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"Wilson, Jennifer"
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ARDS Subphenotypes: Understanding a Heterogeneous Syndrome
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at
https://www.biomedcentral.com/collections/annualupdate2020
. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from
http://www.springer.com/series/8901
.
Journal Article
Theories of happiness : an anthology
\"Theories of Happiness: An Anthology introduces readers to many difficult philosophical questions surrounding the concept of happiness. With historical and contemporary readings in philosophy, psychology, and the social sciences, the anthology reflects a dialogue between ideas, providing for a rich conversation that brings out the key insights and strengths of several competing views. Each of the included readings is contextualized by the editors and situated to speak to the larger issues, including the value of happiness and its connection to well-being, the relationship of happiness to morality, whether happiness can be accurately and meaningfully measured, and whether there are universal standards for a happy life\"--Back cover.
Book
Preclinical side effect prediction through pathway engineering of protein interaction network models
Modeling tools aim to predict potential drug side effects, although they suffer from imperfect performance. Specifically, protein–protein interaction models predict drug effects from proteins surrounding drug targets, but they tend to overpredict drug phenotypes and require well‐defined pathway phenotypes. In this study, we used PathFX, a protein–protein interaction tool, to predict side effects for active ingredient‐side effect pairs extracted from drug labels. We observed limited performance and defined new pathway phenotypes using pathway engineering strategies. We defined new pathway phenotypes using a network‐based and gene expression‐based approach. Overall, we discovered a trade‐off between sensitivity and specificity values and demonstrated a way to limit overprediction for side effects with sufficient true positive examples. We compared our predictions to animal models and demonstrated similar performance metrics, suggesting that protein–protein interaction models do not need perfect evaluation metrics to be useful. Pathway engineering, through the inclusion of true positive examples and omics measurements, emerges as a promising approach to enhance the utility of protein interaction network models for drug effect prediction.
Journal Article
A computational workflow for assessing drug effects on temporal signaling dynamics reveals robustness in stimulus-specific NFκB signaling
Single-cell studies of signal transduction have revealed complex temporal dynamics that determine downstream biological function. For example, the stimulus-specific dynamics of the transcription factor NFκB specify stimulus-specific gene expression programs, and loss of specificity leads to disease. Thus, it is intriguing to consider drugs that may restore signaling specificity in disease contexts, or reduce activity but maintain signaling specificity to avoid unwanted side effects. However, while steady-state dose-response relationships have been the focus of pharmacological studies, there are no established methods for quantifying drug impact on stimulus-response signaling dynamics. Here we evaluated how drug treatments affect the stimulus-specificity of NFκB activation dynamics and its ability to accurately code ligand identity and dose. Specifically, we simulated the dynamic NFκB trajectories in response to 15 stimuli representing various immune threats under treatment of 10 representative drugs across 20 dosage levels. To quantify the effects on coding capacity, we introduced a Stimulus Response Specificity (SRS) score and a stimulus confusion score. We constructed stimulus confusion maps by employing epsilon network clustering in the trajectory space and in various dimensionally reduced spaces: canonical polyadic decomposition (CPD), functional principal component analysis (fPCA), and NFκB signaling codons (i.e., established, informative dynamic features). Our results indicated that the SRS score and the stimulus confusion map based on signaling codons are best-suited to quantify stimulus-specific NFκB dynamics confusion under pharmacological perturbations. Using these tools we found that temporal coding capacity of the NFκB signaling network is generally robust to a variety of pharmacological perturbations, thereby enabling the targeting of stimulus-specific dynamics without causing broad side-effects.
Journal Article
Design history beyond the canon
Design History Beyond the Canon subverts hierarchies of taste which have dominated traditional narratives of design history. The book explores a diverse selection of objects, spaces and media, ranging from high design to mass-produced and mass-marketed objects, as well as counter-cultural and sub-cultural material.0The authors' research highlights the often marginalised role of gender and racial identity in the production and consumption of design, the politics which underpins design practice and the role of designed objects as pathways of nostalgia and cultural memory. While focused primarily on North American examples from the early 20th century onwards, this collection also features essays examining European and Soviet design history, as well as the influence of Asia and Africa on Western design practice. The book is organised in three thematic sections: Consumers, Intermediaries and Designers. The first section analyses a range of designed objects and spaces through the experiences and perspectives of users. The second section considers intermediaries from both technology and the culture industries, as well as the hidden labour within the design process itself by way of patents. The final section focuses on designers from multiple design disciplines including high fashion, industrial design, interior design, graphic design and design history pedagogy. The essays in all three sections utilise different research methods and a wide range of theoretical approaches, including feminist theory, critical race theory, spatial theory, material culture studies, science and technology studies and art history. Design History Beyond the Canon brings together the most recent research which reaches beyond the traditional canon and looks to interdisciplinary methodologies to better understand the practice and consumption of design.
Book
Controlling astrocyte-mediated synaptic pruning signals for schizophrenia drug repurposing with deep graph networks
Schizophrenia is a debilitating psychiatric disorder, leading to both physical and social morbidity. Worldwide 1% of the population is struggling with the disease, with 100,000 new cases annually only in the United States. Despite its importance, the goal of finding effective treatments for schizophrenia remains a challenging task, and previous work conducted expensive large-scale phenotypic screens. This work investigates the benefits of Machine Learning for graphs to optimize drug phenotypic screens and predict compounds that mitigate abnormal brain reduction induced by excessive glial phagocytic activity in schizophrenia subjects. Given a compound and its concentration as input, we propose a method that predicts a score associated with three possible compound effects, i.e., reduce, increase, or not influence phagocytosis. We leverage a high-throughput screening to prove experimentally that our method achieves good generalization capabilities. The screening involves 2218 compounds at five different concentrations. Then, we analyze the usability of our approach in a practical setting, i.e., prioritizing the selection of compounds in the SWEETLEAD library. We provide a list of 64 compounds from the library that have the most potential clinical utility for glial phagocytosis mitigation. Lastly, we propose a novel approach to computationally validate their utility as possible therapies for schizophrenia.
Journal Article
التعرف إلى قصر العظم : دليل الطلاب للتعرف إلى الفنون والعمارة الإسلامية والدمشقية
يهدف هذا الكتاب إلى تعريف الأطفال وتثقيفهم بفنون العمارة الإسلامية والدمشقية، وتفعيل دورهم بأهمية المتاحف وتعزيز خبراتهم في زيارتها لخلق حالة من التواصل فيما بينهم، ويتضمن الدليل الذي أعده مجموعة من الخبراء السوريين والأجانب نشاطا متنوعا يتيح للأطفال مناقشة ميزات الفن والعمارة في قصر العظم مع الآخرين، إضافة إلى تقديم مقترحات للقيام بمهام تتعلق بقاعات العرض يستطيع الطلاب إتمامها في المدرسة والمنزل، إضافة إلى ابتكار طرق التعرف إلى قصر العظم لتعزيز خبرات الطلاب في زيارة المتاحف والرفع من مستوى تقديرهم لمجموعات فن العمارة الغنية الموجودة في قصر العظم، ولتعميق تقديرهم لمدينة دمشق القديمة، يشار إلى أن قصر العظم الذي بناه أسعد باشا العظم عام 1749 ميلادية، يعتبر من أهم المباني التاريخية الضخمة الموجودة في مدينة دمشق القديمة، وواحدا من أفضل نماذج العمارة المبكرة للبيوت الدمشقية الكبيرة الذي يمتد على مساحة 5,500 متر مربع.
BOOK
The tomato yellow leaf curl virus C4 protein alters the expression of plant developmental genes correlating to leaf upward cupping phenotype in tomato
Tomato yellow leaf curl virus (TYLCV), a monopartite begomovirus in the family Geminiviridae , is efficiently transmitted by the whitefly, Bemisia tabaci , and causes serious economic losses to tomato crops around the world. TYLCV-infected tomato plants develop distinctive symptoms of yellowing and leaf upward cupping. In recent years, excellent progress has been made in the characterization of TYLCV C4 protein function as a pathogenicity determinant in experimental plants, including Nicotiana benthamiana and Arabidopsis thaliana . However, the molecular mechanism leading to disease symptom development in the natural host plant, tomato, has yet to be characterized. The aim of the current study was to generate transgenic tomato plants expressing the TYLCV C4 gene and evaluate differential gene expression through comparative transcriptome analysis between the transgenic C4 plants and the transgenic green fluorescent protein ( Gfp) gene control plants. Transgenic tomato plants expressing TYLCV C4 developed phenotypes, including leaf upward cupping and yellowing, that are similar to the disease symptoms expressed on tomato plants infected with TYLCV. In a total of 241 differentially expressed genes identified in the transcriptome analysis, a series of plant development-related genes, including transcription factors, glutaredoxins, protein kinases, R-genes and microRNA target genes, were significantly altered. These results provide further evidence to support the important function of the C4 protein in begomovirus pathogenicity. These transgenic tomato plants could serve as basic genetic materials for further characterization of plant receptors that are interacting with the TYLCV C4.
Journal Article