Spreadsheet data processing in Python

University of Illinois at Urbana-Champaign. Graduate College. Focal Point InitiativeOpe

Magnitude and frequency relations: are there geological constraints to the rockfall size?

The final publication is available at Springer via http://dx.doi.org/10.1007%2Fs10346-017-0910-zThere exists a transition between rockfalls, large rock mass failures, and rock avalanches. The magnitude and frequency relations (M/F) of the slope failure are increasingly used to assess the hazard level. The management of the rockfall risk requires the knowledge of the frequency of the events but also defining the worst case scenario, which is the one associated to the maximum expected (credible) rockfall event. The analysis of the volume distribution of the historical rockfall events in the slopes of the Solà d’Andorra during the last 50 years shows that they can be fitted to a power law. We argue that the extrapolation of the F-M relations far beyond the historical data is not appropriate in this case. Neither geomorphological evidences of past events nor the size of the potentially unstable rock masses identified in the slope support the occurrence of the large rockfall/rock avalanche volumes predicted by the power law. We have observed that the stability of the slope at the Solà is controlled by the presence of two sets of unfavorably dipping joints (F3, F5) that act as basal sliding planes of the detachable rock masses. The area of the basal sliding planes outcropping at the rockfall scars was measured with a terrestrial laser scanner. The distribution of the areas of the basal planes may be also fitted to a power law that shows a truncation for values bigger than 50 m2 and a maximum exposed surface of 200 m2. The analysis of the geological structure of the rock mass at the Solà d’Andorra makes us conclude that the size of the failures is controlled by the fracture pattern and that the maximum size of the failure is constrained. Two sets of steeply dipping faults (F1 and F7) interrupt the other joint sets and prevent the formation of continuous failure surfaces (F3 and F5). We conclude that due to the structural control, large slope failures in Andorra are not randomly distributed thus confirming the findings in other mountain ranges.Peer ReviewedPostprint (author's final draft

When Does Size Matter? An Empirical Study of Consumer Demographics and Product Package Choices

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), 2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Tat Cha

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism

CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RP(o) formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RP(o) that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RP(o) on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera

Integrating transcriptomics and metabonomics to unravel modes-of-action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells

<p>Abstract</p> <p>Background</p> <p>The integration of different 'omics' technologies has already been shown in several <it>in vivo </it>studies to offer a complementary insight into cellular responses to toxic challenges. Being interested in developing <it>in vitro </it>cellular models as alternative to animal-based toxicity assays, we hypothesize that combining transcriptomics and metabonomics data improves the understanding of molecular mechanisms underlying the effects caused by a toxic compound also <it>in vitro </it>in human cells. To test this hypothesis, and with the focus on non-genotoxic carcinogenesis as an endpoint of toxicity, in the present study, the human hepatocarcinoma cell line HepG2 was exposed to the well-known environmental carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).</p> <p>Results</p> <p>Transcriptomics as well as metabonomics analyses demonstrated changes in TCDD-exposed HepG2 in common metabolic processes, e.g. amino acid metabolism, of which some of the changes only being confirmed if both 'omics' were integrated. In particular, this integrated analysis identified unique pathway maps involved in receptor-mediated mechanisms, such as the G-protein coupled receptor protein (GPCR) signaling pathway maps, in which the significantly up-regulated gene son of sevenless 1 (SOS1) seems to play an important role. SOS1 is an activator of several members of the RAS superfamily, a group of small GTPases known for their role in carcinogenesis.</p> <p>Conclusions</p> <p>The results presented here were not only comparable with other <it>in vitro </it>studies but also with <it>in vivo </it>studies. Moreover, new insights on the molecular responses caused by TCDD exposure were gained by the cross-omics analysis.</p

Molecular dissection of RbpA-mediated regulation of fidaxomicin sensitivity in mycobacteria

RNA polymerase (RNAP) binding protein A (RbpA) is essential for mycobacterial viability and regulates transcription initiation by increasing the stability of the RNAP-promoter open complex (R

Domains within RbpA serve specific functional roles that regulate the expression of distinct mycobacterial gene subsets

The RNA polymerase (RNAP) binding protein A (RbpA) contributes to the formation of stable RNAP-promoter open complexes (R

Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer

Malignitats ginecològiques; Fracció al·lel mutant; PI3KNeoplasias ginecológicas; Fracción alélica mutante; PI3KGynecologic malignancies; Mutant allele fraction; PI3KObjectives Aberrant PI3K/AKT/mTOR activation is common in gynaecological malignancies. However, predictive biomarkers of response to PI3K pathway inhibitors (PAMi) have yet to be identified. Methods We analysed the outcomes of patients with advanced gynaecological cancer with available genomic data, treated with PAMi as single agents or in combination in phase I clinical trials. Clinical relevance of the PIK3CA mutant allele fraction (MAF) was investigated. MAF of each variant was normalised for tumour purity in the sample (adjMAFs) to infer clonality of PIK3CA mutations, defined as clonal (≥0.4) or subclonal (<0.4). Results A total of 50 patients with gynaecological cancer (24 ovarian; 15 endometrial; 11 cervical) with available targeted mutation profiling were selected. PAMi therapy was matched to PIK3CA/PTEN mutation in 30 patients (60%). The overall response rate, median time to progression (mTTP) and clinical benefit rate (CBR) of the entire population were 10% (N=5), 3.57 months (2.57–4.4) and 40% (N=18), respectively. Genotype-matched therapy did not lead to a favourable CBR (OR 0.91, p=1 (0.2–3.7)) or mTTP (3.57 months (2.6–4.4) vs 3.73 months (1.9–13.2); HR 1.41; p=0.29). We did not detect differences in mTTP according to therapy or PIK3CA codon mutation (HR 1.71, p=0.24). Overall, 41% of patients had a TTP ratio (TTP PAMi/TTP on immediately prior or subsequent palliative chemotherapy) ≥1.3, without statistically significant differences according to tumour type (p=0.39), molecular alteration status (p=0.13) or therapy (p=0.54). In univariate analysis, genotype-matched therapy in patients with PIK3CA clonal events was associated with improved mTTP (HR 3.6; p=0.03). Conclusions Our study demonstrates that patients with advanced gynaecological cancer, refractory to standard therapies, achieved meaningful clinical benefit from PAMi. The impact of PI3KCA clonality on response to selected PAMi in patients with gynaecological cancer deserves further investigation