Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype.

Tumor-associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9 <sup>Hi</sup> TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM-specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small-molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM-avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM-specific states, an insight a novel therapeutic anticancer approach is used to discover

Chaos assisted instanton tunneling in one dimensional perturbed periodic potential

For the system with one-dimensional spatially periodic potential we demonstrate that small periodic in time perturbation results in appearance of chaotic instanton solutions. We estimate parameter of local instability, width of stochastic layer and correlator for perturbed instanton solutions. Application of the instanton technique enables to calculate the amplitude of the tunneling, the form of the spectrum and the lower bound for width of the ground quasienergy zone

Pumping current of a Luttinger liquid with finite length

We study transport properties in a Tomonaga-Luttinger liquid in the presence of two time-dependent point like weak impurities, taking into account finite-length effects. By employing analytical methods and performing a perturbation theory, we compute the backscattering pumping current (I_bs) in different regimes which can be established in relation to the oscillatory frequency of the impurities and to the frequency related to the length and the renormalized velocity (by the electron-electron interactions) of the charge density modes. We investigate the role played by the spatial position of the impurity potentials. We also show how the previous infinite length results for I_bs are modified by the finite size of the system.Comment: 9 pages, 7 figure

Large scale numerical investigation of excited states in poly(phenylene)

A density matrix renormalisation group scheme is developed, allowing for the first time essentially exact numerical solutions for the important excited states of a realistic semi-empirical model for oligo-phenylenes. By monitoring the evolution of the energies with chain length and comparing them to the experimental absorption peaks of oligomers and thin films, we assign the four characteristic absorption peaks of phenyl-based polymers. We also determine the position and nature of the nonlinear optical states in this model.Comment: RevTeX, 10 pages, 4 eps figures included using eps

The low-lying excitations of polydiacetylene

The Pariser-Parr-Pople Hamiltonian is used to calculate and identify the nature of the low-lying vertical transition energies of polydiacetylene. The model is solved using the density matrix renormalisation group method for a fixed acetylenic geometry for chains of up to 102 atoms. The non-linear optical properties of polydiacetylene are considered, which are determined by the third-order susceptibility. The experimental 1Bu data of Giesa and Schultz are used as the geometric model for the calculation. For short chains, the calculated E(1Bu) agrees with the experimental value, within solvation effects (ca. 0.3 eV). The charge gap is used to characterise bound and unbound states. The nBu is above the charge gap and hence a continuum state; the 1Bu, 2Ag and mAg are not and hence are bound excitons. For large chain lengths, the nBu tends towards the charge gap as expected, strongly suggesting that the nBu is the conduction band edge. The conduction band edge for PDA is agreed in the literature to be ca. 3.0 eV. Accounting for the strong polarisation effects of the medium and polaron formation gives our calculated E(nBu) ca. 3.6 eV, with an exciton binding energy of ca. 1.0 eV. The 2Ag state is found to be above the 1Bu, which does not agree with relaxed transition experimental data. However, this could be resolved by including explicit lattice relaxation in the Pariser- Parr-Pople-Peierls model. Particle-hole separation data further suggest that the 1Bu, 2Ag and mAg are bound excitons, and that the nBu is an unbound exciton.Comment: LaTeX, 23 pages, 4 postscript tables and 8 postscript figure

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

The Challenges of Creativity in Software Organizations

Part 1: Creating ValueInternational audienceManaging creativity has proven to be one of the most important drivers in software development and use. The continuous changing market environment drives companies like Google, SAS Institute and LEGO to focus on creativity as an increasing necessity when competing through sustained innovations. However, creativity in the information systems (IS) environment is a challenge for most organizations that is primarily caused by not knowing how to strategize creative processes in relation to IS strategies, thus, causing companies to act ad hoc in their creative endeavors. In this paper, we address the organizational challenges of creativity in software organizations. Grounded in a previous literature review and a rigorous selection process, we identify and present a model of seven important factors for creativity in software organizations. From these factors, we identify 21 challenges that software organizations experience when embarking on creative endeavors and transfer them into a comprehensive framework. Using an interpretive research study, we further study the framework by analyzing how the challenges are integrated in 27 software organizations. Practitioners can use this study to gain a deeper understanding of creativity in their own business while researchers can use the framework to gain insight while conducting interpretive field studies of managing creativity

Bedmap2: improved ice bed, surface and thickness datasets for Antarctica

We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60° S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km3) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72 m lower and the area of ice sheet grounded on bed below sea level is increased by 10%. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets

Preliminary observations of tag shedding, tag reporting, tag wounds, and tag biofouling for raggedtooth sharks (Carcharias taurus) tagged off the east coast of South Africa

Mark-recapture models do not distinguish how ‘‘deaths’’ accrue to marked animals in the population. If animals lose their tags, then recaptures will be fewer than expected and estimates of survival will be underestimated (Arnason and Mills, 1981; McDonald et al., 2003). Similarly, if the non-reporting rate is unknown and assumed to be negligible, as is the case in some tagging studies (e.g. Cliff et al., 1996, for white sharks Carcharodon carcharias), the probability of capture can be underestimated. The effects of both these problems, inherent in cooperative tagging programmes, lead to too few tagged fish being recovered, with a positive bias on the estimation of population size. These effects are most pronounced when capture probability is low and fewer tags are available for recapture (McDonald et al., 2003)