Evaluation of alternative thermochemical cycles – Part III further development of the Cu–Cl cycle

This is the third in a series of papers on alternative cycle evaluation. Part I described the evaluation methodology. Part II described the down-selection process where the most promising of the nine alternative cycles was determined. The Cu–Cl cycle was selected for further development because it alone meets the four criteria used. The current results indicate that the cycle is chemically viable, feasible with respect to engineering, energy-efficient, and capable of meeting DOE's timeline for an Integrated Laboratory Scale (ILS) demonstration. All of the reactions have been proven and the remaining technical challenges should be met with current technologies. The maximum temperature requirement is around 550 °C (823 K), which can be obtained with a variety of heat sources. The lower temperature should mitigate the demands on the materials of construction. This paper, Part III, describes the procedure used to develop the Cu–Cl cycle beyond the relatively simple Level 3 efficiency calculation completed by the universities. The optimization process consisted of (i) updating the thermodynamic database used in the Aspen Plus^® simulation, (ii) developing a robust flowsheet and optimizing the energy usage therein, (iii) designing a conceptual process incorporating the Aspen Plus^® mass and energy flows, and then (iv) estimating the hydrogen production costs. The results presented here are preliminary because further optimization is ongoing.     

On Dimensionality of Halogen-Bonded Thiophene Solid-State Assemblies

We report on the structures of three dibromothiophene compounds ( 4 , 5 , and 12 ) and the analysis of the patterns of self-assembly in the solid state by C Br⋅⋅⋅Br C halogen bonds of a selected set of 16 di- or poly-bromine (poly)thiophene monomers sorted according to the dimensionality of their halogen-bonded, extended frameworks thereby identifying syn- or anti-strings and layers. We conclude that in 1 , 2 , 9 , and 10 , the antiparallel orientation of successive C Br⋅⋅⋅Br C halogen-bonded dibromothiophene units along extended anti-strings is linked to the occurrence of solid-state polymerization.     

Aging of polyethylene pipes transporting drinking water disinfected by chlorine dioxide. Part II—Lifetime prediction

This article deals with the failure of polyethylene pipes transporting chlorine dioxide (DOC) disinfected water under pressures of few bars. Accelerated aging tries made at 20 or 40°C show that the antioxidant is rapidly consumed in a superficial layer until a depth of about 1.2 mm. Carbonyl groups appear in a sharper layer of few hundreds micrometers. Natural aging results at various places, for various times up to about 30 years, reveal also a superficial attack with a depth of the order of 1.2 mm. An antioxidant loss by migration, in the whole sample thickness, is also observable. The shape of antioxidant concentration profiles indicates that the crossing of interfaces controls partially the whole migration kinetics. Failures, with brittle cracking, were observed in natural aging, after exposure times of the order of 5–15 years, i.e., far before the expected lifetime (50 years). A kinetic model has been elaborated to predict the time to failure. It is based on a chemical unit, which models the radical processes induced by DOC, and a mechanical unit based on an empirical creep law and a failure criterion depending of the molar mass calculated by the chemical unit. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers     

Disulfide Bond Substitution by Directed Evolution in an Engineered Binding Protein

Breaking ties : The antitumour protein, neocarzinostatin (NCS), is one of the few drug‐carrying proteins used in human therapeutics. However, the presence of disulfide bonds limits this protein's potential development for many applications. This study describes a generic directed‐evolution approach starting from NCS‐3.24 (shown in the figure complexed with two testosterone molecules) to engineer stable disulfide‐free NCS variants suitable for a variety of purposes, including intracellular applications.

     

Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound

The expression and activity of DNA-dependent protein kinase (DNA-PK) is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR) is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1-oxidopyridin-2-yl)sulfanyl]-2,1,3-benzoxadiazole (NSC), bearing a nitro-benzoxadiazole (NBD) scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK) rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA-PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells.     

Deactivation and Regeneration of Spent Three-Way Automotive Exhaust Gas Catalysts (TWC)

The effect of oxidation, oxy-chlorination and reduction treatments at elevated temperatures on the dispersion of palladium (Pd) and rhodium (Rh) for commercially aged three-way automotive exhaust gas catalysts (TWC) has been investigated. The catalytic activity of treated samples was compared with a reference sample, which was taken from the corresponding aged TWC and tested using a mini-cuts reactor simulating real driving conditions. In the case of oxygen, the improvement of the noble metal dispersion on the catalysts was dependent on the noble metal loading and the degree of metal sintering. Adding chlorine to the oxygen atmosphere facilitates the restructuring of the metals with an improved increase in the noble metal dispersion. The temperature and the composition of the gas used during these thermal treatments proved to be of importance not only to increase the metal dispersion, but also to prevent possible losses of noble metals, in the form of volatile MO _x Cl _y compounds. TEM-EDS techniques indicated changes in the size of the largest noble metal agglomerates of up to 100 nm in size after thermal gas treatment. BET porosity and XRD analyses were employed to investigate restructuring of the washcoat and showed a decrease in pore size distribution and an increase in surface area.     

A Microfluidic Ion Pump for In Vivo Drug Delivery

Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device is characterized in vitro by delivering γ‐amino butyric acid to a target solution, and demonstrates low‐voltage operation, high drug‐delivery capacity, and high ON/OFF ratio. It is also demonstrated that the device is suitable for cortical delivery in vivo by manipulating the local ion concentration in an animal model and altering neural behavior. These results show that µFIPs represent a significant step forward toward the development of implantable drug‐delivery systems.     

Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.     

Mitochondrial Genome Editing to Treat Human Osteoarthritis—A Narrative Review

Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure OA. Various mutations have been evidenced in the mitochondrial DNA (mtDNA) of cartilage cells (chondrocytes) in OA, leading to a dysfunction of the mitochondrial oxidative phosphorylation processes that significantly contributes to OA cartilage degeneration. The mitochondrial genome, therefore, represents a central, attractive target for therapy in OA, especially using genome editing procedures. In this narrative review article, we present and discuss the current advances and breakthroughs in mitochondrial genome editing as a potential, novel treatment to overcome mtDNA-related disorders such as OA. While still in its infancy and despite a number of challenges that need to be addressed (barriers to effective and site-specific mtDNA editing and repair), such a strategy has strong value to treat human OA in the future, especially using the groundbreaking clustered regularly interspaced short palindromic repeats (CRIPSR)/CRISPR-associated 9 (CRISPR/Cas9) technology and mitochondrial transplantation approaches.