Radon mitigation during the installation of the CUORE 0νββ0\nu\beta\beta decay detector

CUORE - the Cryogenic Underground Observatory for Rare Events - is an experiment searching for the neutrinoless double-beta ($0\nu\beta\beta$) decay of $^{130}$Te with an array of 988 TeO$_2$ crystals operated as bolometers at $\sim$10 mK in a large dilution refrigerator. With this detector, we aim for a $^{130}$Te $0\nu\beta\beta$ decay half-life sensitivity of $9\times10^{25}$ y with 5 y of live time, and a background index of $\lesssim 10^{-2}$ counts/keV/kg/y. Making an effort to maintain radiopurity by minimizing the bolometers' exposure to radon gas during their installation in the cryostat, we perform all operations inside a dedicated cleanroom environment with a controlled radon-reduced atmosphere. In this paper, we discuss the design and performance of the CUORE Radon Abatement System and cleanroom, as well as a system to monitor the radon level in real time.Comment: 10 pages, 6 figures, 1 tabl

2OACTIVATION OF T CELLS UPON TREATMENT WITH BISPECIFIC ANTIBODIES CORRELATES WITH THE EXPRESSION OF CO-INHIBITORY RECEPTORS ON TUMOR-INFILTRATING LYMPHOCYTES IN HUMAN LUNG CANCER

Introduction: T cell bispecific antibodies (TCB) are designed to recruit and simultaneously activate T cells against target cells such as tumor cells expressing a particular surface antigen. However, it is currently unknown how immuno-modulatory mechanisms active in the tumor microenvironment such as the expression of T cell co-inhibitory receptors may influence the therapeutic effect of TCBs. Methods: We performed a comprehensive phenotypic analysis of tumor infiltrating immune cells from lung carcinoma digests by multicolour flow cytometry. In particular, expression of T cell co-inhibitory and -stimulatory receptors was analyzed. Tumor digests were treated with catumaxomab, a TCB directed against CD3 and EpCAM. T cell activation and effector functions were assessed upon exposure to catumaxomab. Results: CD8+ T cells in lung carcinoma showed a broad heterogeneity in expression of the T cell co-inhibitory receptors PD-1, Tim-3, CTLA-4, Lag-3 and BTLA. Tumor stage and nodal status correlated with number and intensity of expressed receptors. Upon exposure to catumaxomab, a considerable heterogeneity in T cell activation among different tumors was observed. Of note, T cells expressing high levels and multiple co-inhibitory receptors were more impaired in their activation and effector functions after treatment with catumaxomab indicating a higher level of exhaustion. In a further analysis of CD8+ TIL subsets we found that BTLA+ T cells expressed more additional inhibitory receptors than all other subsets, namely PD-1, Tim-3, CTLA-4 and Lag-3, whereas only a small part of PD-1+ T cells expressed another receptor. Tim-3+ T cells usually co-expressed PD-1, but multiple receptors were found only on a low number of cells. Conclusion: In summary, our data suggest that the activity of TCBs is largely affected by the expression of T cell co-inhibitory receptors on tumor-infiltrating immune cells. Furthermore, these data provide a clinical rationale for combining bispecific antibodies with compounds which antagonize T cell exhaustion. Disclosure: D. Thommen, J. Schreiner, P. Herzig, P. Mueller and A. Zippelius: received research funding from Roche Glycart; V. Karanikas: is employed by Roche Glycart. All other authors have declared no conflicts of interes

Resonance production by neutrinos: I. J=3/2 Resonances

The article contains general formulas for the production of J=3/2 resonances by neutrinos and antineutrinos. It specializes to the P_{33}(1232) resonance whose form factors are determined by theory and experiment and then are compared with experimental results at low and high energies. It is shown that the minimum in the low Q^2 region is a consequence of a combined effect from the vanishing of the vector form factors, the muon mass and Pauli blocking. Several improvements for the future investigations are suggested.Comment: 10 pages, LaTeX, misprints corrected, 1 reference adde

Poly[diacetonitrile­[μ3-difluoro­(oxalato)borato]sodium]

The title compound, [Na(C2BF2O4)(CH3CN)2]n, forms infinite two-dimensional layers running parallel to (010). The layers lie across crystallographic mirror planes at y = 1/4 and 3/4. The Na, B and two F atoms reside on these mirror planes. The Na+ cations are six-coordinate. Two equatorial coordination positions are occupied by acetonitrile mol­ecules. The other two equatorial coordination sites are occupied by the chelating O atoms from the difluoro­(oxalato)borate anion (DFOB−). The axial coordination sites are occupied by two F atoms from two different DFOB− anions

5PMICROTUBULE-DEPOLYMERIZING AGENTS USED IN ANTIBODY-DRUG-CONJUGATES INDUCE ANTITUMOR ACTIVITY BY STIMULATION OF DENDRITIC CELLS

Antibody drug conjugates (ADCs) are emerging as powerful treatment strategies with outstanding target specificity and high therapeutic activity in cancer patients. While >30 ADCs are currently being investigated in clinical trials, brentuximabvedotin and T-DM1 represent clinically approved ADCs in cancer patients. We hypothesized that their sustained clinical responses could be related to the stimulation of an antitumor immune response. Indeed, the two microtubule-destabilizing agents Dolastatin 10 and Ansamitocin P3, from which the cytotoxic components of brentuximabvedotin and T-DM1 are derived, may serve as prototypes for a class of agents that induce tumor cell death and convert tumor resident, tolerogenic dendritic cells (DCs) into efficient antigen presenting cells (APCs). The two drugs induced phenotypic and functional maturation of murine splenic as well as human monocyte-derived DCs. In contrast, microtubule-stabilizing agents such as taxanes did not display this feature. In tumor models, both Dolastatin 10 and Ansamitocin P3 efficiently promoted antigen uptake and migration of tumor-resident DCs to tumor-draining lymph nodes, thereby potentiating tumor-specific T cell responses. Underlining the requirement of an intact host immune system for the full therapeutic benefit of these two compounds, their antitumor effect was far less pronounced in mice lacking adaptive immunity or dendritic cells. Combinations with immune checkpoint inhibition (anti-CTLA-4/-PD-1) did further augment antitumor immunity and tumor rejection, which was reflected by reduced Treg numbers and elevated effector function of tumor resident T cells. Ultimately, we were able to demonstrate peripheral immune cell activation and brisk T cell infiltration into tumors in patients previously treated with BrentuximabVedotin. Experiments are currently ongoing to investigate the immunological mode of action of T-DM1 using orthotopic breast cancer models and patients undergoing treatment. Our data reveal a novel mode of action for microtubule-depolymerizing agents and provide a strong rationale for clinical treatment regimens combining these with immune-based therapies. Disclosure: All authors have declared no conflicts of interes

Multiplier analysis for agriculture and other industries

The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

Abelian functions associated with a cyclic tetragonal curve of genus six

We develop the theory of Abelian functions defined using a tetragonal curve of genus six, discussing in detail the cyclic curve y^4 = x^5 + λ[4]x^4 + λ[3]x^3 + λ[2]x^2 + λ[1]x + λ[0]. We construct Abelian functions using the multivariate sigma-function associated with the curve, generalizing the theory of theWeierstrass℘-function. We demonstrate that such functions can give a solution to the KP-equation, outlining how a general class of solutions could be generated using a wider class of curves. We also present the associated partial differential equations satisfied by the functions, the solution of the Jacobi inversion problem, a power series expansion for σ(u) and a new addition formula

Spin states of zigzag-edged Mobius graphene nanoribbons from first principles

Mobius graphene nanoribbons have only one edge topologically. How the magnetic structures, previously associated with the two edges of zigzag-edged flat nanoribbons or cyclic nanorings, would change for their Mobius counterparts is an intriguing question. Using spin-polarized density functional theory, we shed light on this question. We examine spin states of zigzag-edged Mobius graphene nanoribbons (ZMGNRs) with different widths and lengths. We find a triplet ground state for a Mobius cyclacene, while the corresponding two-edged cyclacene has an open-shell singlet ground state. For wider ZMGNRs, the total magnetization of the ground state is found to increase with the ribbon length. For example, a quintet ground state is found for a ZMGNR. Local magnetic moments on the edge carbon atoms form domains of majority and minor spins along the edge. Spins at the domain boundaries are found to be frustrated. Our findings show that the Mobius topology (i.e., only one edge) causes ZMGNRs to favor one spin over the other, leading to a ground state with non-zero total magnetization.Comment: 17 pages, 4 figure