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G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases.

Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50–60% (range 47.2–70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.

Introduction Au cours de l’epidemie de COVID-19, un nombre inhabituel de cas d’engelures a ete rapporte en Europe. L’hypothese d’un lien entre ces engelures et la COVID a ete rapidement avancee. Cependant, aucune etude prospective explorant de facon approfondie ces cas d’engelure n’a ete realisee. Materiel et methodes Cette etude prospective monocentrique a ete realisee dans les unites COVID du CHU de Nice. Tous les patients consecutifs avec engelures vus entre le 26 mars et le 17 avril 2020 etaient inclus. Une evaluation multidisciplinaire etait realisee comprenant examen dermatologique, biopsie cutanee, explorations vasculaires, bilan biologique, PCR et serologie COVID-19. Un suivi des patients etait organise. ClinicalTrials.gov identifier : NCT04344119 . Resultats Quarante patients ont ete inclus (âge median 22 ans ; 12 a 67 ans) dont 21 femmes. Tous les patients presentaient un tableau clinique similaire d’engelures, parfois bulleuses ou necrotiques, interessant les orteils ou les mains et dans certains cas les chevilles et les talons. Un acrosyndrome etait present dans 47,5 % des cas. La notion de contact avec une personne ayant presente des symptomes grippaux ou la presence de signes infectieux chez le patient dans 6 semaines precedentes etait notee chez respectivement 60 % et 32 % des cas. Chez 2 familles, 2 personnes avaient eu des engelures de facon concomitante. La PCR SARS-CoV-2 etait negative chez tous les patients. La serologie COVID-19 etait positive chez 12 patients (IgA+ n = 7, IgG+ n = 3, IgM+ et IgG+ n = 1, IgG+ et IgA+ n = 1). Les D-dimeres etaient superieurs a 215 ng/mL dans 61,5 % des cas. Les biopsies realisees chez 19 patients montraient une image histologique compatible avec des lesions de lupus engelure/interferonopathie de type I associees a un epaississement des veinules par hyperplasie des cellules musculaires sous endotheliales correspondant a des pericytes. L’evaluation in vitro de la reponse interferon α etait significativement plus elevee chez les patients avec engelures par rapport aux patients avec des formes moderees a severes de COVID-19 (p Discussion Cette etude conforte l’hypothese d’un lien entre les cas d’engelures et le virus SARS-CoV-2. Elle suggere que les manifestations dermatologiques observees sont la consequence d’une reaction immune, de type interferonopathie reactionnelle de type 1, induite par l’infection et d’une microvasculopathie impliquant les pericytes.

Compressive Sensing (CS) is a novel signal acquisition technique based on the sparsity of many natural signals. If prior knowledge about the signal's sparsity is available, the signal can be reconstructed using fewer samples than those envisaged by Shannon's Theorem. In particular, space applications in the SWIR-FIR spectral range are an appealing field for CS techniques due to the possibility to use of a single element detector instead of 2D arrays and to reduce requirements in terms of payload budgets and downlink requirements. Here we discuss several payload configurations that could benefit from CS approach and perform a pros and cons analysis.

Compressive Sensing (CS) techniques are well suited to the infrared (IR) spectral range where they can be exploited in order to reduce payload budgets, data throughput and costs. This paper presents the preliminary study of a new CS-based instrument concept for space applications. The payload was designed for on-board detection of Near Earth Object (NEO). Although some technologies needed for the payload development are not yet completely mature, the results of simulations are very promising.

The present study concerned the fruit thinning efficacy of the cytokinin 6-benzyladenine (6-BA) at 150 ppm alone or in combination with the naphthalene acetic acid (NAA) at 15 ppm, on ‘Galaxy’ trees grown in two orchards, one in South Tyrol and the other in Emilia-Romagna area. Applications were carried out at different fruit sizes (5–7, 10–12, 14–16 mm of the king fruit diameter, KF O). In warm climatic conditions as in Emilia-Romagna, the best thinning efficacy was observed with the application of 6-BA alone when KF O reached 10–12 mm, while in South Tyrol, where climatic conditions are cooler than Emilia-Romagna, 6-BA alone showed its best thinning efficacy when KF O reached 14–16 mm. However, in this area, the best results were obtained with the combination 6-BA + NAA applied at 5–7 mm KF O. Moreover, all the chemical applications positively affected fruit quality traits at harvest and, in particular, soluble solid content and flesh firmness were higher in treated fruits as compared to control ones. In South Tyrol, the chemical thinners enhanced skin red colour.

Compressive sensing (CS) allows the reconstruction of signals acquired at sampling frequency below the Nyquist rate relying on the assumption that the acquired signal is sparse (i.e it exhibits a certain degree of correlation). The possibility of undersampling a signal without losing significant information is accomplished by means of a specific integral transformation. For radiometric and spectroscopic signals, this transformation is performed by an optical subsystem spatially modulating the light and by a single pixel detector. Due to these characteristics CS can lead to the development of devices characterized by a reduction in terms of mass, volume and memory budgets. CS theory can be applied to a wide range of optical instruments. After a brief theoretical background, the paper will describe some promising CS applications in the infrared spectral range.

OPTIMA project ("Metodologie avanzate per l'analisi, l'integrazione e l'ottimizzazione dei prodotti di livello 1 e 2 della missione PRISMA") is one of the five independent scientific research contracts granted by the Italian Space Agency (ASI) to investigate the performance of the hyperspectral sensor and the panchromatic mediumresolution camera on board of PRISMA mission and to develop novel applications. In the framework of OPTIMA the image simulation tool PRIMUS ("PRISMA Realistic IMage Utility for Simulation") has been developed. PRIMUS takes into account instrumental characteristics and most of the phenomena that affect acquired hyperspectral images, such as atmospheric effects and noise. The simulation tool can be used to test and validate algorithms and procedures, thanks to the controlled flux of data and the presence of "ground truth". Results coming from software implementation are shown and discussed together with the technical solutions adopted for managing the large amount of hyperspectral data.

Temperature and Emissivity Separation (TES) applied to multispectral or hyperspectral Thermal Infrared (TIR) images of the Earth is a relevant issue for many remote sensing applications. The TIR spectral radiance can be modeled by means of the well-known Planck’s law, as a function of the target temperature and emissivity. The estimation of these target's parameters (i.e. the Temperature Emissivity Separation, aka TES) is hindered by the circumstance that the number of measurements is less than the unknown number. Existing TES algorithms implement a temperature estimator in which the uncertainty is removed by adopting some a priori assumption that conditions the retrieved temperature and emissivity. Due to its mathematical structure, the Maximum Entropy formalism (MaxEnt) seems to be well suited for carrying out this complex TES operation. The main advantage of the MaxEnt statistical inference is the absence of any external hypothesis, which is instead characterizes most of the existing the TES algorithms. In this paper we describe the performance of the MaxEnTES (Maximum Entropy Temperature Emissivity Separation) algorithm as applied to ten TIR spectral channels of a MIVIS dataset collected over Italy. We compare the temperature and emissivity spectra estimated by this algorithm with independent estimations achieved with two previous TES methods (the Grey Body Emissivity (GBE), and the Model Emittance Calculation (MEC)). We show that MaxEnTES is a reliable algorithm in terms of its higher output Signal-to-Noise Ratio and the negligibility of systematic errors that bias the estimated temperature in other TES procedures.

The Arx transcription factor is expressed in the developing ventral telencephalon and subsets of its derivatives. Mutation of human ARX ortholog causes neurological disorders including epilepsy, lissencephaly, and mental retardation. We have isolated the mouse Arx endogenous enhancer modules that control its tightly compartmentalized forebrain expression. Interestingly, they are scattered downstream of its coding region and partially included within the introns of the downstream PolA1 gene. These enhancers are ultraconserved noncoding sequences that are highly conserved throughout the vertebrate phylum. Functional characterization of the Arx GABAergic enhancer element revealed its strict dependence on the activity of Dlx transcription factors. Dlx overexpression induces ectopic expression of endogenous Arx and its isolated enhancer, whereas loss of Dlx expression results in reduced Arx expression, suggesting that Arx is a key mediator of Dlx function. To further elucidate the mechanisms involved, a combination of gain-of-function studies in mutant Arx or Dlx tissues was pursued. This analysis provided evidence that, although Arx is necessary for the Dlx-dependent promotion of interneuron migration, it is not required for the GABAergic cell fate commitment mediated by Dlx factors. Although Arx has additional functions independent of the Dlx pathway, we have established a direct genetic relationship that controls critical steps in the development of telencephalic GABAergic neurons. These findings contribute elucidating the genetic hierarchy that likely underlies the etiology of a variety of human neurodevelopmental disorders.

L’acido 3,5,6-triclo-2-piridil-ossacetico (3,5,6-TPA), disponibile in commercio come Maxim® (L.Gobbi srl, Genova), è un auxine sintetica che ha dato ottimi risultati nell’aumento di pezzatura su agrumi e pesco ed è recentemente stata utilizzata con successo anche su frutti di Actinidia. Vengono qui riportati i dati ottenuti in un indagine di quattro anni che ha riguardato lo studio degli effetti di diverse concentrazioni ed epoche di applicazione dell’auxina sulla crescita e sulla maturazione dei frutti della cv Hayward. I risultati ottenuti evidenziano una correlazione positiva tra concentrazione del prodotto ed aumento di dimensioni dei frutti trattati. Il prodotto, inoltre, sembra influenzare il processo di maturazione: alla raccolta ed un mese dopo, infatti, il contenuto in solidi solubili era più basso e la durezza più alta nei frutti trattati rispetto a quelli di controllo, mentre tre mesi dopo la durezza risultava simile ed i solidi solubili si mantenevano più bassi. Questo effetto si traduceva alla raccolta ed un mese dopo in una minore attività dell’ACC-ossidasi (ACO) ed in una minore espressione dei geni per tale enzima e per le espansine e poligalatturonasi C a livello dei tessuti trattati, mentre tre mesi dopo i frutti trattati raggiungevano più alti livelli di trascritti per tutti e tre i geni presi in esame. Per verificare l’insorgenza di effetti di stress di natura secondaria a livello dei tessuti a seguito dei trattamenti con auxine alle dosi più alte, è stata inoltre indagata l’attività dei principali enzimi scavenger delle forme reattive dell’ossigeno, catalasi (CAT) e superossido dismutasi (SOD), e l’effetto sui livelli dell’osmolita prolina. Gli effetti su tali proteine sono stati posti in relazione con variazioni della biosintesi dell’etilene.

L’unico interruttore della dormienza (DBA) utilizzato da anni su Actinidia è l’idrogeno cianamide (Dormex), che viene normalmente applicato durante il periodo di endodormienza. Recentemente, è stato introdotto in commercio un nuovo formulato, il Cytokin, a base di citochinine, che viene invece applicato poco prima della chiusura delle gemme. Il Cytokin è stato applicato sulla cv Hayward a diverse dosi ed epoche di applicazione in due diverse aree dell’Emilia-Romagna. I risultati ottenuti evidenziano che questo formulato è in grado di aumentare la percentuale di germogliamento che è risultato essere più precoce ed uniforme rispetto al controllo. Il Cytokin ha causato anche un aborto dei fiori laterali dell’infiorescenza, determinando un effetto “diradante”che si è tradotto in un considerevole risparmio di tempo necessario per l’operazione di diradamento manuale dei fiori laterali dell’infiorescenza. I risultati ottenuti sulla produzione, invece, sono stati più variabili: in un caso è stato registrato un aumento del peso medio dei frutti trattati, mentre, nell’anno successivo tale aumento non si è verificato anche se va sottolineato che il numero dei frutti è risultato maggiore rispetto al controllo. Inoltre, il Cytokin non ha provocato alcuna tossicità anche ad alte dosi. Ulteriori indagini sono in corso al fine di elucidare il meccanismo di azione del Cytokin per migliorare la sua applicazione nel controllo del germogliamento dell’Actinidia.

L’impiego di fitoregolatori e biostimolanti è oggigiorno da considerare un interessante metodo complementare alle normali operazioni agronomiche per risolvere alcuni problemi colturali e per incrementare le performance produttive e qualitative delle piante. L’atteggiamento verso queste sostanze è tuttavia controverso, ma un attento studio sull’impiego e l’efficacia di tali sostanze può rappresentare un utile strumento per rendere più competitiva la frutticoltura a livello globale. A tale proposito è stato condotto uno studio di due anni sull’impiego di diversi fitoregolatori, a base di auxine (3,5,6 –TPA) e citochinine (forclorfenuron, 6 benziladenina), come promotori di crescita dei frutti di Actinidia deliciosa (cv Hayward). E’ stata inoltre verificata l’influenza di tali prodotti sulla qualità dei frutti alla raccolta ed in frigo-conservazione. L’applicazione dei diversi formulati ha aumentato la pezzatura dei frutti senza provocare perdite di produzione. Per quanto riguarda invece la fitotossicità mentre il formulato a base di auxine ha determinato danni di lieve entità sulle foglie (filloptosi, accorciamento del lembo fogliare) o sui frutti, quelli a base di citochinine non hanno causato alcun danno. Per quel che riguarda l’effetto sulla qualità, i formulati a base di auxine hanno causato un ritardo di maturazione: alla raccolta, infatti, i frutti trattati mostrano una maggior durezza della polpa ed un minor contenuto in solidi solubili ed in sostanza secca. Al contrario, i formulati a base di citochinine hanno determinato un leggero aumento del contenuto in solidi solubili (forclorfenuron). Durante la frigo-conservazione, effettuata sia in refrigerazione normale (RN) che in atmosfera controllata (AC), si sono confermate le differenze tra i formulati: quelli a base auxinica provocano un maggiore calo della durezza dei frutti dopo 70 giorni di conservazione in RN, mentre nei frutti trattati con formulati a base di citochinine non si registrano differenze sostanziali rispetto ai controlli. Gli stessi risultati sono stati ottenuti all’uscita dei frutti dalle celle in AC.

Cryopreservation of porcine hepatocytes for their use in bioartificial liver devices may result in reduced cytochrome P450 (CYP) enzyme activity. The aim of this study was to assess the effects of several CYP inducers on the isoform CYP2E1 protein expression in cryopreserved porcine hepatocytes. Isolated porcine hepatocytes were cryopreserved for 1 month, thawed, and cultured for 3 days. During medium culture, the hepatocytes were exposed to the following CYP inducers: dimethyl sulfoxide, rifampicin, phenobarbital, 3-methylcholanthrene, and dexamethasone. CYP2E1 protein expression was determined by immunoblotting. CYP2E1 protein levels were constantly detected in cryopreserved porcine hepatocytes. CYP inducers did not modify CYP2E1 protein levels. Long-term cryopreserved porcine hepatocytes preserved their capacity for CYP2E1 protein expression, although exposure of these hepatocytes to CYP inducers did not modify the CYP2E1 protein expression.

The complex series of mechanisms that characterized the ripening process depends on a interplay of several classes of plant hormones among them a central role is played by ethylene. Relative to the current knowledge about ethylene, much less is known on the interaction between this hormone and other growth substances, in particular auxins, during fruit growth and ripening in some species as for example Actinidia deliciosa. In the present work we investigated the effect of the synthetic auxin 3,5,6-trichloro-2-pyridyloxyacetic acid (3,5,6-TPA) on fruit growth and quality traits of cv Hayward (Actinidia deliciosa) and the relationship between the obtained effect and ethylene emission, biosynthetic enzyme activity and gene expression. Moreover, expression studies of genes encoding for protein involved in cell wall disassembly (polygalacturonases and expansin) were also performed. During a three-years trial, the auxin, commercially available as Maxim™, was applied at different concentrations and application times and its effects were studied throughout the fruit growing season, at harvest and during a cold storage period. The application of chemical caused a significant increase in kiwifruit weight and affected also ripening dynamics. In fact, at harvest and 1 month later, soluble solids content was lower and flesh firmness was higher in treated fruits as compared to control ones, while 3 months later an opposite trend was observed. This ripening dynamic modification was also confirmed by biochemical and molecular analyses. In fact, at harvest and 1 month later, treated fruit reached ACC-oxidase (ACO) activity and ACO, polygalacturonase C and expansin expressions lower than control fruits, while 3 months later treated fruit reached higher transcript levels in all the 3 considered genes. This suggest to further study the relationship between auxin and ethylene in modifying kiwifruit ripening and its influence on the duration of the storage.

The TDT-bioART project, funded by the Regione Toscana in the frame of the Regional Call POR FESR 2007 - 2013, consisted in a feasibility study of novel methodologies for the diagnostic and treatment in the field of the cultural heritage. The methodologies investigated fulfil two fundamental requirements for this field of application: non-invasiveness and treatment effectiveness. The project focused on issues concerning the biodegradation of artistic, architectural and monumental surfaces, and dealt with techniques and methodologies for both diagnostics and treatment, using however an unconventional approach. An additional objective of the project was to constitute an European network aiming to outline an international research project for the definition of intervention protocols on works of art, based on the best available technologies (BAT) and on the excellence of know-how in this field. Regarding the diagnostics phase, and particularly its early warning capabilities and non invasiveness, the TDT-bioART project has addressed a feasibility study for the transfer of laser induced fluorescence (LIF) techniques, and specifically the fluorescence lidar technique, to the early detection of biodeteriogen colonies on artistic surfaces. For this purpose two research activities have been carried out: 1) preliminary assessment of the effects of low-fluence laser radiation on different types of mural paintings. 2) fluorescence measurements on substrates inoculated with biodeteriogens, in order to assess the feasibility to transfer the fluorescence lidar remote sensing technique - already successfully applied to the detection of biodeteriogens on outdoor monuments - to the remote diagnostics of extended surfaces, even in full sunlight. Regarding the conservation treatment of biodeteriorated artistic assets, the project has addressed a feasibility study on the treatment using microwave radiation. This technique, already successfully applied for the disinfection of xilophage insects in artistic ligneous artefacts, has been applied to the treatment of stone materials colonised by black fungi and lichens and of painted surfaces attacked by micro-fungi colonies in hypogeum sites. The peculiar characteristics of this physical treatment - with respect to other treatments - are: - feasibility of localized treatments by means of the study and implementation of ad hoc applicators; - feasibility of different treatment depths; - elimination of living organisms and their reproductive and resistance forms; - low risk for operators (non ionising radiation). Besides studying thermal-electromagnetic models for the assessment of the interaction with the substrate, we also carried out experimental tests concerning the heating of stone due to the microwaves (acceleration/triggering of decohesion processes) and of mural paintings (pigments and surface pattern alterations). Results open good prospects for the applicability of microwave-based treatments in this field.

The use of high-resolution imagers for determination of solar-induced fluorescence of natural bodies by observing the infilling of Fraunhofer lines has been frequently adopted as a tool for vegetation characterization. The option to perform those measurements from airborne platforms was addressed in the past. In-field observations gave evidence of the main requirements for an imaging spectrometer to be used for Sun-induced fluorescence measurements such as high spectral resolution and fine radiometric accuracy needed to resolve the shape of observed Fraunhofer lines with a high level of accuracy. In this paper, some solutions for the design of a high spectral resolution push-broom imaging spectrometer for Sun-induced fluorescence measurements are analysed. The main constraints for the optical design are a spectral resolution better than 0.01 nm and a wide field of view. Due to the fine instrumental spectral resolution, bidimensional focal plane arrays characterized by high quantum efficiency, low read-out noise, and high sensitivity are requested. The development of a lightweight instrument is a benefit for aerospace implementations of this technology. First results coming from laboratory measurements and optical simulations are presented and discussed taking into account their feasibility.

An optical epifluorescence microscope, coupled to a CCD camera, a standard webcam and a microspectrofluorimeter, are used to record in vivo real-time changes in the autofluorescence of spores and hyphae in Aspergillus niger, a fungus containing melanin, while exposed to UV irradiation. The results point out major changes in both signal intensity and the spectral shape of the autofluorescence signal after only few minutes of exposure, and can contribute to the interpretation of data obtained with other fluorescence techniques, including those, such as GPF labeling, in which endogenous fluorophores constitute a major disturbance.

The bioartificial liver (BAL) represents a promising approach to cell transplantation without immunosuppression as a method to support patients with hepatic insufficiency. The aim of this study was to assess viability and function of cryopreserved encapsulated porcine hepatocytes implanted intraperitoneally in rats without immunosuppression. Isolated porcine hepatocytes were cryopreserved at -196 degrees C for 1 month. Four groups were created: group 1 (n=10), freshly encapsulated porcine hepatocytes cultured in albumin-free medium for 10 days; group 2 (n=10), freshly encapsulated porcine hepatocytes implanted in the rat peritoneum without immunosuppression for 1 month and cultured for 10 days after explantation; group 3 (n=10), cryopreserved encapsulated porcine hepatocytes cultured for 10 days; group 4 (n=10), cryopreserved encapsulated porcine hepatocytes implanted in the rat peritoneum without immunosuppression for 1 month and cultured for 10 days after explantation. We assessed urea and albumin production and hepatocyte viability. The hepatocytes of all groups retained the capacity to produce urea and albumin, although the albumin synthesis was significantly decreased among hepatocytes of group 4 (P< .01). Encapsulated cryopreserved porcine hepatocytes explanted from rat peritoneum after 1 month appeared morphologically viable; their ultrastructure was preserved. In conclusion, long-term cryopreservation of porcine hepatocytes resulted in retention of their biological activity and in significant viability when transplanted into the rat peritoneum without immunosuppression.

On site remote laser induced fluorescence measurements have been performed with application towards non-movable objects. This paper gives an overview of the results obtained from the application of non-invasive hyperspectral fluorescence imaging to two masonry monuments, the Coliseum and the Lateran Baptistery in Rome, during a joint Italian-Swedish experiment. The mobile systems of Lund Institute of Technology, Sweden, and CNR-IFAC, Italy, were placed at the distance of 18-65 m from the façades for the documentation and characterization of surfaces, including materials, protective treatments, biodeteriogens and historic layers.