Identification of Relevant Spectral Ranges in Laser-Induced Breakdown Spectroscopy Imaging Using the Fourier Space.

Laser-induced breakdown spectroscopy (LIBS) imaging has now a well-established position in the subject of spectral imaging, leveraging multi-element detection capabilities and fast acquisition rates to support applications both at academic and technological levels. In current applications, the standard processing pipeline to explore LIBS imaging data sets revolves around identifying an element that is suspected to exist within the sample and generating maps based on its characteristic emission lines. Such an approach requires some previous expert knowledge both on the technique and on the sample side, which hinders a wider and more transparent accessibility of the LIBS imaging technique by non-specialists. To address this issue, techniques based on visual analysis or peak finding algorithms are applied on the average or maximum spectrum, and may be employed for automatically identifying relevant spectral regions. Yet, maps containing relevant information may often be discarded due to low signal-to-noise ratios or interference with other elements. In this context, this work presents an agnostic processing pipeline based on a spatial information ratio metric that is computed in the Fourier space for each wavelength and that allows for the identification of relevant spectral ranges in LIBS. The results suggest a more robust and streamlined approach to feature extraction in LIBS imaging compared with traditional inspection of the spectra, which can introduce novel opportunities not only for spectral data analysis but also in the field of data compression.

From sensor fusion to knowledge distillation in collaborative LIBS and hyperspectral imaging for mineral identification.

Multimodal spectral imaging offers a unique approach to the enhancement of the analytical capabilities of standalone spectroscopy techniques by combining information gathered from distinct sources. In this manuscript, we explore such opportunities by focusing on two well-known spectral imaging techniques, namely laser-induced breakdown spectroscopy, and hyperspectral imaging, and explore the opportunities of collaborative sensing for a case study involving mineral identification. In specific, the work builds upon two distinct approaches: a traditional sensor fusion, where we strive to increase the information gathered by including information from the two modalities; and a knowledge distillation approach, where the Laser Induced Breakdown spectroscopy is used as an autonomous supervisor for hyperspectral imaging. Our results show the potential of both approaches in enhancing the performance over a single modality sensing system, highlighting, in particular, the advantages of the knowledge distillation framework in maximizing the potential benefits of using multiple techniques to build more interpretable models and paving for industrial applications.

Characterization of Functional Coatings on Cork Stoppers with Laser-Induced Breakdown Spectroscopy Imaging.

Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.

The relationships between reading fluency and different measures of holistic word processing.

Recently, paradigms in the face recognition literature have been adopted to reveal holistic processing in word recognition. It is unknown, however, whether different measures of holistic word processing share similar underlying mechanisms, and whether fluent word reading relies on holistic word processing. We measured holistic processing effects in three paradigms (composite, configural sensitivity, part-whole) as well as in reading fluency (3DM task: reading aloud high- and low-frequency words and pseudowords). Bin scores were used to combine accuracy and response time variables in the quest for a more comprehensive, reliable, and valid measure of holistic processing. Weak correlations were found between the different holistic processing measures, with only a significant correlation between the configural sensitivity effect and part-whole effect (r = .32) and a trend of a positive correlation between the word composite effect and configural sensitivity effect (r = .21). Of the three holistic processing measures, only one (part-whole effect) correlated with a lexical access measure of 3DM (r = .23). We also performed a principal component analysis (PCA) of performance in the three lists of 3DM, with the second most probably reflecting lexical access processes. There was a tendency for a positive correlation between part-whole bin measure and Component 2 of PCA. We also found a positive correlation between composite aligned in accuracy and Component 2 of PCA.Our results show that different measures of holistic word processing reflect predominantly different mechanisms, and that differences among normal readers in word reading do not seem to depend highly on holistic processing.

Holistic word processing is correlated with efficiency in visual word recognition.

Holistic processing of visual words (i.e., obligatory encoding of/attending to all letters of a word) could be a marker of expert word recognition. In the present study, we thus examined for the first time whether there is a direct relation between the word-composite effect (i.e., all parts of a visual word are fully processed when observers perform a task on a word part) and fast access to the orthographic lexicon by visual word experts (i.e., fluent adult readers). We adopted an individual differences approach and used the word-frequency effect (i.e., faster recognition of high- than low-frequency words) in an independent lexical decision task as a proxy of fast access to lexical orthographic representations. Fluent readers with larger word-composite effect showed smaller word-frequency effect. This correlation was mainly driven by an association between a larger composite effect and faster lexical decision on low-frequency words, probably because these lexical representations are less stable and integrated/unitized, hence allowing differentiating among fluent readers. We thus showed that holistic processing of visual words is indeed related to higher efficiency in visual word recognition by skilled readers.

Cannabinoid Actions on Neural Stem Cells: Implications for Pathophysiology.

With the increase of life expectancy, neurodegenerative disorders are becoming not only a health but also a social burden worldwide. However, due to the multitude of pathophysiological disease states, current treatments fail to meet the desired outcomes. Therefore, there is a need for new therapeutic strategies focusing on more integrated, personalized and effective approaches. The prospect of using neural stem cells (NSC) as regenerative therapies is very promising, however several issues still need to be addressed. In particular, the potential actions of pharmacological agents used to modulate NSC activity are highly relevant. With the ongoing discussion of cannabinoid usage for medical purposes and reports drawing attention to the effects of cannabinoids on NSC regulation, there is an enormous, and yet, uncovered potential for cannabinoids as treatment options for several neurological disorders, specifically when combined with stem cell therapy. In this manuscript, we review in detail how cannabinoids act as potent regulators of NSC biology and their potential to modulate several neurogenic features in the context of pathophysiology.

Anxiety Assessment in Pre-clinical Tests and in Clinical Trials: A Critical Review.

The identification of anxious symptoms is crucial to diagnose anxiety disorders, as well as to monitor their treatment in clinical practice and research. The aim of this review is to discuss the different ways of assessing anxiety in clinical research, including clinical trials, and the different kinds of animal behavioral tests used to study anxiety and test the efficacy of anxiolytics in pre-clinical studies. In clinical practice, a categorical classification (such as the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Related Health Problems) distinguishes the cases of the disease versus non-disease. Some structured and semi-structured interviews can be used to arrive at these diagnoses. On the other hand, anxiety can also be assessed using a dimensional approach, through self-report or hetero-evaluation questionnaires. Regarding the assessment of anxiety in animals, several behavioral tests are described and evaluated, namely the Social Interaction Test, Elevated Plus Maze and Open Field Test. Under a critical view, these two approaches are presented and discussed, in order to improve the outcome of research in this field.

Depression Assessment in Clinical Trials and Pre-clinical Tests: A Critical Review.

Depression is deeply rooted in human behavior. The development of new antidepressants demands the creation of animal models to investigate new drugs, which potentially could work as antidepressants. The aim of this review is to discuss the different ways of assessing depression in clinical research, including clinical trials, and the different animal behavioral tests used to study depression and test the efficacy of antidepressants in pre-clinical studies. In clinical practice, a categorical classification, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Statistical Classification of Diseases and Related Health Problems (ICD) can be used for diagnosis, through the use of structured and semi-structured interviews. On the other hand, depression can also be assessed using a dimensional approach, through self- or clinicianrated questionnaires. Regarding the assessment of the efficacy of antidepressants in animal models, several tests are routinely used, namely the Forced Swim Test, the Modified Forced Swim Test, the Tail Suspension Test and the Sucrose Preference Test. These tests are informative, providing that the following rules are taken into account: 1) more than one test is used, with coherent results; 2) secondary drug effects, the most frequent being putative changes in motor activity, are taken into account and properly controlled with specific tests run concomitantly; 3) each test and specific protocol is validated with data from at least a gold standard antidepressant drug. We herein briefly discuss the potential and limitations of each of those tests.

Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity.

The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging.

Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PET.

The availability of commercial (68)Ge/(68)Ga cyclotron-independent (68)Ga(3+) generators is making Positron Emission Tomography (PET) accessible to most hospitals, which is generating a surge of interest in the design and synthesis of bi-functional chelators for Ga(3+). In this work we introduce the NO2A-N-(α-amino)propionic acid family of chelators based on the triazacyclononane scaffold. Complexation of the parent NO2A-N-(α-amino)propionic acid chelator and of a low molecular weight (model) amide conjugate with Ga(3+) was studied by (1)H and (71)Ga NMR. The Ga(3+) chelate of the amide conjugate shows pH-independent N3O3 coordination in the pH range 3-10 involving the carboxylate group of the pendant propionate arm in a 6 member chelate. For the Ga[NO2A-N-(α-amino)propionate] chelate, a reversible pH-triggered switch from Ga(3+) coordination to the carboxylate group to coordination to the amine group of the propionate arm was observed upon pH increase/decrease in the pH range 4-6. This phenomenon can conceivably constitute the basis of a physiological pH sensor. Both complexes are stable in the physiological range. The [(67)Ga][NO2A-N-(α-benzoylamido)propionate] chelate was found to be stable in human serum. Biodistribution studies of the (67)Ga(3+)-labeled pyrene butyric acid conjugate NO2A-N-(α-pyrenebutanamido)propionic acid revealed that, despite its high lipophilicity and concentration-dependent aggregation properties, the chelate follows mainly renal elimination with very low liver/spleen accumulation and no activity deposition in bones after 24 hours. Facile synthesis of amide conjugates of the NO2A-N-(α-amino)propionic acid chelator, serum stability of the Ga(3+) chelates and fast renal elimination warrant further evaluation of this novel class of chelators for PET applications.

Amide conjugates of the DO3A-N-(α-amino)propionate ligand: leads for stable, high relaxivity contrast agents for MRI?

A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate chelator is described, using the synthesis of the DO3A-N-(α-benzoylamido)propionate chelator as an illustrative example. The model Gd[DO3A-N-(α-benzoylamido)propionate] chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn(2+). The Gd[DO3A-N-(α-benzoylamido)propionate] complex is mainly excreted via the kidneys, producing a significant increase in the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its higher lipophilicity compared with Gd(DTPA). The results presented suggest that Gd[DO3A-N-(α-amido)propionate] chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.

Gd(DO3A-N-alpha-aminopropionate): a versatile and easily available synthon with optimized water exchange for the synthesis of high relaxivity, targeted MRI contrast agents.

We report the synthesis of a novel, versatile and easily accessible metal chelator, DO3A-N-alpha-aminopropionate, and the relaxometric characterization of its Gd(3+) complex, revealing great potential for the development of high relaxivity targeted contrast agents for magnetic resonance imaging.