodies provide a detailed structural understanding of immunological disease onset mechanisms in a mouse model of rheumatoid arthritis.
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.
The technological development of the digital computer and new options to collect, store and transfer mass data have changed the world in the last 40 years. Moreover, due to the ongoing progress of computer power, the establishment of the Internet as critical infrastructure and the options of ubiquitous sensor systems will have a dramatic impact on economies and societies in the future. We give a brief overview about the technological basics especially with regard to the exponential growth of big data and current turn towards sensor-based data collection. From this stance, we reconsider the various dimensions of personal data and and market mechanisms that have an impact of data usage and protection.
Kulturmanagement
(2017)
Moden und Methoden
(2017)
IT-Portfoliomanagement
(2017)
Unternehmensberatung
(2017)
Continued growth in international experiences for U.S. co++6llege students is a favorable trend. However, the most substantial increase has occurred with of short-term study abroad programs. Many of these programs include extensive travel instead of involving a single site. There is great danger that if not properly managed, these types of international educational experience will default into little more than an organized group tour.
In these types of programs it is challenging to induce student participants to engage meaningfully with local residents as the traveling group tends to form into its own portable society. In addition, the current state of wireless communications means that students participating in these types of programs can easily stay plugged into their home social networks which further reduces meaningful interactions in the cultures being visited.
Incorporating well designed research projects into short-term study abroad programs holds the potential to offset some of the inherent limitations of such programs. Research projects can serve both to prepare the students for the trip and promote meaningful cross-cultural interaction while the program is underway.
In this paper, the authors provide suggestions based on their experiences with short-term travel abroad programs which incorporated student research. Several potential problems are identified and suggestions are given for project design.
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.
"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.
Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis
(2017)
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.
Das autonome Fahren wird die Mobilität revolutionieren. Um die Auswirkung der Vollautomation auf dieEigenschaften der Verkehrsmittel und die Präferenzen der Nutzer besser zu verstehen, haben wir dieNutzenwerte neuen Verkehrsmodi im Vergleich zu den bestehenden Verkehrsmodi analysiert und imRahmen einer Online-Umfrage von potentiellen Nutzern in Form eines vollständigen Paarvergleichsbewerten lassen. Die Studie zeigt, dass der Privat-PKW, unabhängig davon ob traditionell odervollautomatisiert, zwar nach wie vor das präferierte Verkehrsmittel ist, im direkten Vergleich das Carsharingjedoch viel stärker von der Vollautomation profitiert. Darüber hinaus gibt es Hinweise darauf, dass dasvollautomatisierte Carsharing verstärkt in Konkurrenz zum ÖPNV tritt.
Background and Objectives: In advanced β-cell dysfunction, proinsulin is increasingly replacing insulin as major component of the secretion product. It has been speculated that proinsulin has at least the same adipogenic potency than insulin, leading to an increased tendency of lipid tissue formation in patients with late stage β-cell dysfunction. Methods and Results: Mesenchymal stem cells obtained from liposuction material were grown in differentiation media containing insulin (0.01 μmol), proinsulin (0.01 μmol) or insulin+proinsulin (each 0.005 μmol). Cell culture supernatants were taken from these experiments and an untreated control at weeks 1, 2, and 3, and were stored at -80°C until analysis. Cell differentiation was microscopically supervised and adiponectin concentrations were measured as marker for differentiation into mature lipid cells. This experiment was repeated three times. No growth of lipid cells and no change in adiponectin values was observed in the negative control group (after 7/14/12 days: 3.2±0.5/3.3±0.1/4.4±0.5 ng/ml/12 h). A continuous differentiation into mature adipocytes (also confirmed by Red-Oil-staining) and a corresponding increase in adiponectin values was observed in the experiments with insulin (3.6±1.9/5.1±1.4/13.3±1.5 ng/ml/12 h; p<0.05 week 1 vs. week 3) and proinsulin (3.3±1.2/3.5±0.3/12.2±1.2 ng/ml/12 h; p<0.05). Comparable effects were seen with the insulin/proinsulin combination. Conclusions: Proinsulin has the same adipogenic potential than insulin in vitro. Proinsulin has only 10∼20% of the glucose-lowering effect of insulin. It can be speculated that the adipogenic potential of proinsulin may be a large contributor to the increased body weight problems in patients with type 2 diabetes and advanced β-cell dysfunction.
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 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.
The Sparse Matrix Vector Multiplication is an important operation on sparse matrices. This operation is the most time consuming operation in iterative solvers and therefore an efficient execution of that operation is of great importance for many applications. Numerous different storage formats that store sparse matrices efficiently have already been established. Often, these storage formats utilize the sparsity pattern of a matrix in an appropiate manner. For one class of sparse matrices the nonzero values occur in small dense blocks and appropriate block storage formats are well suited for such patterns. But on the other side, these formats perform often poor on general matrices without an explicit / regular block structure. In this paper, the newly developed sparse matrix format DynB is introduced. The aim is to efficiently use several optimization approaches and vectorization with current processors, even for matrices without an explicit block structure of nonzero elements. The DynB matrix format uses 2D rectangular blocks of variable size, allowing fill-ins per block of explicit zero values up to a user controllable threshold. We give a simple and fast heuristic to detect such 2D blocks in a sparse matrix. The performance of the Sparse Matrix Vector Multiplication for a selection of different block formats and matrices with different sparsity structures is compared. Results show that the benefit of blocking formats depend – as to be expected – on the structure of the matrix and that variable sized block formats like DynB can have advantages over fixed size formats and deliver good performance results even for general sparse matrices.