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The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, ‘immune hot’ status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.

Mining High Utility Sequential Patterns (HUSP) is an emerging topic in data mining which attracts many researchers. The HUSP mining algorithms can extract sequential patterns having high utility (importance) in a quantitative sequence database. In real world applications, the time intervals between elements are also very important. However, recent HUSP mining algorithms cannot extract sequential patterns with time intervals between elements. Thus, in this paper, we propose an algorithm for mining high utility sequential patterns with the time interval problem. We consider not only sequential patterns' utilities, but also their time intervals. The sequence weight utility value is used to ensure the important downward closure property. Besides that, we use four time constraints for dealing with time interval in the sequence to extract more meaningful patterns. Experimental results show that our proposed method is efficient and effective in mining high utility sequential pattern with time intervals.

We report airborne organic aerosol (OA) measurements over Los Angeles carried out in May 2010 as part of the CalNex field campaign. The principal platform for the airborne data reported here was the CIRPAS Twin Otter (TO); airborne data from NOAA WP-3D aircraft and Pasadena CalNex ground-site data acquired during simultaneous TO flybys are also presented. Aerodyne aerosol mass spectrometer measurements constitute the main source of data analyzed. The increase in organic aerosol oxidation from west to east in the basin was sensitive to OA mass loading, with a greater spatial trend in O:C associated with lower mass concentration. Three positive matrix factorization (PMF) components (hydrocarbon-like organic aerosol (HOA), semi-volatile oxidized organic aerosol (SVOOA), and low volatility oxidized organic aerosol (LVOOA)) were resolved for the one flight that exhibited the largest variability in estimated O:C ratio. Comparison of the PMF factors with two optical modes of refractory black carbon (rBC)-containing aerosol revealed that the coating of thinly coated rBC-containing aerosol, dominant in the downtown region, is likely composed of HOA, whereas more thickly coated rBC-containing aerosol, dominant in the Banning pass outflow, is composed of SVOOA and LVOOA. The correlation of water-soluble organic mass to oxidized organic aerosol (OOA) is higher in the outflows than in the basin due to the higher mass fraction of OOA/OA in the outflows. By comparison, the average OA concentration over Mexico City MILAGRO (Megacity Initiative: Local and Global Research Observations) campaign was ∼7 times higher than the airborne average during CalNex.

Refractory black carbon (rBC) mass and number concentrations were quantified by a Single Particle Soot Photometer (SP2) in the CalNex 2010 field study on board the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter in the Los Angeles (LA) Basin in May, 2010. The mass concentrations of rBC in the LA Basin ranged from 0.002–0.530 μg m^(−3), with an average of 0.172 μg m^(−3). Lower concentrations were measured in the Basin outflow regions and above the inversion layer. The SP2 afforded a quantification of the mixing state of rBC aerosols through modeling the scattering cross-section with a core-and-shell Mie model to determine coating thickness. The rBC particles above the inversion layer were more thickly coated by a light-scattering substance than those below, indicating a more aged aerosol in the free troposphere. Near the surface, as the LA plume is advected from west to east with the sea breeze, a coating of scattering material grows on rBC particles, coincident with a clear growth of ammonium nitrate within the LA Basin and the persistence of water-soluble organic compounds as the plume travels through the outflow regions. Detailed analysis of the rBC mixing state reveals two modes of coated rBC particles; a mode with smaller rBC core diameters (∼90 nm) but thick (>200 nm) coating diameters and a mode with larger rBC cores (∼145 nm) with a thin (

A precision measurement of the $^{126}$Cs(T$_{1/2}$=1.63m) hfs separation $\Delta\nu$ in the ground $6s\,^{2}\!S\!_{1/2}$ state was obtained by means of atomic beam magnetic resonance on-line with the CERN-PSB-ISOLDE mass separator. The result is $\Delta\nu$ = 3629.514(0.001)MHz. The ultimate goal is a systematic study of the influence of extended nuclear structure on hfs(Bohr-Weisskopf effect). These hfs data can serve to gain knowledge of neutron distributions, of recent interest in nuclear astrophysics and parity non-conservation effects in atomic interactions.

The " Bohr-Weisskopf " effect, or " hyperfine structure (hfs) anomaly ", which results from the effect of the distribution of nuclear magnetization on the electro-nuclear interaction, will be measured systematically at the PS Booster ISOLDE, first for a long chain of radioactive cesium isotopes, analogously to previous isotope shift and hfs studies. In addition to the direct measurement of magnetic moment values, the results are expected to provide independent data for testing nuclear wavefunctions, these will be of importance for interpreting systematic parity non-conservation experiments, complementary to the single isotope study which requires a high precision knowledge of the electron wavefunction. Substantial progress in these calculations has been achieved recently. Precision measurements of the hfs splittings and nuclear magnetic moments are required, with sensitivity adequate for the radioactive isotopes produced. A triple resonance atomic beam magnetic resonance apparatus with optical pumping state selection has been constructed. Detection of the beam atomic state is by laser-induced fluorescence or by magnetic focusing and mass spectrometry. The performance of the apparatus has been tested with stable K and Rb beams. Results obtained for g-values and hfs anomalies are in excellent agreement with published data, and show the technique to be well suited for the on-line experiments at ISOLDE. Nevertheless, the implantation of such an experiment at ISOLDE requires the neutralization of the ISOLDE ion beam and the production of a thermal atomic beam. This corresponds to a very delicate interfacing part of the instrument which posed some problems, but which are now near to being solved. For that, in order to study the properties of various types of neutralizer and improve on the observed efficiency, we have constructed an auxiliary ion source, this allowed us to demonstrate that a neutralization efficiency of 40~\% can be achieved using a simple current heated tantalum tube in which a smaller Yttrium tube was inserted. A more sophisticated neutralizer, an " orthotropic " atomic beam source, has been constructed. It is essentially a small heated chamber, with entrance and exit holes, that contains the small neutralizing element at a negative potential. The neutral atoms, after multiple bounces from the chamber walls, emerge through the exit hole. The ion component returns from the chamber walls to the neutralizer under the action of the field for recycling. This source is expected to increase the efficiency in the thermal neutral beam production; this will be tested very soon using a beam of stable Cs from ISOLDE. Furthermore, to improve the acceptance angle of the apparatus, and thus, the sensitivity; we added, just behind the neutralizer, a new six-pole permanent magnet. Tests on the whole apparatus are in progress.\\ \\