Observation of sub-Bragg diffraction of waves in crystals

We investigate the diffraction conditions and associated formation of stopgaps for waves in crystals with different Bravais lattices. We identify a prominent stopgap in high-symmetry directions that occurs at a frequency below the ubiquitous first-order Bragg condition. This sub-Bragg diffraction condition is demonstrated by reflectance spectroscopy on two-dimensional photonic crystals with a centred rectangular lattice, revealing prominent diffraction peaks for both the sub-Bragg and first-order Bragg condition. These results have implications for wave propagation in 2 of the 5 two-dimensional Bravais lattices and 7 out of 14 three-dimensional Bravais lattices, such as centred rectangular, triangular, hexagonal and body-centred cubic

Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy

Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy. Significance: A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted

Core reconstruction in pseudopotential calculations

A new method is presented for obtaining all-electron results from a pseudopotential calculation. This is achieved by carrying out a localised calculation in the region of an atomic nucleus using the embedding potential method of Inglesfield [J.Phys. C {\bf 14}, 3795 (1981)]. In this method the core region is \emph{reconstructed}, and none of the simplifying approximations (such as spherical symmetry of the charge density/potential or frozen core electrons) that previous solutions to this problem have required are made. The embedding method requires an accurate real space Green function, and an analysis of the errors introduced in constructing this from a set of numerical eigenstates is given. Results are presented for an all-electron reconstruction of bulk aluminium, for both the charge density and the density of states.Comment: 14 pages, 5 figure

Towards Quantum Repeaters with Solid-State Qubits: Spin-Photon Entanglement Generation using Self-Assembled Quantum Dots

In this chapter we review the use of spins in optically-active InAs quantum dots as the key physical building block for constructing a quantum repeater, with a particular focus on recent results demonstrating entanglement between a quantum memory (electron spin qubit) and a flying qubit (polarization- or frequency-encoded photonic qubit). This is a first step towards demonstrating entanglement between distant quantum memories (realized with quantum dots), which in turn is a milestone in the roadmap for building a functional quantum repeater. We also place this experimental work in context by providing an overview of quantum repeaters, their potential uses, and the challenges in implementing them.Comment: 51 pages. Expanded version of a chapter to appear in "Engineering the Atom-Photon Interaction" (Springer-Verlag, 2015; eds. A. Predojevic and M. W. Mitchell

CD4⁺CD25⁻ T Cells Transduced to Express MHC Class I-Restricted Epitope-Specific TCR Synthesize Th1 Cytokines and Exhibit MHC Class I-Restricted Cytolytic Effector Function in a Human Melanoma Model

Cytolytic T cell-centric active specific and adoptive immunotherapeutic approaches might benefit from the simultaneous engagement of CD4⁺ T cells. Considering the difficulties in simultaneously engagingCD4⁺ and CD8⁺ T cells in tumor immunotherapy, especially in an Ag-specific manner, redirecting CD4⁺ T cells to MHC class I-restricted epitopes through engineered expression of MHC class I-restricted epitope-specific TCRs in CD4⁺ T cells has emerged as a strategic consideration. Such TCR-engineered CD4⁺ T cells have been shown to be capable of synthesizing cytokines as well as lysing target cells. We have conducted a critical examination of functional characteristics of CD4⁺ T cells engineered to express the α- and β-chains of a high functional avidity TCR specific for the melanoma epitope, MART-1, as a prototypic human tumor Ag system. We found that unpolarized CD4⁺CD25⁻ T cells engineered to express the MART-1 TCR selectively synthesize Th1 cytokines and exhibit a potent Ag-specific lytic granule exocytosis-mediated cytolytic effector function of comparable efficacy to that of CD8⁺ CTL. Such TCR engineered CD4⁺ T cells, therefore, might be useful in clinical immunotherapy

Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma

<p>Abstract</p> <p>Background</p> <p>CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated.</p> <p>Methods</p> <p>Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4⁺/CD8⁺cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis.</p> <p>Results</p> <p>Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8⁺cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup.</p> <p>Conclusion</p> <p>Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood.</p> <p>Clinical trial registration number</p> <p>NCT00086489</p

Overview of the Opportunity Mars Exploration Rover mission to Meridiani Planum: Eagle crater to Purgatory ripple

The Mars Exploration Rover Opportunity touched down at Meridiani Planum in January 2004 and since then has been conducting observations with the Athena science payload. The rover has traversed more than 5 km, carrying out the first outcrop-scale investigation of sedimentary rocks on Mars. The rocks of Meridiani Planum are sandstones formed by eolian and aqueous reworking of sand grains that are composed of mixed fine-grained siliciclastics and sulfates. The siliciclastic fraction was produced by chemical alteration of a precursor basalt. The sulfates are dominantly Mg-sulfates and also include Ca-sulfates and jarosite. The stratigraphic section observed to date is dominated by eolian bedforms, with subaqueous current ripples exposed near the top of the section. After deposition, interaction with groundwater produced a range of diagenetic features, notably the hematite-rich concretions known as &lsquo;&lsquo;blueberries.&rsquo;&rsquo; The bedrock at Meridiani is highly friable and has undergone substantial erosion by wind-transported basaltic sand. This sand, along with concretions and concretion fragments eroded from the rock, makes up a soil cover that thinly and discontinuously buries the bedrock. The soil surface exhibits both ancient and active wind ripples that record past and present wind directions. Loose rocks on the soil surface are rare and include both impact ejecta and meteorites. While Opportunity&rsquo;s results show that liquid water was once present at Meridiani Planum below and occasionally at the surface, the environmental conditions recorded were dominantly arid, acidic, and oxidizing and would have posed some significant challenges to the origin of life.Additional co-authors: J Farmer, WH Farrand, W Folkner, R Gellert, TD Glotch, M Golombek, S Gorevan, JA Grant, R Greeley, J Grotzinger, KE Herkenhoff, S Hviid, JR Johnson, G Klingelhöfer, AH Knoll, G Landis, M Lemmon, R Li, MB Madsen, MC Malin, SM McLennan, HY McSween, DW Ming, J Moersch, RV Morris, T Parker, JW Rice Jr, L Richter, R Rieder, M Sims, M Smith, P Smith, LA Soderblom, R Sullivan, NJ Tosca, H Wnke, T Wdowiak, M Wolff, A Ye