Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and systemic immune deficiency. Furthermore, the liver is an immunologic organ in itself, which may enhance or suppress the immune response to cancer arising within it. Here, we explore the immunobiology of the liver from its native state to chronic inflammation, fibrosis, cirrhosis and then to cancer, and summarize how this unique microenvironment may affect the response to immunotherapy

Effective forecasting for supply-chain planning: an empirical evaluation and strategies for improvement

Demand forecasting is a crucial aspect of the planning process in supply-chain companies. The most common approach to forecasting demand in these companies involves the use of a simple univariate statistical method to produce a forecast and the subsequent judgmental adjustment of this by the company's demand planners to take into account market intelligence relating to any exceptional circumstances expected over the planning horizon. Based on four company case studies, which included collecting more than 12,000 forecasts and outcomes, this paper examines: i) the extent to which the judgmental adjustments led to improvements in accuracy, ii) the extent to which the adjustments were biased and inefficient, iii) the circumstances where adjustments were detrimental or beneficial, and iv) methods that could lead to greater levels of accuracy. It was found that the judgmentally adjusted forecasts were both biased and inefficient. In particular, market intelligence that was expected to have a positive impact on demand was used far less effectively than intelligence suggesting a negative impact. The paper goes on to propose a set of improvements that could be applied to the forecasting processes in the companies and to the forecasting software that is used in these processes

Entanglement Patterns in Mutually Unbiased Basis Sets for N Prime-state Particles

A few simply-stated rules govern the entanglement patterns that can occur in mutually unbiased basis sets (MUBs), and constrain the combinations of such patterns that can coexist (ie, the stoichiometry) in full complements of p^N+1 MUBs. We consider Hilbert spaces of prime power dimension (as realized by systems of N prime-state particles, or qupits), where full complements are known to exist, and we assume only that MUBs are eigenbases of generalized Pauli operators, without using a particular construction. The general rules include the following: 1) In any MUB, a particular qupit appears either in a pure state, or totally entangled, and 2) in any full MUB complement, each qupit is pure in p+1 bases (not necessarily the same ones), and totally entangled in the remaining p^N-p. It follows that the maximum number of product bases is p+1, and when this number is realized, all remaining p^N-p bases in the complement are characterized by the total entanglement of every qupit. This "standard distribution" is inescapable for two qupits (of any p), where only product and generalized Bell bases are admissible MUB types. This and the following results generalize previous results for qubits and qutrits. With three qupits there are three MUB types, and a number of combinations (p+2) are possible in full complements. With N=4, there are 6 MUB types for p=2, but new MUB types become possible with larger p, and these are essential to the realization of full complements. With this example, we argue that new MUB types, showing new entanglement characteristics, should enter with every step in N, and when N is a prime plus 1, also at critical p values, p=N-1. Such MUBs should play critical roles in filling complements.Comment: 27 pages, one figure, to be submitted to Physical Revie

Measuring Planck beams with planets

Aims. Accurate measurement of the cosmic microwave background (CMB) anisotropy requires precise knowledge of the instrument beam. We explore how well the Planck beams will be determined from observations of planets, developing techniques that are also appropriate for other experiments. Methods. We simulate planet observations with a Planck-like scanning strategy, telescope beams, noise, and detector properties. Then we employ both parametric and non-parametric techniques, reconstructing beams directly from the time-ordered data. With a faithful parameterization of the beam shape, we can constrain certain detector properties, such as the time constants of the detectors, to high precision. Alternatively, we decompose the beam using an orthogonal basis. For both techniques, we characterize the errors in the beam reconstruction with Monte Carlo realizations. For a simplified scanning strategy, we study the impact on estimation of the CMB power spectrum. Finally, we explore the consequences for measuring cosmological parameters, focusing on the spectral index of primordial scalar perturbations, n_s. Results. The quality of the power spectrum measurement will be significantly influenced by the optical modeling of the telescope. In our most conservative case, using no information about the optics except the measurement of planets, we find that a single transit of Jupiter across the focal plane will measure the beam window functions to better than 0.3% for the channels at 100–217 GHz that are the most sensitive to the CMB. Constraining the beam with optical modeling can lead to much higher quality reconstruction. Conclusions. Depending on the optical modeling, the beam errors may be a significant contribution to the measurement systematics for n_s

Dependence of the superconducting critical temperature on the number of layers in homologous series of high-Tc cuprates

We study a model of $n$-layer high-temperature cuprates of homologous series like HgBa_2Ca_(n-1)Cu_nO_(2+2n+\delta) to explain the dependence of the critical temperature Tc(n) on the number $n$ of Cu-O planes in the elementary cell. Focusing on the description of the high-temperature superconducting system in terms of the collective phase variables, we have considered a semi-microscopic anisotropic three-dimensional vector XY model of stacked copper-oxide layers with adjustable parameters representing microscopic in-plane and out-of-plane phase stiffnesses. The model captures the layered composition along c-axis of homologous series and goes beyond the phenomenological Lawrence-Doniach model for layered superconductors. Implementing the spherical closure relation for vector variables we have solved the phase XY model exactly with the help of transfer matrix method and calculated Tc(n) for arbitrary block size $n$, elucidating the role of the c-axis anisotropy and its influence on the critical temperature. Furthermore, we accommodate inhomogeneous charge distribution among planes characterized by the charge imbalance coefficient $R$ being the function of number of layers $n$. By making a physically justified assumption regarding the doping dependence of the microscopic phase stiffnesses, we have calculated the values of parameter $R$ as a function of block size $n$ in good agreement with the nuclear magnetic resonance data of carrier distribution in multilayered high-Tc cuprates.Comment: 15 pages, 10 figures. Submitted to Physical Review

The Use of Vibration Analysis and Telemetry to Measure Bite Frequency and Intensity in Free-Ranging Horned Ruminants

An apparatus is described which detects and measures the vibrations in a ruminant’s horn especially those produced by the animal’s teeth. Vibrations are transmitted by radio to a portable computer where those produced as a result of eating and ruminating can be characterised by their intensity, length and frequency

Contrasting the beam interaction characteristics of selected lasers with a partially stabilised zirconia (PSZ) bio-ceramic

Differences in the beam interaction characteristics of a CO2 laser, a Nd:YAG laser, a high power diode laser (HPDL) and an excimer laser with a partially stabilised zirconia (PSZ) bio-ceramic have been studied. A derivative of Beer-Lambert’s law was applied and the laser beam absorption lengths of the four lasers were calculated as 33.55 x 10-3 cm for the CO2 laser, 18.22 x 10-3 cm for the Nd:YAG laser, 17.17 x 10-3 cm for the HPDL and 8.41 x 10-6 cm for the excimer laser. It was determined graphically that the fluence threshold values at which significant material removal was effected by the CO2 laser, the Nd:YAG laser, the HPDL and the excimer laser were 52 J/cm2, 97 J/cm2, 115 J/cm2 and 0.48 J/cm2 respectively. The thermal loading value for the CO2 laser, the Nd:YAG laser, the HPDL and the excimer laser were calculated as being 1.55 kJ/cm3, 5.32 kJ/cm3, 6.69 kJ/cm3 and 57.04 kJ/cm3 respectively

A Field Evaluation of the LuciTrap and the Western Australian Trap with Three Different Baits Types for Monitoring Lucilia cuprina and Lucilia sericata in New Zealand

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The development and characteristics of a hand-held high power diode laser-based industrial tile grout removal and single-stage sealing system

As the field of laser materials processing becomes ever more diverse, the high power diode laser (HPDL) is now being regarded by many as the most applicable tool. The commercialisation of an industrial epoxy grout removal and single-stage ceramic tile grout sealing process is examined through the development of a hand-held HPDL device in this work. Further, an appraisal of the potential hazards associated with the use of the HPDL in an industrial environment and the solutions implemented to ensure that the system complies with the relevant safety standards are given. The paper describes the characteristics and feasibility of the industrial epoxy grout removal process. A minimum power density of approximately 3 kW/cm2 was found to exist, whilst the minimum interaction time, below which there was no removal of epoxy tile grout, was found to be approximately 0.5 s. The maximum theoretical removal rate that may be achievable was calculated as being 65.98 mm2/s for a circular 2 mm diameter beam with a power density of 3 kW/cm2 and a traverse speed of 42 mm/s. In addition, the characteristics of the single-stage ceramic tile grout sealing are outlined. The single-stage ceramic tile grout sealing process yielded crack and porosity free seals which were produced in normal atmospheric conditions. Tiles were successfully sealed with power densities as low as 550 W/cm2 and at rates of up to 420 mm/min. In terms of mechanical, physical and chemical characteristics, the single-stage ceramic tile grout was found to be far superior to the conventional epoxy tile grout and, in many instances, matched and occasionally surpassed that of the ceramic tiles themselves

Impact of reionization on CMB polarization tests of slow-roll inflation

Estimates of inflationary parameters from the CMB B-mode polarization spectrum on the largest scales depend on knowledge of the reionization history, especially at low tensor-to-scalar ratio. Assuming an incorrect reionization history in the analysis of such polarization data can strongly bias the inflationary parameters. One consequence is that the single-field slow-roll consistency relation between the tensor-to-scalar ratio and tensor tilt might be excluded with high significance even if this relation holds in reality. We explain the origin of the bias and present case studies with various tensor amplitudes and noise characteristics. A more model-independent approach can account for uncertainties about reionization, and we show that parametrizing the reionization history by a set of its principal components with respect to E-mode polarization removes the bias in inflationary parameter measurement with little degradation in precision.Comment: 9 pages, 6 figures; submitted to Phys. Rev.