Inferring neural circuit structure from datasets of heterogeneous tuning curves.

Tuning curves characterizing the response selectivities of biological neurons can exhibit large degrees of irregularity and diversity across neurons. Theoretical network models that feature heterogeneous cell populations or partially random connectivity also give rise to diverse tuning curves. Empirical tuning curve distributions can thus be utilized to make model-based inferences about the statistics of single-cell parameters and network connectivity. However, a general framework for such an inference or fitting procedure is lacking. We address this problem by proposing to view mechanistic network models as implicit generative models whose parameters can be optimized to fit the distribution of experimentally measured tuning curves. A major obstacle for fitting such models is that their likelihood function is not explicitly available or is highly intractable. Recent advances in machine learning provide ways for fitting implicit generative models without the need to evaluate the likelihood and its gradient. Generative Adversarial Networks (GANs) provide one such framework which has been successful in traditional machine learning tasks. We apply this approach in two separate experiments, showing how GANs can be used to fit commonly used mechanistic circuit models in theoretical neuroscience to datasets of tuning curves. This fitting procedure avoids the computationally expensive step of inferring latent variables, such as the biophysical parameters of, or synaptic connections between, particular recorded cells. Instead, it directly learns generalizable model parameters characterizing the network's statistical structure such as the statistics of strength and spatial range of connections between different cell types. Another strength of this approach is that it fits the joint high-dimensional distribution of tuning curves, instead of matching a few summary statistics picked a priori by the user, resulting in a more accurate inference of circuit properties. More generally, this framework opens the door to direct model-based inference of circuit structure from data beyond single-cell tuning curves, such as simultaneous population recordings

Negative Echo in the Density Evolution of Ultracold Fermionic Gases

We predict a nonequilibrium critical phenomenon in the space-time density evolution of a fermionic gas above the temperature of transition into the superfluid phase. On the BCS side of the BEC-BCS crossover, the evolution of a localized density disturbance exhibits a negative echo at the point of the initial inhomogeneity. Approaching the BEC side, this effect competes with the slow spreading of the density of bosonic molecules. However, even here the echo dominates for large enough times. This effect may be used as an experimental tool to locate the position of the transition.Comment: 4 pages, 2 figure

Comparison of flood hazard assessment criteria for pedestrians with a refined mechanics-based method

Floods have caused severe destruction and affected communities in different ways throughout history. Flood events are being exacerbated by climate change and hence it is increasingly necessary to have a more accurate understanding of various aspects of flood hazard, particularly for pedestrians. The focus of this study is therefore to investigate different criteria to assess the flood hazard for pedestrians and to propose improvements in assessing such hazards. The revised mechanics-based approach reported herein gives results based on a full physical analysis of the forces acting on a body and can be universally applied as the method can be fine-tuned for different region of the world. The results from flood hazard assessments can be used to: design evacuation plans, improve resilience of sites prone to flooding and plan more resilient future developments. Extreme flood events in the UK and documented for Boscastle (2004) and Borth (2012) were used as case studies. Two approaches were considered, including: (i) a mechanics-based approach, and (ii) an experimental-based approach, with the criteria for the stability of pedestrians in floods being compared for the criteria used by regulatory authorities in Australia, Spain, UK and USA. The results obtained in this study demonstrate that the mechanics-based methods are preferable in determining flood hazard rating assessments

Engineering E. coli cell surface in order to develop a one-step purification method for recombinant proteins

Sortases are enzymes mostly found in Gram-positive bacteria which cleave proteins site-specifically. This feature makes them a promising tool in molecular biology and biotechnology. In this study, using bacterial surface display of recombinant proteins and ability of sortase A in site-specifically cleavage of the amino acid sequences, a novel method for one-step purification of recombinant proteins was developed. Using computational program tools, a chimeric protein containing a metallothionein (mt) and chitin binding domain (ChBD) was attached to the C-terminal domain of the truncated outer membrane protein A (Lpp�-ompA) using sortase recognition site (amino acid residues: LPQTG) as a separator. The structure of the chimeric protein was simulated using molecular dynamics to determine if the LPQTG motif is accessible to the sortase active site. The designed chimeric protein was expressed and purified. The purified chimeric protein was also displayed on the surface of E. coli cells. Both purified chimeric protein and the E. coli cells displaying Lpp�-ompA-mt-ChBD carrier protein were then treated with sortase to evaluate the efficiency of sortase-mediated cleavage of purified chimeric protein as well as surface displayed-chimeric protein. It is shown that mt-ChBD protein was successfully cleaved and dissociated from Lpp�-ompA carrier and released into the medium after treatment with sortase in both recombinant protein and surface displayed-chimeric protein. The experimental results confirmed the molecular dynamics analysis results. The presented method could be regarded as a novel strategy for one step expression and purification of recombinant proteins. © 2018, The Author(s)

Molecular dynamics simulation and experimental study of the surface-display of SPA protein via Lpp-OmpA system for screening of IgG

Staphylococcal protein A (SpA) is a major virulence factor of Staphylococcus aureus. S. aureus is able to escape detection by the immune system by the surface display of protein A. The SpA protein is broadly used to purify immunoglobulin G (IgG) antibodies. This study investigates the fusion ability of Lpp�-OmpA (46�159) to anchor and display five replicate domains of protein A with 295 residues length (SpA295) of S. aureus on the surface of Escherichia coli to develop a novel bioadsorbent. First, the binding between Lpp�-OmpA-SPA295 and IgGFc and the three-dimensional structure was investigated using molecular dynamics simulation. Then high IgG recovery from human serum by the surface-displayed system of Lpp�-OmpA-SPA295 performed experimentally. In silico analysis was demonstrated the binding potential of SPA295 to IgG after expression on LPP-OmpA surface. Surface-engineered E. coli displaying SpA protein and IgG-binding assay with SDS-PAGE analysis exhibited high potential of the expressed complex on the E. coli surface for IgG capture from human serum which is applicable to conventional immune precipitation. © 2020, The Author(s)

Computational fluid dynamic modelling of NOx formation in diesel engine

The purpose of this study is offering a numerical model to predict the NOx formation of a diesel engine. For this purpose, simulation of combustion and emissions of a diesel engine was performed using CFD FIRE commercial software. The simulation was performed for the condition of 900 rpm for engine speed, 200 bar cylinder pressure, and injection timing (15° CA BTDC). The difference between the experimental and numerical results was reported by about 3.2%. The result of the numerical simulation shown due to the non-homogeneous mixture of air and fuel in a diesel engine, the temperature distribution is not uniform and the temperature in some places reaches 2500 K. In areas with an equilibrium ratio (stoichiometry) and temperatures above 2000 K, nitrogen oxide is the highest. Also, the result shown areas with a temperature range between 1500 and 1900 K are more favorable areas for the formation of soot pollutant

Current tidal power technologies and their suitability for applications in coastal and marine areas

A considerable body of research is currently being performed to quantify available tidal energy resources and to develop efficient devices with which to harness them. This work is naturally focussed on maximising power generation from the most promising sites, and a review of the literature suggests that the potential for smaller scale, local tidal power generation from shallow near-shore sites has not yet been investigated. If such generation is feasible, it could have the potential to provide sustainable electricity for nearby coastal homes and communities as part of a distributed generation strategy, and would benefit from easier installation and maintenance, lower cabling and infrastructure requirements and reduced capital costs when compared with larger scale projects. This article reviews tidal barrages and lagoons, tidal turbines, oscillating hydrofoils and tidal kites to assess their suitability for small-scale electricity generation in shallow waters. This is achieved by discussing the power density, scalability, durability, maintainability, economic potential and environmental impacts of each concept. The performance of each technology in each criterion is scored against axial-flow turbines, allowing for them to be ranked according to their overall suitability. The review suggests that tidal kites and range devices are not suitable for small-scale shallow water applications due to depth and size requirements respectively. Cross-flow turbines appear to be the most suitable technology, as they have high power densities and a maximum size that is not constrained by water depth

Multiplex SNP typing by bioluminometric assay coupled with terminator incorporation (BATI)

A multiplex single-nucleotide polymorphism (SNP) typing platform using ‘bioluminometric assay coupled with terminator [2′,3′-dideoxynucleoside triphosphates (ddNTPs)] incorporation’ (named ‘BATI’ for short) was developed. All of the reactions are carried out in a single reaction chamber containing target DNAs, DNA polymerase, reagents necessary for converting PPi into ATP and reagents for luciferase reaction. Each of the four ddNTPs is dispensed into the reaction chamber in turn. PPi is released by a nucleotide incorporation reaction and is used to produce ATP when the ddNTP dispensed is complementary to the base in a template. The ATP is used in a luciferase reaction to release visible light. Only 1 nt is incorporated into a template at a time because ddNTPs do not have a 3′ hydroxyl group. This feature greatly simplifies a sequencing spectrum. The luminescence is proportional to the amount of template incorporated. Only one peak appears in the spectrum of a homozygote sample, and two peaks at the same intensity appear for a heterozygote sample. In comparison with pyrosequencing using dNTP, the spectrum obtained by BATI is very simple, and it is very easy to determine SNPs accurately from it. As only one base is extended at a time and the extension signals are quantitative, the observed spectrum pattern is uniquely determined even for a sample containing multiplex SNPs. We have successfully used BATI to type various samples containing plural target sequence areas. The measurements can be carried out with an inexpensive and small luminometer using a photodiode array as the detector. It takes only a few minutes to determine multiplex SNPs. These results indicate that this novel multiplexed approach can significantly decrease the cost of SNP typing and increase the typing throughput with an inexpensive and small luminometer