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Filling constraints on translation invariant dipole conserving systems
No full textSystems with conserved dipole moment have drawn considerable interest in light of their realization in recent experiments on tilted optical lattices. An important issue regarding such systems is delineating the conditions under which they admit a unique gapped ground state that is consistent with all symmetries. Here, we study one-dimensional translation-invariant lattices that conserve U(1) charge and ZL dipole moment, where discreteness of the dipole symmetry is enforced by periodic boundary conditions, with Lthe system size. We show that in these systems a symmetric, gapped, and nondegenerate ground state requires not only integer charge filling, but also a fixed value of the dipole filling, while other fractional dipole fillings enforce either a gapless or symmetry-breaking ground state. In contrast with prior results in the literature, we find that the dipole filling constraint depends both on the charge filling as well as the system size, emphasizing the subtle interplay of dipole symmetry with boundary conditions. We support our results with numerical simulations and exact results
Long term results of a prospective multicenter observational study on the use of anti-human T-lymphocyte immunoglobulin (ATLG) in unrelated donor transplantation (ATOS study).
No full textATOS is a prospective observational study evaluating the outcome of patients receiving anti-human T-lymphocyte immunoglobulin (ATLG) in unrelated donor transplantation. Primary endpoint was severe GvHD and relapse-free survival (SGRFS). GvHD prophylaxis consisted of ATLG and CSA/ MTX or MMF. Outcome was compared to the ATLG arm of our prospective randomized phase III multicenter trial trial (RCT) [1, 2]. 165 patients, median age 54 (18; 77) years, with haematological malignancies with early (45.5%), intermediate (17.6%), and advanced (37.0%) disease were included. ATLG dose differed between centers according to local practise (median total ATLG dose of 46 (IQR 32-60, range 15-91) mg/kg). Median follow-up was 70 months. Estimated probabilities at 5 years follow up were for SGRFS 0.27, OS 0.52, DFS 0.43, NRM 0.23, relapse 0.34, acute GvhD °III/IV 0.13, severe chronic GvHD 0.27. OS rates differed dependent on disease status. An effect of the given ATLG dose could not be separated from potential center effects. Despite higher age and more advanced disease in ATOS, outcome was similar to the ATLG arm of our RCT. This long-term, multicenter, experience in routine clinical practice confirms the GvHD-protective effect of ATLG without compromising relapse and non-relapse mortality rates.Clinical Trial Registry: German clinical trials register DRKS00004581
Clonal hematopoiesis and its impact on the aging osteo-hematopoietic niche.
No full textClonal hematopoiesis (CH) defines a premalignant state predominantly found in older persons that increases the risk of developing hematologic malignancies and age-related inflammatory diseases. However, the risk for malignant transformation or non-malignant disorders is variable and difficult to predict, and defining the clinical relevance of specific candidate driver mutations in individual carriers has proved to be challenging. In addition to the cell-intrinsic mechanisms, mutant cells rely on and alter cell-extrinsic factors from the bone marrow (BM) niche, which complicates the prediction of a mutant cell's fate in a shifting pre-malignant microenvironment. Therefore, identifying the insidious and potentially broad impact of driver mutations on supportive niches and immune function in CH aims to understand the subtle differences that enable driver mutations to yield different clinical outcomes. Here, we review the changes in the aging BM niche and the emerging evidence supporting the concept that CH can progressively alter components of the local BM microenvironment. These alterations may have profound implications for the functionality of the osteo-hematopoietic niche and overall bone health, consequently fostering a conducive environment for the continued development and progression of CH. We also provide an overview of the latest technology developments to study the spatiotemporal dependencies in the CH BM niche, ideally in the context of longitudinal studies following CH over time. Finally, we discuss aspects of CH carrier management in clinical practice, based on work from our group and others
Efficient and Deterministic Search Strategy Based on Residual Projections for Point Cloud Registration With Correspondences
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A computation engine for numerical system requirements generation in LLM-based spacecraft design assistants
No full textThe design of spacecraft, and more broadly of space missions, can greatly benefit from LLM-based design assistants supporting engineers in the extraction of relevant information from past missions for its reuse in the new one, as well as in the automatic generation of system parameters or requirements in text at different levels. However, due to the mathematical nature of technical systems, many of the spacecraft parameters or requirements are numerical and involve calculations or the application of first principles. While Large Language Models excel at text generation, predicting the next words in a sequence with the highest probability, they are not suited, being statistical engines, to perform deterministic computations. In this paper, we present the architecture of a computation engine to which numerical calculations are outsourced during the process of generating parameters or requirements by an LLM-based design assistant. We present the integration with the LLM, measure its performance, and benchmark and discuss the improvement in parameters generation with a space mission as a use case. In particular, the computation engine hereby developed follows an object-oriented programming paradigm, mimicking through the classes the subsystems of a spacecraft, through the class properties their parameters, and through the class functions the equations and first principles used to calculate the parameters’ values, which can be then expressed by the LLM as numerical system parameters or requirements with natural language. A high-level programming language and a modular approach are followed in seek of high readability and modifiability, allowing the engine to be extended and its granularity increased in future iterations. Different alternatives for the integration of the computation engine with the LLM and in the design flow are evaluated and compared, and parameters such as the computation speed and error are measured and assessed along different computation platforms. By presenting this computation engine for spacecraft design, we aim at patching the shortcomings of LLM-based design assistants in numerical calculations, paving the way for their adoption and thus helping accelerate and simplify spacecraft design tasks for a broader range of institutions and individuals
