Imaging and manipulating the structural machinery of living cells on the micro- and nanoscale

The structure, physiology, and fate of living cells are all highly sensitive to mechanical forces in the cellular microenvironment, including stresses and strains that originate from encounters with the extracellular matrix (ECM), blood and other flowing materials, and neighbouring cells. This relationship between context and physiology bears tremendous implications for the design of cellular micro-or nanotechnologies, since any attempt to control cell behavior in a device must provide the appropriate physical microenvironment for the desired cell behavior. Cells sense, process, and respond to biophysical cues in their environment through a set of integrated, multi-scale structural complexes that span length scales from single molecules to tens of microns, including small clusters of force-sensing molecules at the cell surface, micron-sized cell-ECM focal adhesion complexes, and the cytoskeleton that permeates and defines the entire cell. This review focuses on several key technologies that have recently been developed or adapted for the study of the dynamics of structural micro-and nanosystems in living cells and how these systems contribute to spatially-and temporally-controlled changes in cellular structure and mechanics. We begin by discussing subcellular laser ablation, which permits the precise incision of nanoscale structural elements in living cells in order to discern their mechanical properties and contributions to cell structure. We then discuss fluorescence recovery after photobleaching and fluorescent speckle microscopy, two live-cell fluorescence imaging methods that enable quantitative measurement of the binding and transport properties of specific proteins in the cell. Finally, we discuss methods to manipulate cellular structural networks by engineering the extracellular environment, including microfabrication of ECM distributions of defined geometry and microdevices designed to measure cellular traction forces at micron-scale resolution. Together, these methods form a powerful arsenal that is already adding significantly to our understanding of the nanoscale architecture and mechanics of living cells and may contribute to the rational design of new cellular micro-and nanotechnologies

The Life²Well Project: Investigating the Relationship between Physiological Stress and Environmental Factors through Data Science, the Internet of Things and Do-it-Yourself Wearables

This chapter reports a study conducted by students as an independent research project under the mentorship of a Research Scientist at the National Institute of Education, Singapore. In the Life2Well Project (Learning at the intersection of AI, physiology, EEG, our environment and well-being) identical units of a wearable device containing environmental sensors (such as ambient temperature, air pressure, infrared radiation and relative humidity) were designed and worn respectively by five adolescents from July to December 2021. Over the same period, data from these sensors was complemented by that obtained from smartwatches (namely blood oxygen saturation, heart rate and its variability, body temperature, respiration rate and sleep score). More than 40,000 data points were eventually collected, and were processed through a random forest regression model, which is a supervised learning algorithm that uses ensemble learning methods for regression. Results showed that the most influential microclimatic factors on biometric indicators were noise, and the concentrations of carbon dioxide and dust. Subsequently, more complex inferences were made from Shapley value interpretation of the regression models. Such findings suggest implications for the design of living conditions with respect to the interaction of microclimate and human health and comfort

Lipid Anti-Lipid Antibody Responses Correlate with Disease Activity in Systemic Lupus Erythematosus

10.1371/journal.pone.0055639PLoS ONE82

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

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The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Search for massive resonances decaying in to WW,WZ or ZZ bosons in proton-proton collisions at root s=13 TeV

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Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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