Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors

GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket. With this aim, we mutated residues located in the benzodiazepine-binding site individually to cysteine. These mutated receptors were combined with benzodiazepine site ligands carrying a cysteine reactive group in a defined position. Proximal apposition of reaction partners will lead to a covalent reaction. We describe here such proximity-accelerated chemical coupling reactions of alpha(1)S205C and alpha(1)T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group (-NCS). We also provide new data that identify alpha(1)H101C and alpha(1)N102C as exclusive sites of the reaction of a diazepam derivative where the -Cl atom is replaced by a -NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors.

Precise Near-to-Head Acoustics with Binaural Synthesis

For enhanced immersion into a virtual scene more than just the visual sense should be addressed by a Virtual Reality system. Additional auditory stimulation appears to have much potential, as it realizes a multisensory system. This is especially useful when the user does not have to wear any additional hardware, e.g., headphones. Creating a virtual sound scene with spatially distributed sources requires a technique for adding spatial cues to audio signals and an appropriate reproduction. In this paper we present a real-time audio rendering system that combines dynamic crosstalk cancellation and multi-track binaural synthesis for virtual acoustical imaging. This provides the possibility of simulating spatially distributed sources and, in addition to that, near-to-head sources for a freely moving listener in room-mounted virtual environments without using any headphones. A special focus will be put on near-to-head acoustics, and requirements in respect of the head-related transfer function databases are discussed.

Professionalism and Information Technology: Positioning and Mediation

The starting point of this paper is the assumption that - on the one hand - information technology (IT) is increasingly shaping the professional knowledge base and on the other the relation between organisation and profession. IT is changing the role, responsibilities and practices of social workers and therefore it is important to deal with the impact of IT on social work (representative for many: Harlow and Webb 2003; Burton and van den Broek 2008). Hence, the general aim of this paper is to stimulate a basic discussion on “IT application in social work“, or rather, in a more general way, on „technology and professions“. Secondly, it is about an analytical differentiation of the process of informatisation, respectively formalisation. Thirdly we want to discuss the assumption and overall combination of efficiency, effectiveness and IT. Therefore this paper is arranged as follows: After some opening remarks (chapter 1) we outline case management systems as research object (2). Further on, we confront the approach of reflexive professionalism (3) with the process of formalization (4). Subsequently, we touch on the debate of “technologies of care” (5) and conclude with some short remarks on a research program (6).

Optical Indoor Positioning of Vehicles

Indoor positioning is the backbone of many advanced intra-logistic applications. As opposed to unified outdoor satellite positioning systems, there are many different technical approaches to indoor positioning. Depending on the application, there are different trade-offs between accuracy, range, and costs. In this paper we present a new concept for a 4-degree-of-freedom (4-DOF) positioning system to be used for vehicle tracing in a logistic facility. The system employs optical data transmission between active infrastructure and receiver devices. Compared to existing systems, these optical technologies promise to achieve better accuracy at lower costs. We will introduce the positioning algorithm and an experimental setup of the system.

Theorizing positioning strategies of secondary capital cities

Capital cities that are not the economic centers of their nations – so-called secondary capital cities (SSCs) – tend to be overlooked in the field of political science. Consequentially, there is a lack of research and resulting theory describing their political economy. This paper proposes a comparative research framework which analyzes how external pressures are influencing the relevant policy makers in the process of (re)positioning the SCC.

Laparoscopic computer-navigated ablation of liver metastases

Objective In order to benefit from the obvious advantages of minimally invasive liver surgery there is a need to develop high precision tools for intraoperative anatomical orientation, navigation and safety control. In a pilot study we adapted a newly developed system for computer-assisted liver surgery (CALS) in terms of accuracy and technical feasibility to the specific requirements of laparoscopy. Here, we present practical aspects related to laparoscopic computer assisted liver surgery (LCALS). Methods Our video relates to a patient presenting with 3 colorectal liver metastases in Seg. II, III and IVa who was selected in an appropriate oncological setting for LCALS using the CAScination system combined with 3D MEVIS reconstruction. After minimal laparoscopic mobilization of the liver, a 4- landmark registration method was applied to enable navigation. Placement of microwave needles was performed using the targeting module of the navigation system and correct needle positioning was confirmed by intraoperative sonography. Ablation of each lesion was carried out by application of microwave energy at 100 Watts for 1 minute. Results To acquire an accurate (less 0.5 cm) registration, 4 registration cycles were necessary. In total, seven minutes were required to accomplish precise registration. Successful ablation with complete response in all treated areas was assessed by intraoperative sonography and confirmed by postoperative CT scan. Conclusions This teaching video demonstrates the theoretical and practical key points of LCALS with a special emphasis on preoperative planning, intraoperative registration and accuracy testing by laparoscopic methodology. In contrast to mere ultrasound-guided ablation of liver lesions, LCALS offers a more dimensional targeting and higher safety control. This is currently also in routine use to treat vanishing lesions and other difficult to target focal lesions within the liver.

Microsurgical and laser ablation analysis of leaf positioning and dorsoventral patterning in tomato

Leaves are arranged according to regular patterns, a phenomenon referred to as phyllotaxis. Important determinants of phyllotaxis are the divergence angle between successive leaves, and the size of the leaves relative to the shoot axis. Young leaf primordia are thought to provide positional information to the meristem, thereby influencing the positioning of new primordia and hence the divergence angle. On the contrary, the meristem signals to the primordia to establish their dorsoventral polarity, which is a prerequisite for the formation of a leaf blade. These concepts originate from classical microsurgical studies carried out between the 1920s and the 1970s. Even though these techniques have been abandoned in favor of genetic analysis, the resulting insights remain a cornerstone of plant developmental biology. Here, we employ new microsurgical techniques to reassess and extend the classical studies on phyllotaxis and leaf polarity. Previous experiments have indicated that the isolation of an incipient primordium by a tangential incision caused a change of divergence angle between the two subsequent primordia, indicating that pre-existing primordia influence further phyllotaxis. Here.. we repeat these experiments and compare them with the results of laser ablation of incipient primordia. Furthermore. we explore to what extent the different pre-existing primordia influence the size and position of new organs. and hence phyllotaxis. We propose that the two youngest primordia (P-1 and P-2) are sufficient for the approximate positioning of the incipient primordium (I-1), and therefore for the perpetuation of the generative spiral, whereas the direct contact neighbours of I-1 (P-2 and P-3) control its delimitation and hence its exact size and position. Finally. we report L I specific cell ablation experiments suggesting that the meristem L-1 layer is essential for the dorsoventral patterning of leaf primordia.

The auxin influx carrier is essential for correct leaf positioning

Auxin is of vital importance in virtually every aspect of plant growth and development, yet, even after almost a century of intense study, major gaps in our knowledge of its synthesis, distribution, perception, and signal transduction remain. One unique property of auxin is its polar transport, which in many well-documented cases is a critical part of its mode of action. Auxin is actively transported through the action of both influx and efflux carriers. Inhibition of polar transport by the efflux inhibitor N-1-naphthylphthalamic acid (NPA) causes a complete cessation of leaf initiation, a defect that can be reversed by local application of the auxin, indole-3-acetic acid (IAA), to the responsive zone of the shoot apical meristem. In this study, we address the role of the auxin influx carrier in the positioning and outgrowth of leaf primordia at the shoot apical meristem of tomato. By using a combination of transport inhibitors and synthetic auxins, we demonstrate that interference with auxin influx has little effect on organ formation as such, but prevents proper localization of leaf primordia. These results suggest the existence of functional auxin concentration gradients in the shoot apical meristem that are actively set up and maintained by the action of efflux and influx carriers. We propose a model in which efflux carriers control auxin delivery to the shoot apical meristem, whereas influx and efflux carriers regulate auxin distribution within the meristem.

Homogeneous reprocessing of GPS, GLONASS and SLR observations

The International GNSS Service (IGS) provides operational products for the GPS and GLONASS constellation. Homogeneously processed time series of parameters from the IGS are only available for GPS. Reprocessed GLONASS series are provided only by individual Analysis Centers (i. e. CODE and ESA), making it difficult to fully include the GLONASS system into a rigorous GNSS analysis. In view of the increasing number of active GLONASS satellites and a steadily growing number of GPS+GLONASS-tracking stations available over the past few years, Technische Universität Dresden, Technische Universität München, Universität Bern and Eidgenössische Technische Hochschule Zürich performed a combined reprocessing of GPS and GLONASS observations. Also, SLR observations to GPS and GLONASS are included in this reprocessing effort. Here, we show only SLR results from a GNSS orbit validation. In total, 18 years of data (1994–2011) have been processed from altogether 340 GNSS and 70 SLR stations. The use of GLONASS observations in addition to GPS has no impact on the estimated linear terrestrial reference frame parameters. However, daily station positions show an RMS reduction of 0.3 mm on average for the height component when additional GLONASS observations can be used for the time series determination. Analyzing satellite orbit overlaps, the rigorous combination of GPS and GLONASS neither improves nor degrades the GPS orbit precision. For GLONASS, however, the quality of the microwave-derived GLONASS orbits improves due to the combination. These findings are confirmed using independent SLR observations for a GNSS orbit validation. In comparison to previous studies, mean SLR biases for satellites GPS-35 and GPS-36 could be reduced in magnitude from −35 and −38 mm to −12 and −13 mm, respectively. Our results show that remaining SLR biases depend on the satellite type and the use of coated or uncoated retro-reflectors. For Earth rotation parameters, the increasing number of GLONASS satellites and tracking stations over the past few years leads to differences between GPS-only and GPS+GLONASS combined solutions which are most pronounced in the pole rate estimates with maximum 0.2 mas/day in magnitude. At the same time, the difference between GLONASS-only and combined solutions decreases. Derived GNSS orbits are used to estimate combined GPS+GLONASS satellite clocks, with first results presented in this paper. Phase observation residuals from a precise point positioning are at the level of 2 mm and particularly reveal poorly modeled yaw maneuver periods.