Elastic Behavior of a Two-dimensional Crystal near Melting

Using positional data from video-microscopy we determine the elastic moduli of two-dimensional colloidal crystals as a function of temperature. The moduli are extracted from the wave-vector-dependent normal mode spring constants in the limit $q\to 0$ and are compared to the renormalized Young's modulus of the KTHNY theory. An essential element of this theory is the universal prediction that Young's modulus must approach $16 \pi$ at the melting temperature. This is indeed observed in our experiment.Comment: 4 pages, 3 figure

Functional Brain Imaging with Multi-Objective Multi-Modal Evolutionary Optimization

Functional brain imaging is a source of spatio-temporal data mining problems. A new framework hybridizing multi-objective and multi-modal optimization is proposed to formalize these data mining problems, and addressed through Evolutionary Computation (EC). The merits of EC for spatio-temporal data mining are demonstrated as the approach facilitates the modelling of the experts' requirements, and flexibly accommodates their changing goals

Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25+ NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25+ NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy

Anisotropic elasticity in confocal studies of colloidal crystals

We consider the theory of fluctuations of a colloidal solid observed in a confocal slice. For a cubic crystal we study the evolution of the projected elastic properties as a function of the anisotropy of the crystal using numerical methods based on the fast Fourier transform. In certain situations of high symmetry we find exact analytic results for the projected fluctuations.Comment: 6 pages, 7 figure

Impact of the European Clinical Trials Directive on prospective academic clinical trials associated with BMT

The European Clinical Trials Directive (EU 2001; 2001/20/EC) was introduced to improve the efficiency of commercial and academic clinical trials. Concerns have been raised by interested organizations and institutions regarding the potential for negative impact of the Directive on non-commercial European clinical research. Interested researchers within the European Group for Blood and Marrow Transplantation (EBMT) were surveyed to determine whether researcher experiences confirmed this view. Following a pilot study, an internet-based questionnaire was distributed to individuals in key research positions in the European haemopoietic SCT community. Seventy-one usable questionnaires were returned from participants in different EU member states. The results indicate that the perceived impact of the European Clinical Trials Directive has been negative, at least in the research areas of interest to the EBMT

Genetic variation in the endangered Southwestern Willow Flycatcher

The Southwestern Willow Flycatcher (Empidonax traillii extimus) is an endangered Neotropical migrant that breeds in isolated remnants of dense riparian habitat in the southwestern United States. We estimated genetic variation at 20 breeding sites of the Southwestern Willow Flycatcher (290 individuals) using 38 amplified fragment length polymorphisms (AFLPs). Our results suggest that considerable genetic diversity exists within the subspecies and within local breeding sites. Statistical analyses of genetic variation revealed only slight, although significant, differentiation among breeding sites (Mantel's r = 0.0705, P < 0.0005; theta = 0.0816, 95% CI = 0.0608 to 0.1034; Phi sub(ST) = 0.0458, P < 0.001). UPGMA cluster analysis of the AFLP markers indicates that extensive gene flow has occurred among breeding sites. No one site stood out as being genetically unique or isolated. Therefore, the small level of genetic structure that we detected may not be biologically significant. Ongoing field studies are consistent with this conclusion. Of the banded birds that were resighted or recaptured in Arizona during the 1996 to 1998 breeding seasons, one-third moved between breeding sites and two-thirds were philopatric. Low differentiation may be the result of historically high rangewide diversity followed by recent geographic isolation of breeding sites, although observational data indicate that gene flow is a current phenomenon. Our data suggest that breeding groups of E. t. extimus act as a metapopulation

Combination Forecasts of Bond and Stock Returns: An Asset Allocation Perspective

We investigate the out-of-sample forecasting ability of the HML, SMB, momentum, short-term and long-term reversal factors along with their size and value decompositions on U.S. bond and stock returns for a variety of horizons ranging from the short run (1 month) to the long run (2 years). Our findings suggest that these factors contain significantly more information for future bond and stock market returns than the typically employed financial variables. Combination of forecasts of the empirical factors turns out to be particularly successful, especially from an an asset allocation perspective. Similar findings pertain to the European and Japanese markets

Peripheral blood mononuclear cells of breast cancer patients can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells [poster abstract]

Barriers limiting the efficacy of adoptive cellular therapy (ACT) for breast cancer patients include immune suppression mediated by myeloid-derived suppressor cells (MDSC) and a low frequency of tumor-reactive memory T cells (Tm). Recently, we developed an ex vivo protocol to reprogram tumor-reactive murine splenocytes; these cells were found to be resistant to MDSC suppression and protected FVBN202 mice from tumor challenge. Here, we evaluated the clinical applicability of reprogramming tumor-sensitized PBMCs isolated from patients with early stage breast cancer by treatment with bryostatin 1 and ionomycin (B/I) combined with IL-2, IL-7 and IL-15. Our data demonstrate that reprogrammed cells are enriched with Tm cells (n=5; p=0.006), as well as activated CD56+(n=6; p=0.003) and CD161+ (n=4; p=0.02) NKT cells, and demonstrate expansion in total cell numbers (n=16; p=0.003) compared to baseline cells. Reprogrammed PBMCs displayed enhanced HER-2/neu-specific IFN-γ producing immune responses (n=6; p=0.04); non-reprogrammed control PBMC IFN-γ production was not significant (n=6; p=0.4). Furthermore, high-throughput sequencing analysis of the T cell receptor (TcR) Vβ in one patient demonstrated clonal expansion of specific TcR VJ recombination events resulting from cellular reprogramming, suggestive of an enriched frequency of specific tumor antigen-primed T cell clones. Interestingly, reprogrammed T cells were resistant to autologous CD33+ CD11b+ HLA-DRlo/- MDSCs, as determined by further enhanced HER-2/neu-specific IFN-γ secretion in the presence of MDSCs (n=6; p=0.03). Activated CD161+ NKT cells comprising 3% or greater of total reprogrammed cells rendered T cells resistant to MDSCs (n=3; p=0.02). Upregulation of NKG2D expression on CD161+(n=5; p=0.0006) and CD56+ (n=5; p=0.04) NKT cells resulted from cellular reprogramming. Therefore, NKG2D signaling was blocked using anti-NKG2D blocking antibody in our co-culture system, resulting in the abrogation of resistance to MDSCs as determined by blunted IFN-γ secretion (n=3; p=0.04). Finally, the phenotype of MDSCs after co-culture with reprogrammed PBMC was examined; we observed downregulation of CD11b expression (n=3; p=0.02) concomitant with HLA-DR upregulation on MDSCs (n=3; p=0.001); suggestive of induced maturation of MDSCs into Dendritic Cells (DC). The results of our study offer the following strategies to improve ACT of breast cancer: i) inclusion of activated NKT cells in ACT to overcome MDSC suppression by inducing MDSC maturation into DCs, and ii) PBMC reprogramming to enrich the frequency of tumor-reactive Tm cells

Evaluation of two interaction techniques for visualization of dynamic graphs

Several techniques for visualization of dynamic graphs are based on different spatial arrangements of a temporal sequence of node-link diagrams. Many studies in the literature have investigated the importance of maintaining the user's mental map across this temporal sequence, but usually each layout is considered as a static graph drawing and the effect of user interaction is disregarded. We conducted a task-based controlled experiment to assess the effectiveness of two basic interaction techniques: the adjustment of the layout stability and the highlighting of adjacent nodes and edges. We found that generally both interaction techniques increase accuracy, sometimes at the cost of longer completion times, and that the highlighting outclasses the stability adjustment for many tasks except the most complex ones.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016