A two-step learning approach for solving full and almost full cold start problems in dyadic prediction

Dyadic prediction methods operate on pairs of objects (dyads), aiming to infer labels for out-of-sample dyads. We consider the full and almost full cold start problem in dyadic prediction, a setting that occurs when both objects in an out-of-sample dyad have not been observed during training, or if one of them has been observed, but very few times. A popular approach for addressing this problem is to train a model that makes predictions based on a pairwise feature representation of the dyads, or, in case of kernel methods, based on a tensor product pairwise kernel. As an alternative to such a kernel approach, we introduce a novel two-step learning algorithm that borrows ideas from the fields of pairwise learning and spectral filtering. We show theoretically that the two-step method is very closely related to the tensor product kernel approach, and experimentally that it yields a slightly better predictive performance. Moreover, unlike existing tensor product kernel methods, the two-step method allows closed-form solutions for training and parameter selection via cross-validation estimates both in the full and almost full cold start settings, making the approach much more efficient and straightforward to implement

Bose-Einstein Condensation of Pions in High Multiplicity Events

We present microcanonical ensemble calculations of particle number fluctuations in the ideal pion gas approaching Bose-Einstein condensation. In the samples of events with a fixed number of all pions, $N_{\pi}$, one may observe a prominent signal. When $N_{\pi}$ increases the scaled variances for particle number fluctuations of both neutral and charged pions increase dramatically in the vicinity of the Bose-Einstein condensation line. As an example, the estimates are presented for $p+p$ collisions at the beam energy of 70 GeV.Comment: 4 pages, 2 figure

High-throughput tertiary amine deoxygenated photopolymerizations for synthesizing polymer libraries

The huge chemical space potential of synthetic polymers means that in many studies only a small parameter range can be realistically synthesized in a short time and hence the “best” formulations may not be optimum. Throughput is traditionally limited by the need for deoxygenation in radical polymerizations, but advances in photopolymerization now provide opportunities for “in-air” polymerizations. Here, we have developed a protocol using liquid handling robots (or multichannel pipettes) with blue light photolysis of reversible addition fragmentation chain transfer agents and tertiary amine deoxygenation to enable the synthesis of polymer libraries in industry-standard 96-well plates with no specialized infrastructure and no degassing step. The roles of solvents and amine deoxygenators are explored to optimize the polymerization, particularly to look at alternatives to dimethyl sulfoxide (DMSO) for hydrophobic monomer (co)polymerization. DMSO is shown to aid the degassing process but is not easy to remove and hence prevents isolation of pure polymers. In contrast, using dioxane in-plate evaporation or precipitation of the tertiary amine allowed isolation of polymers in-plate. This removed all reaction components yielding pure polymers, which is not easily achieved with systems using metal catalysts and secondary reductants, such as ascorbic acid. As an example of the throughput, in just under 40 h, 392 polymers were synthesized and subsequently analyzed direct from plates by a 96-well plate sampling size exclusion chromatography system to demonstrate reproducibility. Due to less efficient degassing in dioxane (compared to DMSO), the molecular weight and dispersity control were limited in some cases (with acrylates giving the lowest dispersities), but the key aim of this system is to access hundreds of polymers quickly and in a format needed to enable testing. This method enables easy exploration of chemical space and development of screening libraries to identify hits for further study using precision polymerization methods

The 6dF galaxy survey: cosmological constraints from the velocity power spectrum

We present scale-dependent measurements of the normalized growth rate of structure fσ8(k, z = 0) using only the peculiar motions of galaxies. We use data from the 6-degree Field Galaxy Survey velocity sample together with a newly compiled sample of low-redshift (z 300 h−1 Mpc, which represents one of the largest scale growth rate measurement to date. We find no evidence for a scale-dependence in the growth rate, or any statistically significant variation from the growth rate as predicted by the Planck cosmology. Bringing all the scales together, we determine the normalized growth rate at z = 0 to ∼15 per cent in a manner independent of galaxy bias and in excellent agreement with the constraint from the measurements of redshift-space distortions from 6-degree Field Galaxy Survey. We pay particular attention to systematic errors. We point out that the intrinsic scatter present in Fundamental Plane and Tully–Fisher relations is only Gaussian in logarithmic distance units; wrongly assuming it is Gaussian in linear (velocity) units can bias cosmological constraints. We also analytically marginalize over zero-point errors in distance indicators, validate the accuracy of all our constraints using numerical simulations, and demonstrate how to combine different (correlated) velocity surveys using a matrix ‘hyperparameter’ analysis. Current and forthcoming peculiar velocity surveys will allow us to understand in detail the growth of structure in the low-redshift universe, providing strong constraints on the nature of dark energy

Nucleotide regulation of goblet cells in human airway epithelial explants: normal exocytosis in cystic fibrosis.

The regulation of mucin secretion by airway goblet cells is poorly understood and the receptor-based regulatory mechanisms have not been described in human airways. In the present study, we report that extracellular triphosphate nucleotides regulate the rate of granule release from goblet cells in both normal and cystic fibrosis (CF) airway epithelial explants. Explants isolated from nasal and tracheobronchial tissues were mounted in perfusion chambers and the secretory activity was assessed by videomicroscopic determination of degranulation in single goblet cells and by ELISA determination of mucins secreted into the mucosal perfusate. Baseline degranulation was measured at 0.05 degranulation events (DE)/min. In normal goblet cells, mucosal ATP (10(-4) M, n = 17) induced a biphasic secretory response comprising 29.1 +/- 4.9 DE during the first 5 min, with an initial rate of 118.2 +/- 10.2 DE/min. Mucosal UTP (10(-4) M, n = 9) induced a similar response to ATP (initial rate: 89.2 +/- 23.9 DE/min, 17.9 +/- 5.1 DE in 5 min), but mucosal 2-MeSATP was not an effective agonist (initial rate: 1.5 +/- 1.4 DE/min, 2.3 +/- 0.5 DE in 5 min). Determination of mucins by ELISA confirmed that both ATP and UTP induced similar secretory responses but that 2-MeSATP was not effective. In CF explants, mucosal UTP (10(-4) M, n = 6) induced similar responses to those observed in normal tissues (initial rate: 82.5 +/- 27.5 DE/min, 18.8 +/- 4.1 DE in 5 min). We conclude that human nasal and tracheobronchial goblet cells are stimulated by mucosal nucleotides, probably via a 5'-nucleotide receptor, and that this response is unaffected by CF

DelIrium VULnerability in GEriatrics (DIVULGE) study: A protocol for a prospective observational study of electroencephalogram associations with incident postoperative delirium

Delirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools.Monique S Boord, Daniel H J Davis, Peter J Psaltis, Scott W Coussens, Daniel Feuerriegel, Marta I Garrido, Alice Bourke, Hannah A D Keag

Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma

BACKGROUND. Surgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%–40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib. METHODS. ccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment. RESULTS. Twenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core profiles. However, a reduction in private mutations followed treatment, suggesting a selective process favoring enrichment of driver mutations. CONCLUSION. Neoadjuvant pazopanib is safe and active in ccRCC. Future genomic analyses may enable the segregation of driver and passenger mutations. Furthermore, tumor infiltrating immune cells persist during therapy, suggesting that pazopanib can be combined with immune checkpoint inhibitors without dampening the immune response. FUNDING. Support was provided by Novartis and GlaxoSmithKline as part of an investigator-initiated study

Indirect search for dark matter: prospects for GLAST

Possible indirect detection of neutralino, through its gamma-ray annihilation product, by the forthcoming GLAST satellite from our galactic halo, M31, M87 and the dwarf galaxies Draco and Sagittarius is studied. Gamma-ray fluxes are evaluated for the two representative energy thresholds, 0.1 GeV and 1.0 GeV, at which the spatial resolution of GLAST varies considerably. Apart from dwarfs which are described either by a modified Plummer profile or by a tidally-truncated King profiles, fluxes are compared for halos with central cusps and cores. It is demonstrated that substructures, irrespective of their profiles, enhance the gamma-ray emission only marginally. The expected gamma-ray intensity above 1 GeV at high galactic latitudes is consistent with the residual emission derived from EGRET data if the density profile has a central core and the neutralino mass is less than 50 GeV, whereas for a central cusp only a substantial enhancement would explain the observations. From M31, the flux can be detected above 0.1 GeV and 1.0 GeV by GLAST only if the neutralino mass is below 300 GeV and if the density profile has a central cusp, case in which a significant boost in the gamma-ray emission is produced by the central black hole. For Sagittarius, the flux above 0.1 GeV is detectable by GLAST provided the neutralino mass is below 50 GeV. From M87 and Draco the fluxes are always below the sensitivity limit of GLAST.Comment: 14 Pages, 7 Figures, 3 Tables, version to appear on Physical Review

Tunneling of quantum rotobreathers

We analyze the quantum properties of a system consisting of two nonlinearly coupled pendula. This non-integrable system exhibits two different symmetries: a permutational symmetry (permutation of the pendula) and another one related to the reversal of the total momentum of the system. Each of these symmetries is responsible for the existence of two kinds of quasi-degenerated states. At sufficiently high energy, pairs of symmetry-related states glue together to form quadruplets. We show that, starting from the anti-continuous limit, particular quadruplets allow us to construct quantum states whose properties are very similar to those of classical rotobreathers. By diagonalizing numerically the quantum Hamiltonian, we investigate their properties and show that such states are able to store the main part of the total energy on one of the pendula. Contrary to the classical situation, the coupling between pendula necessarily introduces a periodic exchange of energy between them with a frequency which is proportional to the energy splitting between quasi-degenerated states related to the permutation symmetry. This splitting may remain very small as the coupling strength increases and is a decreasing function of the pair energy. The energy may be therefore stored in one pendulum during a time period very long as compared to the inverse of the internal rotobreather frequency.Comment: 20 pages, 11 figures, REVTeX4 styl