Urban Prospects: A Search for Poetry in the American City Part 2

This thesis is about establishing an attitude about design which argues building organization, appearance and meaning. Architecture should be a reflection of culture rather than being an instagator of change

Checkpoint Inhibitors in Acute Myeloid Leukemia

The prognosis of acute myeloid leukemia (AML) remains unsatisfactory. Among the reasons for the poor response to therapy and high incidence of relapse, there is tumor cell immune escape, as AML blasts can negatively influence various components of the immune system, mostly weakening T-cells. Since leukemic cells can dysregulate immune checkpoints (ICs), receptor-based signal transductors that lead to the negative regulation of T-cells and, eventually, to immune surveillance escape, the inhibition of ICs is a promising therapeutic strategy and has led to the development of so-called immune checkpoint inhibitors (ICIs). ICIs, in combination with conventional chemotherapy, hypomethylating agents or targeted therapies, are being increasingly tested in cases of AML, but the results reported are often conflicting. Here, we review the main issues concerning the immune system in AML, the main pathways leading to immune escape and the results obtained from clinical trials of ICIs, alone or in combination, in newly diagnosed or relapsed/refractory AML

Present and Future Role of Immune Targets in Acute Myeloid Leukemia

It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens. Though dozens of clinical trials, mostly in phases I and II, are ongoing worldwide, results have still been negatively affected by difficulties in the identification of the optimal targets on LSCs

ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?

Despite the progress in the knowledge of disease pathogenesis and the identification of many molecular markers as potential targets of new therapies, the cure of acute myeloid leukemia remains challenging. Disease recurrence after an initial response and the development of resistance to old and new therapies account for the poor survival rate and still make allogeneic stem cell transplantation the only curative option. Multidrug resistance (MDR) is a multifactorial phenomenon resulting from host-related characteristics and leukemia factors. Among these, the overexpression of membrane drug transporter proteins belonging to the ABC (ATP-Binding Cassette)-protein superfamily, which diverts drugs from their cellular targets, plays an important role. Moreover, a better understanding of leukemia biology has highlighted that, at least in cancer, ABC protein’s role goes beyond simple drug transport and affects many other cell functions. In this paper, we summarized the current knowledge of ABCG2 (formerly Breast Cancer Resistance Protein, BCRP) in acute myeloid leukemia and discuss the potential ways to overcome its efflux function and to revert its ability to confer stemness to leukemia cells, favoring the persistence of leukemia progenitors in the bone marrow niche and justifying relapse also after therapy intensification with allogeneic stem cell transplantation

A PBW basis for Lusztig's form of untwisted affine quantum groups

Let $\mathfrak{g}$ be an untwisted affine Kac-Moody algebra over the field $K \,$, and let $U_q(\mathfrak{g})$ be the associated quantum enveloping algebra; let $\mathfrak{U}_q(g)$ be the Lusztig's integer form of $U_q(\mathfrak{g}) \,$, generated by $q$-divided powers of Chevalley generators over a suitable subring $R$ of $K(q) \,$. We prove a Poincar\'e-Birkhoff-Witt like theorem for $\mathfrak{U}_q(\mathfrak{g}) \,$, yielding a basis over $R$ made of ordered products of $q$-divided powers of suitable quantum root vectors.Comment: 22 pages, AMS-TeX C, Version 2.1c. This is the author's final version, corresponding to the printed journal versio

The Essex-Lopresti lesion

International audienc

Mathematical Programming Algorithms for Spatial Cloaking

We consider a combinatorial optimization problem for spatial information cloaking. The problem requires computing one or several disjoint arborescences on a graph from a predetermined root or subset of candidate roots, so that the number of vertices in the arborescences is minimized but a given threshold on the overall weight associated with the vertices in each arborescence is reached. For a single arborescence case, we solve the problem to optimality by designing a branch-and-cut exact algorithm. Then we adapt this algorithm for the purpose of pricing out columns in an exact branch-and-price algorithm for the multiarborescence version. We also propose a branch-and-price-based heuristic algorithm, where branching and pricing, respectively, act as diversification and intensification mechanisms. The heuristic consistently finds optimal or near optimal solutions within a computing time, which can be three to four orders of magnitude smaller than that required for exact optimization. From an application point of view, our computational results are useful to calibrate the values of relevant parameters, determining the obfuscation level that is achieved