Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.     

An integrated model for designing and optimising an international logistics network

Supply-chain configuration has recently gained increasing attention both from the practitioner's perspective and as a research area. This paper proposes an integrated model for designing and optimising international logistics networks. It consists of a mixed integer linear programming model and a data-mapping section (i.e. methodological guidelines for gathering and processing the data necessary to set up the model). It has been specifically developed for solving the configuration problem for supply chains characterised by a complexity level typical of real-life global logistics networks. Although this topic is well understood and well elaborated at a technical level in the extant literature, it still presents obstacles in practice especially in terms of dealing with real-life complexity, service-level constraints and data mapping. Thus, we developed our integrated approach with the aim to fill these gaps. We designed our model for dealing with multiple-layer, single location-layer, multiple-commodity and time-constrained logistics networks, to be implemented in a single period time horizon and in a deterministic environment. The proposed approach represents an innovative contribution to the existing body of scientific knowledge and facilitates the data gathering and processing activities, which are largely recognised as complex and time-consuming processes for the management of logistics activities.     

Human-robot synchrony: flexible assistance using adaptive oscillators

We propose a novel method for movement assistance that is based on adaptive oscillators, i.e., mathematical tools that are capable of extracting the high-level features (amplitude, frequency, and offset) of a periodic signal. Such an oscillator acts like a filter on these features, but keeps its output in phase with respect to the input signal. Using a simple inverse model, we predicted the torque produced by human participants during rhythmic flexion-extension of the elbow. Feeding back a fraction of this estimated torque to the participant through an elbow exoskeleton, we were able to prove the assistance efficiency through a marked decrease of the biceps and triceps electromyography. Importantly, since the oscillator adapted to the movement imposed by the user, the method flexibly allowed us to change the movement pattern and was still efficient during the nonstationary epochs. This method holds promise for the development of new robot-assisted rehabilitation protocols because it does not require prespecifying a reference trajectory and does not require complex signal sensing or single-user calibration: the only signal that is measured is the position of the augmented joint. In this paper, we further demonstrate that this assistance was very intuitive for the participants who adapted almost instantaneously.     

Anti-fingerprints fluorinated coating for anodized titanium avoiding color alteration

In this study amorphous fluorinated coatings applied to anodized titanium surface have been investigated. A copolymer between tetrafluoroethylene and perfluoro-4-trifluoromethoxy-1,3-dioxole (AD60) and two perfluoropolyether containing ammonium phosphate (F10) or triethoxysilane (S10) functionalities have been tested. To estimate the color alteration of the anodized titanium surfaces due to the application of the coatings, spectrophotometric analyses have been made. Water and n-dodecane contact angles as well as apparent surface energy have been evaluated. Ellipsometry and atomic force microscopy data have been used to measure the thickness of the fluorinated coatings. A tailored mechanical preliminary test has also been explored to evaluate the adhesion of the coatings on the anodized titanium surface. The resistance to surface soiling with castor oil was also preliminarily investigated. The fluorinated coating tested on anodized titanium showed a low apparent surface energy and high chromatic aspect conservation, this is particularly evident for the titanium anodized coated with triethoxysilane functionalities fluoropolymers S10.     

Flexible B2B processes: the answer is in the nodes

The time and costs involved in connecting the IT systems of two companies impact the actual formation of business relationships. A flexible infrastructure for process management is instrumental for rapid and cost-effective B2B integration. One dimension of flexibility that system integrators identify as critical is node-level interaction. In this paper, we discuss the findings of the Nile project on B2B process integration. In particular, we present the methodology defined in Nile for the semi-automatic reconciliation of node-level incompatibilities.     

社会团体的反击

认为web3.0和社交网络会让我们摆脱在公共空间中进行物理交流需求的想法需要再斟酌。事实上,当环境中的技术设施让我们能够用负担得起的可移动设备与世界相联系、让新的工作和社交模式能够在家里甚至喜爱的酒吧中产生的时候,很多在家工作的人和网友开始感受到一种需要重新建立起某些真正的社会团体的需求。因此很容易理解,在过去的几十年中,许多城市成为一种合作机制网络成长的摇篮。合作机制是一种实验,为喜欢与他人共享空间的人们提供廉价、灵活和非正规的生活和工作的解决方案。更准确地说,分享是这些措施中可持续性的关键,因为仅仅通过让一个     

Subspace identification analysis of RFX and T2R reversed-field pinches

Input–output datasets from two magnetic confinement fusion (MCF) experiments of the reversed-field pinch (RFP) type are examined. The RFP datasets, which are samples of the distributed magnetic field dynamics, are naturally divided into many smaller batches due to the pulsed-plasma operation of the experiments. The two RFP experiments considered are (i) EXTRAP T2R (T2R) with 64 inputs and 64 outputs and (ii) RFX-mod (RFX) with 192 inputs and 192 outputs. Both T2R and RFX are magnetohydrodynamically unstable and operates under magnetic feedback with optional dither injection. Using subspace system identification techniques and randomised cross-validation (CV) methods to minimise the generalisation error, state-space orders of the empirical systems are suggested. These system orders are compared to “stabilisation diagrams” commonly used in experimental modal analysis practice. The relation of the CV system order to the decay of the singular values from the subspace method is observed. Both (i) stable vacuum diffusion and (ii) unstable plasma response datasets are analysed. Apparent simulation and prediction errors are quantified for both cases using a deviation-accounted-for index. These results are purely data-driven. A simple approach towards exploitation of the subspace techniques for finite-element model refinement and data confrontation is presented.