Conformational transitions of the sodium-dependent sugar transporter, vSGLT.

Sodium-dependent transporters couple the flow of Na+ ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na+-dependent sugar transporter from Vibrio parahaemolyticus (vSGLT) has previously been reported, but structural details on additional conformations and on how Na+ and ligand influence the equilibrium between other states remains unknown. Here, double electron-electron resonance spectroscopy, structural modeling, and molecular dynamics are utilized to deduce ligand-dependent equilibria shifts of vSGLT in micelles. In the absence and presence of saturating amounts of Na+, vSGLT favors an inward-facing conformation. Upon binding both Na+ and sugar, the equilibrium shifts toward either an outward-facing or occluded conformation. While Na+ alone does not stabilize the outward-facing state, gating charge calculations together with a kinetic model of transport suggest that the resting negative membrane potential of the cell, absent in detergent-solubilized samples, may stabilize vSGLT in an outward-open conformation where it is poised for binding external sugars. In total, these findings provide insights into ligand-induced conformational selection and delineate the transport cycle of vSGLT

EVMDD-based analysis and diagnosis methods of multi-state systems with multi-state components

A multi-state system with multi-state components is a model of systems, where performance, capacity, or reliability levels of the systems are represented as states. It usually has more than two states, and thus can be considered as a multi-valued function, called a structure function. Since many structure functions are monotone increasing, their multi-state systems can be represented compactly by edge-valued multi-valued decision diagrams (EVMDDs). This paper presents an analysis method of multi-state systems with multi-state components using EVMDDs. Experimental results show that, by using EVMDDs, structure functions can be represented more compactly than existing methods using ordinary MDDs. Further, EVMDDs yield comparable computation time for system analysis. This paper also proposes a new diagnosis method using EVMDDs, and shows that the proposed method can infer the most probable causes for system failures more efficiently than conventional methods based on Bayesian networks.Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology (MEXT)Hiroshima City UniversityGrant-in Aid No. 2500050 (MEXT)Grant no. 0206 (HCU)Grant in Aid for Scientific Research (JSPS

Channel Estimation and ICI Cancelation in Vehicular Channels of OFDM Wireless Communication Systems

Orthogonal frequency division multiplexing (OFDM) scheme increases bandwidth efficiency (BE) of data transmission and eliminates inter symbol interference (ISI). As a result, it has been widely used for wideband communication systems that have been developed during the past two decades and it can be a good candidate for the emerging communication systems such as fifth generation (5G) cellular networks with high carrier frequency and communication systems of high speed vehicles such as high speed trains (HSTs) and supersonic unmanned aircraft vehicles (UAVs). However, the employment of OFDM for those upcoming systems is challenging because of high Doppler shifts. High Doppler shift makes the wideband communication channel to be both frequency selective and time selective, doubly selective (DS), causes inter carrier interference (ICI) and destroys the orthogonality between the subcarriers of OFDM signal. In order to demodulate the signal in OFDM systems and mitigate ICIs, channel state information (CSI) is required. In this work, we deal with channel estimation (CE) and ICI cancellation in DS vehicular channels. The digitized model of the DS channels can be short and dense, or long and sparse. CE methods that perform well for short and dense channels are highly inefficient for long and sparse channels. As a result, for the latter type of channels, we proposed the employment of compressed sensing (CS) based schemes for estimating the channel. In addition, we extended our CE methods for multiple input multiple output (MIMO) scenarios. We evaluated the CE accuracy and data demodulation fidelity, along with the BE and computational complexity of our methods and compared the results with the previous CE procedures in different environments. The simulation results indicate that our proposed CE methods perform considerably better than the conventional CE schemes

Spotting local environments in self-assembled monolayer-protected gold nanoparticles

Organic-inorganic (O-I) nanomaterials are versatile platforms for an incredible high number of applications, ranging from heterogeneous catalysis, molecular sensing, cell targeting, imaging, cancer diagnosis and therapy, just to name a few. Much of their potential stems from the unique control of organic environments around inorganic sites within a single O-I nanomaterial, which allows for new properties inaccessible using purely organic or inorganic materials. Structural and mechanistic characterization plays a key role in understanding and rationally designing such hybrid nanoconstructs. Here, we introduce a general methodology to identify and classify local (supra)molecular environments in an archetypal class of O-I nanomaterials, i.e. self-assembled monolayer-protected gold nanoparticles (SAM-AuNPs). By using an atomistic machine-learning guided workflow based on the Smooth Overlap of Atomic Positions (SOAP) descriptor, we analyze a collection of chemically different SAM-AuNPs, and detect and compare local environments in a way that is agnostic and automated, i.e. with no need of a-priori information and minimal user intervention. In addition, the computational results coupled with experimental electron spin resonance measurements prove that is possible to have more than one local environment inside SAMs, being thickness of the organic shell and solvation primary factors in determining number and nature of multiple co-existing environments. These indications are extended to complex mixed hydrophilic-hydrophobic SAMs. This work demonstrates that it is possible to spot out and compare local molecular environments in SAM-AuNPs exploiting atomistic machine-learning approaches, establishes ground rules to control them, and holds the potential for rational design of O-I nanomaterials instructed from data

Constraints First: A New MDD-based Model to Generate Sentences Under Constraints

This paper introduces a new approach to generating strongly constrained texts. We consider standardized sentence generation for the typical application of vision screening. To solve this problem, we formalize it as a discrete combinatorial optimization problem and utilize multivalued decision diagrams (MDD), a well-known data structure to deal with constraints. In our context, one key strength of MDD is to compute an exhaustive set of solutions without performing any search. Once the sentences are obtained, we apply a language model (GPT-2) to keep the best ones. We detail this for English and also for French where the agreement and conjugation rules are known to be more complex. Finally, with the help of GPT-2, we get hundreds of bona-fide candidate sentences. When compared with the few dozen sentences usually available in the well-known vision screening test (MNREAD), this brings a major breakthrough in the field of standardized sentence generation. Also, as it can be easily adapted for other languages, it has the potential to make the MNREAD test even more valuable and usable. More generally, this paper highlights MDD as a convincing alternative for constrained text generation, especially when the constraints are hard to satisfy, but also for many other prospects.Comment: To be published in Proceedings of the Thirty-Second International Joint Conference on Artificial Intelligence, IJCAI 202

Parallel symbolic state-space exploration is difficult, but what is the alternative?

State-space exploration is an essential step in many modeling and analysis problems. Its goal is to find the states reachable from the initial state of a discrete-state model described. The state space can used to answer important questions, e.g., "Is there a dead state?" and "Can N become negative?", or as a starting point for sophisticated investigations expressed in temporal logic. Unfortunately, the state space is often so large that ordinary explicit data structures and sequential algorithms cannot cope, prompting the exploration of (1) parallel approaches using multiple processors, from simple workstation networks to shared-memory supercomputers, to satisfy large memory and runtime requirements and (2) symbolic approaches using decision diagrams to encode the large structured sets and relations manipulated during state-space generation. Both approaches have merits and limitations. Parallel explicit state-space generation is challenging, but almost linear speedup can be achieved; however, the analysis is ultimately limited by the memory and processors available. Symbolic methods are a heuristic that can efficiently encode many, but not all, functions over a structured and exponentially large domain; here the pitfalls are subtler: their performance varies widely depending on the class of decision diagram chosen, the state variable order, and obscure algorithmic parameters. As symbolic approaches are often much more efficient than explicit ones for many practical models, we argue for the need to parallelize symbolic state-space generation algorithms, so that we can realize the advantage of both approaches. This is a challenging endeavor, as the most efficient symbolic algorithm, Saturation, is inherently sequential. We conclude by discussing challenges, efforts, and promising directions toward this goal

Mal de Debarquement Syndrome: A Matter of Loops?

Introduction: Mal de Debarquement Syndrome (MdDS) is a poorly understood neurological disorder affecting mostly perimenopausal women. MdDS has been hypothesized to be a maladaptation of the vestibulo-ocular reflex, a neuroplasticity disorder, and a consequence of neurochemical imbalances and hormonal changes. Our hypothesis considers elements from these theories, but presents a novel approach based on the analysis of functional loops, according to Systems and Control Theory. Hypothesis: MdDS is characterized by a persistent sensation of self-motion, usually occurring after sea travels. We assume the existence of a neuronal mechanism acting as an oscillator, i.e., an adaptive internal model, that may be able to cancel a sinusoidal disturbance of posture experienced aboard, due to wave motion. Thereafter, we identify this mechanism as a multi-loop neural network that spans between vestibular nuclei and the flocculonodular lobe of the cerebellum. We demonstrate that this loop system has a tendency to oscillate, which increases with increasing strength of neuronal connections. Therefore, we hypothesize that synaptic plasticity, specifically long-term potentiation, may play a role in making these oscillations poorly damped. Finally, we assume that the neuromodulator Calcitonin Gene-Related Peptide, which is modulated in perimenopausal women, exacerbates this process thus rendering the transition irreversible and consequently leading to MdDS. Conclusion and Validation: The concept of an oscillator that becomes noxiously permanent can be used as a model for MdDS, given a high correlation between patients with MdDS and sea travels involving undulating passive motion, and an alleviation of symptoms when patients are re-exposed to similar passive motion. The mechanism could be further investigated utilizing posturography tests to evaluate if subjective perception of motion matches with objective postural instability. Neurochemical imbalances that would render individuals more susceptible to developing MdDS could be investigated through hormonal profile screening. Alterations in the connections between vestibular nuclei and cerebellum, notably GABAergic fibers, could be explored by neuroimaging techniques as well as transcranial magnetic stimulation. If our hypothesis were tested and verified, optimal targets for MdDS treatment could be found within both the neural networks and biochemical factors that are deemed to play a fundamental role in loop functioning and synaptic plasticity