HaloTag-Targeted Sirtuin-Rearranging Ligand (SirReal) for the Development of Proteolysis-Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2)**

We have discovered the sirtuin-rearranging ligands (SirReals) as a novel class of highly potent and selective inhibitors of the NAD⁺-dependent lysine deacetylase sirtuin 2 (Sirt2). In previous studies, conjugation of a SirReal with a ligand for the E3 ubiquitin ligase cereblon to form a so-called proteolysis-targeting chimera (PROTAC) enabled small-molecule-induced degradation of Sirt2. Herein, we report the structure-based development of a chloroalkylated SirReal that induces the degradation of Sirt2 mediated by Halo-tagged E3 ubiquitin ligases. Using this orthogonal approach for Sirt2 degradation, we show that other E3 ligases than cereblon, such as the E3 ubiquitin ligase parkin, can also be harnessed for small-molecule-induced Sirt2 degradation, thereby emphasizing the great potential of parkin to be used as an E3 ligase for new PROTACs approaches. Thus, our study provides new insights into targeted protein degradation in general and Sirt2 degradation in particular.     

Multirepresentation,Multiheuristic A* search‐based motion planning for a free‐floating underwater vehicle‐manipulator system in unknown environment

A key challenge in autonomous mobile manipulation is the ability to determine, in real time, how to safely execute complex tasks when placed in unknown or changing world. Addressing this issue for Intervention Autonomous Underwater Vehicles (I‐AUVs), operating in potentially unstructured environment is becoming essential. Our research focuses on using motion planning to increase the I‐AUVs autonomy, and on addressing three major challenges: (a) producing consistent deterministic trajectories, (b) addressing the high dimensionality of the system and its impact on the real‐time response, and (c) coordinating the motion between the floating vehicle and the arm. The latter challenge is of high importance to achieve the accuracy required for manipulation, especially considering the floating nature of the AUV and the control challenges that come with it. In this study, for the first time, we demonstrate experimental results performing manipulation in unknown environment. The Multirepresentation, Multiheuristic A* (MR‐MHA*) search‐based planner, previously tested only in simulation and in a known a priori environment, is now extended to control Girona500 I‐AUV performing a Valve‐Turning intervention in a water tank. To this aim, the AUV was upgraded with an in‐house‐developed laser scanner to gather three‐dimensional (3D) point clouds for building, in real time, an occupancy grid map (octomap) of the environment. The MR‐MHA* motion planner used this octomap to plan, in real time, collision‐free trajectories. To achieve the accuracy required to complete the task, a vision‐based navigation method was employed. In addition, to reinforce the safety, accounting for the localization uncertainty, a cost function was introduced to keep minimum clearance in the planning. Moreover a visual‐servoing method had to be implemented to complete the last step of the manipulation with the desired accuracy. Lastly, we further analyzed the approach performance from both loose‐coupling and clearance perspectives. Our results show the success and efficiency of the approach to meet the desired behavior, as well as the ability to adapt to unknown environments.     

Recovery of an Acid Mine Drainage-Impacted Stream Treated by Steel Slag Leach Beds

Mine Water and the Environment - The East Branch of Raccoon Creek, Ohio is highly impacted by pre-regulation coal mining and contains 10 steel slag leach beds that passively treat the low pH, and...     

In vitro calcification of orthopaedic implant materials

The formation of an apatite-like layer is achieved by immersing Ti6Al4V and TiAl2.5Fe substrata in Hank's Balanced Salt Solution (HBSS). The layer was characterized by several techniques, namely X-ray microanalysis, X-ray diffraction and X-ray photoelectron spectroscopy. The results suggest that the layer produced by immersion in HBSS is in the form of an amorphous apatite. The pH and the concentrations of calcium and phosphate were monitored as a function of time. In vitro tests with rat bone marrow were performed in order to mimic the bone/biomaterial interface. They were performed on both immersed and non-immersed samples. The in vitro bone marrow results suggest that the apatite-like layer formed may improve the bone bonding characteristics of the studied titanium alloys.     

饮用水中铝的评估

近年来，人们发现铝离子对于人体健康和水系统的有害影响不断增加。但是铝在许多饮用水处理厂中仍旧被用作一种混凝剂，导致处理后水中铝浓度的增加。为此，本研究的目的是检测地下水和河水中D．（溶解的）和T．（溶解的和酸溶解的）铝，这些水在Dakahlia Govemorate均作为饮用水水源。来自尼罗河及其支流的水作为地表水。地下水样品采自Met Ghamr，Aga和Al-Synplawin。     

Site‐Specific Labelling of Native Mammalian Proteins for Single‐Molecule FRET Measurements

Human cells are complex entities in which molecular recognition and selection are critical for cellular processes often driven by structural changes and dynamic interactions. Biomolecules appear in different chemical states, and modifications, such as phosphorylation, affect their function. Hence, using proteins in their chemically native state in biochemical and biophysical assays is essential. Single‐molecule FRET measurements allow exploration of the structure, function and dynamics of biomolecules but cannot be fully exploited for the human proteome, as a method for the site‐specific coupling of organic dyes into native, non‐recombinant mammalian proteins is lacking. We address this issue showing the site‐specific engineering of fluorescent dyes into human proteins on the basis of bioorthogonal reactions. We show the applicability of the method to study functional and post‐translationally modified proteins on the single‐molecule level, among them the hitherto inaccessible human Argonaute 2.     

Dielectric properties of modified montmorillonites suspensions in polydimethylsiloxane

The dielectric characteristics of various modified montmorillonites suspensions in polydimethylsiloxane were investigated. Such materials are promising candidates as electrorheological fluids. The effect of small water content and temperature change in the dielectric spectra of suspensions was studied. The electrical conductivity of suspensions rises with filler concentration. Conductivity also increases with frequency for all samples by 5–6 orders of magnitude. The frequency dependence of permittivity changes significantly with temperature and strongly depends on the type of modifier. The positions of relaxation transitions peaks observed in dielectric loss curves substantially depend on the type of filler and water content. Dielectric loss peaks shift to higher frequencies with temperature. Relaxation mechanism is related to filler and described by capacitor model. Based on X‐ray data a model of relaxation transitions is proposed. Also, the activation energy of dielectric relaxation is estimated. The activation energy is independent of filler concentration but is determined by the structural features of fillers in polymer medium. The prospects of dielectric spectroscopy for analyzing the layered nanosilicates structure in polymer solution are demonstrated. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46614.     

Trust Based Detection and Elimination of Packet Drop Attack in the Mobile Ad-Hoc Networks

The mobile ad hoc network (MANET) is communication network of a mobile node without any prior infrastructure of communication. The network does not have any static support; it dynamically creates the network as per requirement by using available mobile nodes. This network has a challenging security problem. The security issue mainly contains a denial of service attacks like packet drop attack, black-hole attack, gray-hole attack, etc. The mobile ad-hoc network is an open environment so the working is based on mutual trust between mobile nodes. The MANETs are vulnerable to packet drop attack in which packets travel through the different node. The network while communicating, the node drops the packet, but it is not attracting the neighboring nodes to drop the packets. This proposed algorithm works with existing routing protocol. The concept of trusted list is used for secure communication path. The trusted list along with trust values show how many times node was participated in the communication. It differentiates between altruism and selfishness in MANET with the help of energy level of mobile components. The trust and energy models are used for security and for the differentiation between altruism and selfishness respectively.