Explanatory machine learning for sequential human teaching

The topic of comprehensibility of machine-learned theories has recently drawn increasing attention. Inductive Logic Programming (ILP) uses logic programming to derive logic theories from small data based on abduction and induction techniques. Learned theories are represented in the form of rules as declarative descriptions of obtained knowledge. In earlier work, the authors provided the first evidence of a measurable increase in human comprehension based on machine-learned logic rules for simple classification tasks. In a later study, it was found that the presentation of machine-learned explanations to humans can produce both beneficial and harmful effects in the context of game learning. We continue our investigation of comprehensibility by examining the effects of the ordering of concept presentations on human comprehension. In this work, we examine the explanatory effects of curriculum order and the presence of machine-learned explanations for sequential problem-solving. We show that 1) there exist tasks A and B such that learning A before B has a better human comprehension with respect to learning B before A and 2) there exist tasks A and B such that the presence of explanations when learning A contributes to improved human comprehension when subsequently learning B. We propose a framework for the effects of sequential teaching on comprehension based on an existing definition of comprehensibility and provide evidence for support from data collected in human trials. Empirical results show that sequential teaching of concepts with increasing complexity a) has a beneficial effect on human comprehension and b) leads to human re-discovery of divide-and-conquer problem-solving strategies, and c) studying machine-learned explanations allows adaptations of human problem-solving strategy with better performance.Comment: Submitted to the International Joint Conference on Learning & Reasoning (IJCLR) 202

Danger: Wolf Crossing! Meantone Tuning and Froberger’s Keyboard Music

This thesis is an exploration of how tuning practices can influence compositional practice, focusing on the way temperament can provide new insights to a close reading of keyboard music by Johann Jakob Froberger (1616–67), a transitional figure between a predominantly meantone-oriented musical environment of the 17th century and the well temperament of the 18th century. Many scholars have pointed to Froberger’s characteristic chromaticism and experimentation with novel keys as indicative of his desire to compose beyond the restrictions of meantone tuning and towards well temperament. In an effort to move away from this oft-cited teleological narrative from unequal to equal, my analyses attend to the ways that Froberger works with the boundaries of meantone, ultimately arguing that a meantone tuning is integral to Froberger’s musical language. Transgressions of these boundaries, as we shall soon see, involve mistunings that result in shocking discordances, a rough aural quality that Froberger exploits to craft structures of expectation in the dimension of discordance that operate independently of harmony

Human Comprehensible Active Learning of Genome-Scale Metabolic Networks

An important application of Synthetic Biology is the engineering of the host cell system to yield useful products. However, an increase in the scale of the host system leads to huge design space and requires a large number of validation trials with high experimental costs. A comprehensible machine learning approach that efficiently explores the hypothesis space and guides experimental design is urgently needed for the Design-Build-Test-Learn (DBTL) cycle of the host cell system. We introduce a novel machine learning framework ILP-iML1515 based on Inductive Logic Programming (ILP) that performs abductive logical reasoning and actively learns from training examples. In contrast to numerical models, ILP-iML1515 is built on comprehensible logical representations of a genome-scale metabolic model and can update the model by learning new logical structures from auxotrophic mutant trials. The ILP-iML1515 framework 1) allows high-throughput simulations and 2) actively selects experiments that reduce the experimental cost of learning gene functions in comparison to randomly selected experiments.Comment: Invited presentation for AAAI Spring Symposium Series 2023 on Computational Scientific Discover

Intracellular Uptake: A Possible Mechanism for Silver Engineered Nanoparticle Toxicity to a Freshwater Alga Ochromonas danica

The behavior and toxicity of silver engineered nanoparticles (Ag-ENs) to the mixotrophic freshwater alga Ochromonas danica were examined in the present study to determine whether any other mechanisms are involved in their algal toxicity besides Ag+ liberation outside the cells. Despite their good dispersability, the Ag-ENs were found to continuously aggregate and dissolve rapidly. When the initial nanoparticle concentration was lower than 10 µM, the total dissolved Ag+ concentration ([Ag+]T) in the suspending media reached its maximum after 1 d and then decreased suggesting that Ag+ release might be limited by the nanoparticle surface area under these conditions. Furthermore, Ag-EN dissolution extent remarkably increased in the presence of glutathione. In the Ag-EN toxicity experiment, glutathione was also used to eliminate the indirect effects of Ag+ that was released. However, remarkable toxicity was still observed although the free Ag+ concentration in the media was orders of magnitude lower than the non-observed effect concentration of Ag+ itself. Such inhibitive effects were mitigated when more glutathione was added, but could never be completely eliminated. Most importantly, we demonstrate, for the first time, that Ag-ENs can be taken in and accumulated inside the algal cells, where they exerted their toxic effects. Therefore, nanoparticle internalization may be an alternative pathway through which algal growth can be influenced

Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

OBJECTIVES There is a need for alternative strategies to combat and prevent antibiotic-resistant bacterial infections. Here, we assessed the potential for bacteriophage prophylaxis in the context of experimental ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats. DESIGN Nebulized phages (aerophages) were delivered to the lungs of rats using a modified vibrating mesh aerosol drug delivery system. Animals were intubated and ventilated for 4 hours, at which point they were infected with methicillin-resistant S. aureus strain AW7 via the endotracheal tube, extubated, and then monitored for 96 hours. SETTING Ventilator-associated pneumonia. SUBJECTS Male Wistar rats. INTERVENTIONS A single application of aerophages prior to ventilation at one of two concentrations (~1010 plaque forming units/mL or ~1011 plaque forming units/mL). MEASUREMENTS AND MAIN RESULTS 1) Animal survival at 96 hours, 2) enumeration of bacteria and phages in the lungs and spleen, and 3) lung tissue histopathology. Animals that received aerophages prior to ventilation and methicillin-resistant S. aureus challenge showed a higher survival rate compared with untreated controls (60% for animals that received 3 × 10 plaque forming units; 70% for animals that received 3 × 10 plaque forming units; 0% for controls; p < 0.01 for each treatment versus untreated). Surviving animals that received aerophage prophylaxis had fewer methicillin-resistant S. aureus in the lungs compared with untreated control animals that succumbed to pneumonia (1.6 × 10 colony forming units/g vs 8.0 × 10; p < 0.01). CONCLUSIONS Prophylactically administered nebulized bacteriophages reduced lung bacterial burdens and improved survival of methicillin-resistant S. aureus infected rats, underscoring its potential in the context of ventilator-associated pneumonia

Combining finite volume and finite element methods to simulate fluid flow in geologic media

The permeability, porosity, and fluid velocities that govern the flow of multi-phase fluids such as water, oil and steam in the earth's subsurface often vary over several orders of magnitude and the scales of interest vary from centimetres to kilometres. We describe a node-centred finite volume method coupled with a finite element method on an unstructured triangular grid to accurately and efficiently model multi-phase flow in geologic media. This is demonstrated by modelling multi-phase flows in complex geometries and with transport parameters that vary over several orders of magnitude

Searching for synergy: combining systemic daptomycin treatment with localised phage therapy for the treatment of experimental pneumonia due to MRSA.

OBJECTIVE Bacteriophages (or phages) are viruses which infect and lyse bacteria. The therapeutic use of phages (phage therapy) has regained attention in the last decades as an alternative strategy to treat infections caused by antimicrobial-resistant bacteria. In clinical settings it is most likely that phages are administered adjunct to antibiotics. For successful phage therapy it is therefore crucial to investigate different phage-antibiotic combinations in vivo. This study aimed to elucidate the combinatorial effects of systemic daptomycin and nebulised bacteriophages for the treatment of experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). RESULTS Using a rat model of ventilator-associated pneumonia caused by MRSA, the simultaneous application of intravenous daptomycin and nebulised phages was not superior to aerophage therapy alone at improving animal survival (55% vs. 50%), or reducing bacterial burdens in the lungs, or spleen. Thus, this combination does not seem to be of benefit for use in patients with MRSA pneumonia

Efficacy assessment of a novel endolysin PlyAZ3aT for the treatment of ceftriaxone-resistant pneumococcal meningitis in an infant rat model.

BACKGROUND Treatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis. METHODS Efficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed. RESULTS PlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 μg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF. CONCLUSION In experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy

Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model

Additional file 3. The animal studies were performed following the ARRIVE guideline