Scintillators, materials that produce light pulses upon interaction with ionizing radiation, are widely employed in radiation detectors. In advanced medical-imaging technologies, fast scintillators ...enabling a time resolution of tens of picoseconds are required to achieve high-resolution imaging at the millimetre length scale. Here we demonstrate that composite materials based on fluorescent metal–organic framework (MOF) nanocrystals can work as fast scintillators. We present a prototype scintillator fabricated by embedding MOF nanocrystals in a polymer. The MOF comprises zirconium oxo-hydroxy clusters, high-Z linking nodes interacting with the ionizing radiation, arranged in an orderly fashion at a nanometric distance from 9,10-diphenylanthracene ligand emitters. Their incorporation in the framework enables fast sensitization of the ligand fluorescence, thus avoiding issues typically arising from the intimate mixing of complementary elements. This proof-of-concept prototype device shows an ultrafast scintillation rise time of ~50 ps, thus supporting the development of new scintillators based on engineered fluorescent MOF nanocrystals.Composites of fluorescent metal–organic framework nanocrystals in a polymer are exploited to create fast scintillators with a rise time of about 50 ps.
Conventional wastewater treatment plants (WWTPs) commonly require large capital investments as well as operation and maintenance costs. Constructed wetlands (CWs) appear as a cost-effective ...treatment, since they can remove a broad range of contaminants by a combination of physical, chemical and biological processes with a low cost. Therefore, CWs can be successfully applied for decentralized wastewater treatment in regions with low population density and/or with large land availability as Brazil. The present work provides a review of thirty nine studies developed on CWs implemented in Brazil to remove wastewater contaminants. Brazil current sanitation data is also considered to evaluate the potential role of CWs as decentralized wastewater treatment. Performance of CWs was evaluated according to (i) type of wetland system, (ii) different support matrix (iii) vegetation species and (iv) removal efficiency of chemical oxygen demand (COD), biological oxygen demand (BOD5), nitrogen (N), and phosphorus (P). The reviewed CWs in overall presented good efficiencies, whereas H-CWs achieved the highest removals for P, while the higher results for N were attained on VF-CW and for COD and BOD5 on HF-CW. Therefore, was concluded that CWs are an interesting solution for decentralized wastewater treatment in Brazil since it has warm temperatures, extensive radiation hours and available land. Additionally, the low percentage of population with access to the sewage network in the North and Northeast regions makes these systems especially suitable. Hence, the further implementation of CW is encouraged by the authors in regions with similar characteristics as Brazil.
•The state-of-art of Brazilian sanitation is presented.•The application of CWs systems in Brazil is reviewed.•Treatment performance of various types of CWs is assessed.•Brazilian native macrophytes species are identified.•The effect of CWs design on removal efficiencies is examined.
Background model of the CUPID-0 experiment Azzolini, O.; Beeman, J. W.; Bellini, F. ...
European physical journal. C, Particles and fields,
07/2019, Letnik:
79, Številka:
7
Journal Article
Recenzirano
Odprti dostop
CUPID-0 is the first large mass array of enriched Zn
82
Se scintillating low temperature calorimeters, operated at LNGS since 2017. During its first scientific runs, CUPID-0 collected an exposure of ...9.95 kg year. Thanks to the excellent rejection of
α
particles, we attained the lowest background ever measured with thermal detectors in the energy region where we search for the signature of
82
Se
neutrinoless double beta decay. In this work we develop a model to reconstruct the CUPID-0 background over the whole energy range of experimental data. We identify the background sources exploiting their distinctive signatures and we assess their extremely low contribution down to
∼
10
-
4
counts/(keV kg year) in the region of interest for
82
Se
neutrinoless double beta decay search. This result represents a crucial step towards the comprehension of the background in experiments based on scintillating calorimeters and in next generation projects such as CUPID.
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA ...mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.
Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late ...nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3‐electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies.
British Journal of Pharmacology (2008) 155, 170–184; doi:10.1038/bjp.2008.263; published online 23 June 2008
State-of-the-art physics experiments require high-resolution, low-noise, and low-threshold detectors to achieve competitive scientific results. However, experimental environments invariably introduce ...sources of noise, such as electrical interference or microphonics. The sources of this environmental noise can often be monitored by adding specially designed “auxiliary devices” (e.g. microphones, accelerometers, seismometers, magnetometers, and antennae). A model can then be constructed to predict the detector noise based on the auxiliary device information, which can then be subtracted from the true detector signal. Here, we present a multivariate noise cancellation algorithm which can be used in a variety of settings to improve the performance of detectors using multiple auxiliary devices. To validate this approach, we apply it to simulated data to remove noise due to electromagnetic interference and microphonic vibrations. We then employ the algorithm to a cryogenic light detector in the laboratory and show an improvement in the detector performance. Finally, we motivate the use of nonlinear terms to better model vibrational contributions to the noise in thermal detectors. We show a further improvement in the performance of a particular channel of the CUORE detector when using the nonlinear algorithm in combination with optimal filtering techniques.
The aim of the study is to assess the effects of the neuroinflammatory microenvironment of a mechanically-induced degenerating intervertebral disc (IVD) on neuroinflammatory like cells such as ...microglia, in order to comprehend the role of microglial cells in degenerative disc disease.
Bovine caudal IVDs were kept in culture in an ex vivo bioreactor under high frequency loading and limited nutrition or in free swelling conditions as control samples. Conditioned media (CM) were collected, analysed for cytokine and neurotrophin content and applied to microglial cells for neuroinflammatory activation assessment.
Degenerative conditioned medium (D-CM) induced a higher production of interleukin (IL)-8, nerve growth factor (NGF), interferon (IFN)-γ, IL-17 from IVD cells than unloaded control conditioned medium (U-CM). Upon 48 h of co-incubation with microglia, D-CM stimulated microglia proliferation, activation, with increased expression of ionized calcium binding adaptor molecule 1 (IBA1) and CD68, and chemotaxis. Moreover, an increment of nitrite production was observed. Interestingly, D-CM caused an upregulation of IL-1β, IL-6, tumour necrosis factor α (TNFα), inducible NO synthase (iNOS), IBA1, and vascular endothelial growth factor (VEGF) genes in microglia. Similar results were obtained when microglia were treated with the combination of the measured cytokines.
Our findings show that in IVD degenerative microenvironment, IL-8, NGF, IFN-γ, IL-17 drive activation of microglia in the spinal cord and increase upregulation of neuroinflammatory markers. This, in turn, enhances the inflammatory milieu within IVD tissues and in the peridiscal space, aggravating the cascade of degenerative events. This study provides evidence for an important role of microglia in maintaining IVD neuroinflammatory microenvironment and probably inducing low back pain.
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The application of ethylene-vinyl acetate (EVA) copolymers in reservoir-type intra-vaginal rings (IVRs) offers advantages over silicones including i) versatile properties, ii) absence ...of curing chemistry, and iii) continuous and flexible processing via co-extrusion. Thus, we investigated the capability of EVA based IVRs to deliver broad ranges of estradiol (E2) thereby, fulfilling the requirements of local and systemic hormone replacement therapy (HRT) and contraception. To circumvent the high material needs associated with co-extrusion, we implemented a small-scale screening procedure that accurately predicts the E2 release from IVRs comprising E2 below its solubility concentration in the core. Rational formulation design yielded the target release for local HRT (<10 µg/day), systemic HRT (50–100 µg/day) and contraception (>150 µg/day, combined with a progestin). Low E2 release was achieved by the combination of low E2 loadings, low VA content of the membrane polymer (also known as coat polymer or outer shell), and increased membrane thickness. Medium E2 release was provided by medium E2 loading, low VA content of the membrane polymer, and low membrane thickness. Combining high E2 loadings, high VA content of the membrane polymer, and low membrane thickness yielded high E2 release. This makes EVA based IVRs a versatile platform that can be used to deliver a broad range of E2 doses.
In the framework of rare event searches, the identification of radioactive contaminants in ultra-pure samples is a challenging task, because the signal is often at the same level of the instrumental ...background. This is a rather common situation for
α
-spectrometers and other detectors used for low-activity measurements. In order to obtain the target sensitivity without extending the data taking live-time, analysis strategies that highlight the presence of the signal sought should be developed. In this paper, we show how to improve the contaminant tagging capability relying on the time-correlation of radioactive decay sequences. We validate the proposed technique by measuring the impurity level of both contaminated and ultra-pure copper samples, demonstrating the potential of this analysis tool in disentangling different background sources and providing an effective way to mitigate their impact in rare event searches.