Development of an estimation model for the evaluation of the energy requirement of dilute acid pretreatments of biomass

This study aims to develop a mathematical model to evaluate the energy required by pretreatment processes used in the production of second generation ethanol. A dilute acid pretreatment process reported by National Renewable Energy Laboratory (NREL) was selected as an example for the model's development. The energy demand of the pretreatment process was evaluated by considering the change of internal energy of the substances, the reaction energy, the heat lost and the work done to/by the system based on a number of simplifying assumptions. Sensitivity analyses were performed on the solid loading rate, temperature, acid concentration and water evaporation rate. The results from the sensitivity analyses established that the solids loading rate had the most significant impact on the energy demand. The model was then verified with data from the NREL benchmark process. Application of this model on other dilute acid pretreatment processes reported in the literature illustrated that although similar sugar yields were reported by several studies, the energy required by the different pretreatments varied significantly

Adverse drug reaction monitoring on antiretroviral therapy in human immunodeficiency virus patients in a tertiary care hospital

Background: The aim of current study was to assess the pattern of adverse drug reactions (ADRs) in patients receiving antiretroviral (ARV) therapy.Methods: A prospective, observational study was carried out for duration of 15 months. Clinical and treatment data were collected from patients, who underwent ARV therapy during the study period. CDSCO forms were used to record the ADRs. Causality, severity and preventability were assessed by suitable scales.Result: Out of 216 patients 165 (76%) patients develop ADRs. Total of 274 ADRs were noted among 165 patients (1.66 ADR/patient). Out of them 100 (60.60%) were males and 65 (39.39%) were females. The most common ADR was gastrointestinal disorders (83, 30.29%). The most numbers of ADRs were observed in ZLN (Zidovudine + Lamivudine + Nevirapine) regimen (54%) followed by SLN (Stavudine + Lamivudine + Nevirapine) regimen (26%). According to WHO causality assessment scale most ADRs were possible (236, 86.13%). Hartwig and Siegel severity scale show 243 (88.69%) ADRs were moderate. Schumock and Thornton scale show all, ADRs were “not preventable.”Conclusion: Early detection of drug toxicity helps to treat the patient and modify the drug regimen to minimize toxic effects

Thalassemia mutations in Gaziantep, Turkey

Ninety-eight postnatal and six prenatal cases of thalassemia were studied by the reverse dot-blot hybridization technique in the city of Gaziantep, Turkey. We found the following mutations: IVS 1.110 (G>A) in 29.1%, IVS 2.1 (G>A) in 12.3%, IVS 1.1 (G>A) in 7.7%, Codon 8 (-AA) in 5.6%, -30 (T>A) in 4.6%, IVS 1.6 (T>C) in 4.6%, Codon 39 (C>T) in 3.6%, Codon 44 (-C) in 3.1%, IVS 2.745 (C>G) in 1.5%, Codon 8/9 (+G) in 2.1%, Codon 36/37 (-T) in 2.1%, IVS 1.5 (G>C) in 2.1%, Codon 22 (7pb del) in 0.5%, Codon 5 (-CT) in 0.5% while 20.9% were undetermined. 54 of the thalassemia patients were homozygotes, 12 were compound heterozygous and 31 were heterozygotes. In one allele of 5 thalassemia patients, - thalassemia mutation (3.7 single gene deletions in 1 patient, anti-3.7 gene triplication in 4 patients) wasdetermined at the same time. Finally, this is the first comprehensive study in this region and percentage of and - globin genes mutation is 2.6 and 79.4%, respectively

Synthetic lethality in CCNE1-amplified high grade serous ovarian cancer through combined inhibition of Polo-like kinase 1 and microtubule dynamics

The taxanes are effective microtubule-stabilizing chemotherapy drugs that inhibit mitosis, induce apoptosis, and produce regression in a fraction of cancers that arise at many sites including the ovary. Novel therapeutic targets that augment taxane effects are needed to improve clinical chemotherapy response in CCNE1-amplified high grade serous ovarian cancer (HGSOC) cells. In this study, we conducted an siRNA-based kinome screen to identify modulators of mitotic progression in CCNE1-amplified HGSOC cells that may influence clinical paclitaxel response. PLK1 is overexpressed in many types of cancer, which correlates with poor prognosis. Here, we identified a novel synthetic lethal interaction of the clinical PLK1 inhibitor BI6727 and the microtubule-targeting drug paclitaxel in HGSOC cell lines with CCNE1-amplification and elucidated the underlying molecular mechanisms of this synergism. BI6727 synergistically induces apoptosis together with paclitaxel in different cell lines including a patient-derived primary ovarian cancer culture. Moreover, the inhibition of PLK1 reduced the paclitaxel-induced neurotoxicity in a neurite outgrowth assay. Mechanistically, the combinatorial treatment with BI6727/paclitaxel triggers mitotic arrest, which initiates mitochondrial apoptosis by inactivation of anti-apoptotic BCL-2 family proteins, followed by significant loss of the mitochondrial membrane potential and activation of caspase-dependent effector pathways. This conclusion is supported by data showing that BI6727/paclitaxel-co-treatment stabilizes FBW7, a component of SCF-type ubiquitin ligases that bind and regulate key modulators of cell division and growth including MCL-1 and Cyclin E. This identification of a novel synthetic lethality of PLK1 inhibitors and a microtubule-stabilizing drug has important implications for developing PLK1 inhibitor-based combination treatments in CCNE1-amplified HGSOC cells

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Isomorphisms of types in the presence of higher-order references (extended version)

We investigate the problem of type isomorphisms in the presence of higher-order references. We first introduce a finitary programming language with sum types and higher-order references, for which we build a fully abstract games model following the work of Abramsky, Honda and McCusker. Solving an open problem by Laurent, we show that two finitely branching arenas are isomorphic if and only if they are geometrically the same, up to renaming of moves (Laurent's forest isomorphism). We deduce from this an equational theory characterizing isomorphisms of types in our language. We show however that Laurent's conjecture does not hold on infinitely branching arenas, yielding new non-trivial type isomorphisms in a variant of our language with natural numbers

High throughput screening of hydrolytic enzymes from termites using a natural substrate derived from sugarcane bagasse

<p>Abstract</p> <p>Background</p> <p>The description of new hydrolytic enzymes is an important step in the development of techniques which use lignocellulosic materials as a starting point for fuel production. Sugarcane bagasse, which is subjected to pre-treatment, hydrolysis and fermentation for the production of ethanol in several test refineries, is the most promising source of raw material for the production of second generation renewable fuels in Brazil. One problem when screening hydrolytic activities is that the activity against commercial substrates, such as carboxymethylcellulose, does not always correspond to the activity against the natural lignocellulosic material. Besides that, the macroscopic characteristics of the raw material, such as insolubility and heterogeneity, hinder its use for high throughput screenings.</p> <p>Results</p> <p>In this paper, we present the preparation of a colloidal suspension of particles obtained from sugarcane bagasse, with minimal chemical change in the lignocellulosic material, and demonstrate its use for high throughput assays of hydrolases using Brazilian termites as the screened organisms.</p> <p>Conclusions</p> <p>Important differences between the use of the natural substrate and commercial cellulase substrates, such as carboxymethylcellulose or crystalline cellulose, were observed. This suggests that wood feeding termites, in contrast to litter feeding termites, might not be the best source for enzymes that degrade sugarcane biomass.</p

Characterization of Annona cherimola mill. Seed oil from Madeira Island: a possible biodiesel feedstock

The possibility of using Annona seed oil as an added value product, namely as a source of biodiesel, is explored. Milled Annona seeds were extracted with hexane at room temperature (72 h) and at solvent boiling point (6 h). Oil content was found to be 25 and 22.4% respec tively. The oil was characterized in terms of lipid compo sition (HPLC–APCI–MS and 13C NMR), resistance to oxidation and acidity index. FAME composition was determined by GC–MS and five major peaks were identi fied. Production of biodiesel from Annona’s seed oil was achieved by base-catalyzed transesterification. Density, viscosity, refraction coefficient, acid value, cold filter plugging point, cloud point and oxidation stability were measured. The iodine value and the ‘‘apparent cetane number’’ were calculated. Density, viscosity, acid value, iodine value, cold filter plugging point and cloud point were within EN14214 specifications and the calculated ‘‘apparent cetane number’’ was also indicative of a suitable product.info:eu-repo/semantics/publishedVersio

Influence of moisture contents on the fast pyrolysis of trommel fines in a bubbling fluidized bed reactor

In this study, the effect of moisture contents [2.69 wt% (bone-dry), 5 wt% and 10 wt%] on product yields and process conversion efficiency during fast pyrolysis of a pre-treated trommel fines feedstock was investigated at 500 °C. Experiments were carried out using a 300 g h −1 bubbling fluidised bed rig. Yields of organic liquids ranged from 15.2 to 19.6 wt% of feedstock, which decreased with increasing moisture content. Hence, the bone-dry feedstock gave the maximum yield and consequently the highest process conversion efficiency of 43%. Increased moisture content also led to increase formation of unidentified gas products, indicating increased conversion of organic liquids. Due to the high ash content of the feedstocks, about 52 wt% solid residues, containing around 82% ash was recovered in the char pot in each case. Hence, to maximize oil yields during fast pyrolysis, trommel fines would require extensive drying to remove the original 46 wt% moisture as well as reducing the ash content considerably. XRF analysis of the ash in the feedstock and solid residues showed that the main elements present included Ca, Si, Fe, Pb, K, Cl and Al. Apart from the presence of Pb (which may be from the glass contents of the feedstock), the solid residues could be used for land reclamation or co-incinerated at cement kilns for cement manufacture