Expression cartography of human tissues using self organizing maps

Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.
Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. 
Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.
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An Approach for the Disassembly of Permanent Magnet Synchronous Rotors to Recover Rare Earth Materials

The extensive electrification of the mobility sector is a crucial part for global decarbonization. To enable a successful transition, the availability of resources must be ensured. In particular, rare earth materials used in permanent magnets of permanent magnet synchronous machines (PMSM) are already considered as a critical resource. Therefore, high performance magnets of existing PMSM rotors must be recovered and remanufactured or recycled. A major challenge to recover the magnets is their fixation inside the rotor lamination stack. Hence, this paper presents an overview of remanufacturing and recycling methods for rare earth magnets. Based on this, a disassembly process for PMSM rotors is developed, technical challenges are pointed out and automation solution are proposed. As results of an experimental study conducted on different magnet configurations, four characteristic phases for the magnet disassembly process were identified and magnets with nickel coating showed significantly higher disassembly forces than magnets with epoxy coating. Moreover, analytical and empirical approaches for modeling the consecutive phases of the disassembly process are proposed

Collaborative Software Performance Engineering for Enterprise Applications

In the domain of enterprise applications, organizations usually implement third-party standard software components in order to save costs. Hence, application performance monitoring activities constantly produce log entries that are comparable to a certain extent, holding the potential for valuable collaboration across organizational borders. Taking advantage of this fact, we propose a collaborative knowledge base, aimed to support decisions of performance engineering activities, carried out during early design phases of planned enterprise applications. To verify our assumption of cross-organizational comparability, machine learning algorithms were trained on monitoring logs of 18,927 standard application instances productively running at different organizations around the globe. Using random forests, we were able to predict the mean response time for selected standard business transactions with a mean relative error of 23.19 percent. Hence, the approach combines benefits of existing measurement-based and model-based performance prediction techniques, leading to competitive advantages, enabled by inter-organizational collaboration

Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Multiple myeloma is a genetically heterogeneous plasma cell malignancy characterized by organ damage and a massive production of (in-)complete monoclonal antibodies. Coping with protein homeostasis and post-translational regulation is therefore essential for multiple myeloma cells to survive. Furthermore, post-translational modifications such as ubiquitination and SUMOylation play key roles in essential pathways in multiple myeloma, including NFκB signaling, epigenetic regulation, as well as DNA damage repair. Drugs modulating the ubiquitin-proteasome system, such as proteasome inhibitors and thalidomide analogs, are approved and highly effective drugs in multiple myeloma. In this review, we focus on ubiquitin and ubiquitin-like modifications in the biology and current developments of new treatments for multiple myeloma

Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases

Simple Summary: It is well known that antibiotics alter the gut microbiome, and because it plays a role in drug metabolism, alterations to the microbiome may lead to ineffective immunotherapy in cancer patients. We investigated a real-world cohort of oral cancer patients who received immunotherapy. Patients were matched for age, sex, BMI, metastases, alcohol and nicotine dependence and sepsis to create two comparable groups. Patients who received antibiotics had a significantly decreased survival compared to those who did not. We believe that this finding is associated with less effective immunotherapy due to antibiotic-related changes in the gut microbiome. Objective: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and after immunotherapy. Methods: We retrieved data from patients diagnosed with head and neck squamous cell carcinoma (HNSCC) (International Classification of Diseases [ICD]-10 codes C00-C14) and receiving immunotherapy with pembrolizumab from the TriNetX network. Two cohorts were built: patients in cohort I did not receive any antibiotics within three months before or up to three months after immunotherapy, while patients in cohort II were administered antibiotics at least once within three months before or after immunotherapy. To exclude confounders, we matched cohorts 1:1 for age, sex, secondary lymph node metastases, nicotine dependence, the insertion of feeding devices, body mass index (BMI) and severe sepsis. After defining the primary outcome as "death", a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. Results: A total of 3651 patients were enrolled, and after matching, each cohort consisted of 1362 patients. Among cohorts I and II, 346 and 511 patients were deceased within one year (risk of death = 25.5 and 38.3%, respectively), whereby the risk difference was significant (p = 0.000; log-rank test). The RR was 0.68 (95% confidence interval: 0.60-0.76), OR was 0.57 (0.48-0.67) and HR was 0.58 (0.51-0.67). Conclusions: Our hypothesis was confirmed: administering antibiotics significantly decreases the drug effectiveness of immunotherapy. We hypothesize that this finding is associated with antibiotic-related changes in the gut microbiome. Prospective clinical studies on the gut microbiome in cancer patients are necessary to understand the complex ecosystem of microbiota during immunotherapy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary

AmbiGaze:direct control of ambient devices by gaze

Eye tracking offers many opportunities for direct device control in smart environments, but issues such as the need for calibration and the Midas touch problem make it impractical. In this paper, we propose AmbiGaze, a smart environment that employs the animation of targets to provide users with direct control of devices by gaze only through smooth pursuit tracking. We propose a design space of means of exposing functionality through movement and illustrate the concept through four prototypes. We evaluated the system in a user study and found that AmbiGaze enables robust gaze-only interaction with many devices, from multiple positions in the environment, in a spontaneous and comfortable manner

Computer-Supported Knowledge Management in SME

Knowledge management (KM) and Knowledge Management Systems (KMS) are not new. With the rise of the Internet, distributed and increasingly social technology, the management principles as well as the tools supporting KM also start to address small and medium-sized enterprises (SME). Todays SMEs are increasingly required to manage knowledge assets in order to sustain their position on the competitive forefront in agile markets. This paper investigates the current state of the art on computer-based KMS (or KM tools as we call them) and commercial KM tools in order to harmonize the picture, derive a joint feature and application system scope and finally inspire future design-oriented research by unveiling gaps. It shows that recent SME-related KM tools do not address KM in a holistic managerial way, fail to link operative data sources such as ERP and CRM, lack effective reward and enabling processes to more quickly establish a knowledge sharing culture amongst SME employees. The main objective of the paper is to inform future design-oriented research

The relative myocardial blood volume differentiates between hypertensive heart disease and athlete's heart in humans

Aims The adaptation of the myocardial microcirculation in humans to pathologic and physiologic stress has not been examined in vivo so far. We sought to test whether the relative blood volume (rBV) measured by myocardial contrast echocardiography (MCE) can differentiate between left ventricular (LV) hypertrophy (LVH) in hypertensive heart disease and athlete's heart. Methods and results Four groups were investigated: hypertensive patients with LVH (n=15), semi-professional triathletes with LVH (n=15), professional football players (n=15), and sedentary control individuals without cardiovascular disease (n=15). MCE was performed at rest and during adenosine-induced hyperaemia. The rBV (mL mL−1), its exchange frequency (β, min−1), and myocardial blood flow (mL min−1 g−1) were derived from steady state and refill sequences of ultrasound contrast agent. Hypertensive patients had lower rBV (0.093±0.013 mL mL−1) than triathletes (0.141±0.012 mL mL−1, P<0.001), football players (0.129±0.014 mL mL−1, P<0.001), and sedentary individuals (0.126±0.018 mL mL−1, P<0.001). Conversely, the exchange frequency (β) was significantly higher in hypertensive patients (11.3±3.8 min−1) than in triathletes (7.4±1.8 min−1), football players (7.7±2.3 min−1), and sedentary individuals (9.0±2.5 min−1). An rBV below 0.114 mL mL−1 distinguished hypertensive patients and triathletes with a sensitivity of 93% and a specificity of 100%. Conclusion Pathologic and physiologic LVH were differentiated non-invasively and accurately by rBV, a measure of vascularisation assessed by MC