Automating Generative Deep Learning for Artistic Purposes: Challenges and Opportunities

We present a framework for automating generative deep learning with a specific focus on artistic applications. The framework provides opportunities to hand over creative responsibilities to a generative system as targets for automation. For the definition of targets, we adopt core concepts from automated machine learning and an analysis of generative deep learning pipelines, both in standard and artistic settings. To motivate the framework, we argue that automation aligns well with the goal of increasing the creative responsibility of a generative system, a central theme in computational creativity research. We understand automation as the challenge of granting a generative system more creative autonomy, by framing the interaction between the user and the system as a co-creative process. The development of the framework is informed by our analysis of the relationship between automation and creative autonomy. An illustrative example shows how the framework can give inspiration and guidance in the process of handing over creative responsibility

Representation of a complex Green function on a real basis: I. General Theory

When the Hamiltonian of a system is represented by a finite matrix, constructed from a discrete basis, the matrix representation of the resolvent covers only one branch. We show how all branches can be specified by the phase of a complex unit of time. This permits the Hamiltonian matrix to be constructed on a real basis; the only duty of the basis is to span the dynamical region of space, without regard for the particular asymptotic boundary conditions that pertain to the problem of interest.Comment: about 40 pages with 5 eps-figure

Active Divergence with Generative Deep Learning - A Survey and Taxonomy

Generative deep learning systems offer powerful tools for artefact generation, given their ability to model distributions of data and generate high-fidelity results. In the context of computational creativity, however, a major shortcoming is that they are unable to explicitly diverge from the training data in creative ways and are limited to fitting the target data distribution. To address these limitations, there have been a growing number of approaches for optimising, hacking and rewriting these models in order to actively diverge from the training data. We present a taxonomy and comprehensive survey of the state of the art of active divergence techniques, highlighting the potential for computational creativity researchers to advance these methods and use deep generative models in truly creative systems

Gaussian process models of potential energy surfaces with boundary optimization

A strategy is outlined to reduce the number of training points required to model intermolecular potentials using Gaussian processes, without reducing accuracy. An asymptotic function is used at a long range, and the crossover distance between this model and the Gaussian process is learnt from the training data. The results are presented for different implementations of this procedure, known as boundary optimization, across the following dimer systems: CO-Ne, HF-Ne, HF-Na+, CO2-Ne, and (CO2)2. The technique reduces the number of training points, at fixed accuracy, by up to ∼49%, compared to our previous work based on a sequential learning technique. The approach is readily transferable to other statistical methods of prediction or modeling problems

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Extensive sampling and thorough taxonomic assessment of Afrotropical Rhyssinae (Hymenoptera, Ichneumonidae) reveals two new species and demonstrates the limitations of previous sampling efforts

Tropical forest invertebrates, such as the parasitoid wasp family Ichneumonidae, are poorly known. This work reports some of the first results of an extensive survey implemented in Kibale National Park, Uganda. A total of 456 individuals was caught of the subfamily Rhyssinae Morley, 1913, which in the Afrotropical region was previously known from only 30 specimens. Here, the six species found at the site are described and the Afrotropical Rhyssinae are reviewed. Two new species, Epirhyssa johanna Hopkins, sp. nov. and E. quagga sp. nov., are described and a key, diagnostic characters, and descriptions for all 13 known Afrotropical species are provided, including the first description of the male of Epirhyssa overlaeti Seyrig, 1937. Epirhyssa gavinbroadi Rousse & van Noort, 2014, syn. nov. is proposed to be a synonym of E. uelensis Benoit, 1951. Extensive sampling with Malaise traps gave an unprecedented sample size, and the method is recommended for other poorly known tropical areas.</p

Research review: young people leaving care

This paper reviews the international research on young people leaving care. Set in the context of a social exclusion framework, it explores young people's accelerated and compressed transitions to adulthood, and discusses the development and classification of leaving care services in responding to their needs. It then considers the evidence from outcome studies and argues that adopting a resilience framework suggests that young people leaving care may fall into three groups: young people 'moving on', 'survivors' and 'victims'. In concluding, it argues that these three pathways are associated with the quality of care young people receive, their transitions from care and the support they receive after care

Testosterone in advance age: a New Zealand longitudinal cohort study: life and living in advanced age (te puāwaitanga o ngā tapuwae kia ora tonu)

OBJECTIVES: Serum testosterone (T) levels in men decline with age. Low T levels are associated with sarcopenia and frailty in men aged &gt;80 years. T levels have not previously been directly associated with disability in older men. We explored associations between T levels, frailty and disability in a cohort of octogenarian men. SETTING: Data from all men from Life and Living in Advanced Age Cohort Study in New Zealand, a longitudinal cohort study in community-dwelling older adults. PARTICIPANTS: Community-dwelling (&gt;80 years) adult men excluding those receiving T treatment or with prostatic carcinoma. OUTCOMES MEASURES: Associations between baseline total testosterone (TT) and calculated free testosterone (fT), frailty (Fried scale) and disability (Nottingham Extended Activities of Daily Living scale (NEADL)) (baseline and 24&thinsp;months) were examined using multivariate regression and Wald\u27s &chi;2 techniques. Subjects with the lowest quartile of baseline TT and fT values were compared with those in the upper three quartiles. RESULTS: Participants: 243 men, mean (SD) age 83.7 (2.0) years. Mean (SD) TT=17.6 (6.8) nmol/L and fT=225.3 (85.4) pmol/L. On multivariate analyses, lower TT levels were associated with frailty: &beta;=0.41, p=0.017, coefficient of determination (R2)=0.10&thinsp;and disability (NEADL) (&beta;=-1.27, p=0.017, R2=0.11), low haemoglobin (&beta;=-7.38, p=0.0016, R2=0.05), high fasting glucose (&beta;=0.38, p=0.038, R2=0.04) and high C reactive protein (CRP) (&beta;=3.57, p=0.01, R2=0.06). Low fT levels were associated with frailty (&beta;=0.39, p=0.024, R2=0.09) but not baseline NEADL (&beta;=-1.29, p=0.09, R2=0.09). Low fT was associated with low haemoglobin (&beta;=-7.83, p=0.0008, R2=0.05) and high CRP (&beta;=2.86, p=0.04, R2=0.05). Relationships between baseline TT and fT, and 24-month outcomes of disability and frailty were not significant. CONCLUSIONS: In men over 80 years, we confirm an association between T levels and baseline frailty scores. The new finding of association between T levels and disability is potentially relevant to debates on T supplementation in older men, though, as associations were not present at 24 months, further work is needed

Targeting the non-canonical NF-κB pathway in chronic lymphocytic leukemia and multiple myeloma

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B-and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation