Impaired metabolism in donor kidney grafts after steroid pretreatment

We recently showed in a randomized control trial that steroid pretreatment of the deceased organ donor suppressed inflammation in the transplant organ but did not reduce the rate or duration of delayed graft function (DGF). This study sought to elucidate such of those factors that caused DGF in the steroid-treated subjects. Genome-wide gene expression profiles were used from 20 steroid-pretreated donor-organs and were analyzed on the level of regulatory protein protein interaction networks. Significance analysis of microarrays (SAM) yielded 63 significantly down-regulated sequences associated with DGF that could be functionally categorized according to Protein ANalysis THrough Evolutionary Relationships ontologies into two main biologic processes: transport (P < 0.001) and metabolism (P < 0.001). The identified genes suggest hypoxia as the cause of DGF, which cannot be counterbalanced by steroid treatment. Our data showed that molecular pathways affected by ischemia such as transport and metabolism are associated with DGF. Potential interventional targeted therapy based on these findings includes peroxisome proliferator-activated receptor agonists or caspase inhibitors

A data-driven approach to predict the saturation magnetization for magnetic 14:2:1 phases from chemical composition

14:2:1 phases enable permanent magnets with excellent magnetic properties. From an application viewpoint, saturation polarization, Curie temperature, and anisotropy constant are important parameters for the magnetic 14:2:1 phases. Novel chemical compositions that represent new 14:2:1 phases require especially maximum saturation magnetization values at application-specific operating temperatures to provide maximum values for the remanence and the maximum energy density in permanent magnets. Therefore, accurate knowledge of the saturation magnetization M$_s$ is important. M$_s$ gets affected by chemical composition in a twofold way, with chemical composition significantly influencing both magnetic moments and crystal structure parameters. Therefore, for magnetic 14:2:1 phases, we have developed a regression model with the aim to predict the saturation magnetization in [µ$_B$/f.u.] at room temperature directly from the chemical composition as input features. The dataset for the training and testing of the model is very diverse, with literature data of 143 unique phases and 55 entries of repeated phases belonging to the ternary, quaternary, quinary, and senary alloy systems. Substitutionally dissolved elements are heavy and light rare earth elements, transition metals, and additional elements. The trained model is a voting regressor model with different weights assigned to four base regressors and has generalized well, resulting in a low mean absolute error of 0.8 [µ$_B$/f.u.] on the unseen test set of 52 phases. This paper could serve as the basis for developing novel magnetic 14:2:1 phases from chemical composition

Fast fabrication of micropillar arrays using a combination of laser and FIB for micromechanical compression tests

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An Interaction Network Predicted from Public Data as a Discovery Tool: Application to the Hsp90 Molecular Chaperone Machine

Understanding the functions of proteins requires information about their protein-protein interactions (PPI). The collective effort of the scientific community generates far more data on any given protein than individual experimental approaches. The latter are often too limited to reveal an interactome comprehensively. We developed a workflow for parallel mining of all major PPI databases, containing data from several model organisms, and to integrate data from the literature for a protein of interest. We applied this novel approach to build the PPI network of the human Hsp90 molecular chaperone machine (Hsp90Int) for which previous efforts have yielded limited and poorly overlapping sets of interactors. We demonstrate the power of the Hsp90Int database as a discovery tool by validating the prediction that the Hsp90 co-chaperone Aha1 is involved in nucleocytoplasmic transport. Thus, we both describe how to build a custom database and introduce a powerful new resource for the scientific community

Grain size analysis in permanent magnets from Kerr microscopy images using machine learning techniques

Understanding the relationships between composition, structure, processing and properties helps in the development of improved materials for known applications as well as for new applications. Materials scientists, chemists and physicists have researched these relationships for many years, until the recent past, by characterizing the bulk properties of functional materials and describing them with theoretical models. Magnets are widly used in electric vehicles (EV), hybrid electric vehicles (HEV), data storage, power generation and transmission, sensors etc. The search for novel magnetic phases requires an efficient quantitative microstructure analysis of microstructural information like phases, grain distribution and micromagnetic structural information like domain patterns, and correlating the information with intrinsic magnetic parameters of magnet samples. The information out of micromagnetic domains helps in obtaining the optimized microstructures in magnets that have good intrinsic magnetic properties. This paper is aimed at introducing the use of a traditional machine learning (ML) model with a higher dimensional feature set and a deep learning (DL) model to classify various regions in sintered NdFeB magnets based on Kerr-microscopy images. The obtained results are compared against reference data, which is generated manually by subject experts. Additionally, the results were compared against the approach for grain analysis, which is based on the electron backscatter diffraction (EBSD) technique. Further, the challenges faced by the traditional machine learning model for classifying microstructures in Kerr micrographs are discussed

Integrative Bioinformatics Analysis of Proteins Associated with the Cardiorenal Syndrome

The cardiorenal syndrome refers to the coexistence of kidney and cardiovascular disease, where cardiovascular events are the most common cause of death in patients with chronic kidney disease. Both, cardiovascular as well as kidney diseases have been extensively analyzed on a molecular level, resulting in molecular features and associated processes indicating a cross-talk of the two disease etiologies on a pathophysiological level. In order to gain a comprehensive picture of molecular factors contributing to the bidirectional interplay between kidney and cardiovascular system, we mined the scientific literature for molecular features reported as associated with the cardiorenal syndrome, resulting in 280 unique genes/proteins. These features were then analyzed on the level of molecular processes and pathways utilizing various types of protein interaction networks. Next to well established molecular features associated with the renin-angiotensin system numerous proteins involved in signal transduction and cell communication were found, involving specific molecular functions covering receptor binding with natriuretic peptide receptor and ligands as well known example. An integrated analysis of identified features pinpointed a protein interaction network involving mediators of hemodynamic change and an accumulation of features associated with the endothelin and VEGF signaling pathway. Some of these features may function as novel therapeutic targets

Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode

The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFb/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFb/BMP receptors are enzymatically active and respond to host derived TGFb/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFb/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFb/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFb. Apart from being responsive to host TGFb/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFb-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFb/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFb is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies

Linking the ovarian cancer transcriptome and immunome

<p>Abstract</p> <p>Background</p> <p>Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive.</p> <p>Results</p> <p>This paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients.</p> <p>Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.</p> <p>Conclusion</p> <p>A link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.</p

Vat photopolymerization of cemented carbide specimen

Numerous studies show that vat photopolymerization enables near-net-shape printing of ceramics and plastics with complex geometries. In this study, vat photopolymerization was investigated for cemented carbide specimens. Custom-developed photosensitive WC-12 Co (wt%) slurries were used for printing green bodies. The samples were examined for defects using quantitative microstructure analysis. A thermogravimetric analysis was performed to develop a debinding program for the green bodies. After sintering, the microstructure and surface roughness were evaluated. As mechanical parameters, Vickers hardness and Palmqvist fracture toughness were considered. A linear shrinkage of 26–27% was determined. The remaining porosity fraction was 9.0%. No free graphite formation, and almost no η-phase formation occurred. WC grain growth was observed. 76% of the WC grains measured were in the suitable size range for metal cutting tool applications. A hardness of 1157 HV10 and a Palmqvist fracture toughness of 12 MPa $\sqrt{m}$ was achieved. The achieved microstructure exhibits a high porosity fraction and local cracks. As a result, vat photopolymerization can become an alternative forming method for cemented carbide components if the amount of residual porosity and defects can be reduced