Ultra-marginal Feature Importance

Scientists frequently prioritize learning from data rather than training the best possible model; however, research in machine learning often prioritizes the latter. Marginal feature importance methods, such as marginal contribution feature importance (MCI), attempt to break this trend by providing a useful framework for quantifying the relationships in data in an interpretable fashion. In this work, we aim to improve upon the theoretical properties, performance, and runtime of MCI by introducing ultra-marginal feature importance (UMFI), which uses preprocessing methods from the AI fairness literature to remove dependencies in the feature set prior to model evaluation. We show on real and simulated data that UMFI performs at least as well as MCI, with significantly better performance in the presence of correlated interactions and unrelated features, while partially learning the structure of the causal graph and substantially reducing the exponential runtime of MCI to super-linear

A Distorted Body Image: Cognitive Behavioral Therapy for Body Dysmorphic Disorder

Body dysmorphic disorder (BDD) is one of the mental disorders that warrant more research due to the current challenges and complexity of human life. A search through Medline, Academic Search Premier, PsycINFO, and PsyArticles, using “body dysmorphic disorder” and “intervention” keywords, showed that a total of 186 articles had been published for the past 25 years. BDD was added to the obsessive-compulsive and related disorder spectrum in the Diagnostic and Statistical Manual of Mental Disorder-5 (2013). BDD is a preoccupation with an imagined defect in physical appearance by individual who looks normal which causes low self-esteem and co-morbids with other mental health problems. Individuals with BDD often end up with dermatological treatment and cosmetic surgery. However, in most cases, they frequently experience a dissatisfaction with the results and worsen the individual condition. Therefore, psychological intervention is needed to treat individuals with BDD to combat their negative perceptions on physical appearance. Research has shown that one of the effective interventions in treating individuals with BDD is cognitive behavioral therapy (CBT). Some techniques that are recommended are psychoeducation, restructuring cognitive, exposure and ritual prevention, and others. This paper aims to discuss the clinical diagnosis and CBT intervention as a treatment for individual with BDD

Nebulisation of IVT mRNA Complexes for Intrapulmonary Administration

During the last years the potential role of in vitro transcribed (IVT) mRNA as a vehicle to deliver genetic information has come into focus. IVT mRNA could be used for anti-cancer therapies, vaccination purposes, generation of pluripotent stem cells and also for genome engineering or protein replacement. However, the administration of IVT mRNA into the target organ is still challenging. The lung with its large surface area is not only of interest for delivery of genetic information for treatment of e.g. for cystic fibrosis or alpha-1-antitrypsin deficiency, but also for vaccination purposes. Administration of IVT mRNA to the lung can be performed by direct intratracheal instillation or by aerosol inhalation/nebulisation. The latter approach shows a non-invasive tool, although it is not known, if IVT mRNA is resistant during the process of nebulisation. Therefore, we investigated the transfection efficiency of non-nebulised and nebulised IVT mRNA polyplexes and lipoplexes in human bronchial epithelial cells (16HBE). A slight reduction in transfection efficiency was observed for lipoplexes (Lipofectamine 2000) in the nebulised part compared to the non-nebulised which can be overcome by increasing the amount of Lipofectamine. However, Lipofectamine was more than three times more efficient in transfecting 16HBE than DMRIE and linear PEI performed almost 10 times better than its branched derivative. By contrast, the nebulisation process did not affect the cationic polymer complexes. Furthermore, aerosolisation of IVT mRNA complexes did neither affect the protein duration nor the toxicity of the cationic complexes. Taken together, these data show that aerosolisation of cationic IVT mRNA complexes constitute a potentially powerful means to transfect cells in the lung with the purpose of protein replacement for genetic diseases such as cystic fibrosis or alpha-1-antitrypsin deficiency or for infectious disease vaccines, while bringing along the advantages of IVT mRNA as compared to pDNA as transfection agent

Nebulisation of IVT mRNA Complexes for Intrapulmonary Administration

During the last years the potential role of in vitro transcribed (IVT) mRNA as a vehicle to deliver genetic information has come into focus. IVT mRNA could be used for anti-cancer therapies, vaccination purposes, generation of pluripotent stem cells and also for genome engineering or protein replacement. However, the administration of IVT mRNA into the target organ is still challenging. The lung with its large surface area is not only of interest for delivery of genetic information for treatment of e.g. for cystic fibrosis or alpha-1-antitrypsin deficiency, but also for vaccination purposes. Administration of IVT mRNA to the lung can be performed by direct intratracheal instillation or by aerosol inhalation/nebulisation. The latter approach shows a non-invasive tool, although it is not known, if IVT mRNA is resistant during the process of nebulisation. Therefore, we investigated the transfection efficiency of non-nebulised and nebulised IVT mRNA polyplexes and lipoplexes in human bronchial epithelial cells (16HBE). A slight reduction in transfection efficiency was observed for lipoplexes (Lipofectamine 2000) in the nebulised part compared to the non-nebulised which can be overcome by increasing the amount of Lipofectamine. However, Lipofectamine was more than three times more efficient in transfecting 16HBE than DMRIE and linear PEI performed almost 10 times better than its branched derivative. By contrast, the nebulisation process did not affect the cationic polymer complexes. Furthermore, aerosolisation of IVT mRNA complexes did neither affect the protein duration nor the toxicity of the cationic complexes. Taken together, these data show that aerosolisation of cationic IVT mRNA complexes constitute a potentially powerful means to transfect cells in the lung with the purpose of protein replacement for genetic diseases such as cystic fibrosis or alpha-1-antitrypsin deficiency or for infectious disease vaccines, while bringing along the advantages of IVT mRNA as compared to pDNA as transfection agent

The Jamming Donut: A Free-Space Gripper based on Granular Jamming

Fruit harvesting has recently experienced a shift towards soft grippers that possess compliance, adaptability, and delicacy. In this context, pneumatic grippers are popular, due to provision of high deformability and compliance, however they typically possess limited grip strength. Jamming possesses strong grip capability, however has limited deformability and often requires the object to be pushed onto a surface to attain a grip. This paper describes a hybrid gripper combining pneumatics (for deformation) and jamming (for grip strength). Our gripper utilises a torus (donut) structure with two chambers controlled by pneumatic and vacuum pressure respectively, to conform around a target object. The gripper displays good adaptability, exploiting pneumatics to mould to the shape of the target object where jamming can be successfully harnessed to grip. The main contribution of the paper is design, fabrication, and characterisation of the first hybrid gripper that can use granular jamming in free space, achieving significantly larger retention forces compared to pure pneumatics. We test our gripper on a range of different sizes and shapes, as well as picking a broad range of real fruit

Gold Adatoms and Dimers on Relaxed Graphite Surfaces

The interaction of deposited gold adatoms and dimers with multilayer relaxed graphite surfaces is investigated through a density functional approach with numerical orbitals and a relativistic core pseudopotential. The energy landscape for a gold adatom along [110] agrees with scanning tunneling microscopy observations including the preferred β binding site for adatoms and the mobility difference between silver and gold adatoms. Deposited particles are shown to induce surface deformation and polarization. Static relaxation and dynamic simulations indicate that the energetically preferred binding orientation for a gold dimer is normal rather than parallel to the graphite surface. The dimer response to a simulated scanning tunneling microscopy tip is investigated by molecular dynamics simulations

Artificial horizontal transfer of retroposons.

PhDMany factors may explain why certain transposable elements (TEs) spread in some species and not others. On the one hand, they include processes that affect the rate of transposition, such as differences in the regulation of expression; on the other hand, they include characteristics of a genome that affect the consequences of transposition. In particular genome size may have an effect: a genome that is large due to non-essential repetitive DNA may be permissive for TE movement, as insertion events are less likely to be deleterious. Genome size may also help explain the pattern of TE distribution between species of mosquitoes, including the important vectors of arboviruses, Aedes aegypti and Culex pipiens sensu lato. These species have genomes 3- 5 times larger than a third genus, the Anopheles mosquitoes, which includes the malaria vectors. While all mosquitoes carry a diverse range of TEs, only culicines have the super abundant retroposon, Juan which can contribute up to 3% of the genome. The genome sequences of various insect species were compared and the mosquitoes show a significant trend of increase in genome size, which can be attributed to the increase in retroposon sequences. Two variants of Juan are reported, and new information is added regarding these elements. Previous publication of these elements contained errors in their sequences. A unique triple repeat of a cysteine rich region with a CCHC motif is present in the open reading frame. This sequence is a zinc-knuckle domain, important for the replication mechanism of these elements. In comparison, a third recently active but very low copy number retroposon, termed Pip1, is also described. The results show that Pip1 is related to the Juan elements and also possess the triple CCHC motif. The PCR results also supports previous findings of polymorphism in insertion sites of this element, suggesting that Pip1 was active after the establishment of the different strains. Pip1 copies can be grouped into three distinct groups based on nucleotide differences. Pip1 could also be using an alternative start codon to initiate transcription. Full length intact copies of the three TEs in this study were been cloned into a germline transformation vector based on piggyBac and used for germline transformation in Drosophila melanogaster. Drosophila melanogaster has no Juan or Pip1 elements and an even smaller genome than anophelines mosquitoes, so insertion events from unregulated TE movement should be more detectable. We found that the elements have been successfully introduced into the Drosophila lines. The lines were inbred to obtain a homozygous population. A range of transformed lines were monitored. No effects of hybrid dysgenesis was found. Flies with black spotted eyes were identified in a Pip1 line but this phenotype was not heritable. Whole genome sequencing was carried out on the flies using next generation sequencing (NGS) technology. Retroposon sequences was detected at a high frequency. Insertion junctions were not detected but this result does not eliminate the possibility that a junction is present but the sequencing was not sensitive enough. A possible explanation is the retroposon is present as extrachromosomal plasmid DNAQueen Mary University of London

The role of the two splice variants and extranuclear pathway on Ki-67 regulation in non-cancer and cancer cells

Ki-67 is a nuclear protein that has been used in cancer diagnostic because of its specific cell-cycle dependent expression profile. After quantifying and characterising the expression level of Ki-67, as a function of the cell cycle, we found out that the two main splice variants of the protein (i.e. α and β) are differently regulated in non-cancerous and cancerous cells both at mRNA and protein level. We were able to correlate the presence of the α variant of the protein with the progression through the interphase of cell cycle. We also observed that the different expression profiles correspond to different degradation pathways for non-cancerous and cancerous cells. Furthermore, Ki-67 is continuously regulated and degraded via proteasome system in both cell types, suggesting an active control of the protein. However we also observed a putative extranuclear elimination pathway of Ki-67 where it is transported to the Golgi apparatus. Our evidence in the different expression of the splice variants may represent a milestone for the development of new targets for cancer diagnostic and prognostic. Additionally, the unexpected extranuclear elimination of Ki-67 strongly suggests that this protein must be looked at also outside of the "nuclear box", as thought to date