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The technique of molecular-beam, mass spectrometric (MBMS) sampling is applied to the elucidation of the molecular pathways in the fast pyrolysis of wood and its principal isolated constituents. The goal is the optimization of high-value fuel products by thermal and catalytic means. The positive-ion mass spectra shown are obtained from real-time, direct sampling of light gases, reactive intermediates, and condensible vapors simultaneously. The cellulose, lignin, and hemicellulose (e.g., xylan) components of wood pyrolyze largely to monomer and monomer-related fragments and give characteristic mass spectral signatures. Whole wood appears to behave as the sum of its constituents, with few if any vapor species derived from interaction of the main polymer constituents. An important interaction, however, is the influence of mineral matter in the wood on the carbohydrate pyrolysis pathways. Vapor phase cracking of the primary products proceeds through a stage of light hydrocarbons and oxygenates to the ultimate formation of aromatic tars and H2, CO, C02, and H20. These steps are illustrated and discussed. Consistent with these observations, a relatively simple pyrolysis reaction scheme is proposed.

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B-lymphoid transcription factors (e.g. PAX5, IKZF1) are critical for early B-cell development1–2, yet genetic lesions occur in >80% of cases of B-cell acute lymphoblastic leukemia (ALL)3–4. The significance of these lesions in ALL remained unclear. Combining ChIP-seq and RNA-seq studies, we identified a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK5–7. Dominant-negative mutants of PAX5 and IKZF1 relieved glucose and energy restriction. Studying a transgenic pre-B ALL mouse model, heterozygous deletion of Pax5 increased glucose uptake and ATP-levels by >25-fold. Reconstitution of PAX5 and IKZF1 in pre-B ALL patient samples restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5- and IKZF1- transcriptional targets identified NR3C1 (glucocorticoid receptor)8, TXNIP (glucose feedback sensor)9 and CNR2 (cannabinoid receptor)10 as central effectors of B-lymphoid restriction of glucose and energy supply. Interestingly, transport-independent lipophilic methyl-conjugates of pyruvate and TCA cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukemic transformation. Conversely, pharmacological TXNIP- and CNR2-agonists and a small molecule AMPK-inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapy-targets. Furthermore, our results provide a mechanistic explanation for the empiric finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. We conclude that B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.

The gas-phase photocatalytic oxidation of trichloroethylene (TCE) over titanium dioxide was investigated as a potential method for destroying this common pollutant. The results from this study agree with earlier studies in that high levels of destruction of TCE were achieved. Accompanying these high rates of destruction were high quantum yields (approaching unity). However, directsampling mass spectrometry and gas-phase Fourier transform infrared (FTIR) spectroscopy revealed that there are significant quantities of byproducts produced [phosgene, dichloroacetyl chloride (DCAC), carbon monoxide, molecular chlorine]. The DCAC has been rationalized on the basis of a chemical reaction mechanism in which the TCE molecules are oxidized in a chain reaction involving C1 atoms. This mechanism appears to be validated by tests with other chlorinated ethylenes (perchloroethylene, dichloroethylenes). Phosgene may arise at least partially from the photocatalytic oxidation of DCAC, and molecular chlorine may result from the recombination of chlorine atoms. The results of this study are discussed relative to aqueous-phase photocatalytic oxidation of TCE where chlorinated intermediates have been observed.

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Complex gene regulation is one of the key requirements for the evolution of higher eukaryotes. 1 In these organisms, many genes are regulated by enhancers that are 10 4 -10 6 base pairs (bp) distant from the promoter. Enhancer sequences usually contain multiple small transcription factor binding sites (typically ~10bp), and physical contact between the promoter and enhancer is thought to be required to modulate gene expression. 2 Current methods have extensively defined chromatin architecture at scales above 1 kb but until now it has not been possible to define physical contacts at the scale of the key proteins determining gene expression. Here we define the interactions between different classes of regulatory elements (enhancers, promoters and boundary elements) in unprecedented detail, using a novel chromosome conformation capture method (Micro Capture-C (MCC)), which allows physical contacts to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show, using base pair resolution plots of ligation junctions, that transcription factors generate a key component of the contacts between enhancers and promoters. Our data show that contacts from CTCF sites highly correlate with cooccupancy of cohesin and that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. We also find that promoters make the strongest contacts with both enhancers and CTCF sites and that while CTCF sites contact promoters strongly they only make weak contacts with enhancers. The highly punctate nature of the contacts is an unexpected finding because the current view is that physical contacts are constrained by much larger domains such as topological associated domains (TADs). 3 Our results support a model in which chromatin loop extrusion 4-6 is dependent on cohesin loading at active promoters and enhancers, explaining the formation of tissue-specific chromatin domains without changes in CTCF binding. The data suggest that a separate mechanism to loop extrusion underlies enhancer-/promoter contacts, which likely involves DNA binding proteins at enhancers and promoters. The unprecedented