Unprecedented Biodegradable Cellulose-Derived Polyesters with Pendant Citronellol Moieties: From Monomer Synthesis to Enzymatic Degradation

Levoglucosenone (LGO) is a cellulose-derived molecule that is present commercially on a multi-ton/year scale. Taking advantage of the α,β-conjugated ketone of LGO, a new citronellol-containing 5-membered lactone (HBO-citro) was synthesized through a one-pot two-step pathway involving oxa-Michael addition and Baeyer-Villiger oxidation. The solvent-free treatment of HBO-citro with NaBH4 at room temperature led to the full reduction of the lactone moiety which gave a novel fully renewable triol monomer having a citronellol side chain (Triol-citro). Noticeably, by simply changing the reducing agent, temperature and reaction duration, the partial reduction of HBO-citro can be achieved to yield a mixture of 5- and 6-membered Lactol-citro molecules. Triol-citro was chosen to prepare functional renewable polyesters having citronellol pendant chains via polycondensation reactions with diacyl chlorides having different chain lengths. Good thermal stability (Td5% up to 170 °C) and low glass transition temperatures (as low as −42 °C) were registered for the polyesters obtained. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan® 50 BG) to assess their biodegradability. A higher degradation profile was found for the polyesters prepared using co-monomers (acyl chlorides) having longer chain lengths. This is likely due to the decreased steric hindrance around the ester bonds which allowed enhanced accessibility of the enzyme.

Safety, Tolerability, and Clinical Pharmacology of ANX009, an Inhibitory Antibody Fab Fragment Against C1q, Administered Subcutaneously to Healthy Volunteers

Certain autoantibodies that bind to tissue antigens or that deposit in tissues as a component of immune complexes can activate the classical complement cascade, leading to inflammation and tissue damage. As the initiating molecule of the classical complement cascade, C1q is an attractive target for preventing complement activation and its multiple tissue-damaging effects. ANX009 is an antigen binding fragment (Fab) of a humanized antibody against C1q that inhibits C1q substrate interactions and fully blocks activation of all downstream classical complement components. While inhibiting the classical cascade, ANX009 leaves the lectin and alternative complement pathways intact for their normal immune functions. ANX009 is formulated for subcutaneous (SC) administration and is designed for treatment of blood-based and vascular antibody-mediated autoimmune diseases, such as autoimmune hemolytic anemia (AIHA) and lupus nephritis, where complement activation is a key component of disease pathology. A phase 1 first-in-human single ascending dose (SAD) and multiple ascending dose (MAD) study of ANX009 with subcutaneous administration was conducted in 48 healthy volunteers (NCT04535752). Four SAD cohorts were enrolled followed by two MAD cohorts evaluating daily dosing for 7 days or twice weekly dosing x 4 doses. Each cohort had eight participants randomized in a 6:2 active:placebo ratio. Safety and tolerability were assessed, along with serum pharmacokinetics (unbound drug), pharmacodynamics (unbound C1q target), and an ex vivo measure of C1q activity (CH 50 hemolysis of antibody-sensitized sheep red blood cells). All dose levels were well-tolerated. No drug-related safety signals, dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuations were observed. Mild, transient, local injection site reactions were observed. A clear dose-response relationship was observed in SAD cohorts. Negligible reduction in free C1q was observed in the two lowest dose cohorts. A maximum mean reduction in free C1q of 80% was observed at 48 hours post-dose at the third dose level, and full reduction of free C1q through 72 hours was observed at the highest dose level. Similarly, full reduction of free C1q was observed in the MAD cohort with daily dosing as well as in the second MAD cohort with twice weekly dosing. Full reduction of C1q was maintained for 4 days following the last dose in the second MAD cohort. Ex vivo functional activity of C1q was completely inhibited in close correspondence with free C1q levels. Combined safety, tolerability, and clinical pharmacology results from this phase 1 study support advancement of ANX009 to studies in patients with complement-mediated autoimmune disorders. Disclosures Grover: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Teigler: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Radomile: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Rose: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Yednock: Annexon Inc: Current Employment, Current equity holder in publicly-traded company. Keswani: Annexon Inc: Current Employment, Current equity holder in publicly-traded company.

Understanding the Deactivation Phenomena of Small-Pore Mo/H-SSZ-13 during Methane Dehydroaromatisation

Small pore zeolites have shown great potential in a number of catalytic reactions. While Mo-containing medium pore zeolites have been widely studied for methane dehydroaromatisation (MDA), the use of small pore supports has drawn limited attention due to the fast deactivation of the catalyst. This work investigates the structure of the small pore Mo/H-SSZ-13 during catalyst preparation and reaction by operando X-ray absorption spectroscopy (XAS), in situ synchrotron powder diffraction (SPD), and electron microscopy; then, the results are compared with the medium pore Mo/H-ZSM-5. While SPD suggests that during catalyst preparation, part of the MoOx anchors inside the pores, Mo dispersion and subsequent ion exchange was less effective in the small pore catalyst, resulting in the formation of mesopores and Al2(MOO4)3 particles. Unlike Mo/H-ZSM-5, part of the Mo species in Mo/H-SSZ-13 undergoes full reduction to Mo0 during MDA, whereas characterisation of the spent catalyst indicates that differences also exist in the nature of the formed carbon deposits. Hence, the different Mo speciation and the low performance on small pore zeolites can be attributed to mesopores formation during calcination and the ineffective ion exchange into well dispersed Mo-oxo sites. The results open the scope for the optimisation of synthetic routes to explore the potential of small pore topologies.

Study of the Reduction of Fe on Reduced Graphene Oxide as a Catalyst for Carbon Monoxide Reduction

This work aims at optimizing the H2 reduction time of Fe/rGO as a preparatory step for the use of the reduced catalyst in Fisher-Tropsch synthesis (FTS). The catalytic system used was Iron Nanoparticles (NPs) loaded on reduced graphene oxide (rGO) support. The as prepared sample was analyzed by TEM, FTIR and XRD spectroscopy. Samples of the produced Fe/rGO catalyst were used to optimize the reduction conditions in the FBR reactor. The three samples were reduced under 1atm H2 gas flow of 50 sccm at 500°C for 8, 12 and 24 hrs. The samples were collected after reduction and analyzed by XRD, FTIR and TEM imaging. The best condition showing full reduction with minimal sintering was at 12hr.

THERMODYNAMIC ANALYSIS OF IRON OXIDES REDUCTION USING CARBON AND WATER VAPOUR

Thermodynamic analysis was performed for complete reduction of iron oxide during heating the initial system «Fe3O4 (eo mol) – H2O (bo mol) – C (excess) » with isothermal exposure. By the nature of ongoing reactions, processes in the system can be divided into four stages. Carbon gasification by water vapor at temperatures below 880 K activates water gas reaction and CO dissociation to form black carbon. Composition of the resulting H2 – H2O – CO – CO2 gas mixture depends only on the temperature. The consumption of carbon at 880 K is ~0,4446 moles on 1 mole of water. Reduction of Fe3O4 to wustite FeO1+x with varying degrees of oxidation occurs in the temperature range 880 – 917 K. Hydrogen reduces oxide at temperatures above 888 K. The percentage part of a whole oxide Fe3O4 reduced by hydrogen into this temperature range increases from zero to ~63 %. The total number of Fe3O4, reduced to wustite at 917 K is ~123 moles for 1 mole of water. It is possible only with repeated regeneration of reductants CO and H2 according to the reactions of carbon gasification by water vapor and by dioxide CO2. The carbon expense is about 78 moles. Wustite FeO1.092 formed at 917 K can be reduced by monoxide CO only at temperatures of 917 – 955 K to wustite FeO1.054 with a lower degree of oxidation. Carbon is gasified only by dioxide CO2, the carbon expense is approximately 18 moles. When isothermal exposure is ~955 K, wustite is reduced to iron. Wustite can be reduced only by carbon monoxide. The carbon expense is approximately 257 mol. For full reduction of 123 mol of Fe3O4 in a mixture with an excess of carbon in a closed system at 1 atm, 1 mole of water is sufficient. The total carbon consumption is ~353 moles for obtaining 368 moles of Fe, or ~0.21 kg/kg iron.

Heterogeneous copper-catalyzed direct reduction of C-glycosidic enones to saturated alcohols in water

Heterogeneous copper-catalysed full reduction of enones in a single procedure providing a library of C-glycosidic saturated alcohols.

Modeling of economic feasibility of transition to own power generation

Cross subsidizing in power industry is the mechanism allowing one groups of consumers to pay the electric power at the price below limit costs, at the same time for other groups of consumers establishing the price above limit costs. Similar price discrimination leads to that the industrial enterprises buying the electric power on raised tariffs, are compelled to look for cheaper alternative ways of power supply. In this connection the enterprises gradually make the decision on construction of own generating capacities. In this article it is investigated to pass how favorably to a question to the enterprises of various branches to own generation of the electric power at the developed and predicted price level on the electric power for the industrial enterprises taking into account cross subsidizing and on condition of its full reduction.

A helicase-independent activity of eIF4A in promoting mRNA recruitment to the human ribosome

In the scanning model of translation initiation, the decoding site and latch of the 40S subunit must open to allow the recruitment and migration of messenger RNA (mRNA); however, the precise molecular details for how initiation factors regulate mRNA accommodation into the decoding site have not yet been elucidated. Eukaryotic initiation factor (eIF) 3j is a subunit of eIF3 that binds to the mRNA entry channel and A-site of the 40S subunit. Previous studies have shown that a reduced affinity of eIF3j for the 43S preinitiation complex (PIC) occurs on eIF4F-dependent mRNA recruitment. Because eIF3j and mRNA bind anticooperatively to the 43S PIC, reduced eIF3j affinity likely reflects a state of full accommodation of mRNA into the decoding site. Here, we have used a fluorescence-based anisotropy assay to quantitatively determine how initiation components coordinate their activities to reduce the affinity of eIF3j during the recruitment of mRNA to the 43S PIC. Unexpectedly, we show that a full reduction in eIF3j affinity for the 43S PIC requires an ATP-dependent, but unwinding-independent, activity of eIF4A. This result suggests that in addition to its helicase activity, eIF4A uses the free energy of ATP binding and hydrolysis as a regulatory switch to control the conformation of the 43S PIC during mRNA recruitment. Therefore, our results define eIF4A as a universal initiation factor in cap-dependent translation initiation that functions beyond its role in RNA unwinding.

Assessment of ductile failure models in single-pass wire drawing processes

The present work reports a comparative study of ductile failure models applied to an Al-2011 aluminum alloy single-pass wire drawing process using different reductions. The material damage experienced in the wire after passing through the die is evaluated using the well-known Rice and Tracey, Cockcroft and Latham, Brozzo and Modified Chaouadi models. Due to the fact that nonrealistic damage predictions are found for the highest studied wire reduction, an alternative uncoupled failure criterion combining the effect of deformation and triaxility is proposed. The ability of these five models in predicting the formation of chevrons in the process is the main focus of this research. First, the model parameters are characterized by means of numerical simulations of the tensile test. Then, the predictions of the numerical analyses of the drawing process are compared with available experimental results where physical evidence of chevrons was found. Relevant variables are analyzed to determine their incidence in the formation of central bursts. Finally, the performance of this new model is assessed for the full reduction scenarios.

Relative functional and optical absorption cross-sections of PSII and other photosynthetic parameters monitored in situ, at a distance with a time resolution of a few seconds, using a prototype light induced fluorescence transient (LIFT) device

The prototype light-induced fluorescence transient (LIFT) instrument provides continuous, minimally intrusive, high time resolution (~2 s) assessment of photosynthetic performance in terrestrial plants from up to 2 m. It induces a chlorophyll fluorescence transient by a series of short flashes in a saturation sequence (180 ~1μs flashlets in <380 μs) to achieve near-full reduction of the primary acceptor QA, followed by a relaxation sequence (RQA; 90 flashlets at exponentially increasing intervals over ~30 ms) to observe kinetics of QA re-oxidation. When fitted by the fast repetition rate (FRR) model (Kolber et al. 1998) the QA flash of LIFT/FRR gives smaller values for FmQA from dark adapted leaves than FmPAM from pulse amplitude modulated (PAM) assays. The ratio FmQA/FmPAM resembles the ratio of fluorescence yield at the J/P phases of the classical O-J-I-P transient and we conclude that the difference simply is due to the levels of PQ pool reduction induced by the two techniques. In a strong PAM-analogous WL pulse in the dark monitored by the QA flash of LIFT/FRR φPSIIWL ≈ φPSIIPAM. The QA flash also tracks PQ pool reduction as well as the associated responses of ETR QA → PQ and PQ → PSI, the relative functional (σPSII) and optical absorption (aPSII) cross-sections of PSII in situ with a time resolution of ~2 s as they relax after the pulse. It is impractical to deliver strong WL pulses at a distance in the field but a longer PQ flash from LIFT/FRR also achieves full reduction of PQ pool and delivers φPSIIPQ ≈ φPSIIPAM to obtain PAM-equivalent estimates of ETR and NPQ at a distance. In situ values of σPSII and aPSII from the QA flash with smaller antenna barley (chlorina-f2) and Arabidopsis mutants (asLhcb2–12, ch1–3 Lhcb5) are proportionally similar to those previously reported from in vitro assays. These direct measurements are further validated by changes in antenna size in response to growth irradiance. We illustrate how the QA flash facilitates our understanding of photosynthetic regulation during sun flecks in natural environments at a distance, with a time resolution of a few seconds.