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The lifetime of deep-ultraviolet light-emitting diodes (LEDs) is still limited by a number of factors, which are mainly related to semiconductor defects, and still need to be clarified. This paper improves the understanding of UV LED degradation, by presenting an analysis based on combined deep-level transient spectroscopy (C-DLTS), electro-optical characterization, and simulations, carried out before and during a constant current stress test. The original results of this paper are (i) C-DLTS measurements allowed us to identify three traps, two associated with Mg-related defects, also detected in the unaged device, and one related to point defects that were generated by the ageing procedure. (ii) Based on these results and on TCAD simulations, we explain the variation in the forward I–V by the degradation of the p-contact, due to Mg passivation. (iii) On the other hand, optical degradation is ascribed to an increase in defectiveness of the active region and surrounding areas, which led to a decrease in injection efficiency, to an increase in non-radiative recombination, and to an increase in trap-assisted tunneling processes. [ABSTRACT FROM AUTHOR]

We investigate the impact of Mg-doping on the performance and degradation kinetics of AlGaN-based UV-C light-emitting diodes (LEDs). By comparing LEDs from three wafers with different nominal doping levels [Mg/(Al+Ga) ratio: 0.15%, 0.5%, and 1% in the gas phase during epitaxy] in the AlGaN:Mg electron-blocking layer (EBL), we demonstrate the following results: (i) A higher Mg-doping in the EBL results in a higher optical power at low current levels, which is ascribed to an increased hole injection efficiency. (ii) The reduction of the optical power follows a non-exponential trend, which can be reproduced by using the Hill's formula and is ascribed to the generation/activation of defects within the quantum wells. (iii) A higher Mg-doping in the EBL mitigates the degradation rate. An interpretation of the experimental data is proposed, assuming that hydrogen, which is present in and moving from the EBL, can reduce the rate of de-hydrogenation of point defects in the active region, which is responsible for degradation. [ABSTRACT FROM AUTHOR]

Recent studies demonstrated that the performance of InGaN/GaN quantum well (QW) light emitting diodes (LEDs) can be significantly improved through the insertion of an InGaN underlayer (UL). The current working hypothesis is that the presence of the UL reduces the density of non-radiative recombination centers (NRCs) in the QW itself: during the growth of the UL, surface defects are effectively buried in the UL, without propagating towards the QW region. Despite the importance of this hypothesis, the concentration profile of defects in the quantum wells of LEDs with and without the UL was never investigated in detail. This paper uses combined capacitance-voltage and steady-state photocapacitance measurements to experimentally identify the defects acting as NRCs and to extract a depth-profile of the traps, thus proving the incorporation upon indium-reaction. Specifically: (i) we demonstrate that LEDs without UL have a high density (9.2 × 1015 cm−3) of defects, compared to samples with UL (0.8 × 1015 cm−3); (ii) defects are located near midgap (EC-1.8 eV, corresponding to Ei-ET ∼ 0.3 eV), thus acting as efficient NRCs; (iii) crucially, the density of defects has a peak within the QWs, indicating that traps are segregated at the first grown InGaN layers; (iv) we propose a model to calculate trap distribution in the QW, and we demonstrate a good correspondence with experimental data. These results provide unambiguous demonstration of the role of UL in limiting the propagation of defects towards the QWs, and the first experimental characterization of the properties of the related traps. [ABSTRACT FROM AUTHOR]

The assessment of differentially expressed microRNAs in patients and healthy controls is important to identify potential tumor biomarkers. Recently, it has been shown that the microRNA levels in exosomes are more correlated with the clinical-pathological variables than vesicle-free microRNAs (miRNAs) in biofluids; therefore, there is an increasing interest in these specific evaluations. However, these measurements can be affected by experimental problems that not always are evaluated and/or by inadequate procedural choices. In particular, exosome isolation and miRNA extraction procedures are crucial to avoid contaminations, and even the choice of the most suitable purity controls is important. Moreover, a stable endogenous RNA should be used for normalization of miRNA expression obtained by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) in order to make these measures comparable among different samples. A rushed choice of the endogenous control can bias study conclusions without revealing inconsistencies. Unfortunately, a few studies systematically identified the best normalizer for their specific experimental context. Instead, sometimes, the normalization procedures were performed in a disputable way or the normalizer choices simply based on the previous literature. Here, we reviewed the studies where the exosomal miRNA profiling was assessed in human biofluids to point out the adopted procedures and the specific endogenous controls chosen for normalization. [ABSTRACT FROM AUTHOR]

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway. [ABSTRACT FROM AUTHOR]

Atmospheric pollution from vehicular traffic is a matter of growing interest, often leading to temporary restrictions in urban areas. Although guidelines indicate limits for several parameters, the real toxicologic impacts remain largely unexplored in field conditions. In this study our aim was to validate an ecotoxicologic approach to evaluate both bioaccumulation and toxicologic effects caused by airborne pollutants. Specimens of the land snail Helix aspersa were caged in five sites in the urban area of Ancona, Italy. After 4 weeks, trace metals (cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc) and polycyclic aromatic hydrocarbons (PAHs) were measured and these data integrated with the analyses of molecular and biochemical responses. Such biomarkers reflected the induction of detoxification pathways or the onset of cellular toxicity caused by pollutants. Biomarkers that correlated with contaminant accumulation included levels of metallothioneins, activity of biotransformation enzymes (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase), and peroxisomal proliferation. More general responses were investigated as oxidative stress variations, including efficiency of antioxidant defenses (catalase, glutathione reductase, glutathione S-transferases, glutathione peroxidases, and total glutathione) and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals, onset of cellular damages (i.e., lysosomal destabilization), and loss of DNA integrity. Results revealed a marked accumulation of metals and PAHs in digestive tissues of organisms maintained in more traffic-congested sites. The contemporary appearance of several alterations confirmed the cellular reactivity of these chemicals with toxicologic effects of potential concern for human health. The overall results of this exploratory study suggest the utility of H. aspersa as a sentinel organism for biomonitoring the biologic impact of atmospheric pollution in urban areas. Key words: atmospheric pollutants, bioindicators, biomarkers, DNA integrity, lysosomes, metallothioneins, oxidative stress, peroxisomes, polycyclic aromatic hydrocarbons, trace metals. [ABSTRACT FROM AUTHOR]

Fenbufen is an analgesic, antipyretic and anti-inflammatory drug that is characterized by poor water solubility, a defect increased by very low wettability. Poor water solubility, particularly at low pH, could decrease absorption in the upper part of the gastrointestinal tract, which would be inconvenient for good bioavailability. Different spherical crystallization processes have been considered as methods to improve fenbufen dissolution behavior. A two-solvent system, in the presence of a bridging liquid, is the only method capable of producing spherical fenbufen crystals. In a first step, fenbufen solubility was considered in different solvents. The drug crystals formed were typically needle shaped. This characteristic was considered as a favorable parameter to obtain spherical crystals. After the selection of the best fenbufen solvent, several ratios of solvent (S)–nonsolvent (NS) (tetrahydrofuran [THF]–demineralized water) were studied. The addition of a bridging liquid (isopropyl acetate) improved spherical crystallization. The results from this method were reproducible batch to batch. The spherical crystals obtained showed a clear improvement in dissolution capacity, probably due to better wettability. Dissolution studies were then carried out on these spherical crystals stored for 1 month at different relative humidities (RHs). The dissolution profiles remained unchanged. [ABSTRACT FROM AUTHOR]

In the present study, the possible direct effects of opioids on the release of LHRH have been studied utilizing the GTI-1 cell model. It has been shown that only opioid agonists which bind to δ receptors bring about a significant inhibition of the release of LHRH, when this is stimulated by forskolin- or PGE[sub 2]. The effects of δ opioid agonists are dose-dependent, and are reversed by the δ specific antagonist naltrindole. If one assumes that the GTI-1 cells represent a good model for the study of LHRH-secreting neurons, the obvious conclusion from these data is that endogenous opioid peptides may influence LHRH secretion also by acting directly on LHRH-secreting neurons. In another study it has been shown that GTI-1 cells possess high affinity-low capacity binding sites for estradiol and androgens. Moreover, a two-fold induction of androgen-binding sites has been observed after treatment of GTI-1 cells with estradiol, indicating that estrogen receptors are functional. The present observations suggest that gonadal steroids might influence LHRH release acting directly on the cells which manufacture and release the hypothalamic hormone. In order to evaluate the possible existence of a humoral communication between glial cells and LHRH-secreting neurons, two different approaches have been used: (a) GT1-1 cells were co-incubated with purified cultures of type 1 astrocytes; (b) GT1-1 cells were exposed to the conditioned medium (CM, untreated or submitted to different experimental procedures) where type 1 astrocytes were grown for 24 h. In both sets of experiments LHRH was measured by RIA in the incubation media of GT1-1 cells. The data show that short periods of either co-culture or exposure to previously frozen or heated CM significantly increase the release of LHRH from the GT1-1 cells. The stimulatory effect on LHRH release appears to be specific for type 1 astrocytes. Surprisingly, fresh CM proved to be inactive; this suggested that the... [ABSTRACT FROM AUTHOR]