647 research outputs found

    A structural study of Hypocrea jecorina Cel5A

    Get PDF
    Interest in generating lignocellulosic biofuels through enzymatic hydrolysis continues to rise as nonrenewable fossil fuels are depleted. The high cost of producing cellulases, hydrolytic enzymes that cleave cellulose into fermentable sugars, currently hinders economically viable biofuel production. Here, we report the crystal structure of a prevalent endoglucanase in the biofuels industry, Cel5A from the filamentous fungus Hypocrea jecorina. The structure reveals a general fold resembling that of the closest homolog with a high-resolution structure, Cel5A from Thermoascus aurantiacus. Consistent with previously described endoglucanase structures, the H. jecorina Cel5A active site contains a primarily hydrophobic substrate binding groove and a series of hydrogen bond networks surrounding two catalytic glutamates. The reported structure, however, demonstrates stark differences between side-chain identity, loop regions, and the number of disulfides. Such structural information may aid efforts to improve the stability of this protein for industrial use while maintaining enzymatic activity through revealing nonessential and immutable regions

    A Multipoint Flux Mixed Finite Element Method

    Full text link

    Mixed Finite Element Methods on Nonmatching Multiblock Grids

    Full text link

    Comparing the CASI-4R and the PGBI-10 M for Differentiating Bipolar Spectrum Disorders from Other Outpatient Diagnoses in Youth

    Get PDF
    We compared 2 rating scales with different manic symptom items on diagnostic accuracy for detecting pediatric bipolar spectrum disorder (BPSDs) in outpatient mental health clinics. Participants were 681 parents/guardians of eligible children (465 male, mean age = 9.34) who completed the Parent General Behavior Inventory-10-item Mania (PGBI-10M) and mania subscale of the Child and Adolescent Symptom Inventory-Revised (CASI-4R). Diagnoses were based on KSADS interviews with parent and youth. Receiver operating characteristic (ROC) analyses and diagnostic likelihood ratios (DLRs) determined discriminative validity and provided clinical utility, respectively. Logistic regressions tested for incremental validity in the CASI-4R mania subscale and PGBI-10M in predicting youth BPSD status above and beyond demographic and common diagnostic comorbidities. Both CASI-4R and PGBI-10M scales significantly distinguished BPSD (N=160) from other disorders (CASI-4R: Area under curve (AUC) = .80, p .05). Diagnostic likelihood ratios indicated low scores on either scale (CASI: 0–5; PGBI-10M: 0–6) cut BPSD odds to 1/5 of those with high scores (CASI DLR− = 0.17; PGBI-10M DLR− = 0.18). High scores on either scale (CASI: 14+; PGBI-10M: 20+) increased BPSD odds about fourfold (CASI DLR+ = 4.53; PGBI-10M DLR+ = 3.97). Logistic regressions indicated the CASI-4R mania subscale and PGBI-10M each provided incremental validity in predicting youth BPSD status. The CASI-4R is at least as valid as the PGBI-10M to help identify BPSDs, and can be considered as part of an assessment battery to screen for pediatric BPSDs

    Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

    Get PDF
    PurposeWe compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.Methods and MaterialsWe reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity.ResultsAt 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction.ConclusionsSurvival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function
    • …
    corecore