22,857 research outputs found

    Sensitivity analysis for ReaxFF reparameterization using the Hilbert-Schmidt independence criterion

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    We apply a global sensitivity method, the Hilbert-Schmidt independence criterion (HSIC), to the reparameterization of a Zn/S/H ReaxFF force field to identify the most appropriate parameters for reparameterization. Parameter selection remains a challenge in this context as high dimensional optimizations are prone to overfitting and take a long time, but selecting too few parameters leads to poor quality force fields. We show that the HSIC correctly and quickly identifies the most sensitive parameters, and that optimizations done using a small number of sensitive parameters outperform those done using a higher dimensional reasonable-user parameter selection. Optimizations using only sensitive parameters: 1) converge faster, 2) have loss values comparable to those found with the naive selection, 3) have similar accuracy in validation tests, and 4) do not suffer from problems of overfitting. We demonstrate that an HSIC global sensitivity is a cheap optimization pre-processing step that has both qualitative and quantitative benefits which can substantially simplify and speedup ReaxFF reparameterizations.Comment: author accepted manuscrip

    Corporate Social Responsibility: the institutionalization of ESG

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    Understanding the impact of Corporate Social Responsibility (CSR) on firm performance as it relates to industries reliant on technological innovation is a complex and perpetually evolving challenge. To thoroughly investigate this topic, this dissertation will adopt an economics-based structure to address three primary hypotheses. This structure allows for each hypothesis to essentially be a standalone empirical paper, unified by an overall analysis of the nature of impact that ESG has on firm performance. The first hypothesis explores the evolution of CSR to the modern quantified iteration of ESG has led to the institutionalization and standardization of the CSR concept. The second hypothesis fills gaps in existing literature testing the relationship between firm performance and ESG by finding that the relationship is significantly positive in long-term, strategic metrics (ROA and ROIC) and that there is no correlation in short-term metrics (ROE and ROS). Finally, the third hypothesis states that if a firm has a long-term strategic ESG plan, as proxied by the publication of CSR reports, then it is more resilience to damage from controversies. This is supported by the finding that pro-ESG firms consistently fared better than their counterparts in both financial and ESG performance, even in the event of a controversy. However, firms with consistent reporting are also held to a higher standard than their nonreporting peers, suggesting a higher risk and higher reward dynamic. These findings support the theory of good management, in that long-term strategic planning is both immediately economically beneficial and serves as a means of risk management and social impact mitigation. Overall, this contributes to the literature by fillings gaps in the nature of impact that ESG has on firm performance, particularly from a management perspective

    Examples of works to practice staccato technique in clarinet instrument

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    Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır. Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur. Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir. Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır. Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır

    Metabolomics-based discovery of XHP as a CYP3A4 inhibitor against pancreatic cancer

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    Background: Xihuang Wan (XHW), a purgative and detoxifying agent, is commonly utilized in modern medicine as a treatment and adjuvant therapy for various malignancies, including breast cancer, liver cancer, and lung cancer. A clinical study demonstrated the potential usefulness of the combination of XHW and gemcitabine as a therapy for pancreatic cancer (PC), indicating that XHW’s broad-spectrum antitumor herbal combination could be beneficial in the treatment of PC. However, the precise therapeutic efficacy of XHW in treating pancreatic cancer remains uncertain.Aim: This study assessed the biological activity of XHW by optimizing the therapeutic concentration of XHW (Xihuang pills, XHP). We performed cell culture and developed an animal test model to determine whether XHP can inhibit pancreatic cancer (PC). We also applied the well-known widely targeted metabolomics analysis and conducted specific experiments to assess the feasibility of our method in PC therapy.Materials and Methods: We used UPLC/Q-TOF-MS to test XHP values to set up therapeutic concentrations for the in vivo test model. SW1990 pancreatic cancer cells were cultured to check the effect the anti-cancer effects of XHP by general in vitro cell analyses including CCK-8, Hoechst 33258, and flow cytometry. To develop the animal model, a solid tumor was subcutaneously formed on a mouse model of PC and assessed by immunohistochemistry and TUNEL apoptosis assay. We also applied the widely targeted metabolomics method following Western blot and RT-PCR to evaluate multiple metabolites to check the therapeutic effect of XHP in our cancer test model.Results: Quantified analysis from UPLC/Q-TOF-MS showed the presence of the following components of XHP: 11-carbonyl-β-acetyl-boswellic acid (AKBA), 11-carbonyl-β-boswellic acid (KBA), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo [5.2.0]nonane, and (1S-endo)-2-methyl-3-methylene-2-(4-methyl-3-3-pentenyl)-bicyclo [2.2.1heptane]. The results of the cell culture experiments demonstrated that XHP suppressed the growth of SW1990 PC cells by enhancing apoptosis. The results of the animal model tests also indicated the suppression effect of XHP on tumor growth. Furthermore, the result of the widely targeted metabolomics analysis showed that the steroid hormone biosynthesis metabolic pathway was a critical factor in the anti-PC effect of XHP in the animal model. Moreover, Western blot and RT-PCR analyses revealed XHP downregulated CYP3A4 expression as an applicable targeted therapeutic approach.Conclusion: The results of this study demonstrated the potential of XHP in therapeutic applications in PC. Moreover, the widely targeted metabolomics method revealed CYP3A4 is a potential therapeutic target of XHP in PC control. These findings provide a high level of confidence that XHP significantly acts as a CYP3A4 inhibitor in anti-cancer therapeutic applications

    Machine learning for discovering laws of nature

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    A microscopic particle obeys the principles of quantum mechanics -- so where is the sharp boundary between the macroscopic and microscopic worlds? It was this "interpretation problem" that prompted Schr\"odinger to propose his famous thought experiment (a cat that is simultaneously both dead and alive) and sparked a great debate about the quantum measurement problem, and there is still no satisfactory answer yet. This is precisely the inadequacy of rigorous mathematical models in describing the laws of nature. We propose a computational model to describe and understand the laws of nature based on Darwin's natural selection. In fact, whether it's a macro particle, a micro electron or a security, they can all be considered as an entity, the change of this entity over time can be described by a data series composed of states and values. An observer can learn from this data series to construct theories (usually consisting of functions and differential equations). We don't model with the usual functions or differential equations, but with a state Decision Tree (determines the state of an entity) and a value Function Tree (determines the distance between two points of an entity). A state Decision Tree and a value Function Tree together can reconstruct an entity's trajectory and make predictions about its future trajectory. Our proposed algorithmic model discovers laws of nature by only learning observed historical data (sequential measurement of observables) based on maximizing the observer's expected value. There is no differential equation in our model; our model has an emphasis on machine learning, where the observer builds up his/her experience by being rewarded or punished for each decision he/she makes, and eventually leads to rediscovering Newton's law, the Born rule (quantum mechanics) and the efficient market hypothesis (financial market)

    Exploring Potential Domains of Agroecological Transformation in the United States

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    There is now substantial evidence that agroecology constitutes a necessary pathway towards socially just and ecologically resilient agrifood systems. In the United States, however, agroecology remains relegated to the margins of research and policy spaces. This dissertation explores three potential domains of agroecological transformation in the US. Domains of transformation are sites of contestation in which agroecology interfaces with the industrial agrifood system; these material and conceptual spaces may point to important pathways for scaling agroecology. To explore this concept, I examine formal agroecology education (Chapter 1), extension services and statewide discourses around soil health (Chapter 2), and models of farmland access not based on private property (Chapter 3). While these constitute three distinct topics, I seek to demonstrate that they are linked by similar forces that enable and constrain the extent to which these domains can be sites of agroecological transformation. First, I use case study methodology to explore the evolution of an advanced undergraduate agroecology course at the University of Vermont. I examine how course content and pedagogy align with a transformative framing of agroecology as inherently transdisciplinary, participatory, action-oriented, and political. I find that student-centered pedagogies and experiential education on farms successfully promote transformative learning whereby students shift their understanding of agrifood systems and their role(s) within them. In my second chapter, I zoom out to consider soil health discourses amongst farmers and extension professionals in Vermont. Using co-created mental models and participatory analysis, I find that a singular notion of soil health based on biological, chemical, and physical properties fails to capture the diverse ways in which farmers and extension professionals understand soil health. I advocate for a principles-based approach to soil health that includes social factors and may provide a valuable heuristic for mobilizing knowledge towards agroecology transition pathways. My third chapter, conducted in collaboration with the national non-profit organization Agrarian Trust, considers equitable farmland access. Through semi-structured interviews with 13 farmers and growers across the US, I explore both farmer motivations for engaging with alternative land access models (ALAMs) and the potential role(s) these models may play within broader transformation processes. I argue that ALAMs constitute material and conceptual ‘third spaces’ within which the private property regime is challenged and new identities and language around land ownership can emerge; as such, ALAMs may facilitate a (re)imagining of land-based social-ecological relationships. I conclude the dissertation by identifying conceptual and practical linkages across the domains explored in Chapters 1-3. I pay particular attention to processes that challenge neoliberal logics, enact plural ways of knowing, and prefigure just futures. In considering these concepts, I apply an expansive notion of pedagogy to explore how processes of teaching and (un)learning can contribute to cultivating foundational capacities for transition processes

    A Decision Support System for Economic Viability and Environmental Impact Assessment of Vertical Farms

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    Vertical farming (VF) is the practice of growing crops or animals using the vertical dimension via multi-tier racks or vertically inclined surfaces. In this thesis, I focus on the emerging industry of plant-specific VF. Vertical plant farming (VPF) is a promising and relatively novel practice that can be conducted in buildings with environmental control and artificial lighting. However, the nascent sector has experienced challenges in economic viability, standardisation, and environmental sustainability. Practitioners and academics call for a comprehensive financial analysis of VPF, but efforts are stifled by a lack of valid and available data. A review of economic estimation and horticultural software identifies a need for a decision support system (DSS) that facilitates risk-empowered business planning for vertical farmers. This thesis proposes an open-source DSS framework to evaluate business sustainability through financial risk and environmental impact assessments. Data from the literature, alongside lessons learned from industry practitioners, would be centralised in the proposed DSS using imprecise data techniques. These techniques have been applied in engineering but are seldom used in financial forecasting. This could benefit complex sectors which only have scarce data to predict business viability. To begin the execution of the DSS framework, VPF practitioners were interviewed using a mixed-methods approach. Learnings from over 19 shuttered and operational VPF projects provide insights into the barriers inhibiting scalability and identifying risks to form a risk taxonomy. Labour was the most commonly reported top challenge. Therefore, research was conducted to explore lean principles to improve productivity. A probabilistic model representing a spectrum of variables and their associated uncertainty was built according to the DSS framework to evaluate the financial risk for VF projects. This enabled flexible computation without precise production or financial data to improve economic estimation accuracy. The model assessed two VPF cases (one in the UK and another in Japan), demonstrating the first risk and uncertainty quantification of VPF business models in the literature. The results highlighted measures to improve economic viability and the viability of the UK and Japan case. The environmental impact assessment model was developed, allowing VPF operators to evaluate their carbon footprint compared to traditional agriculture using life-cycle assessment. I explore strategies for net-zero carbon production through sensitivity analysis. Renewable energies, especially solar, geothermal, and tidal power, show promise for reducing the carbon emissions of indoor VPF. Results show that renewably-powered VPF can reduce carbon emissions compared to field-based agriculture when considering the land-use change. The drivers for DSS adoption have been researched, showing a pathway of compliance and design thinking to overcome the ‘problem of implementation’ and enable commercialisation. Further work is suggested to standardise VF equipment, collect benchmarking data, and characterise risks. This work will reduce risk and uncertainty and accelerate the sector’s emergence

    A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues

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    In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing. Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency. Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms
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