On the black-box complexity of Sperner's Lemma

We present several results on the complexity of various forms of Sperner's Lemma in the black-box model of computing. We give a deterministic algorithm for Sperner problems over pseudo-manifolds of arbitrary dimension. The query complexity of our algorithm is linear in the separation number of the skeleton graph of the manifold and the size of its boundary. As a corollary we get an $O(\sqrt{n})$ deterministic query algorithm for the black-box version of the problem {\bf 2D-SPERNER}, a well studied member of Papadimitriou's complexity class PPAD. This upper bound matches the $\Omega(\sqrt{n})$ deterministic lower bound of Crescenzi and Silvestri. The tightness of this bound was not known before. In another result we prove for the same problem an $\Omega(\sqrt[4]{n})$ lower bound for its probabilistic, and an $\Omega(\sqrt[8]{n})$ lower bound for its quantum query complexity, showing that all these measures are polynomially related.Comment: 16 pages with 1 figur

Redirecting T Cells to Ewing's Sarcoma Family of Tumors by a Chimeric NKG2D Receptor Expressed by Lentiviral Transduction or mRNA Transfection

We explored the possibility to target Ewing's sarcoma family of tumors (ESFT) by redirecting T cells. To this aim, we considered NKG2D-ligands (NKG2D-Ls) as possible target antigens. Detailed analysis of the expression of MICA, MICB, ULBP-1, -2, and -3 in fourteen ESFT cell lines revealed consistent expression of at least one NKG2D-L. Thus, for redirecting T cells, we fused a CD3ζ/CD28-derived signaling domain to the ectodomain of NKG2D, however, opposite transmembrane orientation of this signaling domain and NKG2D required inverse orientation fusion of either of them. We hypothesized that the particularly located C-terminus of the NKG2D ectodomain should allow reengineering of the membrane anchoring from a native N-terminal to an artificial C-terminal linkage. Indeed, the resulting chimeric NKG2D receptor (chNKG2D) was functional and efficiently mediated ESFT cell death triggered by activated T cells. Notably, ESFT cells with even low NKG2D-L expression were killed by CD8pos and also CD4pos cells. Both, mRNA transfection and lentiviral transduction resulted in high level surface expression of chNKG2D. However, upon target-cell recognition receptor surface levels were maintained by tranfected RNA only during the first couple of hours after transfection. Later, target-cell contact resulted in strong and irreversible receptor down-modulation, whereas lentivirally mediated expression of chNKG2D remained constant under these conditions. Together, our study defines NKG2D-Ls as targets for a CAR-mediated T cell based immunotherapy of ESFT. A comparison of two different methods of gene transfer reveals strong differences in the susceptibility to ligand-induced receptor down-modulation with possible implications for the applicability of RNA transfection

Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes

BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. DESIGN: Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility