Active Selection of Classification Features

Some data analysis applications comprise datasets, where explanatory variables are expensive or tedious to acquire, but auxiliary data are readily available and might help to construct an insightful training set. An example is neuroimaging research on mental disorders, specifically learning a diagnosis/prognosis model based on variables derived from expensive Magnetic Resonance Imaging (MRI) scans, which often requires large sample sizes. Auxiliary data, such as demographics, might help in selecting a smaller sample that comprises the individuals with the most informative MRI scans. In active learning literature, this problem has not yet been studied, despite promising results in related problem settings that concern the selection of instances or instance-feature pairs. Therefore, we formulate this complementary problem of Active Selection of Classification Features (ASCF): Given a primary task, which requires to learn a model f: x-> y to explain/predict the relationship between an expensive-to-acquire set of variables x and a class label y. Then, the ASCF-task is to use a set of readily available selection variables z to select these instances, that will improve the primary task's performance most when acquiring their expensive features z and including them to the primary training set. We propose two utility-based approaches for this problem, and evaluate their performance on three public real-world benchmark datasets. In addition, we illustrate the use of these approaches to efficiently acquire MRI scans in the context of neuroimaging research on mental disorders, based on a simulated study design with real MRI data.Comment: Accepted for publication at the 19th Intelligent Data Analysis Symposium, 2021. The final authenticated publication will be made available online at springer.co

Human neutrophil elastase degrades the therapeutic monoclonal antibodies effective in IBD

A significant proportion of inflammatory bowel disease (IBD) patients are primary non-responders to biological therapies. Human Neutrophil Elastase (HNE) is highly expressed in IBD mucosa, especially in ulcerative colitis (UC). The aim of this study was to determine whether HNE degrades biologics, rendering them ineffective, and whether its action can be reversed by its natural inhibitor, Elafin.Instituto de Estudios Inmunológicos y Fisiopatológico

Co-combustion of oil palm trunk biocoal / sub-bituminous coal fuel blends

Biomass is a promising alternative for the reduction of global dependency on fossil fuels. However, there are some issues with the direct application of raw biomass such as high moisture content, low heating value, and poor grindability. To alleviate the problems, biomass-derived biocoal is introduced and utilised as fuel in power plants. Oil palm trunk biocoal (OPTC) is produced from pyrolysis of oil palm trunk biomass (OPTB) in a top-lit, updraft reactor at a constant air flowrate of 4.63 L/min and maximum temperature of 550 °C. OPTC is co-combusted at temperatures between 600 and 900 °C with sub-bituminous coal (SBC). Pollutant emission and ash production from combustion of fuel blends containing 20% and 50% biocoal are analysed and compared with pure SBC, OPTB and OPTC. NOx and SO2 emission profiles from all tested fuel blends are well below the limits imposed under Environmental Quality (Clean Air) Regulation 2014 of 296 and 190 ppm respectively. Response surface methodology (RSM) analysis indicates that the operation of combustion is optimised with 92.16% efficiency at 774 °C and air flowrate of 16.6 SCFH to emit 16.38% CO2, and the findings are validated against experimental results. The optimised combustion process produces ash with 67.9% silicon compounds

Quantum teleportation on a photonic chip

Quantum teleportation is a fundamental concept in quantum physics which now finds important applications at the heart of quantum technology including quantum relays, quantum repeaters and linear optics quantum computing (LOQC). Photonic implementations have largely focussed on achieving long distance teleportation due to its suitability for decoherence-free communication. Teleportation also plays a vital role in the scalability of photonic quantum computing, for which large linear optical networks will likely require an integrated architecture. Here we report the first demonstration of quantum teleportation in which all key parts - entanglement preparation, Bell-state analysis and quantum state tomography - are performed on a reconfigurable integrated photonic chip. We also show that a novel element-wise characterisation method is critical to mitigate component errors, a key technique which will become increasingly important as integrated circuits reach higher complexities necessary for quantum enhanced operation.Comment: Originally submitted version - refer to online journal for accepted manuscript; Nature Photonics (2014

Mass transfer in fibrous media with varying anisotropy for flow battery electrodes: Direct numerical simulations with 3D X-ray computed tomography

The final publication is available at Elsevier via https://doi.org/10.1016/j.ces.2018.10.049. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/A numerical method for calculating the mass transfer coefficient in fibrous media is presented. First, pressure driven flow was modelled using the Lattice Boltzmann Method. The advection-diffusion equation was solved for convective-reacting porous media flow, and the method is contrasted with experimental methods such as the limiting current diffusion technique, for its ability to determine and simulate mass transfer systems that are operating at low Reynolds number flows. A series of simulations were performed on three materials; specifically, commercially available carbon felts, electrospun carbon fibers and electrospun carbon fibers with anisotropy introduced to the microstructure. Simulations were performed in each principal direction (x,y,z) for each material in order to determine the effects of anisotropy on the mass transfer coefficient. In addition, the simulations spanned multiple Reynolds and Péclet numbers, to fully represent highly advective and highly diffusive systems. The resulting mass transfer coefficients were compared with values predicted by common correlations and a good agreement was found at high Reynolds numbers, but less so at lower Reynolds number typical of cell operation, reinforcing the utility of the numerical approach. Dimensionless mass transfer correlations were determined for each material and each direction in terms of the Sherwood number. These correlations were analyzed with respect to each materials’ permeability tensor. It was found that as the permeability of the system increases, the expected mass transfer coefficient decreases. Two general mass transfer correlations are presented, one correlation for isotropic fibrous media and the other for through-plane flow in planar fibrous materials such as electrospun media and carbon paper. The correlations are Sh = 0.879 Re0.402 Sc0.390 and Sh = 0.906 Re0.432 Sc0.432 respectively.The authors acknowledge support from the EPSRC under grants EP/L014289/1 and EP/N032888/1, as well as the STFC Extended Network in Batteries and Electrochemical Energy Devices (ST/N002385/1) for funding of travel for Rhodri Jervis to Canada. Paul R Shearing acknowledges the support of the Royal Academy of Engineering. This work was supported by the Natural Science and Engineering Research Council (NSERC) of Canada. MDR Kok is grateful to the Eugenie Ulmer Lamothe Endowment as well as the Vadasz Family Doctoral Fellowship for funding his work, as well the McGill University’s Graduate Mobility Award for funding his travel to the UK

Observational pain assessment in older persons with dementia in four countries:observer agreement of items and factor structure of the Pain Assessment in Impaired Cognition

Background: Recognition of pain in people with dementia is challenging. Observational scales have been developed, but there is a need to harmonize and improve the assessment process. In EU initiative COST-Action TD1005, 36 promising items were selected from existing scales to be tested further. We aimed to study the observer agreement of each item, and to analyse the factor structure of the complete set. Methods: One hundred and ninety older persons with dementia were recruited in four different countries (Italy, Serbia, Spain and The Netherlands) from different types of healthcare facilities. Patients represented a convenience sample, with no pre-selection on presence of (suspected) pain. The Pain Assessment in Impaired Cognition (PAIC, research version) item pool includes facial expressions of pain (15 items), body movements (10 items) and vocalizations (11 items). Participants were observed by health professionals in two situations, at rest and during movement. Intrarater and interrater reliability was analysed by percentage agreement. The factor structure was examined with principal component analysis with orthogonal rotation. Results: Health professionals performed observations in 40–57 patients in each country. Intrarater and interrater agreement was generally high (≥70%). However, for some facial expression items, agreement was sometimes below 70%. Factor analyses showed a six-component solution, which were named as follows: Vocal pain expression, Face anatomical descriptors, Protective body movements, Vocal defence, Tension and Lack of affect. Conclusions: Observation of PAIC items can be done reliably in healthcare settings. Observer agreement is quite promising already without extensive training. Significance: In this international project, promising items from existing observational pain scales were identified and evaluated regarding their reliability as an alternative to pain self-report in people with dementia. Analysis on factor structure helped to understand the character of the items. Health professionals from four countries using four different European languages were able to rate items reliably. The results contributed to an informed reduction of items for a clinical observer scale (Pain Assessment in Impaired Cognition scale with 15 items: PAIC15)

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas

We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT–PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas

A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure

Published online: 29 August 2022Therapy-related myeloid neoplasm (tMN) is considered a direct consequence of DNA damage in hematopoietic stem cells. Despite increasing recognition that altered stroma can also drive leukemogenesis, the functional biology of the tMN microenvironment remains unknown. We performed multiomic (transcriptome, DNA damage response, cytokine secretome and functional profiling) characterization of bone marrow stromal cells from tMN patients. Critically, we also compared (i) patients with myeloid neoplasm and another cancer but without cytotoxic exposure, (ii) typical primary myeloid neoplasm, and (iii) age-matched controls to decipher the microenvironmental changes induced by cytotoxics vs. neoplasia. Strikingly, tMN exhibited a profoundly senescent phenotype with induction of CDKN1A and β-Galactosidase, defective phenotype, and proliferation. Moreover, tMN stroma showed delayed DNA repair and defective adipogenesis. Despite their dormant state, tMN stromal cells were metabolically highly active with a switch toward glycolysis and secreted multiple pro-inflammatory cytokines indicative of a senescent-secretory phenotype that inhibited adipogenesis. Critically, senolytics not only eliminated dormant cells, but also restored adipogenesis. Finally, sequential patient sampling showed senescence phenotypes are induced within months of cytotoxic exposure, well prior to the onset of secondary cancer. Our data underscores a role of senescence in the pathogenesis of tMN and provide a valuable resource for future therapeutics.Monika M. Kutyna, Chung Hoow Kok, Yoon Lim, Elizabeth Ngoc Hoa Tran, David Campbell, Sharon Paton, Chloe Thompson-Peach, Kelly Lim, Dimitrios Cakouros, Agnes Arthur, Timothy Hughes, Sharad Kumar, Daniel Thomas, Stan Gronthos, and Devendra K. Hiwas

Decreasing the expression of PICALM reduces endocytosis and the activity of β-secretase: Implications for Alzheimer's disease

© 2016 The Author(s). Background: Polymorphisms in the gene for phosphatidylinositol binding clathrin assembly protein (PICALM), an endocytic-related protein, are associated with a small, increased risk of developing Alzheimer's disease (AD), strongly suggesting that changes in endocytosis are involved in the aetiology of the disease. We have investigated the involvement of PICALM in the processing of amyloid precursor protein (APP) to understand how PICALM could be linked to the development of AD. We used siRNA to deplete levels of PICALM, its isoforms and clathrin heavy chain in the human brain-derived H4 neuroglioma cell line that expresses endogenous levels of APP. We then used Western blotting, ELISA and immunohistochemistry to detect intra- and extracellular protein levels of endocytic-related proteins, APP and APP metabolites including β-amyloid (Aβ). Levels of functional endocytosis were quantified using ALEXA 488-conjugated transferrin and flow cytometry as a marker of clathrin-mediated endocytosis (CME). Results: Following depletion of all the isoforms of PICALM by siRNA in H4 cells, levels of intracellular APP, intracellular β-C-terminal fragment (β-CTF) and secreted sAPPβ (APP fragments produced by β-secretase cleavage) were significantly reduced but Aβ40 was not affected. Functional endocytosis was significantly reduced after both PICALM and clathrin depletion, highlighting the importance of PICALM in this process. However, depletion of clathrin did not affect APP but did reduce β-CTF levels. PICALM depletion altered the intracellular distribution of clathrin while clathrin reduction affected the subcellular pattern of PICALM labelling. Both PICALM and clathrin depletion reduced the expression of BACE1 mRNA and PICALM siRNA reduced protein levels. Individual depletion of PICALM isoforms 1 and 2 did not affect APP levels while clathrin depletion had a differential effect on the isoforms, increasing isoform 1 while decreasing isoform 2 expression. Conclusions: The depletion of PICALM in brain-derived cells has significant effects on the processing of APP, probably by reducing CME. In particular, it affects the production of β-CTF which is increasingly considered to be an important mediator in AD independent of Aβ. Thus a decrease in PICALM expression in the brain could be beneficial to slow or prevent the development of AD