Dispatcher3 D1.1 - Technical resources and problem definition

This deliverable starts with the proposal of Dispatcher3 and incorporates the development produced during the first five months of the project: activities on different workpackages, interaction with Topic Manager and Project Officer, and input received during the first Advisory Board meeting and follow up consultations. This deliverable presents the definition of Dispatcher3 concept and methodology. It includes the high level the requirements of the prototype, preliminary data requirements, preliminary technical infrastructure requirements, preliminary data processing and analytic techniques identification and a preliminary definition of scenarios. The deliverable aims at defining the view of the consortium on the project at these early stages, incorporating the feedback obtained from the Advisory Board and highlighting the further activities required to define some of the aspects of the project

Dispatcher3 D5.1 - Verification and validation plan

In this deliverable, we present a verification and validation plan designed to carry out all necessary activities along Dispatcher3 prototype development. Given the nature of the project, the deliverable points to a data-centric approach to machine learning that treats training and testing models as an important production asset, together with the algorithm and infrastructure used throughout the development. The verification and validation activities will be presented in the document. The proposed framework will support the incremental development of the prototype based on the principle of iterative development paradigm. The core of the verification and validation approach is structured around three different and inter-related phases including data acquisition and preparation, predictive model development and advisory generator model development which are combined iteratively and in close coordination with the experts from the consortium and the Advisory Board. For each individual phase, a set of verification and validation activities will be performed to maximise the benefits of Dispatcher3. Thus, the methodological framework proposed in this deliverable attempts to address the specificities of the verification and validation approach in the domain of machine learning, as it differs from the canonical approach which are typically based on standardised procedures, and in the domain of the final prospective model. This means that the verification and validation of the machine learning models will also be considered as a part of the model development, since the tailoring and enhancement of the model highly relies on the verification and validation results. The deliverable provides an approach on the definition of preliminary case studies that ensure the flexibility and tractability in their selection through different machine learning model development. The deliverable finally details the organisation and schedule of the internal and external meetings, workshops and dedicated activities along with the specification of the questionnaires, flow-type diagrams and other tool and platforms which aim to facilitate the validation assessments with special focus on the predictive and prospective models

Considering TMA holding uncertinaty into in-flight trajectory optimisation

Aircraft crew are aware of the delay they have experienced at departure. However, uncertainties ahead, and in particular holdings at arrival, can have an impact on the final performance of their operations. When optimising a trajectory the expected cost at the arrival gate should be considered. Consequently, taking into account potential congestion and extra delay at the arrival airspace is paramount to avoid taking sub-optimal decisions at the early stages of the flight. This paper presents a framework to optimise trajectories in the execution phase of the flight considering expected delays at arrival. A flight from Athens (LGAV) to London Heathrow (EGLL) is used as illustrative example, systematically exploring a range of departure delays and expected holdings at arrival

NOSTROMO - D1.2 - Final Project Results Report

The main objective of the NOSTROMO project has been to develop, demonstrate and evaluate an innovative modelling approach for the rigorous and comprehensive assessment of the performance impact of future ATM concepts and solutions at ECAC network level. This approach brings together the ability of bottom-up microscopic models to capture emergent behaviour and interdependencies between different solutions with the level of tractability and interpretability required to effectively support decision-making. This report provides a summary of NOSTROMO accomplishments and contributions to the SESAR Programme. It gathers technical lessons learned and concludes proposing further developments to facilitate the use of the NOSTROMO methodology in the future SESAR 3 Programme

Pilot3 D5.2 - Verification and validation report

The deliverable provides the outcomes from the verification and validation activities carried during the course of work package 5 of the Pilot3 project, and according to the verification and validation plan defined in deliverable D5.1 (Pilot3 Consortium, 2020c). Firstly, it presents the main results of the verification activities performed during the development and testing of the different software versions. Then, this deliverable reports on the results of internal and external validation activities, which aimed to demonstrate the operational benefit of the Pilot3 tool, assessing the research questions and hypothesis that were defined at the beginning of the project. The Agile principle adopted in the project accompanying with the five five-level hierarchy approach on the definition of scenarios and case studies enabled the flexibility and tractability in the selection of experiments through different versions of prototype development. As a result of this iterative development of the tool, some of the research questions initially defined have been revisited to better reflect the validation results. The deliverable also reports the feedback received from the experts during the internal and external meetings, workshops and dedicated (on-line) site visits. During the validation campaign, both subjective qualitative information and objective quantitative data were collected and analysed to assess the Pilot3 tool. The document also summarises the results of the survey that were distributed to the external experts to assess the human-machine interface (HMI) mock-up developed in the project

Pilot3 D1.1 - Technical resources and problem definition

This deliverable starts with the proposal of Pilot3 but incorporates the development produced during the first four months of the project: activities on different workpackages, interaction with Topic Manager and Project Officer, and input received during the first Advisory Board meeting. This deliverable presents the definition of Pilot3 concept and methodology. It includes the high level the requirements of the prototype, preliminary data requirements, preliminary indicators that will be considered and a preliminary definition of case studies. The deliverable aims at defining the view of the consortium on the project at these early stages, while highlighting the feedback obtained from the Advisory Board and the further activities required to define some of the aspects of the project

Far-infrared spectroscopy of a nanocomposite of polyvinyl alcohol and lead sulfide nanoparticles

A nanocomposite consisting of lead sulfide (PbS) nanoparticles (NPs) with average diameter of 26 angstrom, according to absorption threshold shift, and polyvinyl alcohol (PVA) was characterized using far-infrared absorption spectroscopy. The experimental results are consistent with theoretical calculations that include proper mechanical boundary conditions at the nanocrystal-host interface

An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML

CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inositol and MARCH5 as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting MARCH5 in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets. SIGNIFICANCE: There is an unmet need to improve the clinical outcome of AML. We developed an integrated in vivo screening approach to prioritize and validate AML dependencies with high translational potential. We identified SLC5A3 as a metabolic vulnerability and MARCH5 as a critical apoptosis regulator in AML, both of which represent novel therapeutic opportunities.This article is highlighted in the In This Issue feature, p. 275

Discovery of a Selective Inhibitor of Doublecortin Like Kinase 1

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool to investigate DCLK1 biology and establish its role in cancer

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

<p>Abstract</p> <p>Background</p> <p>Alendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.</p> <p>Results</p> <p>Three simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.</p> <p>Conclusion</p> <p>The proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.</p> <p>Graphical abstract</p> <p><display-formula><graphic file="1752-153X-6-25-i3.gif"/></display-formula></p