Robust Analysis of Metabolic Pathways

Flux Balance Analysis (FBA) is a widely used computational model for studying the metabolic pathways of cells and the role individual metabolites and reactions play in maintaining cell function. However, the successes of FBA have been limited by faulty biological assumptions and computational imperfections. We introduce Robust Analysis of Metabolic Pathways (RAMP) to provide a more theoretically sound and computationally accurate model of cellular metabolism. RAMP overcomes the faulty assumptions of traditional FBA by allowing deviation from steady-state and accounting for variability across a cellular culture. Computationally, RAMP more successfully predicts the lethality of gene knockouts and reduces degeneracy in optimal ux values. Analytical results establish the stability of RAMP under perturbations in modeling parameters. The inclusion of new modeling parameters in RAMP opens the possibility of modeling different cellular cultures in a wider range of conditions, including non- optimized cultures. We conclude that RAMP is an improvement over traditional FBA and deserves further study

Relationships Between Dual Enrollment Parameters and Community College Success in Tennessee

The purpose of this non-experimental quantitative study was to evaluate the relationships between completion of high school dual enrollment courses and subsequent success of first-time, full-time community college students as measured by completion of an associate degree and time to completion of the degree. In addition to comparing dual and non-dual enrollment student performance, the effects of the number of dual enrollment courses completed and the subject areas of those courses were evaluated. Student subgroups reviewed included gender, race, socioeconomic status, and prior academic preparation (ACT score). Archival data from Tennessee community colleges used in this study included 62,644 students across four years (2015-2018) comprising 11,949 dual enrollment students and 50,695 non-dual enrollment students. Six research questions were answered from these data utilizing independent samples t tests, twoway contingency tables using crosstabs, Pearson correlations, logistic regression, or descriptive statistics. Findings revealed that completing just one dual enrollment course significantly increased the probability of completing an associate degree, and this finding was consistent across all subgroups studied. In addition, dual enrollment students completed associate degrees in significantly less time. Completing more dual enrollment courses tended to further increase the probability of completing a degree and further reduce the time to completion

Weekly nab-Paclitaxel in Combination With Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Analysis of Safety and Efficacy in Patients With Diabetes

AbstractPurposeTo examine outcomes in a phase 3 trial of nab-paclitaxel plus carboplatin (nab-P/C) versus solvent-based paclitaxel plus carboplatin (sb-P/C) in a subset of patients with advanced non–small-cell lung cancer (NSCLC) and diabetes.Patients and MethodsPatients with stage IIIB/IV NSCLC received nab-P 100 mg/m2 on days 1, 8, and 15 or sb-P 200 mg/m2 on day 1, both with C at an area under the curve of 6 mg·min/mL on day 1 every 3 weeks. Overall response rate (ORR) and progression-free survival (PFS) were determined by blinded, independent, centralized review. P values were based on chi-square test for ORR and log-rank test for overall survival (OS) and PFS.ResultsOf the 1052 randomized patients in the phase 3 trial, 61 had diabetes according to prespecified terms (nab-P/C, 31; sb-P/C, 30). ORR for nab-P/C versus sb-P/C in this subset was 52% versus 27% (relative risk ratio, 1.935; P = .046), median PFS was 10.9 versus 4.9 months (hazard ratio, 0.420; P = .016), and median OS was 17.5 versus 11.1 months (hazard ratio, 0.550; P = .057). Treatment differences in PFS remained significant (P ≤ .036) after adjusting for histology, region, stage, race, and age and also remained significant in OS for histology (P = .039). Patients with diabetes experienced lower rates of grade 3 or higher neutropenia and peripheral neuropathy and higher rates of thrombocytopenia and anemia with nab-P/C versus sb-P/C.Conclusionnab-P/C demonstrated improved efficacy and manageable tolerability in patients with advanced NSCLC and diabetes

How effective is ‘greening’ of urban areas in reducing human exposure to ground-level ozone concentrations, UV exposure and the ‘urban heat island effect’? An updated systematic review

Abstract Background This review updates a systematic review published in 2010 ( http://www.environmentalevidence.org/completed-reviews/how-effective-is-greening-of-urban-areas-in-reducing-human-exposure-to-ground-level-ozone-concentrations-uv-exposure-and-the-urban-heat-island-effect ) which addressed the question: How effective is ‘greening’ of urban areas in reducing human exposure to ground-level ozone concentrations, UV exposure and the ‘urban heat island effect’? Methods Searches of multiple databases and journals for relevant published articles and grey literature were conducted. Organisational websites were searched for unpublished articles. Eligibility criteria were applied at title, abstract and full text and included studies were critically appraised. Consistency checks of these processes were undertaken. Pre-defined data items were extracted from included studies. Quantitative synthesis was performed through meta-analysis and narrative synthesis was undertaken. Review findings 308 studies were included in this review. Studies were spread across all continents and climate zones except polar but were mainly concentrated in Europe and temperate regions. Most studies reported on the impact of urban greening on temperature with fewer studies reporting data on ground-level UV radiation, ozone concentrations (or precursors) or public health indicators. The findings of the original review were confirmed; urban green areas tended to be cooler than urban non-green areas. Air temperature under trees was on average 0.8 °C cooler but treed areas could be warmer at night. Cooling effect showed tree species variation. Tree canopy shading was a significant effect modifier associated with attenuation of solar radiation during the day. Urban forests were on average 1.6 °C cooler than comparator areas. Treed areas and parks and gardens were associated with improved human thermal comfort. Park or garden cooling effect was on average 0.8 °C and trees were a significant influence on this during the day. Park or garden cooling effect extended up to 1.25 kms beyond their boundaries. Grassy areas were cooler than non-green comparators, both during daytime and at night, by on average 0.6 °C. Green roofs and walls showed surface temperature cooling effect (2 and 1.8 °C on average respectively) which was influenced by substrate water content, plant density and cover. Ground-level concentrations of nitrogen oxides were on average lower by 1.0 standard deviation units in green areas, with tree species variation in removal of these pollutants and emission of biogenic volatile organic compounds (precursors of ozone). No clear impact of green areas on ground level ozone concentrations was identified. Conclusions Design of urban green areas may need to strike a balance between maximising tree canopy shading for day-time thermal comfort and enabling night-time cooling from open grassy areas. Choice of tree species needs to be guided by evapotranspiration potential, removal of nitrogen oxides and emission of biogenic volatile organic compounds. Choice of plant species and substrate composition for green roofs and walls needs to be tailored to local thermal comfort needs for optimal effect. Future research should, using robust study design, address identified evidence gaps and evaluate optimal design of urban green areas for specific circumstances, such as mitigating day or night-time urban heat island effect, availability of sustainable irrigation or optimal density and distribution of green areas. Future evidence synthesis should focus on optimal design of urban green areas for public health benefit

Constraints on the Heating of High Temperature Active Region Loops: Observations from Hinode and SDO

We present observations of high temperature emission in the core of a solar active region using instruments on Hinode and SDO. These multi-instrument observations allow us to determine the distribution of plasma temperatures and follow the evolution of emission at different temperatures. We find that at the apex of the high temperature loops the emission measure distribution is strongly peaked near 4 MK and falls off sharply at both higher and lower temperatures. Perhaps most significantly, the emission measure at 0.5 MK is reduced by more than two orders of magnitude from the peak at 4 MK. We also find that the temporal evolution in broad-band soft X-ray images is relatively constant over about 6 hours of observing. Observations in the cooler SDO/AIA bandpasses generally do not show cooling loops in the core of the active region, consistent with the steady emission observed at high temperatures. These observations suggest that the high temperature loops observed in the core of an active region are close to equilibrium. We find that it is possible to reproduce the relative intensities of high temperature emission lines with a simple, high-frequency heating scenario where heating events occur on time scales much less than a cooling time. In contrast, low-frequency heating scenarios, which are commonly invoked to describe nanoflare models of coronal heating, do not reproduce the relative intensities of high temperature emission lines and predict low-temperature emission that is approximately an order of magnitude too large. We also present an initial look at images from the SDO/AIA 94 A channel, which is sensitive to Fe XVIII.Comment: Movies are available at http://tcrb.nrl.navy.mil/~hwarren/temp/papers/active_region_core/ Paper has been refereed and revise