Tumor type M2-pyruvate-kinase levels in pleural fluid versus plasma in cancer patients: a further tool to define the need for invasive procedures

Pleural effusion is a common diagnostic problem and a challenge to the thoracic surgeon. The analysis of serum and body fluids for tumor markers is an established diagnostic procedure. Among various markers, tumors are linked to the overexpression of a glycolytic isoenzyme, M2-pyruvate-kinase (M2-PK). This preliminary study evaluated this enzyme as a tumor marker to differentiate malignant from benign pleural effusion

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Combining metal nanoparticles and nanobodies to boost the biomedical imaging in neurodegenerative diseases

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution.Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks.Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain.Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique

Elemental fragmentation cross sections for a O-16 beam of 400 MeV/u kinetic energy interacting with a graphite target using the FOOT Delta E-TOF detectors

The study of nuclear fragmentation plays a central role in many important applications: from the study of Particle Therapy (PT) up to radiation protection for space (RPS) missions and the design of shielding for nuclear reactors. The FragmentatiOn Of Target (FOOT) collaboration aims to study the nuclear reactions that describe the interactions with matter of different light ions (like H-1, He-4, C-12, O-16) of interest for such applications, performing double differential fragmentation cross section measurements in the energy range of interest for PT and RPS. In this manuscript, we present the analysis of the data collected in the interactions of an oxygen ion beam of 400 MeV/u with a graphite target using a partial FOOT setup, at the GSI Helmholtz Center for Heavy Ion Research facility in Darmstadt. During the data taking the magnets, the silicon trackers and the calorimeter foreseen in the final FOOT setup were not yet available, and hence precise measurements of the fragments kinetic energy, momentum and mass were not possible. However, using the FOOT scintillator detectors for the time of flight (TOF) and energy loss (Delta E) measurements together with a drift chamber, used as beam monitor, it was possible to measure the elemental fragmentation cross sections. The reduced detector set-up and the limited available statistics allowed anyway to obtain relevant results, providing statistically significant measurements of cross sections eagerly needed for PT and RPS applications. Whenever possible the obtained results have been compared with existing measurements helping in discriminating between conflicting results in the literature and demonstrating at the same time the proper functioning of the FOOT Delta E-TOF system. Finally, the obtained fragmentation cross sections are compared to the Monte Carlo predictions obtained with the FLUKA software

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experi- ment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z >= 3 fragments and an emulsion spectrometer for Z <= 3 fragments. The first data taking was performed in 2019 at the GSI facility(Darmstadt, Germany). In this study, the charge identifi-cation of fragments induced by exposing an emulsion detector, embedding a C2H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identifica-tion is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response

Instrumental Perspectivism: Is AI Machine Learning Technology like NMR Spectroscopy?

The question, “Will science remain human?” expresses a worry that deep learning algorithms will replace scientists in making crucial judgments of classification and inference and that something crucial will be lost if that happens.  Ever since the introduction of telescopes and microscopes humans have relied on technologies to “extend” beyond human sensory perception in acquiring scientific knowledge.  In this paper I explore whether the ways in which new learning technologies “extend” beyond human cognitive aspects of science can be treated instrumentally. I will consider the norms for determining the reliability of a detection instrument, nuclear magnetic resonance spectroscopy, in predicting models of protein atomic structure. Do the same norms that apply in that case be used to judge the reliability of Artificial Intelligence deep learning algorithms

Measuring the Impact of Nuclear Interaction in Particle Therapy and in Radio Protection in Space: the FOOT Experiment

In Charged Particle Therapy (PT) proton or 12C beams are used to treat deep-seated solid tumors exploiting the advantageous characteristics of charged particles energy deposition in matter. For such projectiles, the maximum of the dose is released at the end of the beam range, in the Bragg peak region, where the tumour is located. However, the nuclear interactions of the beam nuclei with the patient tissues can induce the fragmentation of projectiles and/or target nuclei and needs to be carefully taken into account when planning the treatment. In proton treatments, the target fragmentation produces low energy, short range fragments along all the beam path, that deposit a non-negligible dose especially in the first crossed tissues. On the other hand, in treatments performed using 12C, or other (4He or 16O) ions of interest, the main concern is related to the production of long range fragments that can release their dose in the healthy tissues beyond the Bragg peak. Understanding nuclear fragmentation processes is of interest also for radiation protection in human space flight applications, in view of deep space missions. In particular 4He and high-energy charged particles, mainly 12C, 16O, 28Si and 56Fe, provide the main source of absorbed dose in astronauts outside the atmosphere. The nuclear fragmentation properties of the materials used to build the spacecrafts need to be known with high accuracy in order to optimise the shielding against the space radiation. The study of the impact of these processes, which is of interest both for PT and space radioprotection applications, suffers at present from the limited experimental precision achieved on the relevant nuclear cross sections that compromise the reliability of the available computational models. The FOOT (FragmentatiOn Of Target) collaboration, composed of researchers from France, Germany, Italy and Japan, designed an experiment to study these nuclear processes and measure the corresponding fragmentation cross sections. In this work we discuss the physics motivations of FOOT, describing in detail the present detector design and the expected performances, coming from the optimization studies based on accurate FLUKA MC simulations and preliminary beam test results. The measurements planned will be also presented

Performance of the ToF detectors in the foot experiment

The FOOT (FragmentatiOn Of Target) experiment aims to deter- mine the fragmentation cross-sections of nuclei of interest for particle therapy and radioprotection in space. The apparatus is composed of several detectors that allow fragment identification in terms of charge, mass, energy and direction. The frag- ment time of flight (ToF) along a lever arm of ∼2 m is used for particle ID, requiring a resolution below 100ps to achieve a sufficient resolution in the fragment atomic mass identification. The timing performance of the ToF system evaluated with 12C and 16O beams is reviewed in this contribution

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experiment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z ≥ 3 fragments and an emulsion spectrometer for Z ≤ 3 fragments. The first data taking was performed in 2019 at the GSI facility (Darmstadt, Germany). In this study, the charge identification of fragments induced by exposing an emulsion detector, embedding a C2 H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identification is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response

Pushing the high count rate limits of scintillation detectors for challenging neutron-capture experiments

One of the critical aspects for the accurate determination of neutron capture cross sections when combining time-of-flight and total energy detector techniques is the characterization and control of systematic uncertainties associated to the measuring devices. In this work we explore the most conspicuous effects associated to harsh count rate conditions: dead-time and pile-up effects. Both effects, when not properly treated, can lead to large systematic uncertainties and bias in the determination of neutron cross sections. In the majority of neutron capture measurements carried out at the CERN n\_TOF facility, the detectors of choice are the C$_{6}$D$_{6}$ liquid-based either in form of large-volume cells or recently commissioned sTED detector array, consisting of much smaller-volume modules. To account for the aforementioned effects, we introduce a Monte Carlo model for these detectors mimicking harsh count rate conditions similar to those happening at the CERN n\_TOF 20~m fligth path vertical measuring station. The model parameters are extracted by comparison with the experimental data taken at the same facility during 2022 experimental campaign. We propose a novel methodology to consider both, dead-time and pile-up effects simultaneously for these fast detectors and check the applicability to experimental data from $^{197}$Au($n$,$\gamma$), including the saturated 4.9~eV resonance which is an important component of normalization for neutron cross section measurements