FCC coprocessing oil sands heavy gas oil and canola oil. 2. Gasoline hydrocarbon type analysis

This study set out to gain a deeper understanding of a fluid catalytic cracking (FCC) coprocessing approach using canola oil mixed with bitumen-derived heavy gas oil (HGO), for the production of partially-renewable gasoline, with respect to its composition and quality. The FCC coprocessing approach may provide an alternative solution to reducing the carbon footprint and to meet government regulatory demands for renewable transportation fuels. In this study, a mixture of 15 v% canola oil in HGO was catalytically cracked with a commercial equilibrium catalyst under typical FCC conditions. Cracking experiments were performed using a bench-scale Advanced Cracking Evaluation (ACE) unit at a fixed weight hourly space velocity of 8 h−1, 490–530 °C, and catalyst/oil ratios of 4–12 g/g. The total liquid product samples were injected via an automatic sampler and a prefractionator (to remove +254 °C) into a gas chromatographic system containing a series of columns, traps, and valves designed to separate each of the hydrocarbon types. The analyzer gives detailed hydrocarbon types of −200 °C gasoline, classified into paraffins, iso-paraffins, olefins, naphthenes, and aromatics by carbon number up to C11 (C10 for aromatics). For a feed cracked at a given temperature, the gasoline aromatics show the highest selectivity in terms of weight percent conversion, followed by saturated iso-paraffins, saturated naphthenes, unsaturated iso-paraffins, unsaturated naphthenes, unsaturated normal paraffins, and saturated normal paraffins. As conversion increases, both aromatics and saturated iso-paraffins increase monotonically at the expense of other components. Hydrocarbon type analysis and octane numbers with variation in feed type, process severity (temperature and catalyst/oil ratio), and conversion are also presented and discussed. Keywords: Oil sands heavy gas oil (HGO), Canola oil, Advanced Cracking Evaluation (ACE) unit, PIONA analysi

Interleukin-21 Enhances Rituximab Activity in a Cynomolgus Monkey Model of B Cell Depletion and in Mouse B Cell Lymphoma Models

<div><p>Rituximab, a monoclonal antibody targeting CD20 on B cells, is currently used to treat many subtypes of B cell lymphomas. However, treatment is not curative and response rates are variable. Recombinant interleukin-21 (rIL-21) is a cytokine that enhances immune effector function and affects both primary and transformed B cell differentiation. We hypothesized that the combination of rIL-21 plus rituximab would be a more efficacious treatment for B cell malignancies than rituximab alone. We cultured human and cynomolgus monkey NK cells with rIL-21 and found that their activity was increased and proteins associated with antibody dependent cytotoxicity were up-regulated. Studies in cynomolgus monkeys modeled the effects of rIL-21 on rituximab activity against CD20 B cells. In these studies, rIL-21 activated innate immune effectors, increased ADCC and mobilized B cells into peripheral blood. When rIL-21 was combined with rituximab, deeper and more durable B cell depletion was observed. In another series of experiments, IL-21 was shown to have direct antiproliferative activity against a subset of human lymphoma cell lines, and combination of murine IL-21 with rituximab yielded significant survival benefits over either agent alone in xenogeneic mouse tumor models of disseminated lymphoma. Therefore, our results do suggest that the therapeutic efficacy of rituximab may be improved when used in combination with rIL-21.</p></div

Genomic epidemiology of SARS-CoV-2 in Cambodia, January 2020 to February 2021

International audienceThe first case of coronavirus disease 2019 (COVID-19) in Cambodia was confirmed on 27 January 2020 in a traveller from Wuhan. Cambodia subsequently implemented strict travel restrictions, and although intermittent cases were reported during the first year of the COVID-19 pandemic, no apparent widespread community transmission was detected. Investigating the routes of severe acute respiratory coronavirus 2 (SARS-CoV-2) introduction into the country was critical for evaluating the implementation of public health interventions and assessing the effectiveness of social control measures. Genomic sequencing technologies have enabled rapid detection and monitoring of emerging variants of SARS-CoV-2. Here, we detected 478 confirmed COVID-19 cases in Cambodia between 27 January 2020 and 14 February 2021, 81.3 per cent in imported cases. Among them, fifty-four SARS-CoV-2 genomes were sequenced and analysed along with representative global lineages. Despite the low number of confirmed cases, we found a high diversity of Cambodian viruses that belonged to at least seventeen distinct PANGO lineages. Phylogenetic inference of SARS-CoV-2 revealed that the genetic diversity of Cambodian viruses resulted from multiple independent introductions from diverse regions, predominantly, Eastern Asia, Europe, and Southeast Asia. Most cases were quickly isolated, limiting community spread, although there was an A.23.1 variant cluster in Phnom Penh in November 2020 that resulted in a small-scale local transmission. The overall low incidence of COVID-19 infections suggests that Cambodia’s early containment strategies, including travel restrictions, aggressive testing and strict quarantine measures, were effective in preventing large community outbreaks of COVID-19

Murine IL-21 plus rituximab prolongs the survival of SCID mice bearing disseminated lymphoma tumor cells.

<p>(<b>A, B</b>) SCID mice (n = 10/group) were injected i.v. with 10⁶ lymphoma cells and then treated with rituximab alone (20 µg on days 3, 7, 11, 15, 19), mIL-21 alone (100 µg days 1–5), or mIL-21 and rituximab. Significant prolongation of survival was observed in the rituximab plus mIL-21 group when compared to rituximab alone (<i>p</i> = 0.0006) in the HS-Sultan model (A). Mice in the Raji model (B) were treated as above, except that mIL-21 was given on days 3–7 and rituximab was given on days 5, 9, 13, 17, and 21. Mice in the combination group survived longer than those treated with rituximab alone (<i>p</i> = 0.0079). (<b>C, D, E</b>) Test of effector cell function with Raji lymphoma models established in SCID or NOD/SCID mice as described above. (C) NOD/SCID mice with impaired NK cells compared to SCID mice. Equivalent survival times were observed for NOD/SCID and SCID mice given rituximab plus rIL-21 (p = 0.012) or rituximab alone. (D) SCID mice injected i.p. with 50 µg of anti-Gr-1 antibody on day -1, 4, 9 and 14 to deplete granulocytes or with PBS (control). Survival was significantly decreased for depleted mice given rituximab plus rIL-21 (p = 0.012) or rituximab alone (p = 0.001) compared with non-depleted mice. (E) SCID mice injected i.v. with liposomes containing clodronate to deplete macrophages or PBS (control). Survival was significantly decreased for depleted mice given rituximab plus rIL-21 treatment (p = 0.0115) or rituximab alone (p = 0.0011) compared with non-depleted mice.</p

Activation of innate effector cells in cynomolgus monkeys treated with rIL-21.

<p>(A) ADCC activity in PBMC preparations in animals treated with vehicle control, weekly rituximab (0.05 mg/kg), rIL-21 (0.5 mg/kg for 3 days), or a combination of rituximab (0.05 mg/kg) and rIL-21 (0.5 mg/kg for 3 days). Gray bars indicate rIL-21 dosing days; rituximab was co-administered before the first rIL-21 dose in each cycle (days 1, 8, and 20). (B) Percentage of peripheral blood NK cells and cytotoxic T lymphocytes (CTL) staining positive for perforin. Gray bars in C indicate dosing days, error bars show standard error of the mean (SEM). (A, B) N = 3 animals per group.</p

IL-21R expression, STAT phosphorylation, and growth inhibition in human B lymphoma lines treated with rIL-21.

1<p>Mean fluorescence intensity (MFI) minus background staining with isotype-matched control antibody.</p>2<p>Ratio of MFI for P-STAT staining in stimulated versus control cells after 15 minute treatment with 10 ng/mL rIL-21. Mean and SD are from 2 experiments. Following rIL-21 stimulation, STAT5 phosphorylation was detected in only two cell lines, MC-116 and IM-9.</p>3<p>Percentage growth inhibition was determined by live cell counts after 7 days culture with 50 ng/mL rIL-21 or control media (representative data from one of two experiments). Similar results were observed with ³H incorporation.</p

Monoclonal antibodies used in flow cytometry.

1<p>BD Biosciences, Franklin Lakes, NJ.</p>2<p>Caltag Laboratories, Burlingame, CA.</p>3<p>Beckman Coulter, Brea, CA.</p>4<p>R&D Systems, Minneapolis, MN.</p

rIL21 induced STAT1 signaling and growth inhibition for IM-9 but not Raji lymphoma cells.

<p>Growth curves for (A) IM-9 and (B) Raji cells when cultured with 50 ng/ml of rIL-21 after 3 days pre-treatment under the same conditions. Insets show phospho-STAT1 signaling IM-9 and Raji cells after 15 min culture with 10 ng/ml IL-21. Lower panels show survival curves for SCID mice (6–10/group) injected i.v. with 10⁶ cells of the (C) IM-9, (D) Raji, or (E) H-S Sultan lymphoma lines. Human rIL-21 or control treatment (PBS) was administered by 28-day mini-osmotic pump implanted one day after tumor cell injection.</p

Treatment with rIL-21 enhances ADCC activity in human NK cells.

<p>(A) Induction of granzyme B in NK cells cultured with rIL-21, IgG or both. (B, C) Purified human NK cells were cultured with rIL-21 (25 ng/ml) or media for 3 days and then placed in ADCC assays with control IgG or rituximab (2 µg/ml). Percentage lysis in representative assays against DOHH2 targets (B), and lysis of Ramos cells compared to Namalwa cells (C) are shown. <i>Insets</i> show CD20 expression on target cell lines. Data shown are representative results from 2 separate co-culture experiments (A) and from separate experiments using 6 NK cell donors and 5 lymphoma lines (B, C). E:T = effector to target cell ratio.</p

rIL-21 enhances rituximab-mediated B cell depletion in cynomolgus monkeys.

<p>B cell depletion in animals treated with 10 mg/kg rituximab (Group 1) and in animals given 10 mg/kg rituximab plus rIL-21 at 0.3 mg/kg (Group 2) or 1.5 mg/kg (Group 3) for four weekly doses, followed by a dose-free period of 30 days. Immunohistochemistry of CD20+ cells in spleen (A) and mandibular lymph node (B) at end of dosing (terminal sacrifice) and end of the study. Images were collected using an Olympus BX51 microscope equipped with a PlanApo 2×/0.08 lens and U-CMAD3 camera, and captured with Colorview and analySIS Soft Imaging System software (Olympus, Tokyo Japan). (C) Lymphoid atrophy scores in lymphoid tissues collected at the end of dosing and at the end of the study. Histopathology scores for severity of atrophy were subjectively assigned as 0, none; 1, minimal; 2, slight; 3, moderate; 4, marked. Bar indicates median group score.</p