The effect of high pressure on the NMDA receptor: molecular dynamics simulations

Professional divers exposed to ambient pressures above 11 bar develop the high pressure neurological syndrome (HPNS), manifesting as central nervous system (CNS) hyperexcitability, motor disturbances, sensory impairment, and cognitive deficits. The glutamate-type N-methyl-D-aspartate receptor (NMDAR) has been implicated in the CNS hyperexcitability of HPNS. NMDARs containing different subunits exhibited varying degrees of increased/decreased current at high pressure. The mechanisms underlying this phenomenon remain unclear. We performed 100 ns molecular dynamics (MD) simulations of the NMDAR structure embedded in a dioleoylphosphatidylcholine (DOPC) lipid bilayer solvated in water at 1 bar, hydrostatic 25 bar, and in helium at 25 bar. MD simulations showed that in contrast to hydrostatic pressure, high pressure helium causes substantial distortion of the DOPC membrane due to its accumulation between the two monolayers: reduction of the Sn-1 and Sn-2 DOPC chains and helium-dependent dehydration of the NMDAR pore. Further analysis of important regions of the NMDAR protein such as pore surface (M2 α-helix), Mg2+ binding site, and TMD-M4 α-helix revealed significant effects of helium. In contrast with previous models, these and our earlier results suggest that high pressure helium, not hydrostatic pressure per se, alters the receptor tertiary structure via protein-lipid interactions. Helium in divers’ breathing mixtures may partially contribute to HPNS symptoms. © 2019, The Author(s).The Oak Ridge Leadership Computational Facility (OLCF) at Oak Ridge National Laboratory provided access to the Titan supercomputer. The authors wish to thank Mr. Bogdan Iaparov for calculating the DOPC order parameters, Veronika Bikova and Anastasia Bazhutina for molecular volume and RDF calculations. Y.M. was partly supported by UrFU Competitiveness Enhancement Program (agreement 02.A03.21.0006)

Triathlon of Lightweight Block Ciphers for the Internet of Things

In this paper, we introduce a framework for the benchmarking of lightweight block ciphers on a multitude of embedded platforms. Our framework is able to evaluate the execution time, RAM footprint, as well as binary code size, and allows one to define a custom "figure of merit" according to which all evaluated candidates can be ranked. We used the framework to benchmark implementations of 19 lightweight ciphers, namely AES, Chaskey, Fantomas, HIGHT, LBlock, LEA, LED, Piccolo, PRESENT, PRIDE, PRINCE, RC5, RECTANGLE, RoadRunneR, Robin, Simon, SPARX, Speck, and TWINE, on three microcontroller platforms: 8-bit AVR, 16-bit MSP430, and 32-bit ARM. Our results bring some new insights into the question of how well these lightweight ciphers are suited to secure the Internet of things. The benchmarking framework provides cipher designers with an easy-to-use tool to compare new algorithms with the state of the art and allows standardization organizations to conduct a fair and consistent evaluation of a large number of candidates

The Effects of Thujone on the Function of Nicotinic Acetylcholine Receptors

Thujone is a natural compound found in plants such as “wormwood” and “sage” and it’s also found in the alcoholic drink “Absinthe”. Thujone has been suggested as a neurotoxic compound and reported to modulate GABAA receptors. In this study, we investigated the pharmacology of Thujone on nicotinic receptors expressed in Xenopus oocytes using the two electrode voltage clamp method. Thujone (100μM) caused an 80% inhibition of Acetylcholine (ACh) induced currents in human α7-nAChRs expressed in frog oocytes while only 30% inhibition currents in α4β2 expressed oocytes and no effect on α3β4, α3β2 and α4β4 nAChRs. The mechanisms of Thujone effect on the α7-nAChR were further investigated and found to be independent of membrane potential and did not compete with ACh. Furthermore, Thujone did not affect the activity of endogenous Ca2+ dependent Cl- channels. In conclusion, Thujone inhibits human nAChRs with different potencie

Attitude and Tension Control of a Tethered Formation of Aerial Vehicles

In this thesis we deal with the problem of formation control exploiting external constraints. In particular, we want to tether two quadrotors to each other and to a fixed point by ropes. Then, we want to control the quadrotors in order to drive the orientation of the formation, keeping the cables tautopenEmbargo per motivi di segretezza e/o di proprietà dei risultati e/o informazioni sensibil

State of the Art in Lightweight Symmetric Cryptography

Lightweight cryptography has been one of the ``hot topics'' in symmetric cryptography in the recent years. A huge number of lightweight algorithms have been published, standardized and/or used in commercial products. In this paper, we discuss the different implementation constraints that a ``lightweight'' algorithm is usually designed to satisfy. We also present an extensive survey of all lightweight symmetric primitives we are aware of. It covers designs from the academic community, from government agencies and proprietary algorithms which were reverse-engineered or leaked. Relevant national (\nist{}...) and international (\textsc{iso/iec}...) standards are listed. We then discuss some trends we identified in the design of lightweight algorithms, namely the designers' preference for \arx{}-based and bitsliced-S-Box-based designs and simple key schedules. Finally, we argue that lightweight cryptography is too large a field and that it should be split into two related but distinct areas: \emph{ultra-lightweight} and \emph{IoT} cryptography. The former deals only with the smallest of devices for which a lower security level may be justified by the very harsh design constraints. The latter corresponds to low-power embedded processors for which the \aes{} and modern hash function are costly but which have to provide a high level security due to their greater connectivity

The expression of hydrolytic enzymes in germinating barley grain

Modification of the barley grain endosperm in germination is fundamental to successful plant growth but also has important ramifications for down-stream industrial uses of barley, particularly in the malting and brewing industries. There are a battery of enzymes that are involved in the modification process but the sites of synthesis and action of only of a few of these have been described in detail and most have only been studied in isolated tissues. The development of a sensitive and robust in situ mRNA hybridization (ISH) procedure, which allows the detection of specific transcripts representing proteins in grain sections is described here. This first required the optimization of grain fixation, embedding and sectioning procedures as well as the adaptation of a staining method using calcofluor white to accurately assess the modification state of each grain prior to processing. Once these technical parameters were established, the non-radioactive ISH protocol was developed to allow the detection of transcripts of (1,3;1,4)-β-glucanases, (1→4)-β-endo-xylanases, limit dextrinase and limit dextrinase inhibitor in grain sections of the two barley cultivars Sloop and Himalaya. The panel of enzymes selected for study covers several aspects of grain modification, such as (1,3;1,4)-β-glucan, xylan and starch breakdown, which are all important for successful grain germination. The successful ISH technique proved sensitive enough to discriminate between the (1,3;1,4)-β-glucanase and xylanase isoenzymes and clearly defined whether the transcipts for these enzymes were synthesized in both a tissue-specific manner and a fixed temporal sequence during grain germination. The use of monoclonal antibodies specific for the two (1,3;1,4)-β-glucanase isoforms in a related immunolabelling procedure, using the same fixed grains, also allowed the patterns of transcript and protein appearance to be correlated. As expected, use of the ISH method showed that the transcripts of the (1,3;1,4)-β-glucanase, xylanase and limit dextrinase inhibitor genes are variously found in the aleurone cells, the starchy endosperm tissue and the scutellum. However, there were also substantial amounts of transcript detected in the tissues of the growing embryo which suggests that these enzymes may also contribute substantially to early seedling development.Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 201

sCAM: An Untethered Insertable Laparoscopic Surgical Camera Robot

Fully insertable robotic imaging devices represent a promising future of minimally invasive laparoscopic vision. Emerging research efforts in this field have resulted in several proof-of-concept prototypes. One common drawback of these designs derives from their clumsy tethering wires which not only cause operational interference but also reduce camera mobility. Meanwhile, these insertable laparoscopic cameras are manipulated without any pose information or haptic feedback, which results in open loop motion control and raises concerns about surgical safety caused by inappropriate use of force.This dissertation proposes, implements, and validates an untethered insertable laparoscopic surgical camera (sCAM) robot. Contributions presented in this work include: (1) feasibility of an untethered fully insertable laparoscopic surgical camera, (2) camera-tissue interaction characterization and force sensing, (3) pose estimation, visualization, and feedback with sCAM, and (4) robotic-assisted closed-loop laparoscopic camera control. Borrowing the principle of spherical motors, camera anchoring and actuation are achieved through transabdominal magnetic coupling in a stator-rotor manner. To avoid the tethering wires, laparoscopic vision and control communication are realized with dedicated wireless links based on onboard power. A non-invasive indirect approach is proposed to provide real-time camera-tissue interaction force measurement, which, assisted by camera-tissue interaction modeling, predicts stress distribution over the tissue surface. Meanwhile, the camera pose is remotely estimated and visualized using complementary filtering based on onboard motion sensing. Facilitated by the force measurement and pose estimation, robotic-assisted closed-loop control has been realized in a double-loop control scheme with shared autonomy between surgeons and the robotic controller.The sCAM has brought robotic laparoscopic imaging one step further toward less invasiveness and more dexterity. Initial ex vivo test results have verified functions of the implemented sCAM design and the proposed force measurement and pose estimation approaches, demonstrating the technical feasibility of a tetherless insertable laparoscopic camera. Robotic-assisted control has shown its potential to free surgeons from low-level intricate camera manipulation workload and improve precision and intuitiveness in laparoscopic imaging

International Journal of Medical Students - Year 2013 - Volume 1 - Supplement 1

International Journal of Medical Students - Year 2013 - Volume 1 - Supplement 1 The Sixth Young European Scientist Meeting Special Supplemen

Sleep studies in mice - open and closed loop devices for untethered recording and stimulation

Sleep is an important biological processes that has been studied extensively to date. Research in sleep typically involves mice experiments that use heavy benchtop equipment or basic neural loggers to record ECoG/EMG signals which are then processed offline in workstations. These systems limit the complexity of experiments that can be carried out to only simple open loop recordings, due to either the tethered setup used, which restricts animal movements, or the lack of devices that can offer more advanced features without compromising its portability. With rising popularity in exploring more physiological features that can affect sleep, such as temperature, whose importance has been highlighted in several papers [1][2][3] and advances in optogenetic stimulation, allowing high temporal and spatial neural control, there is now an unprecedented demand for experimental setups using new closed loop paradigms. To address this, this thesis presents compact and lightweight neural logging devices that are not only capable of measuring ECoG and EMG signals for core sleep analysis but also capable of taking high resolution temperature recordings and delivering optogenetic stimulus with fully adjustable parameters. Together with its embedded on-board automatic sleep stage scoring algorithm, the device will allow researchers for the first time to be able to quickly uncover the role a neural circuit plays in sleep regulation through selective neural stimulation when the animal is under the target sleep vigilance state. Original contributions include: the development of two novel multichannel neural logging devices, one for core sleep analysis and another for closed loop experimentation; the development and implementation of a lightweight, fast and highly accurate automatic on-line sleep stage scoring algorithm; and the development of a custom optogenetic coupler that is compatible with most current optogenetic setups for LED-Optical fibre coupling.Open Acces