Numerical Modeling of Coupled Groundwater and Surface Water Interactions in an Urban Setting

The Dominguez Channel Watershed (DCW), located in the southern portion of Los Angeles County (Figure A.1), drains about 345 square miles into the Los Angeles Harbor. The cities and jurisdictions in DCW are shown in Figure A.2. The largest of these include the cities of Los Angeles, Carson, and Torrance. This watershed is unique in that 93% of its land area is highly developed (i.e. urbanized). The watershed boundaries are defined by a complex network of storm drains and flood control channels, rather than being defined by natural topography. Table (1) shows a summary of different land uses in the Dominguez Channel Watershed (MEC, 2004). The Dominguez Watershed has the highest impervious area of all watersheds in the Los Angeles region. The more impervious the surface, the more runoff is generated during a storm. Storm water runoff can carry previously accumulated contaminants and transport them into receiving water systems. Point sources such as industrial wastewater and municipal sewage as well as urban runoff from commercial, residential, and industrial areas are all recognized as contributors to water quality degradation at DWC. Section 303(d) of the 1972 Federal Clean Water Act (CWA) requires states to identify and report all waters not meeting water quality standards and to develop action plans to pursue the water quality objectives. These plans specify the maximum amount of a given pollutant that the water body of concern can receive and still meet water quality standards. Such plans are called Total Maximum Daily Loads (TMDLs). TMDLs also specify allocations of pollutant loadings to point and non-point sources taking into account natural background pollutant levels. This demonstrates the importance of utilizing scientific tools, such as flow and transport models, to identify contaminant sources, understand integrated flow paths, and assess the effectiveness of water quality management strategies. Since overland flow is a very important component of the water balance and hydrology of DCW, a parallel, distributed watershed model that treats flow in groundwater and surface water in a dynamically coupled manner will be used to build a flow model of the watershed. This coupled model forms the basis for modeling and understanding the transport of contaminants through the Dominguez Channel Watershed, which can be used in designing and implementing TMDLs to manage the water quality in this basin. In this report, the coupled surface water-groundwater flow model of DCW will be presented. This flow model was calibrated against a storm that occurred in February 21st, 2004. The model and approach are explained further in the following sections

Implementation and scaling of the fully coupled Terrestrial Systems Modeling Platform (TerrSysMP) in a massively parallel supercomputing environment – a case study on JUQUEEN (IBM Blue Gene/Q)

Continental-scale hyper-resolution simulations constitute a grand challenge in characterizing non-linear feedbacks of states and fluxes of the coupled water, energy, and biogeochemical cycles of terrestrial systems. Tackling this challenge requires advanced coupling and supercomputing technologies for earth system models that are discussed in this study, utilizing the example of the implementation of the newly developed Terrestrial Systems Modeling Platform (TerrSysMP) on JUQUEEN (IBM Blue Gene/Q) of the Jülich Supercomputing Centre, Germany. The applied coupling strategies rely on the Multiple Program Multiple Data (MPMD) paradigm and require memory and load balancing considerations in the exchange of the coupling fields between different component models and allocation of computational resources, respectively. These considerations can be reached with advanced profiling and tracing tools leading to the efficient use of massively parallel computing environments, which is then mainly determined by the parallel performance of individual component models. However, the problem of model I/O and initialization in the peta-scale range requires major attention, because this constitutes a true big data challenge in the perspective of future exa-scale capabilities, which is unsolved

Design of InP membrane SOA with butt-joint active passive interface

A butt-joint SOA design for InP on Si membrane (IMOS) platform is proposed. The new design features the butt-joint interface between the SOA and passive nanophotonic waveguide, which makes the interface a factor of 2 to 6 shorter than in the current twin-guide SOAs, with possibility to reduce it further to factor of 5-10. This makes the new SOA a promising candidate for high-speed directly modulated lasers (DML) applications, where extremely short SOAs (40-100 μm long) and short distances between reflectors are usually required

Adherence to 6-Mercaptopurine in children and adolescents with Acute Lymphoblastic Leukemia

OBJECTIVE: Studies on children with Acute Lymphoblastic Leukemia (ALL) reported non-adherence in 2–54% of cases. The primary objective of this study was to assess rates of adherence to 6-MP using two different methods in children and adolescents with ALL. Secondary aim was to identify factors that influence adherence to 6-MP in children with ALL. METHODS: All eligible children with ALL who are (≤ 19) years old and receive 6-MP therapy for at least 1 month were approached to participate in the study. A total of 52 children with ALL and their primary caregivers were recruited. Adherence measures included an objective method (measuring 6-MP metabolites in packed Red Blood Cells (RBCs)) and a subjective method (using parent and child self-report via the Medication Adherence Report Scale; MARS; Adherence was defined as 90% or greater). RESULTS: Rates of adherence varied across the measurement methods. Packed RBCs sample analysis indicated forty-four patients (84.6%) to be adherent. Using the MARS questionnaires, a total of 49 children (94.2%) were classified as being adherent according to the parental MARS questionnaire scores, while all the 15 children (100%) who answered the MARS (child) questionnaire were classified as adherent. Overall adherence rate was 80.8% within the studied population. CONCLUSION: MARS scale was shown to overestimate adherence compared to measurement of 6-MP metabolites in the blood. A combination of both methods led to increased detection of non-adherence to thiopurine in children with ALL

Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma

Background: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target. Methods: In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells. Results: Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway. Conclusion: Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma

Quality-of-life methodology in hormone receptor–positive advanced breast cancer: Current tools and perspectives for the future

Health-related quality of life (HRQOL) is increasingly recognized as important when evaluating cancer treatments. The use, reporting, and analysis of patient-reported outcome measures (PROMs), however, are not standardized in clinical trials and are often poorly implemented in clinical practice. We report the results of a systematic literature review (PubMed search: January 1, 2000 to August 15, 2020) of PROM use, reporting, and analysis in phase 3 clinical trials of hormone receptor–positive (HR+) advanced breast cancer (ABC). Further inspection of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor publications was performed to examine PROMs in the HR+/human epidermal growth factor receptor 2–negative setting. A total of 88 results were identified in the initial search; 32 were included in the final analysis. Among included studies, most (66%) had been published in the last 5 years (2015 to 2020). CDK4/6 inhibitors (38%) were the most common agents reported. No clear standard for PROM use, reporting, or analysis was found. The most common PROMs were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; 59%) and the Functional Assessment of Cancer Therapy–Breast (FACT-B; 34%). Important differences, among studies that reported them, ranged from 5 to 10 points for the EORTC QLQ-C30 and 8 points for the FACT-B total score. This review showed that a lack of clear consistency remains for PROM use, reporting, and analysis in phase 3 clinical trials of HR+ ABC. However, HRQOL is of high interest in the literature, including for CDK4/6 inhibitors

Expressed repetitive elements are broadly applicable reference targets for normalization of reverse transcription-qPCR data in mice

Reverse transcription quantitative PCR (RT-qPCR) is the gold standard method for gene expression analysis on mRNA level. To remove experimental variation, expression levels of the gene of interest are typically normalized to the expression level of stably expressed endogenous reference genes. Identifying suitable reference genes and determining the optimal number of reference genes should precede each quantification study. Popular reference genes are not necessarily stably expressed in the examined conditions, possibly leading to inaccurate results. Stably and universally expressed repetitive elements (ERE) have previously been shown to be an excellent alternative for normalization using classic reference genes in human and zebrafish samples. Here, we confirm that in mouse tissues, EREs are broadly applicable reference targets for RT-qPCR normalization, provided that the RNA samples undergo a thorough DNase treatment. We identified Orr1a0, Rltr2aiap, and Rltr13a3 as the most stably expressed mouse EREs across six different experimental conditions. Therefore, we propose this set of ERE reference targets as good candidates for normalization of RT-qPCR data in a plethora of conditions. The identification of widely applicable stable mouse RT-qPCR reference targets for normalization has great potential to facilitate future murine gene expression studies and improve the validity of RT-qPCR data

A g316a polymorphism in the ornithine decarboxylase gene promoter modulates mycn‐driven childhood neuroblastoma

Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR‐cas9 technology was used to investigate the effects of AG clones from wildtype MYCN‐amplified SK‐N‐BE(2)‐C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neu-roblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN‐amplified and non‐amplified patients, re-spectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele‐specific regulation by the MYCN oncoprotein