Numerically Predicted Burning Velocities of C1 and C2 Hydrofluorocarbon Refrigerant Flames with Air

Due to their high global warming potentials, many existing working fluids for heating, cooling and refrigeration equipment are being phased out. Their replacements will often be flammable or slightly flammable, and the burning velocity of refrigerant-air mixtures is being used as a metric to rank their flammability. To allow industry to estimate the flammability of new blends of agents, predictive tools for the burning velocity of refrigerants are being developed, and calculating burning velocity requires a kinetic mechanism. The National Institute of Standards and Technology hydrofluorocarbon (HFC) mechanism was developed 20 years ago to describe hydrocarbon-air flames with added trace amounts of hydrofluorocarbon fire retardants (primarily CH2F2, CF3H, CF4, C2H2F4, C2HF5, and C2F6). In the present work, the mechanism has been updated slightly to include new HFC compounds, more recent rate data, and rate data for new species. The modified mechanism is used to predict steady, planar, 1D, unstretched burning velocities for mixtures of air with each of the one- and two-carbon saturated HFC compounds R41 (CH3F), R32 (CH2F2), R161 (C2F5H), R152 (CH2F-CH2F), R152a (CH3-CHF2), R143 (CH2F-CHF2), R143a (CH3-CF3), R134 (CHF2-CHF2), and R134a (CH2F-CF3), for which existing experimental data were available. Simulation results are present for a range of fuel-air equivalence ratio ϕ, for comparison with the available experimental data. Agreement is reasonable, and major kinetic pathways and radical populations are explored to uncover the general reaction properties of these new flames

The effect of gas phase flame retardants on fire effluent toxicity

Standard industry formulations of flame retarded aliphatic polyamides, meeting UL 94 V-0, have been burned under controlled conditions, and the yields of the major asphyxiants, carbon monoxide (CO) and hydrogen cyanide (HCN) have been quantified. Although both the combination of aluminium phosphinate and melamine polyphosphate, and the combination of brominated polystyrene and antimony oxide, inhibit combustion reactions in the gas phase, this study shows that the phosphorus causes a much smaller increase in the CO and HCN yields than antimony-bromine. The mechanisms of CO and HCN generation and destruction are related to the flame inhibition reactions. Both CO and HCN form early in the flame, and the OH radical is critical for their destruction. Crucial, in the context of the flame inhibition mechanism, is the observation that the phosphorus system reduces the H and O radical concentrations without a corresponding decrease in the OH radical concentration; conversely, the bromine system reduces all three of the key radical concentrations, H, O and OH, and thus increases the fire toxicity, by inhibiting decomposition of CO and HCN. Moreover, while the phosphorus flame retardant is effective as an ignition suppressant at lower temperatures (corresponding to early flaming), this is effect “switches off” at high temperatures, minimising the potential increase in fire toxicity, once the fire develops. Since flame retardants are most effective as ignition suppressants, and at the early stages of flaming combustion, while most fire deaths and injuries result from toxic gas inhalation from more developed fires, it is clearly advantageous to have an effective gas phase flame retardant which only causes a small increase in the toxic product yield

Discovery of short pseudogenes derived from messenger RNAs

More than 40% of the human genome is generated by retrotransposition, a series of in vivo processes involving reverse transcription of RNA molecules and integration of the transcripts into the genomic sequence. The mechanism of retrotransposition, however, is not fully understood, and additional genomic elements generated by retrotransposition may remain to be discovered. Here, we report that the human genome contains many previously unidentified short pseudogenes generated by retrotransposition of mRNAs. Genomic elements generated by non-long terminal repeat retrotransposition have specific sequence signatures: a poly-A tract that is immediately downstream and a pair of duplicated sequences, called target site duplications (TSDs), at either end. Using a new computer program, TSDscan, that can accurately detect pseudogenes based on the presence of the poly-A tract and TSDs, we found 654 short (≤300 bp), previously unknown pseudogenes derived from mRNAs. Comprehensive analyses of the pseudogenes that we identified and their parent mRNAs revealed that the pseudogene length depends on the parent mRNA length: long mRNAs generate more short pseudogenes than do short mRNAs. To explain this phenomenon, we hypothesize that most long mRNAs are truncated before they are reverse transcribed. Truncated mRNAs would be rapidly degraded during reverse transcription, resulting in the generation of short pseudogenes

Fluorinated halon replacement agents in explosion inerting

The US Federal Aviation Administration (FAA) observed during explosion tests that at a low concentration of agent, some candidate halon replacement agents increased the explosion severity instead of mitigating the event. At UTC Aerospace Systems a test program was developed to assess the behaviour of alternative agents at values below inerting concentration. Two agents were selected, C2HF5 (Penta- fluoroethane, HFC-125) and C6F12O (FK-5-1-12, Novec™1230). Baseline tests were performed with unsuppressed C3H8 (propane)/air mixtures and C3H8/air mixtures with CF3Br (Halon 1301) and N2 (nitrogen). Using CF3Br or N2 at below inerting concentrations mitigated the explosion. C2HF5 was tested against C3H8 at stoichiometric (4 vol%) and lower explosion limit (LEL) (2 vol%). Against 4 vol% C3H8 the combustion was mitigated, proportional to agent concentration; however, low concentrations of C2HF5 with 2 vol% C3H8 enhanced the explosion. Tests with N2 against a volatile mixture of C3H8 with C2HF5 showed that N2 mitigated the events. Final tests were performed with low concentrations of C6F12O against C3H8/air mixtures. This showed similar behaviour to that observed with the C2HF5 tests. Normally during qualification tests for new agents the stoichiometric concentration of a fuel is deemed to be the worst case scenario and the baseline against which agents are tested. The above described test results show that this assumption may need to be reconsidered. This work shows that contrary to common assumption the agents investigated are unlikely to have acted chemically at the flame front, but most likely, mainly cooled the flame and changed the stoichiometry, i.e. the ratio of components of the flammable mixture

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Alternative splicing of the mouse embryonic poly(A) binding protein (Epab) mRNA is regulated by an exonic splicing enhancer: a model for post-transcriptional control of gene expression in the oocyte

Embryonic poly(A) binding protein (EPAB), expressed in oocytes and early embryos, binds and stabilizes maternal mRNAs, and mediates initiation of their translation. We identified an alternatively spliced form of Epab lacking exon 10 (c.Ex10del) and investigated the regulation of Epab mRNA alternative splicing as a model for alternative splicing in oocytes and early preimplantation embryos. Specifically, we evaluated the following mechanisms: imprinting; RNA editing and exonic splicing enhancers (ESEs). Sequence analysis led to the identification of two single nucleotide polymorphisms (SNPs): one was detected in exon 9 (rs55858A/G), and served as a marker for the parental origin of the alternatively spliced form, and the other was found in exon 10 (rs56574G/C), and co-segregated with the exon 9 SNP. We found that the presence of rs56574G in exon 10 led to the formation of an ESE, leading to efficient exclusion of exon 10. Real-time RT–PCR results revealed a 5-fold increase in the expression of the c.Ex10del alternative splicing variant in animals carrying rs56574G/G in exon 10 compared with rs56574C/C at the same locus. Our findings suggest that SNPs may alter the ratio between alternative splicing variants of oocyte-specific proteins. The role that these subtle differences play in determining individual reproductive outcome remains to be determined

Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults : Recommendations for Genetic Diagnosis, Clinical Management and Follow-up

Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.Peer reviewe

Somatic expression of LINE-1 elements in human tissues

LINE-1 expression damages host DNA via insertions and endonuclease-dependent DNA double-strand breaks (DSBs) that are highly toxic and mutagenic. The predominant tissue of LINE-1 expression has been considered to be the germ line. We show that both full-length and processed L1 transcripts are widespread in human somatic tissues and transformed cells, with significant variation in both L1 expression and L1 mRNA processing. This is the first demonstration that RNA processing is a major regulator of L1 activity. Many tissues also produce translatable spliced transcript (SpORF2). An Alu retrotransposition assay, COMET assays and 53BP1 foci staining show that the SpORF2 product can support functional ORF2 protein expression and can induce DNA damage in normal cells. Tests of the senescence-associated β-galactosidase expression suggest that expression of exogenous full-length L1, or the SpORF2 mRNA alone in human fibroblasts and adult stem cells triggers a senescence-like phenotype, which is one of the reported responses to DNA damage. In contrast to previous assumptions that L1 expression is germ line specific, the increased spectrum of tissues exposed to L1-associated damage suggests a role for L1 as an endogenous mutagen in somatic tissues. These findings have potential consequences for the whole organism in the form of cancer and mammalian aging

Metformin for treatment of cytopenias in children and young adults with Fanconi anemia

Fanconi anemia (FA), a genetic DNA repair disorder characterized by marrow failure and cancer susceptibility. In FA mice, metformin improves blood counts and delays tumor development. We conducted a single institution study of metformin in nondiabetic patients with FA to determine feasibility and tolerability of metformin treatment and to assess for improvement in blood counts. Fourteen of 15 patients with at least 1 cytopenia (hemoglobin < 10 g/dL; platelet count < 100 000 cells/µL; or an absolute neutrophil count < 1000 cells/µL) were eligible to receive metformin for 6 months. Median patient age was 9.4 years (range 6.0-26.5). Thirteen of 14 subjects (93%) tolerated maximal dosing for age; 1 subject had dose reduction for grade 2 gastrointestinal symptoms. No subjects developed hypoglycemia or metabolic acidosis. No subjects had dose interruptions caused by toxicity, and no grade 3 or higher adverse events attributed to metformin were observed. Hematologic response based on modified Myelodysplastic Syndrome International Working Group criteria was observed in 4 of 13 evaluable patients (30.8%; 90% confidence interval, 11.3-57.3). Median time to response was 84.5 days (range 71-128 days). Responses were noted in neutrophils (n = 3), platelets (n = 1), and red blood cells (n = 1). No subjects met criteria for disease progression or relapse during treatment. Correlative studies explored potential mechanisms of metformin activity in FA. Plasma proteomics showed reduction in inflammatory pathways with metformin. Metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefit. This trial was registered at as #NCT03398824