Mastermind is NP-Complete

In this paper we show that the Mastermind Satisfiability Problem (MSP) is NP-complete. The Mastermind is a popular game which can be turned into a logical puzzle called Mastermind Satisfiability Problem in a similar spirit to the Minesweeper puzzle. By proving that MSP is NP-complete, we reveal its intrinsic computational property that makes it challenging and interesting. This serves as an addition to our knowledge about a host of other puzzles, such as Minesweeper, Mah-Jongg, and the 15-puzzle

Beam Enumeration: Probabilistic Explainability For Sample Efficient Self-conditioned Molecular Design

Generative molecular design has moved from proof-of-concept to real-world applicability, as marked by the surge in very recent papers reporting experimental validation. Key challenges in explainability and sample efficiency present opportunities to enhance generative design to directly optimize expensive high-fidelity oracles and provide actionable insights to domain experts. Here, we propose Beam Enumeration to exhaustively enumerate the most probable sub-sequences from language-based molecular generative models and show that molecular substructures can be extracted. When coupled with reinforcement learning, extracted substructures become meaningful, providing a source of explainability and improving sample efficiency through self-conditioned generation. Beam Enumeration is generally applicable to any language-based molecular generative model and notably further improves the performance of the recently reported Augmented Memory algorithm, which achieved the new state-of-the-art on the Practical Molecular Optimization benchmark for sample efficiency. The combined algorithm generates more high reward molecules and faster, given a fixed oracle budget. Beam Enumeration is the first method to jointly address explainability and sample efficiency for molecular design

Continuous Isolation of Monocytes using a Magnetophoretic-based Microfluidic Chip

Monocytes play an important role in the immune system and are responsible for phagocytizing and degrading foreign microorganisms in the body. The isolation of monocytes is important in various immunological applications such as in-vitro culture of dendritic cells. We present a magnetophoretic-based microfluidic chip for rapid isolation of highly purified, untouched monocytes from human blood by a negative selection method. This bioseparation platform integrates several unique features into a microfluidic device, including locally engineered magnetic field gradients and a continuous flow with a buffer switching scheme to improve the performance of the cell separation process. The results indicate high monocyte purity and recovery performances at a volumetric flow rate that is nearly an order of magnitude larger than comparable microfluidic devices reported in literature. In addition, a comprehensive 2-D computational modeling is performed to determine the cell trajectory and trapping length within the microfluidic chip. Furthermore, the effects of channel height, substrate thickness, cell size, number of beads per cell, and sample flow rate on the cell separation performance are studied

Bayesian Optimization for Chemical Reactions

Reaction optimization is challenging and traditionally delegated to domain experts who iteratively propose increasingly optimal experiments. Problematically, the reaction landscape is complex and often requires hundreds of experiments to reach convergence, representing an enormous resource sink. Bayesian optimization (BO) is an optimization algorithm that recommends the next experiment based on previous observations and has recently gained considerable interest in the general chemistry community. The application of BO for chemical reactions has been demonstrated to increase efficiency in optimization campaigns and can recommend favorable reaction conditions amidst many possibilities. Moreover, its ability to jointly optimize desired objectives such as yield and stereoselectivity makes it an attractive alternative or at least complementary to domain expert-guided optimization. With the democratization of BO software, the barrier of entry to applying BO for chemical reactions has drastically lowered. The intersection between the paradigms will see advancements at an ever-rapid pace. In this review, we discuss how chemical reactions can be transformed into machine-readable formats which can be learned by machine learning (ML) models. We present a foundation for BO and how it has already been applied to optimize chemical reaction outcomes. The important message we convey is that realizing the full potential of ML-augmented reaction optimization will require close collaboration between experimentalists and computational scientists

Path Tracking of a Wheeled Mobile Manipulator through Improved Localization and Calibration

This chapter focuses on path tracking of a wheeled mobile manipulator designed for manufacturing processes such as drilling, riveting, or line drawing, which demand high accuracy. This problem can be solved by combining two approaches: improved localization and improved calibration. In the first approach, a full-scale kinematic equation is derived for calibration of each individual wheel’s geometrical parameters, as opposed to traditionally treating them identical for all wheels. To avoid the singularity problem in computation, a predefined square path is used to quantify the errors used for calibration considering the movement in different directions. Both statistical method and interval analysis method are adopted and compared for estimation of the calibration parameters. In the second approach, a vision-based deviation rectification solution is presented to localize the system in the global frame through a number of artificial reflectors that are identified by an onboard laser scanner. An improved tracking and localization algorithm is developed to meet the high positional accuracy requirement, improve the system’s repeatability in the traditional trilateral algorithm, and solve the problem of pose loss in path following. The developed methods have been verified and implemented on the mobile manipulators developed by Shanghai University

DGR mutagenic transposition occurs via hypermutagenic reverse transcription primed by nicked template RNA.

Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed by an adenine residue in TR RNA and is dependent on the DGR-encoded reverse transcriptase (bRT) and accessory variability determinant (Avd ), but is VR-independent. We also find that the catalytic center of bRT plays an essential role in site-specific cleavage of TR RNA for cDNA priming. Adenine-specific mutagenesis occurs during reverse transcription and does not involve dUTP incorporation, indicating it results from bRT-catalyzed misincorporation of standard deoxyribonucleotides. In vivo assays show that this hybrid RNA-cDNA molecule is required for mutagenic transposition, revealing a unique mechanism of DNA hypervariation for microbial adaptation

Street recovery in the age of COVID-19: Simultaneous design for mobility, customer traffic and physical distancing

This paper explores the relationship between urban traffic, retail location and disease control during the COVID-19 pandemic crisis and tries to find a way to simultaneously address these issues for the purpose of street recovery. Drawing on the concept of the 15 min city, the study also aims at seeking COVID-19 exit paths and next-normal operating models to support long-term business prosperity using a case study of Royal Street, East Perth in Western Australia. Nearly half of the shops became vacant or closed at the end of 2020 along the east section of Royal Street, demonstrating the fragility of small business in a car-oriented street milieu that is inadequately supported by proper physical, digital and social infrastructure. A key finding from the analysis is the formulation of the concept of the Minute City. This describes a truly proximity-centred and socially driven hyper-local city, where residents and retailers work together on the local street as a walkable public open space (other than movement space), and benefit from ameliorated traffic flow, improved business location and a safer, connected community

Thermal-Mechanical Properties of Polyurethane-Clay Shape Memory Polymer Nanocomposites

Shape memory nanocomposites of polyurethane (PU)-clay were fabricated by melt mixing of PU and nano-clay. Based on nano-indentation and microhardness tests, the strength of the nanocomposites increased dramatically as a function of clay content, which is attributed to the enhanced nanoclay–polymer interactions. Thermal mechanical experiments demonstrated good mechanical and shape memory effects of the nanocomposites. Full shape memory recovery was displayed by both the pure PU and PU-clay nanocomposites.

A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 A resolution.

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like ('Johnson') for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001