Rational Insights Research Articles

Oxygen Substitution to Enhance Chemo-Mechanical Stability at the Cathode-Sulfide Electrolyte Interface in All-Solid-State Batteries.

The high interface resistance at the cathode-sulfide electrolyte interface is still a crucial drawback in an all-solid-state battery, unlike the initial expectation that the all-solid-state interface would enhance electrochemical stability by reducing side reactions at the interface. In this study, we examined the fundamental mechanism of unexpected reactions at the interface of LiNi0.8Co0.1Mn0.1O2 (NCM811) and argyrodite (Li6PS5Br0.5Cl0.5, LPSBC) sulfide solid electrolytes based on the combined method of multiscale simulations and electrochemical experiments. The high interface resistance originates from the formation of a passivating layer at the interface combined with irregular atomic and electronic structures, Li depletion, mutual element exchange, and mechanical contact loss between the oxide cathode and sulfide solid electrolyte. We also confirmed that these side reactions were suppressed by O substitutions to sulfide solid electrolyte (LPSOBC), and then the chemo-mechanical stability of the all-solid battery was enhanced by alleviating the side reactions at the interface. This study provides rational insights into the design of an interface for all-solid-state batteries.

Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF–κB and STAT3 signaling pathways

Amlexanox is an anti-inflammatory and anti-allergic agent used clinically for the treatment of aphthous ulcers, allergic rhinitis, and asthma. Recent studies have demonstrated that amlexanox, a selective inhibitor of IkB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1), suppresses a range of diseases or inflammatory conditions, such as obesity-related metabolic dysfunction and type 2 diabetes. However, the effects of amlexanox on neuroinflammatory responses to amlexanox have not yet been comprehensively studied. In this study, we investigated the novel therapeutic effect of amlexanox on LPS-induced neuroinflammation in vivo, and intraperitoneal injection of amlexanox markedly reduced LPS-induced IKKε levels, proinflammatory cytokines, and microglial activation, as evidenced by ionized calcium-binding adapter molecule 1 (Iba1) immunostaining. Furthermore, amlexanox significantly reduced proinflammatory cytokines and chemokines in LPS-induced bone marrow-derived macrophages (BMDM), murine BV2, and human HMC3 microglial cells. This data provided considerable evidence that amlexanox can be used as a preventive and curative therapy for neuroinflammatory and neurodegenerative diseases. In terms of mechanism aspects, our results demonstrated that the anti-inflammatory action of amlexanox in BV2 microglial cells was through the downregulation of NF-κB and STAT3 signaling pathways. In addition, the combination of amlexanox and SPI (a STAT3 selective inhibitor) showed high efficiency in inhibiting the production of neurotoxic and pro-inflammatory mediators. Overall, our data provide rational insights into the mechanisms of amlexanox as a potential therapeutic strategy for neuroinflammation-related diseases.

Phase Evolution on the Hydrogen Adsorption Kinetics of NiFe-Based Heterogeneous Catalysts for Efficient Water Electrolysis.

Transition metal layered double hydroxides, especially nickel-iron layered double hydroxide (NiFe-LDH)shows significant advancement as efficient oxygen evolution reaction (OER) electrocatalyst but also plays a momentous role as a precursor for NiFe-based hydrogen evolution reaction (HER) catalysts. Herein, a simple strategy for developing Ni-Fe-derivative electrocatalysts via phase evolution of NiFe-LDH under controllable annealing temperatures in an argon atmosphere is reported. The optimized catalyst annealed at 340 o C (denoted NiO/FeNi3 ) exhibits superior HER properties with an ultralow overpotential of 16 mV@10mA cm-2 . Density functional theory simulation and in situ Raman analyses reveal that the excellent HER properties of the NiO/FeNi3 can be attributed to the strong electronic interaction at the interface of the metallic FeNi3 and semiconducting NiO, which optimizes the H2 Oand Hadsorption energies for efficient HER and OER catalytic processes. This work will provide rational insights into the subsequent development of related HER electrocatalysts and other corresponding compounds via LDH-based precursors.

Survey on natural language processing in medical image analysis.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.

Cerebral Malaria: Current Clinical and Immunological Aspects.

This review focuses on current clinical and immunological aspects of cerebral malaria induced by Plasmodium falciparum infection. Albeit many issues concerning the inflammatory responses remain unresolved and need further investigations, current knowledge of the underlying molecular mechanisms is highlighted. Furthermore, and in the light of significant limitations in preventative diagnosis and treatment of cerebral malaria, this review mainly discusses our understanding of immune mechanisms in the light of the most recent research findings. Remarkably, the newly proposed CD8+ T cell-driven pathophysiological aspects within the central nervous system are summarized, giving first rational insights into encouraging studies with immune-modulating adjunctive therapies that protect from symptomatic cerebral participation of Plasmodium falciparum infection.

Deciphering the molecular mechanisms of selective non-covalency demonstrated differentially by 9-Allylnaphtho[1,8-ef]isoindole-7,8,10(9H)-trione (C11) against fibroblast growth factor receptors 1–4

The specific inhibition of aberrant Fibroblast Growth Factor Receptors (FGFRs) has been identified as a feasible strategy to therapeutically ameliorate their respective carcinogenic involvements. High homology among these proteins has however limited efforts towards the discovery of selective small-molecule compounds due to undesirable effects elicited by pan-FGFR inhibitors. A recent study showed the selective activity of a new compound C11 which was >52 times more potent against FGFR1 than FGFR2 and FGFR3, and 4 times than FGFR4. This C11 selective non-covalency was investigated in this study using computational methods since it has remained unresolved. Structural findings revealed that C11 enhanced structural perturbations in FGFR1 with less prominent effects in other FGFRs. High deviations also characterized the C11-bound active pocket of FGFR1 with notable fluctuations across the constituent P-loop, αC helix, hinge region, catalytic, and activation loops. These induced motions were essential for optimal C11 motion an d positioning of its phenalenone ring and prop-2-en-l-yl moiety at the FGFR1 active pocket to interact stably and strongly with A564FGFR1, L484FGFR1, Y563FGFR1, and E562FGFR1 which as well had high energy contributions. C11 exhibited highly unstable binding in F GFRs2-3 with a more steady interaction with FGFR4. Free binding energy ( ΔGbind ) analyses further estimated the highest interaction energy for C11-FGFR1 with favorable desolvation energy that indicated a deep hydrophobic pocket binding for C11 in FGFR1 compared to other FGFRs. We believe rational insights from this study will contribute to the structure-based design of highly specific FGFR1 inhibitors. Communicated by Ramaswamy H. Sarma

Rheological stability of carbomer in hydroalcoholic gels: Influence of alcohol type.

Rheological stability of carbomer in hydroalcoholic gels: Influence of alcohol type.

Molecular Mechanism Exploration of Potent Fluorinated PI3K Inhibitors with a Triazine Scaffold: Unveiling the Unusual Synergistic Effect of Pyridine-to-Pyrimidine Ring Interconversion and CF3 Defluorination.

The phosphatidylinostitol-3-kinase (PI3K)/AKT/mammalian target of rapamycin signaling pathway is a vital regulator of cell proliferation, growth, and survival, which is frequently overactivated in many human cancers. To this effect, PI3K, which is an important mediator of this pathway, has been pinpointed as a crucial target in cancer therapy and hence the importance of PI3K inhibitors. It was recently reported that defluorination and pyridine-to-pyrimidine ring interconversion increase the potency of specific small-molecule inhibitors of PI3K. Compound 4, an inhibitor with the difluorinated pyrimidine motif, was found to be eight times more potent against PI3K than compound 1, an inhibitor with the trifluorinated pyridine motif. This observation presents the need to rationally resolve the differential inhibitory mechanisms exhibited by both compounds. In this present work, we employed multiple computational approaches to investigate and distinguish the binding modes of 1 and 4 in addition to the effects they mediate on the secondary structure of PI3K. Likewise, we evaluated two other derivatives, compounds 2 with the difluorinated pyridine motif and 3 with the trifluorinated pyrimidine motif, to investigate the cooperativity effect between the defluorination of CF3 and pyridine-to-pyrimidine ring interconversion. Findings revealed that PI3K, upon interaction with 4, exhibited a series of structural changes that favored the binding of the inhibitor at the active-site region. Furthermore, a positive (synergistic) cooperativity effect was observed between CF3 defluorination and pyridine-to-pyrimidine ring interconversion. Moreover, there was a good correlation between the binding free energy estimated and the biological activity reported experimentally. Energy decomposition analysis revealed that the major contributing force to binding affinity variations between 1 and 4 is the electrostatic energy. Per-residue energy-based hierarchical clustering analysis further identified four hot-spot residues ASP841, TYR867, ASP964, and LYS833 and four warm-spot residues ASP836, SER806, ASP837, and LYS808, which essentially mediate the optimal and higher-affinity binding of compound 4 to PI3K relative to 1. This study therefore provides rational insights into the mechanisms by which 4 exhibited superior PI3K-inhibitory activities over 1, which is vital for future structure-based drug discovery efforts in PI3K targeting.

Insights on the structure-function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies.

ATP‐binding cassette (ABC) transporters superfamily mediates multidrug resistance in cancer by extruding structurally distinct chemotherapeutic agents, causing failure in chemotherapy. Among the 49 ABC transporters, multidrug resistance protein 7 (MRP7 or ABCC10) is relatively new and has been identified as the efflux pump of multiple anticancer agents including Vinca alkaloids and taxanes. Herein, we construct and validate a homology model for human MRP7 based on the cryo‐EM structures of MRP1. Structure–function relationship of MRP7 was obtained from molecular dynamics simulations and docking studies and was in accordance with previous studies of ABC transporters. The motion patterns correlated with efflux mechanism were discussed. Additionally, predicted substrate‐ and modulator‐binding sites of MRP7 were described for the first time, which provided rational insights in understanding the drug binding and functional regulation in MRP7. Our findings will benefit the high‐throughput virtual screening and development of MRP7 modulators in the future.

20.8% Slot‐Die Coated MAPbI3 Perovskite Solar Cells by Optimal DMSO‐Content and Age of 2‐ME Based Precursor Inks

AbstractSolar cells incorporating metal‐halide perovskite (MHP) semiconductors are continuing to break efficiency records for solution‐processed solar cell devices. Scaling MHP‐based devices to larger area prototypes requires the development and optimization of scalable process technology and ink formulations that enable reproducible coating results. It is demonstrated that the power conversion efficiency (PCE) of small‐area methylammonium lead iodide (MAPbI3) devices, slot‐die coated from a 2‐methoxy‐ethanol (2‐ME) based ink with dimethyl‐sulfoxide (DMSO) used as an additive depends on the amount of DMSO and age of the ink formulation. When adding 12 mol% of DMSO, small‐area devices of high performance (20.8%) are achieved. The effect of DMSO content and age on the thin film morphology and device performance through in situ X‐ray diffraction and small‐angle X‐ray scattering experiments is rationalized. Adding a limited amount of DMSO prevents the formation of a crystalline intermediate phase related to MAPbI3 and 2‐ME (MAPbI3‐2‐ME) and induces the formation of the MAPbI3 perovskite phase. Higher DMSO content leads to the precipitation of the (DMSO)2MA2Pb3I8 intermediate phase that negatively affects the thin‐film morphology. These results demonstrate that rational insights into the ink composition and process control are critical to enable reproducible large‐scale manufacturing of MHP‐based devices for commercial applications.

The enhanced human vs. the virtuous human: a post-phenomenological perspective

The new generations of bioenhancement technologies and traditional Virtue Theory both try to make a meaningful connection between the improvement of human states and characteristics on one hand, and attainment to the good life, on the other. Considering the main elements of virtuousness in Farabi’s thought—namely rational inquiry and deliberative insights, alongside volitional discipline within various social contexts, one can conclude that although the trajectories of enhancement technologies—be they in the field of genetic engineering, neurostimulation technologies, or pharmacology—do not in themselves satisfy the constitutive determinants of virtuousness, they function as having both mediative and amplificative/reductive roles in a life which is dedicated to the pursuit of happiness in the light of the cultivation of virtue.

The impact of steel emissions on air quality and pollution control strategy in Caofeidian, North China

Pollutant emission from steel industries is an important source of air pollution in Beijing-Tianjin-Hebei region. Using WRF-FLEXPART atmospheric diffusion model, this paper simulated the pollutant diffusion processes of two steel industries from Oct. 2018 to Mar. 2019 in Caofeidian district, and then analysed the pollutant diffusion characteristics, the impacts of atmospheric circulation and local circulation on pollutants diffusion, the contribution of steel industry emissions on air quality nearby emission sources and air quality observation stations. According to the statistics, the emissions of particulate matter from Jingtang (JT)and Wenfeng (WF) steelworks are 669 and 69tonsduring the period of Oct. 2018–Mar. 2019, respectively. Under the influence of East Asian winter monsoon circulation, most of the pollutants emitted from JT and WF are diffused and transported to the Bohai Sea. The contribution of emissions from JT and WF on the concentration of particulate matter with aerodynamic diameters of less than 2.5(PM2.5) in Caofeidian is relatively small, with the daily maximums of local contribution rate on PM2.5 concentration from JT and WF reaching about 15% for both. Compared to the local contribution, the contribution rate in air quality observation stations is obviously lower, with the daily maximumsless than 2% and 5% for JT and WF respectively. It is significant that the pollutant diffusion and its contribution on air quality are affected by the large-scale atmospheric circulation and local sea-land breeze circulation, providing rational insights for policy makers to formulate control strategies.

Relational asymmetry, trust, and innovation in supply chain management: a non-linear approach

PurposeThe purpose of this paper is to examine the non-linear aspects of the asymmetry-performance relationship under varying conditions of trust and innovation. Its novel approach is useful for addressing the strategic elements of supply chain management (SCM) relationships based on trust and innovation decisions.Design/methodology/approachResults are based on a study of 90 managers from small- and medium-sized firms in Spain. Instead of a classical linear relationship analysis, the authors performed a non-linear analysis, using polynomial modeling and Warp 3 partial least squares method, which provides a more nuanced view of the data and constitutes an original approach to empirical research in SCM.FindingsThis study adds a new viewpoint on SC relationships by suggesting that not all trust and innovation development leads directly to performance improvement. The principal finding is, in varying trust and innovation contexts, that the influences of asymmetry on performance have uneven characteristics and follow non-linear paths.Research limitations/implicationsThis study focuses on only one particular institutional environment in one country. The data are also cross-sectional, which makes it difficult to empirically test causality.Practical implicationsThe findings provide rational insights to managers on when it is appropriate to reduce (or not) asymmetric relationships with partners.Originality/valueTrust and innovation are important and ones of the key requirements of supply chain relationships in any environment, this study argues that the interactions of key SCM elements that drive members to better performance are more complex and non-linear.

Can asymmetry impact performance, collaboration and integration? An empirical study

PurposeThe purpose of this paper is to examine the influence of asymmetric environments on collaboration, integration, and performance during supply chain management processes.Design/methodology/approachThe study conducted in the industrial sector of two markets – Spain and Poland – considering disparate behaviors among organizations and their managers. Using data collected from 133 firms and advanced partial least squares regression modeling, a number of direct and moderating effects are hypothesized and tested.FindingsThe authors found that existing asymmetry may prevent achievement of optimum equilibrium. Seven of the ten research hypotheses were validated, providing strong support for the significant role that asymmetry can play in managing supply chains (SCs). This result suggests that managers need to consider whether maximum collaboration or integration with SC partners is possible under the strong influence of asymmetry. The findings provide rational insights to SC managers regarding adequate measures to reduce imbalanced relationships and establish equilibrium between partners under varying contexts of collaboration and integration.Research limitations/implicationsThis study was conducted in only two countries, so generalizations are limited. Furthermore, there are improvements to be made in sample design to allow for further validation and enhancement of the model and method.Practical implicationsFindings provide rational insights to managers regarding when it is adequate to reduce imbalanced relationships with partners under varying contexts of collaboration and integration.Originality/valueCollaboration and integration have been well studied in many fields but this research suggests that managers in asymmetric environments must understand that development of strategies based on integration might be impossible to realize.

The Great Recession and real estate cycles – challenges, opportunities, and lessons learned

PurposeThe purpose of this paper is twofold: the authors initially survey a sample of literature published after the Great Recession that address macroeconomic and commercial real estate forecasting methods related to the Great Recession and compare significant lessons learned, or lack thereof. The authors then seek to identify new models to improve the predictability of commercial real estate early warning signals regarding cyclical turning points which result in negative appreciation rates.Design/methodology/approachThe authors develop a probit model to estimate quarterly probabilities of negative office appreciation returns using an alternative methodology to Tsolaco et al. (2014). The authors’ alternative method incorporates generally publicly available macroeconomic and real estate variables such as gross domestic product, office-related employment sectors, cap rate spreads, and commercial mortgage flow of funds into a probit model in order to estimate the probability of future quarterly negative office appreciation rates.FindingsThe authors’ models demonstrate the predictive power of macroeconomic variables typically associated with office demand. The probit model specification shows probabilities of negative office appreciations rates greater than 50 percent either as the quarterly office returns become negative, or in some cases several quarters before office returns become negative, for both the Great Recession and the recession occurring in the early 1990s. The models fail to show probabilities greater than 50 percent of negative office returns until after they occur for the recession in 2001. While this indicates need for further improvement in early warning models, the models do predict the more severe periods of negative office returns in advance, indicating the findings useful to real estate investors to monitor the changes in economic and real estate data identified as statistically significant in the results.Practical implicationsThe Great Recession is a unique laboratory of significant contractions, recessions, and recoveries that challenge pre-recessionary real estate cycle models. The models provide guidance on which historical economic indicators are important to track, and gives a framework with which to calculate the probability that office prices are likely to decline. Because the models use macroeconomic indicators that are publicly available from at least one quarter in the past, the models or variations of them may provide real estate professionals with some indication of an impending decrease in office prices, even if that indication comes only one quarter in advance. Armed with this information, property owners, investors, and brokers can make more informed decisions on whether to buy or sell, and how sensitive their real estate transactions may be to timing.Originality/valueThe authors introduce several new models that examine the ability of historical macroeconomic indicators to provide early warning signals and identify turning points in real estate valuations, specifically negative office appreciation rates caused by the Great Recession. Using data from at least one quarter in the past, all the data in the models are publicly available (excluding National Council of Real Estate Investment Fiduciaries data) at the observed return quarter being predicted, which gives practitioners rational insights that can provide at least one source of guidance about the likelihood of an impending decrease in office prices.

Graphene and functionalized graphene: Extraordinary prospects for nanobiocomposite materials

Abstract Graphene research, already prized, is nonetheless challenged to provide material advantages that bring about unique and novel applications rather than simply an improved substitute to existing materials. Arguably driving significant progress are new approaches to its manufacture including combination with other atoms and nanobiocomposite materials that introduce new functional properties. Functionalized graphene can interface with biomolecules to provide new health sector benefits in the form of highly sensitive biosensors that may offer continuous label-free measurement of key bioactive cell molecules, innovative nanoparticles for tissue targeted drug delivery and scaffolds for tissue engineering with previously unachievable qualities favouring tissue integration and biocompatibility. We here describe graphene functionalization methods and provide recent examples of how graphene can be used to achieve biological interactions with innovative outcomes. Above all, these laboratory focused advances each contribute to an incrementally improved understanding of how different forms of graphene and its derivatives can best be tailored to meet biological demands. Much has yet to be discovered with regard to safety profiles and improved manufacture yet considering how carefully derived rational insights might be combined with computational biology to accelerate complex performance models, prospects that graphene-based biomaterials can achieve extraordinary real-world benefits are optimistically poised.

Modernity, Community, and Place in Brian Friel’s Drama by Richard Rankin Russell (review)

Richard Rankin Russell. Modernity, Community, and Place in Brian Friel's Drama. Syracuse, NY: Syracuse University Press, 2014. Pp. xi + 317. $39.95. The concept encapsulated in term the is traditionally thought of in Ireland as an agricultural event signifying relationship between people and land, when at close of harvest season farming community would gather its crops, rejoice in fruits of hard labor, and mark moment that closes summer and enters autumn. That idea of gathering literally and conceptually frames Richard Rankin Russell's recent publication on Brian Friel's major plays, but, importantly, book approaches it in a wider sense to also suggest travel, machines, ritual, fertility, festival, community, family, and place. Brian Friel, arguably one of worlds greatest living English-language dramatists, continues to be researched, studied, and performed internationally, and Russell's book-length study of five of Friel's major plays is a welcome addition to ever-expanding studies. Language, community, exile, memory, place, ritual, violence, and individual and cultural identity are familiar concerns related to body of research on Friel's work, and Russell's book is not different in this regard. What it is, however, is a comprehensive study of place and space in five of Friel's critically acclaimed plays and impact these have on community. Acknowledging contributions of philosopher Rene Descartes, and drawing on phenomenologist Edward Casey's notion of place and its resistance to modernity, Russell takes his understanding of and as a movement pervading all areas of knowledge, where rational insights produced homogenous accounts of natural events and human experience over dogmatic tradition. This is Russell's third monograph on a Northern Irish writer (one on Bernard McLaverty in 2009 and another on Michael Longley in 2010), with a forthcoming one on Seamus Heaney in 2014. He has essays on Stewart Parker, Brendan Behan, and Friel, and two edited collections: on Martin McDonagh, published in 2007, and on Irish poet Peter Fallon, in 2013. Across his publications, his research reflects a strong interest in borders and boundaries, between inner and outer worlds, always moveable and forever fragile, which signal concerns with cultural erosion, loss, and displacement in various ways. Modernity, Community, and Place in Brian Friel's Drama contains five chapters, each dedicated to a major play: Philadelphia Here I Come!, The Freedom of City, Faith Healer, Translations, and Dancing at Lughnasa. Each chapter expands on author's identified elements of modernism in five plays and how they impact and relate to immediate and distant communities in their environments as well as to each other. What is most interesting, despite Russell's narrow modernist paradigm and his choice to represent Friel by writing on just five of his most popular works, is his discussion of how Friel assimilated aspects of modernity and modernism into environments in his works but did not fully accommodate them. Russell argues that onslaught of modernity is responded to both creatively and with great resistance in Friel's works, demonstrating how different versions of modernity coexist within Ireland's cultural landscape. However, author's examination of modernity does not offer a nuanced enough reading of developments of modernity and modernism as they swept through Europe, Britain, and Ireland at different speeds and with varying impact on countries and regions, to include a broad range of issues such as economies, nations, trade, citizenship, belief systems, capitalism, educational reforms, and so on. Thus, there is a repetitive feel to modernist trajectory and its bearing on concerns in plays throughout. Surprisingly, Henri Lefebvre's The Production of Space and Gay McAuley's Space in Performance, important books that connect real and imagined space in making meaning in theater, are not part of research. …

Rational design of 13C-labeling experiments for metabolic flux analysis in mammalian cells

Background13C-Metabolic flux analysis (13C-MFA) is a standard technique to probe cellular metabolism and elucidate in vivo metabolic fluxes. 13C-Tracer selection is an important step in conducting 13C-MFA, however, current methods are restricted to trial-and-error approaches, which commonly focus on an arbitrary subset of the tracer design space. To systematically probe the complete tracer design space, especially for complex systems such as mammalian cells, there is a pressing need for new rational approaches to identify optimal tracers.ResultsRecently, we introduced a new framework for optimal 13C-tracer design based on elementary metabolite units (EMU) decomposition, in which a measured metabolite is decomposed into a linear combination of so-called EMU basis vectors. In this contribution, we applied the EMU method to a realistic network model of mammalian metabolism with lactate as the measured metabolite. The method was used to select optimal tracers for two free fluxes in the system, the oxidative pentose phosphate pathway (oxPPP) flux and anaplerosis by pyruvate carboxylase (PC). Our approach was based on sensitivity analysis of EMU basis vector coefficients with respect to free fluxes. Through efficient grouping of coefficient sensitivities, simple tracer selection rules were derived for high-resolution quantification of the fluxes in the mammalian network model. The approach resulted in a significant reduction of the number of possible tracers and the feasible tracers were evaluated using numerical simulations. Two optimal, novel tracers were identified that have not been previously considered for 13C-MFA of mammalian cells, specifically [2,3,4,5,6-13C]glucose for elucidating oxPPP flux and [3,4-13C]glucose for elucidating PC flux. We demonstrate that 13C-glutamine tracers perform poorly in this system in comparison to the optimal glucose tracers.ConclusionsIn this work, we have demonstrated that optimal tracer design does not need to be a pure simulation-based trial-and-error process; rather, rational insights into tracer design can be gained through the application of the EMU basis vector methodology. Using this approach, rational labeling rules can be established a priori to guide the selection of optimal 13C-tracers for high-resolution flux elucidation in complex metabolic network models.

China und der Konfuzianismus - Einige Aspekte ihrer Rezeptionsgeschichte in Deutschland aus Anlass der Ehrenpromotion von Helmut Schmidt durch die Philipps-Universität Marburg

In February 2007 Helmut Schmidt, the former German Chancellor, received an honorary doctorate at Marburg University. To mark the occasion he gave a lecture entitled Responsibility and Conscience of the Politician in which he emphasized the importance of a system of morals and values based only on rational insights, and not on religious faith. Schmidt argues that Confucianism is a kind of philosophy which is grounded, not in religion, but in rational deliberations, and that it is therefore nowadays of high interest in a world of growing religious conflicts. The present article shows that this reception of Confucianism has a long tradition in the European, and especially the German history of philosophy. It started with Mateo Ricci, a Jesuit missionary to China at the end of the 16 th century, and reached its peak during the early Enlightenment movement with Leibniz and Wolf. After a long period of decreasing interest in Confucianism, the formation of the science of religions, sinology and sociology as academic disciplines led to a new interest in research on Confucianism and its religious roots. Max Weber’s studies on Daoism and Confucianism were more sophisticated, and open to the complexity of Chinese traditions. Schmidt’s interpretation of Confucianism as a practical philosophy represents a tradition which has not come to its end. It is the critical view of religions in general which lies behind the image of Confucianism as a rational philosophy without any religious basis, and taken in this way, it is a very Eurocentric view of an important Asian tradition.

Folk Psychology and the Psychological Background of Scientific Reasoning

Folk Psychology and the Psychological Background of Scientific Reasoning Harald Walach (bio) Keywords theory of psychology, theory of science, psychology of science, mind-body problem, folk psychology, scientific world view Some protagonists of science who are still married to a positivist model of how science functions see science as the pure pursuit of knowledge, free of any preconceptions, free of any personal interest, yielding clear and ideally everlasting truths beckoning humanity over from a superstition ridden dark age of beliefs and would-be knowledge toward the dawn of rational insights that allow for the bettering of mankind’s problems. Scientists have followed such an implicit model since Francis Bacon’s Novum Organon, and the most recent reverberations we hear in popular science books like The God Delusion by Dawkins (2006) or in more scientific ones on how an eliminative materialist account of mental events such as Patricia Churchland’s might work (Churchland 1986). Here, it is explicitly stated that our folk-psychological accounts such as “I love Emma,” or “I have a nasty back ache” is nothing but sloppy speaking and will soon be replaced by a more scientific account, once we know the interior workings of our brains, such as “Neuron assembly xyz in my nucleus abc in brain areas efg is firing” or “Fast A1 fibers are transmitting stimuli from my lumbar region to the brain, where they override endorphin- and enkephalin-mediated inhibiting pathways, enabling the pain network to go crazy.” It has been more than twenty years now since the publication of that somewhat futuristic account, and a whole decade of the brain and countless papers have taught us that we are very far, in fact light years away, from such knowledge as eliminative and even less eliminative materialists would have us gained by now, or in another twenty years from now. Folk psychology is well and alive, and even more vital than ever, it seems. People go about having their beliefs and ideas about God, the mind, the soul, the world, and human beings in general just as well, eliminative materialists and neuroscience notwithstanding. The data presented by Fahrenberg speak a clear language: Students of different disciplines, but most prominently psychology students, adhere mostly to a dualist—ontological or methodological—world view that allows for some substantiality of consciousness. They suppose that some transcendent reality is active and about, they assume that paranormal events such as spiritual and distant healing can [End Page 209] happen, that telepathy is an option, to name but the more prominent statements to be gleaned by Fahrenberg’s tables. Sure, these are students at the beginning of their career, as they come from school, some of them in their second year, some of them mature after having done some other training. They have had contact with the scientific world view mostly through their schooling and private reading, and, of course, through our folk culture. It would be extremely interesting to see a longitudinal study, surveying the same students after four years of studies. Will they then be more conformist with the mainstream scientific notion? Will they then have changed their initial belief systems? Will they have integrated and absorbed the knowledge they were taught into their private lives and worldviews, or will they have kept them apart from each other? We do not have the answer to these questions, and surely, a next step would be to follow a cohort of students, albeit small, through their journey as they progress. Meanwhile, we can all take ourselves as an example to follow this thought along as a gedan-kenexperiment. Did we allow the knowledge we absorbed from studying to permeate our whole private life? How did we deal with any cognitive dissonance arising from information coming out of our studies conflicting with our private belief systems? Did we throw away our personal beliefs or did we organize our lives in two compartments, one for our private life, and one for our scientific knowledge? Fahrenberg’s data are unique in the sense that nobody bothers about folk psychology, and these data are the only ones that actually tap into the belief systems of those that will become scientists, teachers, therapists and trainers...