Nanoparticle-based cerebral drug-delivery systems and antiangiogenic approach in gliomas treatment

The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.     

Main aspects of geothermal energy in Mexico

With an installed geothermal electric capacity of 853 MW_e, Mexico is currently the third largest producer of geothermal power worldwide, after the USA and the Philippines. There are four geothermal fields now under exploitation: Cerro Prieto, Los Azufres, Los Humeros and Las Tres Vírgenes. Cerro Prieto is the second largest field in the world, with 720 MW_e and 138 production wells in operation; sedimentary (sandstone) rocks host its geothermal fluids. Los Azufres (88 MW_e), Los Humeros (35 MW_e) and Las Tres Vírgenes (10 MW_e) are volcanic fields, with fluids hosted by volcanic (andesites) and intrusive (granodiorite) rocks. Four additional units, 25 MW_e each, are under construction in Los Azufres and due to go into operation in April 2003. One small (300 kW) binary-cycle unit is operating in Maguarichi, a small village in an isolated area with no link to the national grid. The geothermal power installed in Mexico represents 2% of the total installed electric capacity, but the electricity generated from geothermal accounts for almost 3% of the national total.     

Digital compensation of second‐ and third‐order nonlinear distortions generated by blocker signals

Deeply integrated systems in chips commonly include a digital and an analog front end on the same die. These analog front‐end schemes for wireless communications could be implemented under the concept called software‐defined radio (SDR). Digital signal processing is commonly used to perform signal filtering and channel equalization, and, recently, to improve front‐end radio performance by removing the undesirable effects of the analog front‐end imperfections. These wide‐band SDR are currently implemented without the surface acoustic wave (SAW) filter, because it is difficult to integrate a highly configurable one, as is required in wide‐band systems. An analog front end without this filter has no efficient protection against blocker signal effects, specifically against nonlinear distortions due to the analog front‐end imperfections. This paper proposes an algorithm to simultaneously remove second‐ and third‐order nonlinear distortions caused by a blocker signal, departing from a behavioral model and a band‐pass sampling pure digital algorithm to recover the blocker signal information. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Nurse′s A‐Phase: Synthesis and Characterization in the Binary System Ca2SiO4–Ca3(PO4)2

In the present study, a new single phase Si–Ca–P‐based ceramic was obtained by conventional sintering of compacted mixtures of calcium hydrogen phosphate anhydrous, calcium carbonate, and silicon oxide. The synthesis conditions were the followings: heated up to 1550°C for a total period of time of 72 h (3 d), with quenching in liquid nitrogen, milling, pressing, and reheating every 24 h. Second, heating at 1300°C/3 h and subsequent annealed at 1200°C/24 h. Mineralogical and microstructural characterization of the obtained Si–Ca–P‐based material was determined by Differential Thermal Analysis, X‐ray diffraction, Scanning Electron Microscopy with attached wavelength dispersive spectroscopy, Micro‐Raman and Fourier Transform Infrared Spectrometer. The results showed a single Si–Ca–P phase material with a Ca₂SiO₄/Ca₃(PO₄)₂ molar ratio equal to 2:1. The parameters of the Weibull distribution of strength, determined by diametrical compression of disks, were: modulus, m = 13, and characteristic strength σ₀ = 0.60 MPa.     

Analytical investigation of elastic period of infilled RC MRF buildings

Fundamental period of vibration, dependent on mass and stiffness structure characteristics, is a key parameter in assessing seismic demand. The period can be evaluated both by means of empirical formulas and modal analysis carried out on a structure numerical model. The presence of external or internal infill elements, usually considered as “non-structural” elements, is generally not taken into account in structural modelling, although these elements can significantly increase the lateral stiffness of a Reinforced Concrete (RC) Moment Resisting Frame (MRF) building leading to a modification in dynamic properties.In this study, results of modal analyses carried out on 3D numerical RC MRF building models are presented, varying structure morphology (height, surface area, ratio between plan dimensions) and infill characteristics. Simplified formulas based on regression analysis of obtained numerical data are presented and discussed. These relationships are also compared with similar literature numerical expressions and empirical data from experimental measurements on existing buildings.     

Shallow Water Flows in Channels

We consider the shallow water equations for flows through channels with arbitrary cross section. The system forms a hyperbolic set of balance laws. Exact steady-state solutions are available and are controlled by the relation between the bottom topography and the channel geometry. We use a Roe-type upwind scheme for the system. Considerations of conservation, near steady-state accuracy, velocity regularization and positivity near dry states are discussed. Numerical solutions are presented illustrating the merits of the scheme for a variety of flows and demonstrating the effect of the interplay between the topography and the geometry on the solution.     

Fluorescence Lifetime Phasor Analysis of the Decamer–Dimer Equilibrium of Human Peroxiredoxin 1

Protein self-assembly is a common feature in biology and is often required for a myriad of fundamental processes, such as enzyme activity, signal transduction, and transport of solutes across membranes, among others. There are several techniques to find and assess homo-oligomer formation in proteins. Naturally, all these methods have their limitations, meaning that at least two or more different approaches are needed to characterize a case study. Herein, we present a new method to study protein associations using intrinsic fluorescence lifetime with phasors. In this case, the method is applied to determine the equilibrium dissociation constant (K_D) of human peroxiredoxin 1 (hPrx1), an efficient cysteine-dependent peroxidase, that has a quaternary structure comprised of five head-to-tail homodimers non-covalently arranged in a decamer. The hPrx1 oligomeric state not only affects its activity but also its association with other proteins. The excited state lifetime of hPrx1 has distinct values at high and low concentrations, suggesting the presence of two different species. Phasor analysis of hPrx1 emission lifetime allowed for the identification and quantification of hPrx1 decamers, dimers, and their mixture at diverse protein concentrations. Using phasor algebra, we calculated the fraction of hPrx1 decamers at different concentrations and obtained K_D (1.1 × 10⁻²⁴ M⁴) and C_0.5 (1.36 μM) values for the decamer–dimer equilibrium. The results were validated and compared with size exclusion chromatography. In addition, spectral phasors provided similar results despite the small differences in emission spectra as a function of hPrx1 concentration. The phasor approach was shown to be a highly sensitive and quantitative method to assess protein oligomerization and an attractive addition to the biophysicist’s toolkit.     

Microstructural Features of RF-sputtered SOFC Anode and Electrolyte Materials

Thin-film samples of yttria-stabilized zirconia (YSZ), nickel oxide (NiO)-YSZ, and YSZ/nickel (Ni)-YSZ bilayer were fabricated by RF-sputtering. The single YSZ layer and YSZ/Ni-YSZ bilayer samples were annealed while the NiO-YSZ layer remained as-deposited. Cross-section transmission electron microscopy (TEM) samples of these thin-films were then prepared, which allowed detailed chemical and structural characterization of these thin-films on the nanometer-scale. Both YSZ and NiO-YSZ layers were fully dense and exhibiting equiaxed grain morphologies. Selected area electron diffraction (SAED) showed the YSZ crystal structure to be predominantly cubic in the annealed samples and amorphous in the as-deposited NiO-YSZ sample. It was found that YSZ film was 70 nm thick and dense, with equiaxed grains ranging from 12–20 nm. Surface roughness of the YSZ in the bilayer fell in the range of 5–20 nm. The Ni-YSZ film in the bilayer was 230 nm thick and porous, which consisted of columnar grains 13–75 nm in length and 9–22 nm in width. The bilayer sample showed no delamination or cracking along the YSZ/Ni-YSZ interface. It is believed that the nano-sized grains, minimal surface roughness and thin layers found in these films are desirable microstructural features for the anode and electrolyte in micro-solid oxide fuel cells (SOFCs). Correlation between microstructural features and electrochemical performance will be reported in a separate study.     

The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows

Simple SummaryAdvances in molecular genetics have radically changed all aspects of cancer prevention, screening and treatment and, today, women who are suspected of being at risk of hereditary cancer should always undergo genetic counselling. Furthermore, today there is growing attention on the tumor suppressor genes BRCA 1 and BRCA2. In addition, there is growing attention on women who carry mutations of the tumor suppressor genes BRCA 1 and BRCA2 and undergo a prophylactic risk-reducing salpingo-oophorectomy. This paper explores the pathobiology of BRCA1\2 cancer genes in a translational perspective, focusing on molecular aspects of hormonal therapy in early menopausal women as well as on the latest evidence-based guidelines for clinicians. Physicians should counsel motivated patients who ask for relief from early menopausal symptoms about the risks and benefits of hormonal therapy, as well as tailoring and appropriate treatment for selected patients. AbstractAll cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35–40 years in BRCA1 mutation carriers and between 40–45 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment.