Synthesis and testing of photoaffinity probes for the site-selective chemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.[1] It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photolabile building blocks via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photo-labile moieties that show nanomolar binding affinities for the orthosteric binding site. Further on we developed a stable 5-HT3R overexpressing cell line and a purification method to yield the receptor in a high purity. Currently we are investigating crosslinking experiments and subsequent MS – analysis.

Synthesis and testing of photoaffinity probes for the site-selectivechemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.1 It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photophores via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photolabile moieties that show nanomolar binding affinities for the orthosteric binding site. Furthermore we established a stable h5-HT3R expressing cell line and a purification protocol to yield the receptor in a high purity. Currently we are investigating the photo crosslinking of these ligands with the 5-HT3R.

Synthesis and testing of photoaffinity probes for the site-selective chemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.1 It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photophores via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photolabile moieties that show nanomolar binding affinities for the orthosteric binding site. Furthermore we established a stable h5-HT3R expressing cell line and a purification protocol to yield the receptor in a high purity. Currently we are investigating the photo crosslinking of these ligands with the 5-HT3R.

Dynamic intraligamentary stabilization and primary repair: A new concept for the treatment of knee dislocation.

BACKGROUND Traumatic knee dislocation represents a rare but devastating injury. Several controversies persist regarding type of treatment, surgical timing, graft selection, repair versus reconstruction of the medial and lateral structures, surgical techniques and postoperative rehabilitation. A new technique for primary ACL stabilization, dynamic intaligamentary stabilization (DIS) was developed at the authors' institution. The purpose of this study was to analyze the clinical and radiological outcomes of surgically treated traumatic knee dislocations by means of the DIS technique for the ACL, primary suturing for PCL, MCL and LCL. METHODS Between 2009 and 2012, 35 patients treated surgically for traumatic knee dislocation with primary anterior cruciate ligament (ACL) reconstruction with DIS, suturing of the posterior cruciate ligament (PCL) and primary complete repair of collaterals, were evaluated clinically (IKDC score, SF12 health survey, Lysholm score, Tegner score) and radiologically with a mean follow up of 2.2 years (range 1.00-3.50 years) years. Instrumented anterior-posterior translation was measured (KT-2000). RESULTS Anterior/posterior translation (KT-2000) for the healthy and injured limb was 4.8mm (range 3-8mm) and 7.3mm (range 5-10) (89N) respectively. Valgus and varus stress testing in 30° flexion was normal in 26 (75%) and 29 (83%) patients, respectively. The IKDC score was B in 29 (83%) and C in 6 (17%) patients, while the mean Tegner score was 6 (range 4-8). The mean Lysholm score was 90.83 (range 81-95) and mean SF-12 physical and mental scores were 54.1 (range 45-60) and 51.0 (range 39-62) respectively. In 2 patients, a secondary operation was performed. CONCLUSIONS Early, one stage reconstruction with DIS can achieve good functional results and patient satisfaction with overall restoration of sports and working capacity without graft requirements.

Twinning and grain subdivision during dynamic deformation of a Mg AZ31 sheet alloy at room temperature

The microstructural evolution of an AZ31 rolled sheet during dynamic deformation at strain rates of ∼103 s−1 has been investigated by electron backscatter diffraction, X-ray and neutron diffraction. The influence of orientation on the predominant deformation mechanisms and on the recovery processes taking place during deformation has been systematically examined. The results have been compared with those corresponding to the same alloy tested quasi-statically under equivalent conditions. It has been found that strain rate enhances the activation of extension twinning dramatically, while contraction and secondary twinning are not significantly influenced. The polarity of extension twinning is even reversed in some grains under selected testing conditions. Significant grain subdivision by the formation of geometrically necessary boundaries (GNBs) takes place during both quasi-static and dynamic deformation of this AZ31 alloy. It is remarkable that GNBs of high misorientations form even at the highest strain rates. The phenomenon of recovery has been found to be orientation dependent

AUTOFLY-Aid: Flight Deck Automation Support with Dynamic 4D Trajectory Management for Responsive and Adaptive Airborne Collision Avoidance

AUTOFLY-Aid Project aims to develop and demonstrate novel automation support algorithms and tools to the flight crew for flight critical collision avoidance using “dynamic 4D trajectory management”. The automation support system is envisioned to improve the primary shortcomings of TCAS, and to aid the pilot through add-on avionics/head-up displays and reality augmentation devices in dynamically evolving collision avoidance scenarios. The main theoretical innovative and novel concepts to be developed by AUTOFLY-Aid project are a) design and development of the mathematical models of the full composite airspace picture from the flight deck’s perspective, as seen/measured/informed by the aircraft flying in SESAR 2020, b) design and development of a dynamic trajectory planning algorithm that can generate at real-time (on the order of seconds) flyable (i.e. dynamically and performance-wise feasible) alternative trajectories across the evolving stochastic composite airspace picture (which includes new conflicts, blunder risks, terrain and weather limitations) and c) development and testing of the Collision Avoidance Automation Support System on a Boeing 737 NG FNPT II Flight Simulator with synthetic vision and reality augmentation while providing the flight crew with quantified and visual understanding of collision risks in terms of time and directions and countermeasures.

Influence of crowds in the dynamic characteristics of a structure

The interest for modelling of human actions acting on structures has been recurrent since the first accidents on suspension bridges in the nineteenth century like Broughton (1831) in the U.K. or Angers (1850) in France. Stadiums, gymnasiums are other type of structure where the human induced vibration is very important. In these structures appear particular phenomenon like the interaction person-structure (lock-in), the person-person synchronization, and the influence of the mass and damping of the people in the structure behaviour. This work focuses on the latter topic. The dynamic characteristic of a structure can be changed due to the presence of people on it. In order to evaluate these property modifications several testing have been carried out on a structure designed to be a gymnasium. For the test an electro-dynamic shaker was installed in a fixed point of the gym slab and different groups of people were located around the shaker. In each test the number of people was changed and also their posture (standing and sitting). Test data were analyzed and processed to verify modifications in the structure behaviour.

Modelling and testing volatility spillovers in oil and financial markets for USA, UK and China

The primary purpose of the paper is to analyze the conditional correlations, conditional covariances, and co-volatility spillovers between international crude oil and associated financial markets. The paper investigates co-volatility spillovers (namely, the delayed effect of a returns shock in one physical or financial asset on the subsequent volatility or co-volatility in another physical or financial asset) between the oil and financial markets. The oil industry has four major regions, namely North Sea, USA, Middle East, and South-East Asia. Associated with these regions are two major financial centers, namely UK and USA. For these reasons, the data to be used are the returns on alternative crude oil markets, returns on crude oil derivatives, specifically futures, and stock index returns in UK and USA. The paper will also analyze the Chinese financial markets, where the data are more recent. The empirical analysis will be based on the diagonal BEKK model, from which the conditional covariances will be used for testing co-volatility spillovers, and policy recommendations. Based on these results, dynamic hedging strategies will be suggested to analyze market fluctuations in crude oil prices and associated financial markets.

Dynamic investigation of an ancient masonry bell tower with operational modal analysis: a non-destructive experimental technique to obtain the dynamic characteristics of a structure

This paper shows the results of an experimental analysis on the bell tower of “Chiesa della Maddalena” (Mola di Bari, Italy), to better understand the structural behavior of slender masonry structures. The research aims to calibrate a numerical model by means of the Operational Modal Analysis (OMA) method. In this way realistic conclusions about the dynamic behavior of the structure are obtained. The choice of using an OMA derives from the necessity to know the modal parameters of a structure with a non-destructive testing, especially in case of cultural-historical value structures. Therefore by means of an easy and accurate process, it is possible to acquire in-situ environmental vibrations. The data collected are very important to estimate the mode shapes, the natural frequencies and the damping ratios of the structure. To analyze the data obtained from the monitoring, the Peak Picking method has been applied to the Fast Fourier Transforms (FFT) of the signals in order to identify the values of the effective natural frequencies and damping factors of the structure. The main frequencies and the damping ratios have been determined from measurements at some relevant locations. The responses have been then extrapolated and extended to the entire tower through a 3-D Finite Element Model. In this way, knowing the modes of vibration, it has been possible to understand the overall dynamic behavior of the structure.

Similarity Measurement of Biological Signals Using Dynamic Time Warping Algorithm

The problem of similarity measurement of biological signals is considered on this article. The dynamic time warping algorithm is used as a possible solution. A short overview of this algorithm and its modifications are given. Testing procedure for different modifications of DTW, which are based on artificial test signals, are presented.

Accident investigation studies in conjunction with FMVSS 301 compliance testing (1981 model year). Final report.

National Highway Traffic Safety Administration, Office of Vehicle Safety Compliance, Washington, D.C.

Accident investigation studies in conjunction with FMVSS 301 compliance testing. Final report.

National Highway Traffic Safety Administration, Washington D.C.

Accident investigation studies on 1979 model automobiles in conjunction with FMVSS 301 compliance testing. Final report.

National Highway Traffic Safety Administration, Office of Vehicle Safety Compliance, Washington, D.C.

Accident investigation studies on 1980 model automobiles in conjunction with FMVSS 301 compliance testing. Final report.

National Highway Traffic Safety Administration, Office of Vehicle Safety Compliance, Washington, D.C.

Vehicle seat back latch systems; evaluation and testing. Final report.

National Highway Traffic Safety Administration, Washington, D.C.