A generalized drift-diffusion model for rectifying Schottky contact simulation

We present a discussion on the modeling of Schottky barrier rectifying contacts (diodes) within the framework of partial-differential-equation-based physical simulations. We propose a physically consistent generalization of the drift-diffusion model to describe the boundary layer close to the Schottky barrier where thermionic emission leads to a non-Maxwellian carrier distribution, including a novel boundary condition at the contact. The modified drift-diffusion model is validated against Monte Carlo simulations of a GaAs device. The proposed model is in agreement with the Monte Carlo simulations not only in the current value but also in the spatial distributions of microscopic quantities like the electron velocity and concentratio

On-board hydrogen production using multifunctional catalytic hollow fibre-based reactors

Faced with the imminent depletion of fossil resources and the large environmental impact associated with their use, the 21st century society demands a gradual change from an economy based on fossil sources to one based on sustainable resources and processes compatible with the environment. In this respect, green ammonia (NH3) has been proposed as promising hydrogen (H2) carrier candidate for on-board application. However, since on-board space constraints represent a significant challenge facing the adoption of NH3 as a future fuel carrier, this work focused on the design and assessment of a pioneering technology for on-board H2 production via NH3 decomposition, i.e. multifunctional catalytic hollow fibre-based reactors. Today, the most prominent technology for hydrogen production via NH3 decomposition is a traditional catalytic packed bed reactor (PBR) that uses a precious metal-based catalyst. As a result, this expensive technology is outsized, thereby limiting its applicability to NH3-fuelled vehicles. The use of hollow fibre-based reactors represents a unique opportunity for innovative solutions in the development of a suitable technology for the production of H2 on-board. This is because they can overcome the limitations of traditional PBRs and allow for decreased required catalyst loading and/or the operating temperatures when compared with a PBR. However, thermodynamic limitations of NH3 decomposition reaction at low temperature (i.e. ���������������� = 100% at T ≥ 450°C) and the NH3 poisoning effect on the fuel cell installed on H2-fuelled vehicles, represent still a barrier for the adoption of NH3 as a future fuel carrier for vehicular applications. Therefore, to tackle these problems, the development of a hollow fibre palladium-based membrane hollow fibre reactor (MHFR) has been included in this study as well. In this respect, the MHFR would combine both the reaction and separation units integrating a palladium (Pd) membrane with a 100% selectivity to H2. The approach adopted in this work was to develop a MHFR able to achieve a 99.99999% NH3 conversion in order to ensure an NH3 concentration at the exhaust lower than 0.1 ppm. By Le Chatelier’s principle, the membrane allows increasing the NH3 conversion beyond thermodynamic equilibrium limits by continuously removing the produced H2, enabling the membrane reactor to produce high-purity H2 at lower temperatures than conventional catalytic reactors. This research work has been carried out at three different levels, i) materials development and characterisation (i.e. Chapters 2-5), ii) reactor design and performance studies during the NH3 decomposition reaction (i.e. Chapters 4- 6), and iii) feasibility study of the different reactors for on-board H2 production (i.e. Chapter 6). Chapter 2 describes the methods used to synthesise and characterise the catalyst supports proposed, i.e. one carbon xerogel (i.e. CX), two activated carbon xerogels (i.e. ACX1h and ACX5h), and two N-doped carbon xerogels (i.e. UCX and NCX). Similarly, the procedures adopted to synthesise and characterise three series of catalysts, i.e. un-promoted and sodium-promoted ruthenium-based catalysts (i.e. Ru and Ru/Na), and cobalt/molybdenumbased catalysts (i.e. Co/Mo), were described in this chapter. Chapter 3 provides a detailed description of the textural, chemical and structural properties of the carbon xerogels. For example, the nitrogen adsorption and desorption isotherms at -196°C showed that carbon dioxide (CO2) activation treatment of the carbon xerogels lead to two distinct effects, depending on its duration. Furthermore, it was found that the N-doping of carbon xerogels induced a reduction of the specific surface area and total pore volume of both UCX and NCX due to the addition of heteroatoms to their carbon lattice. Likewise, the Temperature Programmed Desorption and X-Ray Photoelectron Spectroscopy experiments confirmed that due to the presence of fewer oxygen surface groups and more nitrogen groups on their surface, both UCX and NCX exhibit a more basic character compared to CX, ACX1h, and ACX5h. Finally, based on their higher burning temperatures, N-doped carbon xerogels were also found to be more thermally stable than their nondoped counterparts. Ru-based catalysts were extensively described in Chapter 4 of this thesis. Particular attention was paid to how the properties of the different carbon xerogels and the use of Na as catalyst promoter affected the performance of the catalysts during the NH3 decomposition reaction. In this respect, it was found that among all un-promoted catalysts, Ru-NCX exhibited the best performance due to, in part, the higher basicity and electron conductivity of NCX when compared to the other carbon xerogels. The performance studies, together with the Transmission Electron Microscopy results, showed that catalysts with a Ru average particle size higher than 2.5 nm exhibited higher reaction rates. Likewise, it was found that the addition of Na had a positive effect on the performance of all catalysts studied during the NH3 decomposition reaction (i.e. at least 3.7 and 1.5 times higher reaction rates at 450°C after the first and second reaction run, respectively). Finally, regardless of the use of Na, all Ru-based catalysts exhibited high thermal stability and catalyst preservability at the operating conditions (i.e. 450°C, 1 atm), as shown by 10 h reaction experiments and elemental analysis performed after the stability test. Similarly, Chapter 5 provides a detailed description of the series of Co/Mobased catalysts studied in this work. It was found that Co/Mo-NCX was the most suitable catalyst candidate for the NH3 decomposition reaction and that the optimal metal particle size for Co/Mo-based catalysts is around 2.2 nm. Furthermore, also Co/Mo-based catalysts showed excellent thermal stability, as proven by the constant ammonia conversion achieved during the long-term stability tests (i.e. 100 h for Co/Mo-NCX and 10 h for the other Co/Mo-based catalysts). The design of the hollow fibre reactors (HFRs) and the hollow fibre membrane reactor (MHFR) used in this work was covered in Chapter 6 and Chapter 7, respectively. In order to develop the hollow fibre reactors, the best performing Ru-based and Co/Mo-based catalysts were deposited into a 4-channelled hollow fibre (HF) substrate by adopting a two steps approach that ensured a homogeneous distribution of the catalyst. More specifically, a single HF unit 10 cm long was used for the deposition of Ru/Na-NCX, whereas a module of 10 HF units 5 cm long was used for the deposition of Co/Mo-NCX. Likewise, for the development of the MHFR, the HF was used as a support of a Pd membrane, and Ru/Na-NCX was packed in contact with the membrane in the shell side of the MHFR. The catalysts performance was assessed during the NH3 decomposition reaction between 100°C and 600°C using HFRs, and between 300°C and 450°C using the MHFR, to prevent damaging the Pd membrane. Furthermore, the thermal stability during the reaction experiments using HFRs was assessed at 450°C. To conclude, Chapter 6 and Chapter 7 include the feasibility study of the different catalytic reactors presented in this work for on-board H2 production. With this scope, the PBRs, HFRs, and MHFR were compared in terms of volume, catalyst loading, and efficiency. This investigation demonstrated the superiority of the HF-based reactors over the traditional PBRs, not only in terms of remarkably high NH3 decomposition reaction rates but also by their noteworthy advantages in terms of costs, volume occupied, and efficiency

Limitations of Anti-Angiogenic Treatment of Tumors

Clinical trials using anti-vascular endothelial growth factor /(VEGF) molecules induce a modest improvement in overall survival, measurable in weeks to just a few months, and tumors respond differently to these agents. In this review article, we have exposed some tumor characteristics and processes that may impair the effectiveness of anti-angiogenic approaches, including genotypic changes on endothelial cells, the vascular normalization phenomenon, and the vasculogenic mimicry. The usage of anti-angiogenic molecules leads to hypoxic tumor microenvironment which enhances tumor invasiveness. The role of tumor-infiltrating cells, including tumor associated macrophages and fibroblasts (TAMs and TAFs) in the therapeutic response to anti-angiogenic settings was also highlighted. Finally, among the new therapeutic approaches to target tumor vasculature, anti-PD-1 or anti-PD-L1 therapy sensitizing and prolonging the efficacy of anti-angiogenic therapy, have been discussed

Micro RNA facilitated chemoresistance in gastric cancer: a novel biomarkers and potential therapeutics

Introduction: In spite of the substantial advances in clinical practice, Gastric cancer (GC) remains the third leading cause of cancer death worldwide. The incidence of drug resistance remains a hindrance to effective treatment for GC. Although the molecular mechanisms of chemoresistance have broadly studied, the gene regulation and expression mechanisms of miRNA have not entirely understood. Methods: Online databases of PubMed, Scopus, Google Scholar, and Embase databases were searched to retrieve relevant publications. The following keywords were used: MicroRNA, Noncoding RNA, miRNA, Gastric cancer, drug resistance, and chemoresistance. Results: miRNAs play a pivotal role in the initiation, progression of tumor and metastasis, as well as in the development of pathways mediating resistance to chemotherapy in GC. Unluckily, to date, there is no consistent, reliable biomarker available to predict the response of chemotherapy before the start of the treatment. Discussion: In this review, we would like to provide an overview of the miRNAs and miRNA facilitated chemoresistance machinery in GC to develop a personalized treatment to overcome GC drug resistance

HGF/Met axis has anti-apoptotic and anti-autophagic function in hypoxic cardiac injury

Ischaemic heart disease is the main cause of death in western countries. Cardiac tissue is primarily damaged by cardiomyocyte cell death triggered by low oxygen supply to the heart (hypoxia). The current therapeutic approach is coronary angioplastic intervention or thrombolytic treatments to resume blood flow in the ischaemic heart. Unfortunately, reperfusion itself causes a burst of ROS production responsible for cardiomyocyte death and myocardial dysfunction. Indeed, the majority of patients surviving to acute myocardial infarction undergoes progressive heart failure, with 50% mortality at five years from diagnosis. Apoptosis of cardiomyocytes is dangerous both during ischaemia and reperfusion. In line with this concept, we have shown that treatment of H9c2 cardiomyoblasts with cobalt chloride (CoCl2), a chemical mimetic of hypoxia, induces caspase-dependent apoptosis. Unexpectedly, we found that 3-methyladenine, an inhibitor of autophagy initiation, partially prevents CoCl2-mediated cell death, indicating that also autophagy contributes to cardiomyoblast death. Consistently, we found an increase in the autophagic flux in dying cells. Mechanistically, we have shown that CoCl2 upregulates Redd1, Bnip3 and phospho-AMPK proteins and causes inhibition of mTOR, the main negative regulator of autophagy.  In light of these observations, it is important to discover new therapeutic tools displaying a dual prosurvival mechanism. To this aim, we have analyzed the cardioprotective action of HGF/Met axis in hypoxic injury. To activate Met signaling we have used either the HGF ligand or two different monoclonal antibodies (mAbs) directed against the extracellular moiety of Met receptor. Owing a divalent structure, the two mAbs can dimerize and activate Met receptor, thus displaying agonist activity. Hypoxic injury was fully prevented by either HGF or Met agonist mAbs through both anti-apoptotic and anti-autophagic functions. By pharmacological inhibition we showed that activation of mTOR is the protective signaling downstream to Met, being involved in the anti-autophagic effect. In conclusion, HGF or Met agonist mAbs promote cell survival by negative dual regulation of apoptotic and autophagic cell death and represent promising new therapeutic tools to manage cardiac diseases

Post-Thyroidectomy Hypocalcemia: Timing of Discharge Based on Serum Calcium Levels

Purpose: The study concerns about the evaluation of Calcium serum levels in patients who underwent total thyroidectomy. Our previous experience underlined how patients who had levels of serum Calcium more than 9 mg/dl at the first day after surgery, did not show Hypocalcemia in the next days,so that this value could be considered a good cut-off for the decision of an early discharge. With regards to this experience, the aim of our current study was to confirm the effective feasibility of an early discharge based on the levels of serum Calcium at the first post-operative day. Patients and Methods: Our study included 102 consecutive patients (82 F; 20 M, age with a range between 14-78 year sold, average 52.6) that were submitted to total thyroidectomy in the years 2010 to 2014, performed by the same operator and all done with sutureless technique (Ligasure precise©) We classify hypocalcemia, according to their normal range (8.6 to 10.4 mg/dl), in mild (not less than 7.6 mg/dL), moderate (between 7.5 mg/dL and 7 mg/dL) and severe (less than 7 mg/dL) We classified the normal range of serum Calcium between 8.6 mg/dl and 10.4 mg/dl. Patients that showed levels of serum Calcium under this limit (<8.6 mg/dl) were treated with 6 fials of Gluconate Calcium 40 mEq in 500 ml of saline solution NaCl 0.9% i.v. (one per day), until the return to the normal range. Patients who had serum Calcium levels more than 9 mg/dl at the first post-operative days, and did not have other complications, were discharged at the same day and revaluated after 7 days. Discussion and Conclusion: Moreover our study has been useful to confirm what we observed in the previous experience, that levels of serum Calcium more than 9 mg/dl at the first postoperative day can be considered a feasible cut-off to exclude the appearance of hypocalcaemia in future. Therefore, according to our results, we assume to propose an early discharge for the patients who have serum Calcium levels more than 9 mg/dl, asking them to come back for controls one week after discharge