Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting ...chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.
We report on fabrication of high-confinement and low loss silicon nitride (Si 3 N 4 ) waveguides using the photonic Damascene process. This process scheme represents a novel fabrication approach ...enabling reliable, wafer-scale fabrication of highconfinement optical waveguides. A reflow step of the silica preform reduces sidewall scattering to values not attainable with conventional etching, and reduces losses and backscattering significantly, resulting in a waveguide attenuation of 5.5 dB/m. We discuss the critical aspects of the process in detail and demonstrate the fabrication of high stress Si 3 N 4 waveguides with unprecedentedly large dimensions (1.75 μm × 1.425 μm) providing high-confinement at midinfrared wavelengths. A device characterization strategy allowing for systematic extraction of statistically relevant loss values is discussed and reveals the effects of the sidewall smoothing.
Malignant melanoma is highly lethal due to its aggressive invasive properties and metastatic dissemination. The transcription factor E2F1 is crucial for melanoma progression through poorly understood ...mechanisms. Here, we show that the miR‐224/miR‐452 cluster is significantly increased in advanced melanoma and invasive/metastatic cell lines that express high levels of E2F1. miR‐224/miR‐452 expression is directly activated by E2F1 through transactivation of the GABRE gene. Ectopic expression of miR‐224/miR‐452 in less aggressive cells induces EMT and cytoskeletal rearrangements and enhances migration/invasion. Conversely, miR‐224/miR‐452 depletion in metastatic cells induces the reversal of EMT, inhibition of motility, loss of the invasive phenotype and an absence of lung metastases in mice. We identify the metastasis suppressor TXNIP as new target of miR‐224/miR‐452 that induces feedback inhibition of E2F1 and show that miR‐224/452‐mediated downregulation of TXNIP is essential for E2F1‐induced EMT and invasion. The E2F1‐miR‐224/452‐TXNIP axis constitutes a molecular signature that predicts patient survival and may help to set novel therapies.
Synopsis
The E2F1‐miR‐244/452‐TXNIP pathway is shown to be crucial for melanoma invasion and metastasis in vivo. By activating the expression of miR‐224/452, E2F1 leads to the downregulation of its inhibitor, TXNIP, and induces EMT.
In early primary tumors, high levels of TXNIP restrict E2F1 activity through p16 activation and subsequent inhibition of RB.
Increasingly high levels of E2F1 during cancer progression lead to the transcriptional upregulation of the miR‐224/452 cluster.
miR‐224 and miR‐452 repress the expression of TXNIP to induce E2F1‐dependent EMT and invasion.
The E2F1‐miR‐244/452‐TXNIP pathway is shown to be crucial for melanoma invasion and metastasis in vivo. By activating the expression of miR‐224/452, E2F1 leads to the downregulation of its inhibitor, TXNIP, and induces EMT.
Purpose - The purpose of the paper is to propose a reference model describing a holistic view of the master data lifecycle, including strategic, tactical and operational aspects. The Master Data ...Lifecycle Management (MDLM) map provides a structured approach to analyze the master data lifecycle.Design methodology approach - Embedded in a design oriented research process, the paper applies the Component Business Model (CBM) method and suggests a reference model which identifies the business components required to manage the master data lifecycle. CBM is a patented IBM method to analyze the key components of a business domain. The paper uses a participative case study to evaluate the suggested model.Findings - Based on a participative case study, the paper shows how the reference model makes it possible to analyze the master data lifecycle on a strategic, a tactical and an operational level, and how it helps identify areas of improvement.Research limitations implications - The paper presents design work and a participative case study. The reference model is grounded in existing literature and represents a comprehensive framework forming the foundation for future analysis of the master data lifecycle. Furthermore, the model represents an abstraction of an organization's master data lifecycle. Hence, it forms a "theory for designing". More research is needed in order to more thoroughly evaluate the presented model in a variety of real-life settings.Practical implications - The paper shows how the reference model enables practitioners to analyze the master data lifecycle and how it helps identify areas of improvement.Originality value - The paper reports on an attempt to establish a holistic view of the master data lifecycle, including strategic, tactical and operational aspects, in order to provide more comprehensive support for its analysis and improvement.
Background
Knowledge of the stabilizing mechanisms of soil organic matter (SOM) is extremely important for numerous soil functions. For this, insight into the nature of organic matter through ...appropriate model concepts are crucial.
Aims
For several years, a heated debate has emerged on the transformation and stabilization of SOM. In the present work, we try to contribute to this debate using molecular modeling and providing a comprehensive overview of the history of application of molecular modeling tools and developing structural concepts of SOM.
Methods
Molecular modeling methods based on quantum and/or classical mechanics were used to model SOM and related properties including interactions with reactive surfaces of soil minerals.
Results
Modeling of SOM aggregates revealed that hydrogen bonds and cation bridges are the main stabilizing factors in soil solution, whereas pH modifies the stability. The modeled supramolecular SOM aggregates exhibit physicochemical properties, similar to those of humic substances (HS) described in literature. The interactions of the HS models with surfaces in kaolinite nanopores led to a partial disintegration of the aggregates into individual molecules and/or smaller subaggregates.
Conclusions
From the molecular modeling point of view, supramolecular microaggregate models that exhibit the properties of HS are stable in the soil solution. However, their binding to reactive mineral soil constituents can be also in the form of individual molecules or subaggregates. Thus, HS microaggregate stability is relative, depending on the interacting environment. This reconciles two points of view of HS: either as small molecules and/or supramolecular structures.
A new instrument and method is described for laterally resolved mass spectrometric surface analysis. Fields of application are in both the life sciences and the material sciences. The instrument ...provides for imaging of the distribution of selected sample components from natural and artificial surfaces. Samples are either analyzed by laser desorption ionization (LDI) time-of-flight mass spectrometry or, after preparation with a suitable matrix, by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. Areas of 100 × 100 μm are scanned with minimal increments of 0.25 μm, and between 10,000 and 160,000 mass spectra are acquired per image within 3 to 50 min (scan rate up to 50 pixels per s). The effective lateral resolution is in the range of 0.6 to 1.5 μm depending on sample properties, preparation methods and laser wavelength. Optical investigation of the same sample area by UV confocal scanning laser microscopy was found to be very attractive in combination with scanning MALDI mass analysis because pixel-identical images can be created with both techniques providing for a strong increase in analytical information. This article describes the method and instrumentation, including first applicational examples in elemental analysis, imaging of pine tree roots, and investigation of MALDI sample morphology in biomolecular analysis.
A generalized model is developed to quantitatively describe the smoothing effects from different polishing tools used for optical surfaces. The smoothing effect naturally corrects mid-to-high spatial ...frequency errors that have features small compared to the size of the polishing lap. The original parametric smoothing model provided a convenient way to compare smoothing efficiency of different polishing tools for the case of sinusoidal surface irregularity, providing the ratio of surface improvement via smoothing to the bulk material removal. A new correlation-based smoothing model expands the capability to quantify smoothing using general surface data with complex irregularity. For this case, we define smoothing as a band-limited correlated component of the change in the surface and original surface. Various concepts and methods, such as correlation screening, have been developed and verified to manipulate the data for the calculation of smoothing factor. Data from two actual polishing runs from the Giant Magellan Telescope off-axis segment and the Large Synoptic Survey Telescope monolithic primary-tertiary mirror were processed, and a quantitative evaluation for the smoothing efficiency of a large pitch lap and a conformal lap with polishing pads is provided.
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