Explore the vast range of titles available.

Understanding cells as integrated systems is central to modern biology. Although fluorescence microscopy can resolve subcellular structure in living cells, it is expensive, is slow, and can damage cells. We present a label-free method for predicting three-dimensional fluorescence directly from transmitted-light images and demonstrate that it can be used to generate multi-structure, integrated images. The method can also predict immunofluorescence (IF) from electron micrograph (EM) inputs, extending the potential applications.

We introduce a framework for end-to-end integrative modeling of 3D single-cell multi-channel fluorescent image data of diverse subcellular structures. We employ stacked conditional β -variational autoencoders to first learn a latent representation of cell morphology, and then learn a latent representation of subcellular structure localization which is conditioned on the learned cell morphology. Our model is flexible and can be trained on images of arbitrary subcellular structures and at varying degrees of sparsity and reconstruction fidelity. We train our full model on 3D cell image data and explore design trade-offs in the 2D setting. Once trained, our model can be used to predict plausible locations of structures in cells where these structures were not imaged. The trained model can also be used to quantify the variation in the location of subcellular structures by generating plausible instantiations of each structure in arbitrary cell geometries. We apply our trained model to a small drug perturbation screen to demonstrate its applicability to new data. We show how the latent representations of drugged cells differ from unperturbed cells as expected by on-target effects of the drugs.

Characterizing the spatial distribution of proteins directly from microscopy images is a difficult problem with numerous applications in cell biology (e.g. identifying motor-related proteins) and clinical research (e.g. identification of cancer biomarkers). Here we describe the design of a system that provides automated analysis of punctate protein patterns in microscope images, including quantification of their relationships to microtubules. We constructed the system using confocal immunofluorescence microscopy images from the Human Protein Atlas project for 11 punctate proteins in three cultured cell lines. These proteins have previously been characterized as being primarily located in punctate structures, but their images had all been annotated by visual examination as being simply \"vesicular\". We were able to show that these patterns could be distinguished from each other with high accuracy, and we were able to assign to one of these subclasses hundreds of proteins whose subcellular localization had not previously been well defined. In addition to providing these novel annotations, we built a generative approach to modeling of punctate distributions that captures the essential characteristics of the distinct patterns. Such models are expected to be valuable for representing and summarizing each pattern and for constructing systems biology simulations of cell behaviors.

BackgroundBlack and Hispanic people are more likely to contract COVID-19, require hospitalization, and die than White people due to differences in exposures, comorbidity risk, and healthcare access.ObjectiveTo examine the association of race and ethnicity with treatment decisions and intensity for patients hospitalized for COVID-19.DesignRetrospective cohort analysis of manually abstracted electronic medical records.Patients7,997 patients (62% non-Hispanic White, 16% non-Black Hispanic, and 23% Black) hospitalized for COVID-19 at 135 community hospitals between March and June 2020Main MeasuresAdvance care planning (ACP), do not resuscitate (DNR) orders, intensive care unit (ICU) admission, mechanical ventilation (MV), and in-hospital mortality. Among decedents, we classified the mode of death based on treatment intensity and code status as treatment limitation (no MV/DNR), treatment withdrawal (MV/DNR), maximal life support (MV/no DNR), or other (no MV/no DNR).Key ResultsAdjusted in-hospital mortality was similar between White (8%) and Black patients (9%, OR=1.1, 95% CI=0.9–1.4, p=0.254), and lower among Hispanic patients (6%, OR=0.7, 95% CI=0.6–1.0, p=0.032). Black and Hispanic patients were significantly more likely to be treated in the ICU (White 23%, Hispanic 27%, Black 28%) and to receive mechanical ventilation (White 12%, Hispanic 17%, Black 16%). The groups had similar rates of ACP (White 12%, Hispanic 12%, Black 11%), but Black and Hispanic patients were less likely to have a DNR order (White 13%, Hispanic 8%, Black 7%). Among decedents, there were significant differences in mode of death by race/ethnicity (treatment limitation: White 39%, Hispanic 17% (p=0.001), Black 18% (p<0.0001); treatment withdrawal: White 26%, Hispanic 43% (p=0.002), Black 28% (p=0.542); and maximal life support: White 21%, Hispanic 26% (p=0.308), Black 36% (p<0.0001)).ConclusionsHospitalized Black and Hispanic COVID-19 patients received greater treatment intensity than White patients. This may have simultaneously mitigated disparities in in-hospital mortality while increasing burdensome treatment near death.

The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.

Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine 1 , 2 . Here we reduced this complexity by focusing on cellular organization—a key readout and driver of cell behaviour 3 , 4 —at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the ‘wiring’ of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring. A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

HVAC systems in a typical laboratory facility can use five to 10 times as much energy as the systems in a typical office building. This higher energy use is due to many factors including 100% outside air systems; 24-hour-a-day operation; high internal heat gains; high air change rate requirements; equipment exhaust requirements; and high fan energy. Meanwhile, laboratories require significant resources to construct and operate and the number of laboratory facilities will continue to grow. HVAC designers should consider methods to reduce a facility's impact on the environment by reducing water use and recovering water for reuse where appropriate. While the designer's first obligation is to the safety of the laboratory users, visitors and maintenance personnel, it is possible to creatively reduce the energy use of facilities. Here, Johnson discusses creative ways to design safe and sustainable laboratories for the future.

Few cross‐national reports have examined suicide rates among adolescents and young adults. A survey of suicides among 15–24‐year‐olds in 34 of the wealthiest nations demonstrated that 15,555 youths killed themselves in a 1‐year study period. Thirty‐four percent of these suicides were firearm‐related. Finland led the participating nations in total and firearm‐related suicide rates. An association was found between divorce rates and youth suicide rates, firearm‐related suicide among youths, and suicide rates among young males. For a smaller sample of countries, an association was found between firearm availability and firearm‐related suicide rates among youths and suicide rates among young males.

Characterizing the spatial distribution of proteins directly from microscopy images is a difficult problem with numerous applications in cell biology (e.g. identifying motor-related proteins) and clinical research (e.g. identification of cancer biomarkers). Here we describe the design of a system that provides automated analysis of punctate protein patterns in microscope images, including quantification of their relationships to microtubules. We constructed the system using confocal immunofluorescence microscopy images from the Human Protein Atlas project for 11 punctate proteins in three cultured cell lines. These proteins have previously been characterized as being primarily located in punctate structures, but their images had all been annotated by visual examination as being simply \"vesicular\". We were able to show that these patterns could be distinguished from each other with high accuracy, and we were able to assign to one of these subclasses hundreds of proteins whose subcellular localization had not previously been well defined. In addition to providing these novel annotations, we built a generative approach to modeling of punctate distributions that captures the essential characteristics of the distinct patterns. Such models are expected to be valuable for representing and summarizing each pattern and for constructing systems biology simulations of cell behaviors.

This book discusses the political philosophy of Paul Ricoeur. More precisely, it offers a sustained engagement with Ricoeur's political thought in a way that demonstrates both the significance of the political in his own thinking throughout his career, and how Ricoeur's understanding of the political offers something valuable to current discussions in political philosophy. A second goal is to begin to fill a gap in Ricoeur studies and situate his work on political ethics more fully in contemporary discussions about political thought. In this way, Ricoeur can be seen as a figure pertinent to recent trends in political philosophy that make political thinking more realistic to the conditions for political life. The various essays in the book move along intersecting but different trajectories. First, as some of these essays attest, the concept of the political is a pervasive theme that runs throughout Ricoeur's corpus. In this way a theme throughout the book examines this notion of the political, as well as how it relates to his more well-known work in other areas. Second, and related, the historical understanding of perennial issues in political philosophy are most often updated by those standing in the lineage of those who have come before. As such, Ricoeur's hermeneutical orientation has moved him to engage contemporaries who attempt to \"think forward\" in various ways this tradition for current situations. Unlike most who engage in political thought, Ricoeur goes where others dare not, namely, to those who appear to be opponents but, as he shows, offer perspectives worth more consideration in the name of the best of political thinking. In this light, Ricoeur's hermeneutical orientation is again a unique framework for understanding the nature of political engagement, an orientation in what follows that highlights the ways that Ricoeur and a Ricoeurian perspective cross philosophical orientations to develop a unique understanding of political thought that is different.