Abstract Poplar (Populus tremula × alba) lignins with exceedingly high syringyl monomer levels are produced by overexpression of the ferulate 5-hydroxylase (F5H) gene driven by a cinnamate ...4-hydroxylase (C4H) promoter. Compositional data derived from both standard degradative methods and NMR analyses of the entire lignin component (as well as isolated lignin fraction) indicated that the C4H∷F5H transgenic's lignin was comprised of as much as 97.5% syringyl units (derived from sinapyl alcohol), the remainder being guaiacyl units (derived from coniferyl alcohol); the syringyl level in the wild-type control was 68%. The resultant transgenic lignins are more linear and display a lower degree of polymerization. Although the crucial β-ether content is similar, the distribution of other interunit linkages in the lignin polymer is markedly different, with higher resinol (β-β) and spirodienone (β-1) contents, but with virtually no phenylcoumarans (β-5, which can only be formed from guaiacyl units). p-Hydroxybenzoates, acylating the γ-positions of lignin side chains, were reduced by >50%, suggesting consequent impacts on related pathways. A model depicting the putative structure of the transgenic lignin resulting from the overexpression of F5H is presented. The altered structural features in the transgenic lignin polymer, as revealed here, support the contention that there are significant opportunities to improve biomass utilization by exploiting the malleability of plant lignification processes.
BACKGROUND:Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking.
OBJECTIVE:We evaluated ...effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality.
METHODS:A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested.
RESULTS:Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio OR2.67, 95% confidence interval CI1.34-5.27, P < .01), previous cancer diagnosis (OR3.64, 95% CI1.69-7.85, P < .001), focal (OR3.90, 95% CI1.91-8.00, P < .001) and enhancing (OR5.03, 95% CI2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR9.34, 95% CI4.29-20.33, P < .001), and use of intraoperative navigation (OR6.59, 95% CI3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR2.51, 95% CI1.23-5.28, P < .05) and age older than 60 years (OR2.66, 95% CI1.36-5.18, P < .01).
CONCLUSION:Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.
ABBREVIATIONS:AUC, area under the curveCI, confidence intervalICH, intracranial hemorrhage
On June 26, 2007, IBM announced the Blue Gene/P(TM) system as the leading offering in its massively parallel Blue Gene® supercomputer line, succeeding the Blue Gene/L(TM) system. The Blue Gene/P ...system is designed to scale to at least 262,144 quad-processor nodes, with a peak performance of 3.56 petaflops. More significantly, the Blue Gene/P system enables this unprecedented scaling via architectural and design choices that maximize performance per watt, performance per square foot, and mean time between failures. This paper describes our vision of this petascale system, that is, a system capable of delivering more than a quadrillion (10^sup 15^) floating-point operations per second. We also provide an overview of the system architecture, packaging, system software, and initial benchmark results. PUBLICATION ABSTRACT
Mutations reducing the functional activity of leptin, the leptin receptor, alpha-melanocyte stimulating hormones (alpha-MSH) and the melanocortin-4 receptor (Mc4r) all lead to obesity in mammals. ...Moreover, mutant mice that ectopically express either agouti (Ay/a mice) or agouti-related protein (Agrp), antagonists of melanocortin signalling, become obese. These data suggest that alpha-MSH signalling transduced by Mc4r tonically inhibits feeding; however, it is not known to what extent this pathway mediates leptin signalling. We show here that Mc4r-deficient (Mc4r-/-) mice do not respond to the anorectic actions of MTII, an MSH-like agonist, suggesting that alpha-MSH inhibits feeding primarily by activating Mc4r. Obese Mc4r-/-mice do not respond significantly to the inhibitory effects of leptin on feeding, whereas non-obese Mc4r-/- mice do. These data demonstrate that melanocortin signalling transduced by Mc4r is not an exclusive target of leptin action and that factors resulting from obesity contribute to leptin resistance. Leptin resistance of obese Mc4r-/- mice does not prevent their response to the anorectic actions of ciliary neurotrophic factor (CNTF), corticotropin releasing factor (CRF), or urocortin; or the orexigenic actions of neuropeptide Y (NPY) or peptide YY (PYY), indicating that these neuromodulators act independently or downstream of Mc4r signalling.
The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), has become the primary target of foliar insecticides in cotton, Gossypium hirsutum L., throughout the Midsouth ...over the past several years. This prompted a reevaluation of existing action thresholds for flowering cotton under current production practices and economics. A trial was conducted at 19 locations throughout the Midsouth during 2006 and 2007. Threshold treatments ranged from a weekly automatic insecticide application to a very high threshold of 10 tarnished plant bugs per 1.5 row-m on a black drop cloth. Individually, all locations reached the lowest threshold, and eight locations had a significant yield loss from tarnished plant bugs. Across all locations, lint yield decreased 0.85 to 1.72% for each threshold increase of one tarnished plant bug per 1.5 row-m. Yield loss was most closely correlated to pest density during the latter half of the flowering period. The relationship between plant bug density or damage and yield was similar for drop cloth, sweep net, and dirty square sampling methods, but the correlations among these sampling methods were not high. Incorporating actual insecticide application data from the trial and average production and economic factors for Midsouth cotton, the economic threshold, if monitoring once per week, should be between 1.6 and 2.6 tarnished plant bugs per 1.5 row-m during the flowering period. More frequent monitoring or situations where insecticide applications are more efficacious may alter this threshold.
Gas-puff imaging data is used to investigate the dynamics of blob-like structures in the scrape-off layer of Alcator C-Mod. A blob-tracking algorithm is developed and used to compute blob propagation ...velocities and cross-field sizes for a series of discharges where the line-averaged particle density n¯e is varied. We find that the mean radial blob velocity increases from 150ms-1 for n¯e/nG=0.15 to 450ms-1 for n¯e/nG=0.48, where is the nG the Greenwald density. The cross-field size of the blobs is independent of the line-averaged particle densities. With increasing n¯e/nG the observed blob velocities become larger than predicted by simple blob models for sheath-connected plasma filaments.
The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role ...in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma.
Chronic anal fissure (CAF) is perpetuated by high sphincter pressures and secondary local ischemia. Pharmacological approaches include topical nitrates and botulinum toxin (BT), which both help to ...decrease the sphincter pressure.
The aims of the present study were to assess the efficacy and safety of BT injection and combined treatment with BT injection and lowered dose glyceryltrinitrate (GTN) cream for the treatment of CAF. We hypothesised that combined treatment would have a synergistic effect on healing.
Forty-one consecutive patients with CAF were randomly assigned to receive one of the following treatments: Group A, injection of BT (20 U into internal anal sphincter) and Group B, BT injection (20 units) and subsequent thrice daily topical applications of half-dose 0.2% GTN cream for 6 weeks. Patients were followed up at 6 and 12 weeks and were assessed for healing of anal fissure, by means of visual inspection using fissure grades; for faecal incontinence, using Cleveland Clinic incontinence scores; and for fissure pain and headache using a numeric pain rating scale.
Fissure healing was similar in the two groups at both 6 (30% in BT and GTN and 33% in BT only) and 12 weeks (50% in BT and GTN vs 57% in BT-only group). Neither the change in pain score from 6 to 12 weeks, nor the overall level of pain was significantly different in the 2 groups. Moderate or severe headaches were suffered by 58% of patients using GTN.
Single-agent treatment by means of BT injection alone was well tolerated compared with combination treatment with BT injection and GTN cream, with no significant differences in healing of CAF observed in this small study.
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