Hydrogenophilic and bioelectrochemical production of acetate with a pure culture of Acetobacterium Woodii

In recent years there has been a growing interest in the potential use of autotrophic acetogenic bacteria to produce compounds of interest through CO2 fixation, representing an alternative solution to currently used CO2 storage technologies. This group of microorganisms are ubiquitous in nature and they are characterised by a Wood-Ljungdahl pathway that combines CO2 fixation with adenosine triphosphate (ATP) synthesis by using H2 as electron donor. In this work the autotrophic production of acetate by a pure colture of Acetobacterium woodii has been tested under hydrogenophilic or bioelectrochemical conditions. More in details, the hydrogenophilic tests were conducted at two different pH values (5.5 and 7.5) with an H2 partial pressure of 0.52 atm, while bioelectrochemical tests were performed at an applied cathodic potential of -0.90 V vs. SHE (Standard Hydrogen Electrode). The bioelectrochemical tests were set up in H-type reactors (250 mL), in which graphite rods were used as electrodic material and an anion exchange membrane served to separate the anodic and cathodic chambers while allowing anions migration for electroneutrality maintenance. The hydrogenophilic tests resulted in different kinetics depending on the applied pH value. The bioelectrochemical tests, performed at a pH value of 7.5, reached an acetate production rate 2 times higher than in the hydrogenophilic experiments at pH 7.5, as well as an increase in the efficiency of using the reducing power, suggesting an improvement in hydrogen uptake. At pH 5.5, on the other hand, production is improved by increasing the partial pressure of H

Production of short-chain fatty acid from CO2 through mixed and pure culture in a microbial electrosynthesis cell

The continuous accumulation of atmospheric CO2 requires the development of new technologies for its mitigation. Carbon capture and utilization (CCU) technologies aim to convert CO2 into precious compounds like chemicals and fuels. Biological fixation is an attractive CCU strategy in terms of cost, sustainability and variety of products. Chemoautotrophic microorganisms such as methanogens and acetogens are able to reduce CO2 into acetate and methane, respectively. Acetogens bacteria are able to use CO2 for cell growth through the Wood Liujhundal pathway, moreover, the final precursor (i.e. Acetyl-CoA) of the autotrophic metabolism, is also used in energy metabolism with acetate production as a waste product. Furthermore, it is possible to obtain multicarbon products of autotrophic origin starting from acetyl-CoA and acetate. The biotechnological use of these microorganisms requires the presence of H2 as substrate, which is used as an electron donor in the pathway. This reaction can be sustained by a biocathode in a microbial electrosynthesis cell, in which the reducing power is generated by a polarized electrode. This study proposes the use of a microbial electrosynthesis cell for conversion to acetate in H-cells by either a mixed culture enriched with Acetobacterium woodii or a pure culture of Acetobacterium woodii, to observe the difference in terms of acetate production and reducing power consumption efficiency. The mixed culture was obtained from a mixture of activated sludge and anaerobic digestate, treated by a protocol capable to select acetogenic microorganisms without the use of specific chemical inhibitors (2-Bromoethanesulfonate). Both inoculums were tested at room temperature (25°C) in the cathodic chamber of the H-cell at potentials in the range of -0.7 to -1.1 V vs SHE. The obtained results showed that the enriched mixed culture produced at -0.7 vs SHE a mixture of volatile fatty acids including C4 and C5 molecules with an overall coulombic efficiency of 50%, while at the potential of -0.9 vs SHE methane constituted the main product of the biocathode. The pure culture, on the other hand, showed a specific production of acetate with a coulombic efficiency of 44% at -0.9 vs SHE and 63% at -1.1 vs SHE. Furthermore, a drastic decrease in biocathode biomass was observed in pure culture, suggesting a higher tendency to form biofilms on the electrode unlike the mixed culture, which showed a standard growth profile in the bulk

Acetogenic inoculum selection for acetate production from waste biomasses via thermal shock treatment

Innovative treatment and utilization of waste biomass streams are crucial for increase environmental sustainability of human activities. Sewage sludge from the biological degradation of biomass can be valorized for the selection of biocatalysts capable to convert CO2 into valuable products. Indeed, chemoautotrophic microorganisms, like methanogens and acetogens, respectively, are able to convert CO2 into CH4 or acetate by using hydrogen as electron donor, i.e., their utilization for several bio-based CO2 reutilization processes has been widely proposed by several authors. Chemoautothrophic acetogens are widely present in waste streams deriving from the organic matter degradation, however, due to the syntrophic relationship between acetogens and acetoclastic methanogens in anaerobic environments, autothropihc acetate results immediately converted into methane. Therefore, the selection of an acetogenic inoculum which allow to obtain CO2 reduction into acetate, requires methanogens inhibition. Among the different methanogen’s inhibition strategies, the most common method is the use of BES (bromo-ethane sulphonate) which results a not scalable technique for large scale application. A most promising and sustainable approach is offered by the adoption of a thermal treatment which allows to the selection of an acetogenic inoculum, thanks ot the sporogenous capacity of acetogenic bacteria. This work presents the results obtained in the thermal pre-treatment of different type of waste biomasses coming from pilot and full-scale biological processes for the selection of an acetogenic inoculum able to convert CO2 into acetate. Each waste biomass was treated by a thermal shock procedure that consisted in the treatment of the dried biomass at 120°C for 2 hours. Acetogenic inoculums obtained by the thermal pre-treatment of an acidogenic fermentate, an activated sludge and a mesophilic anaerobic digestate, were tested under hydrogenophilic conditions in comparison with blank tests and raw inoculums. The results clearly indicate the effectiveness of the thermal pre-treatment in the selection of the acetogenic microorg

Reactions of a Be-10 beam on proton and deuteron targets

The extraction of detailed nuclear structure information from transfer reactions requires reliable, well-normalized data as well as optical potentials and a theoretical framework demonstrated to work well in the relevant mass and beam energy ranges. It is rare that the theoretical ingredients can be tested well for exotic nuclei owing to the paucity of data. The halo nucleus Be-11 has been examined through the 10Be(d,p) reaction in inverse kinematics at equivalent deuteron energies of 12,15,18, and 21.4 MeV. Elastic scattering of Be-10 on protons was used to select optical potentials for the analysis of the transfer data. Additionally, data from the elastic and inelastic scattering of Be-10 on deuterons was used to fit optical potentials at the four measured energies. Transfers to the two bound states and the first resonance in Be-11 were analyzed using the Finite Range ADiabatic Wave Approximation (FR-ADWA). Consistent values of the spectroscopic factor of both the ground and first excited states were extracted from the four measurements, with average values of 0.71(5) and 0.62(4) respectively. The calculations for transfer to the first resonance were found to be sensitive to the size of the energy bin used and therefore could not be used to extract a spectroscopic factor.Comment: 16 Pages, 10 figure

Phase 1b Trial of Proteasome Inhibitor Carfilzomib with Irinotecan in Lung Cancer and Other Irinotecan-Sensitive Malignancies That Have Progressed on Prior Therapy (Onyx IST Reference Number: CAR-IST-553)

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 + 3 design. Results Overall, 16 patients were enrolled to three dose levels, with four patients replaced. Three patients experienced dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) was exceeded in Cohort 3. The RP2 dose was carfilzomib 20/36 mg/m2 (given on Days 1, 2, 8, 9, 15, and 16) and irinotecan 125 mg/m2 (Days 1, 8 and 15). Common Grade (Gr) 3 and 4 toxicities included fatigue (19%), thrombocytopenia (19%), and diarrhea (13%). Conclusions Irinotecan and carfilzomib were well tolerated, with common toxicities of fatigue, thrombocytopenia and neutropenic fever. Objective clinical response was 19% (one confirmed partial response (PR) in small cell lung cancer (SCLC) and two unconfirmed); stable disease (SD) was 6% for a disease control rate (DCR) of 25%. The recommended phase II dose was carfilzomib 20/36 mg/m2 and irinotecan125 mg/m2. The phase II evaluation is ongoing in relapsed small cell lung cancer

Comprehensive Genomic Profiling in Routine Clinical Practice Leads to a Low Rate of Benefit from Genotype-Directed Therapy

Background: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options. Methods: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT. Results: A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease. Conclusions: CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT

Real-World Evaluation of Universal Germline Screening for Cancer Treatment-Relevant Pharmacogenes

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with cancer. More than 90% carried any clinically relevant pharmacogenetic variant. At least one disease-relevant variant impacting anti-cancer agents was identified in 26.5% (77/291). Nine patients with toxicity-associated pharmacogenomic variants were treated with a relevant medication: seven UGT1A1 intermediate metabolizers were treated with irinotecan, one intermediate DPYD metabolizer was treated with 5-fluorouracil, and one TPMT poor metabolizer was treated with mercaptopurine. These individuals were more likely to experience treatment-associated toxicities than their wild-type counterparts (p = 0.0567). One UGT1A1 heterozygote died after a single dose of irinotecan due to irinotecan-related adverse effects. Identifying germline pharmacogenomic variants was feasible using whole-exome sequencing. Actionable pharmacogenetic variants are common and relevant to patients undergoing cancer treatment. Universal pharmacogenomic screening can be performed using whole-exome sequencing data originally obtained for quality control purposes and could be considered for patients who are candidates for irinotecan, 5-fluorouracil, capecitabine, and mercaptopurine

Measurement of Nuclear Transparency for the A(e,e' pi^+) Reaction

We have measured the nuclear transparency of the A(e,e' pi^+) process in ^{2}H,^{12}C, ^{27}Al, ^{63}Cu and ^{197}Au targets. These measurements were performed at the Jefferson Laboratory over a four momentum transfer squared range Q^2 = 1.1 - 4.7 (GeV/c)^2. The nuclear transparency was extracted as the super-ratio of $(\sigma_A/\sigma_H)$ from data to a model of pion-electroproduction from nuclei without pi-N final state interactions. The Q^2 and atomic number dependence of the nuclear transparency both show deviations from traditional nuclear physics expectations, and are consistent with calculations that include the quantum chromodynamical phenomenon of color transparency.Comment: 5 pages, 3 figs Changes to figure 2 and 3 (error band updated and theory curves updated