From data towards knowledge: Revealing the architecture of signaling systems by unifying knowledge mining and data mining of systematic perturbation data

Genetic and pharmacological perturbation experiments, such as deleting a gene and monitoring gene expression responses, are powerful tools for studying cellular signal transduction pathways. However, it remains a challenge to automatically derive knowledge of a cellular signaling system at a conceptual level from systematic perturbation-response data. In this study, we explored a framework that unifies knowledge mining and data mining approaches towards the goal. The framework consists of the following automated processes: 1) applying an ontology-driven knowledge mining approach to identify functional modules among the genes responding to a perturbation in order to reveal potential signals affected by the perturbation; 2) applying a graph-based data mining approach to search for perturbations that affect a common signal with respect to a functional module, and 3) revealing the architecture of a signaling system organize signaling units into a hierarchy based on their relationships. Applying this framework to a compendium of yeast perturbation-response data, we have successfully recovered many well-known signal transduction pathways; in addition, our analysis have led to many hypotheses regarding the yeast signal transduction system; finally, our analysis automatically organized perturbed genes as a graph reflecting the architect of the yeast signaling system. Importantly, this framework transformed molecular findings from a gene level to a conceptual level, which readily can be translated into computable knowledge in the form of rules regarding the yeast signaling system, such as "if genes involved in MAPK signaling are perturbed, genes involved in pheromone responses will be differentially expressed"

Critical Landscape Planning during the Belt and Road Initiative

This open access book traces the development of landscapes along the 414-kilometer China–Laos Railway, one of the first infrastructure projects implemented under China’s Belt and Road Initiative (BRI) and which is due for completion at the end of 2021. Written from the perspective of landscape architecture and intended for planners and related professionals engaged in the development and conservation of these landscapes, this book provides history, planning pedagogy and interdisciplinary framing for working alongside the often-opaque planning, design and implementation processes of large-scale infrastructure. It complicates simplistic notions of development and urbanization frequently reproduced in the Laos–China frontier region. Many of the projects and sites investigated in this book are recent “firsts” in Laos: Laos’s first wildlife sanctuary for trafficked endangered species, its first botanical garden and its first planting plan for a community forest. Most often the agents and accomplices of neoliberal development, the planning and design professions, including landscape architecture, have little dialogue with either the mainstream natural sciences or critical social sciences that form the discourse of projects in Laos and comparable contexts. Covering diverse conceptions and issues of development, including cultural and scientific knowledge exchanges between Laos and China, nature tourism, connectivity and new town planning, this book also features nine planning proposals for Laos generated through this research initiative since the railway's groundbreaking in 2016. Each proposal promotes a wider "landscape approach" to development and deploys landscape architecture’s spatial and ecological acumen to synthesize critical development studies with the planner's capacity, if not naive predilection, to intervene on the ground. Ultimately, this book advocates the cautious engagement of the professionally oriented built-environment disciplines, such as regional planning, civil engineering and landscape architecture, with the landscapes of development institutions and environmental NGOs

Identify facilitators and challenges in computerized checklist implementation

Safety checklists have been considered as a promising tool for improving patient safety for decades. Computerized checklists have better performance compared with paper-based checklists, though there are barriers to their adoption. Given previous literature, it is still unclear what assists implementations and their challenges. To address this issue, this paper summarizes the implementation of two successful computerized checklist implementations in two countries for two different clinical scenarios and analyzes their facilitators and challenges.</p

A combined "electrochemical-frustrated Lewis pair" approach to hydrogen activation: surface catalytic effects at platinum electrodes

Herein, we extend our “combined electrochemical–frustrated Lewis pair” approach to include Pt electrode surfaces for the first time. We found that the voltammetric response of an electrochemical–frustrated Lewis pair (FLP) system involving the B(C6F5)3/[HB(C6F5)3]− redox couple exhibits a strong surface electrocatalytic effect at Pt electrodes. Using a combination of kinetic competition studies in the presence of a H atom scavenger, 6-bromohexene, and by changing the steric bulk of the Lewis acid borane catalyst from B(C6F5)3 to B(C6Cl5)3, the mechanism of electrochemical–FLP reactions on Pt surfaces was shown to be dominated by hydrogen-atom transfer (HAT) between Pt, [Pt[BOND]H] adatoms and transient [HB(C6F5)3]⋅ electrooxidation intermediates. These findings provide further insight into this new area of combining electrochemical and FLP reactions, and proffers additional avenues for exploration beyond energy generation, such as in electrosynthesis

Impact of Diet on Colorectal Cancer

Background Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide. Modifiable risk factors such as diet have been linked to the development of CRC but results of previous research have been inconsistent. We utilized the National Health and Nutrition Examination Survey (NHANES) to determine whether the consumption of dietary variables contributed to increased diagnosis of colorectal cancer. Methods Participants from NHANES 2015-2016 database aged 16 years or older, with available two-day dietary and CRC information were included. Study exposure included dietary consumptions (salt, cholesterol, sugar, fat, and carbohydrates); the outcome was self-reported CRC. Descriptive analysis was performed with chi-square tests to elicit the relationship between dietary consumptions and CRC, and a multivariate logistic regression model, adjusted for sociodemographic characteristics age, race, sex, income, BMI, smoking status, dietary consumptions, and complex sample design. Results A total of 76,044 participants were included. Individuals with older age (66-80 years vs. \u3c65: \u3e74% vs. 26%; p$35,000: 62% vs. 38%; p Conclusions A significant association was found between income, age and self-reported CRC. Although literature supports a relationship between diet and colorectal cancer, a more extensive dietary history may be needed to elicit the relationship.https://scholarscompass.vcu.edu/gradposters/1097/thumbnail.jp

Label-free detection of human prostate-specific antigen (hPSA) using film bulk acoustic resonators (FBARs)

Label-free detection of cancer biomarkers using low cost biosensors has promising applications in clinical diagnostics. In this work, ZnO-based thin film bulk acoustic wave resonators (FBARs) with resonant frequency of ∼1.5 GHz and mass sensitivity of 0.015 mg/m2 (1.5 ng/cm2) have been fabricated for their deployment as biosensors. Mouse monoclonal antibody, anti-human prostate-specific antigen (Anti-hPSA) has been used to bind human prostate-specific antigen (hPSA), a model cancer used in this study. Ellipsometry was used to characterize and optimise the antibody adsorption and antigen binding on gold surface. It was found that the best amount of antibody at the gold surface for effective antigen binding is around 1 mg/m2, above or below which resulted in the reduced antigen binding due to either the limited binding sites (below 1 mg/m2) or increased steric effect (above 1 mg/m2). The FBAR data were in good agreement with the data obtained from ellipsometry. Antigen binding experiments using FBAR sensors demonstrated that FBARs have the capability to precisely detect antigen binding, thereby making FBARs an attractive low cost alternative to existing cancer diagnostic sensors.This work was supported by the Engineering and Physical Sciences Research Council [grants EP/F062966/1, EP/F063865/1 and EP/F06294X/1], the Royal Society [grant RG120061] and the National Natural Science Foundation of China (NSFC) [grant 61150110485].This is the accepted manuscript version. The final published version of the article is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0925400513011052

Differential roles of two homologous cyclin-dependent kinase inhibitor genes in regulating cell cycle and innate immunity in arabidopsis\u3csup\u3e1[OPEN]\u3c/sup\u3e

© 2016 American Society of Plant Biologists. All Rights Reserved. Precise cell-cycle control is critical for plant development and responses to pathogen invasion. Two homologous cyclindependent kinase inhibitor genes, SIAMESE (SIM) and SIM-RELATED 1 (SMR1), were recently shown to regulate Arabidopsis (Arabidopsis thaliana) defense based on phenotypes conferred by a sim smr1 double mutant. However, whether these two genes play differential roles in cell-cycle and defense control is unknown. In this report, we show that while acting synergistically to promote endoreplication, SIM and SMR1 play different roles in affecting the ploidy of trichome and leaf cells, respectively. In addition, we found that the smr1-1 mutant, but not sim-1, was more susceptible to a virulent Pseudomonas syringae strain, and this susceptibility could be rescued by activating salicylic acid (SA)-mediated defense. Consistent with these results, smr1-1 partially suppressed the dwarfism, high SA levels, and cell death phenotypes in acd6-1, a mutant used to gauge the change of defense levels. Thus, SMR1 functions partly through SA in defense control. The differential roles of SIM and SMR1 are due to differences in temporal and spatial expression of these two genes in Arabidopsis tissues and in response to P. syringae infection. In addition, flow-cytometry analysis of plants with altered SA signaling revealed that SA is necessary, but not sufficient, to change cell-cycle progression. We further found that a mutant with three CYCD3 genes disrupted also compromised disease resistance to P. syringae. Together, this study reveals differential roles of two homologous cyclin-dependent kinase inhibitors in regulating cell-cycle progression and innate immunity in Arabidopsis and provides insights into the importance of cell-cycle control during host-pathogen interactions

Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices

Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43μm, 4.76μm, and 5.98μm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63μm (Zeiss) and 7.63μm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (P<0.05), with these discrepancies generally characterized by an overall offset (bias) and correlations with axial eye length for the foveal subfield and outer ring (P<0.05). This correlation was reduced to an insignificant level in all cases when AEL-dependent scaling was used. Overall, the Iowa Reference Algorithms are viable for clinical and research use in healthy eyes imaged with these devices, however ocular biometry is required for accurate quantification of OCT images