Optimistic Optimization of Gaussian Process Samples

Bayesian optimization is a popular formalism for global optimization, but its computational costs limit it to expensive-to-evaluate functions. A competing, computationally more efficient, global optimization framework is optimistic optimization, which exploits prior knowledge about the geometry of the search space in form of a dissimilarity function. We investigate to which degree the conceptual advantages of Bayesian Optimization can be combined with the computational efficiency of optimistic optimization. By mapping the kernel to a dissimilarity, we obtain an optimistic optimization algorithm for the Bayesian Optimization setting with a run-time of up to $\mathcal{O}(N \log N)$. As a high-level take-away we find that, when using stationary kernels on objectives of relatively low evaluation cost, optimistic optimization can be strongly preferable over Bayesian optimization, while for strongly coupled and parametric models, good implementations of Bayesian optimization can perform much better, even at low evaluation cost. We argue that there is a new research domain between geometric and probabilistic search, i.e. methods that run drastically faster than traditional Bayesian optimization, while retaining some of the crucial functionality of Bayesian optimization.Comment: 10 pages, 6 figure

Cross-kingdom comparison of the developmental hourglass.

The developmental hourglass model has its foundations in classic anatomical studies by von Baer and Haeckel. In this context, even the conservation of animal body plans has been explained by evolutionary constraints acting on mid-embryogenic development. Recent studies have shown that developmental hourglass patterns also exist on the transcriptomic level, mirroring the corresponding morphological patterns. The identification of similar patterns in embryonic, post-embryonic, and life cycle spanning transcriptomes in plant and fungus development, however, contradict the notion of a direct coupling between morphological and molecular patterns. To explain the existence of hourglass patterns across kingdoms and developmental processes, we propose the organizational checkpoint model that integrates the developmental hourglass model into a framework of transcriptome switches

Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior

Since the solution of the molecular structures of members of the voltage dependent anion channels (VDACs), the N-terminal α-helix has been the main focus of attention, since its strategic location, in combination with its putative conformational flexibility, could define or control the channel’s gating characteristics. Through engineering of two double-cysteine mVDAC1 variants we achieved fixing of the N-terminal segment at the bottom and midpoint of the pore. Whilst cross-linking at the midpoint resulted in the channel remaining constitutively open, cross-linking at the base resulted in an “asymmetric” gating behavior, with closure only at one electric field´s orientation depending on the channel’s orientation in the lipid bilayer. Additionally, and while the native channel adopts several well-defined closed states (S1 and S2), the cross-linked variants showed upon closure a clear preference for the S2 state. With native-channel characteristics restored following reduction of the cysteines, it is evident that the conformational flexibility of the N-terminal segment plays indeed a major part in the control of the channel’s gating behavior

Differential and shared effects of psychological skills training and mindfulness training on performance-relevant psychological factors in sport: a randomized controlled trial

Background: Mental training intends to support athletes in mastering challenges in sport. The aim of our study was to investigate the differential and shared effects of psychological skills training and mindfulness training on psychological variables relevant to athletic performance (e.g., handling emotions or attention control). We assumed that each approach has its own strengths (e.g., mindfulness has a differential effect on the acceptance of emotions), but for some goals (e.g., attention control), both training forms are expected to be equally successful (i.e., shared effects). Methods: A total of 95 athletes (Mage = 24.43, SDage = 5.15; 49% female) were randomly assigned into three groups: psychological skills training intervention (PST), mindfulness training intervention (MT), and wait-list control group (WL). Participants completed a questionnaire battery before and after the training (pretest and posttest). We assessed mindfulness, use of mental strategies, handling of emotions, attention in training and competition, as well as the dealing with failure. The two intervention programs each consisted of four 90-min group workshops conducted over a period of 4 weeks. Results: Both interventions passed the manipulation check, that is, PST led to more mental strategies being used (probabilities > 95%), and MT led to an increase in two of three aspects of mindfulness (probabilities > 98%) when compared to WL. Compared to WL, both interventions equally improved in the ability to not let emotions interfere with performance (probabilities > 99%) and in controlling attention in training and competition (probabilities > 89%). To a lesser extend, both interventions showed shared improvements in dealing with failure indicated by more action orientation (probabilities > 82%). We found a differential effect of MT on decreased experiential avoidance: MT decreased compared to WL and PST (probabilities > 92%), whereas PST did not differ from WL. Conclusion: We conclude that both forms of mental training lead to improvements in performance-relevant psychological factors, especially concerning the handling of emotions and attention control. The results of our study suggest that different paths may lead to the desired outcomes, and accordingly, both forms of mental training seem justified

Comparative Life Cycle Assessment Of Conventionally Manufactured And Additive Remanufactured Electric Bicycle Motors

In a circular economy, remanufacturing is crucial in reducing the use of primary raw materials and energy compared to new production. However, poor availability of non-standardized wear components can prevent remanufacturing. Additive manufacturing is a promising alternative to conventional manufacturing or spare part purchase for those wear components required for remanufacturing. However, there is uncertainty regarding the environmental impact of using additive manufacturing for remanufacturing. This paper compares conventional and additive spare parts manufacturing to evaluate the potential environmental savings of remanufacturing electric bicycle motors. Therefore, a reference motor was selected, and its manufacturing processes were modeled in SimaPro using the ecoinvent 3.8 Life Cycle Assessment database and the latest knowledge on processing and manufacturing processes. The results show that conventional production of electric bicycle motors has a climate warming potential of around 28 kg CO2-eq. Additive remanufacturing of electric bicycle motors at the end of their life cycle offers significant environmental savings potential. The extent of savings depends on the condition of the used electric bicycle motor and, accordingly, the number of components that need to be replaced. According to the IPCC method for the electric bicycle motor investigated, the study estimates that approximately 90.4 % savings potential can be achieved in terms of Global Warming Potential

Impact of Different Catheter Lock Strategies on Bacterial Colonization of Permanent Central Venous Hemodialysis Catheters

Thirty-nine hemodialysis patients with permanent central venous catheters were analyzed for bacterial catheter colonization comparing different catheter-lock strategies. The closed needleless Tego connector with sodium chloride lock solution was significantly more frequently colonized with bacteria than the standard catheter caps with antimicrobially active citrate lock solution (odds ratio, 0.22 [95% confidence interval, 0.07-0.71]; P = .011

Identification of novel regulators in T-cell differentiation of aplastic anemia patients

BACKGROUND: Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3(+ )T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR. RESULTS: Among more than 22.200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response. CONCLUSION: Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes