Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

ESD sensitivity of a GaAs MMIC microwave power amplifier

The EOS/ESD sensitivity of the main circuit blocks of a complete GaAs multi-stage power amplifier for microwave applications was investigated under HBM, MM and TLP regimes. Hard breakdown failure modes were identified due to passive components failure. The high current injection state of active components was also analyzed.     

On Adaptive Density Deployment to Mitigate the Sink-Hole Problem in Mobile Sensor Networks

The use of mobile sensors is of great relevance to monitor critical areas where sensors cannot be deployed manually. The presence of data collector sinks causes increased energy depletion in their proximity, due to the higher relay load under multi-hop communication schemes (sink-hole phenomenon). We propose a new approach towards the solution of this problem by means of an autonomous deployment algorithm that guarantees the adaptation of the sensor density to the sink proximity and enables their selective activation. The proposed algorithm also permits a fault tolerant and self-healing deployment, and allows the realization of an integrated solution for deployment, dynamic relocation and selective sensor activation. We formally prove the termination of our algorithm. Performance comparisons between our proposal and previous approaches show how the former can efficiently reach a deployment at the desired variable density with moderate energy consumption under a wide range of operative settings.     

Push &; Pull: autonomous deployment of mobile sensors for a complete coverage

Mobile sensor networks are important for several strategic applications devoted to monitoring critical areas. In such hostile scenarios, sensors cannot be deployed manually and are either sent from a safe location or dropped from an aircraft. Mobile devices permit a dynamic deployment reconfiguration that improves the coverage in terms of completeness and uniformity. In this paper we propose a distributed algorithm for the autonomous deployment of mobile sensors called Push & Pull. According to our proposal, movement decisions are made by each sensor on the basis of locally available information and do not require any prior knowledge of the operating conditions or any manual tuning of key parameters. We formally prove that, when a sufficient number of sensors are available, our approach guarantees a complete and uniform coverage. Furthermore, we demonstrate that the algorithm execution always terminates preventing movement oscillations. Numerous simulations show that our algorithm reaches a complete coverage within reasonable time with moderate energy consumption, even when the target area has irregular shapes. Performance comparisons between Push & Pull and one of the most acknowledged algorithms show how the former one can efficiently reach a more uniform and complete coverage under a wide range of working scenarios.     

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

Controlled filling and external cleaning of multi-wall carbon nanotubes using a wet chemical method

A controlled, material-independent and adaptable cold wet chemical procedure is described. It allows organic and inorganic compounds to be confined inside multi-wall carbon nanotubes. The procedure mainly consists of a lyophilization process to fill multi-wall carbon nanotubes (MWCNTs), and a washing method to clean their outer surface without removing the encapsulated material. The technique was tested by synthesizing CdS crystals inside the nanotubes. Morphological and structural studies of the CdS crystals demonstrated a complete control of the synthesis process, and the possibility of maximizing the crystal size and the filling efficiency that approached 70% of open-ended nanotubes.     

The binding mode of progesterone to its receptor deduced from molecular dynamics simulations

An unambiguous understanding of the binding mode of human progesterone to its receptor still eludes experimental search. According to the X-ray structure of the ligand-binding domain, only one (O3) of the two keto groups at the ligand ends (O3 and O20) should play a role. This result is in conflict with chemical intuition and the results of site-directed mutagenesis experiments. Herein, we report classical molecular dynamics simulations that reveal the dynamic nature of the binding in solution, elucidate the reasons why X-ray studies failed to determine the role of O20, and clarify the effects of the mutations. The predictive power of the force field is ensured by the consistent introduction of a first-principles representation of the ligand.     

Conversion and hydroconversion of hydrocarbons on zeolite-based catalysts: an FT-IR study

The interaction of HZSM5 and Mo-ZSM5 with benzene, naphthalene, toluene, ortho-xylene, para-xylene, n-butane, isobutane, n-heptane, and methylcyclohexane, in the range 100–773 K has been investigated using FT-IR spectroscopy. Hydrogen bonded species with the internal bridging and the external terminal OHs has been detected. The reactivity at high temperature has also been studied. The access to the internal cavities and to the strongly acidic OHs is at least partly hindered in the case of Mo-ZSM5. The catalytic activity of ZSM5 was moderated by the addition of molybdenum, with lower cracking and higher liquid yields.     

An FT-IR study of the adsorption of aromatic hydrocarbons and of 2,6-lutidine on H-FER and H-ZSM-5 zeolites

The interaction of aromatic hydrocarbons benzene, toluene, o-, m- and p-xylene and of methyl pyridines (in particular 2,6-lutidine) with H-ZSM-5 and H-FER zeolites has been studied. Two different H-ZSM-5 samples with strongly different intensity ratios between the two main OH stretching bands have been used. Benzene, toluene and p-xylene enter easily the cavities and give rise to three different H-bonded complexes. Two of them are strongly bonded while the third is likely a very hindered and distorted one. o-Xylene enters slowly the cavities and m-xylene even more slowly. Faster diffusion occurs at higher temperatures. On the contrary, xylenes do not enter the FER cavities. In spite of its steric hindrance, supposed to be the same of m-xylene, 2,6-lutidine enters fast the ZSM channels and is protonated by the internal sites. On the contrary, it does not enter the FER cavities, but it is protonated too on the external silanols sites. Evidence is provided for some kind of heterogeneity of the internal sites of ZSM-5 zeolite. Additionally, it is concluded that other effects besides the molecular sieving effect may play a role in the access and diffusion of molecules into the zeolite channels.