Building a Structural Model: Parameterization and Structurality

A specific concept of structural model is used as a background for discussing the structurality of its parameterization. Conditions for a structural model to be also causal are examined. Difficulties and pitfalls arising from the parameterization are analyzed. In particular, pitfalls when considering alternative parameterizations of a same model are shown to have lead to ungrounded conclusions in the literature. Discussion of observationally equivalent models related to different economic mechanisms are used to make clear the connection between an economicall meaningful parameterization and an economically meaningful decomposition of a complex model. The design of economic policy is used for drawing some practical implications of the proposed analysis

Causality in Econometric Modeling. From Theory to Structural Causal Modeling

This paper examines different approaches for assessing causality as typically followed in econometrics and proposes a constructive perspective for improving statistical models elaborated in view of causal analysis. Without attempting to be exhaustive, this paper examines some of these approaches. Traditional structural modeling is first discussed. A distinction is then drawn between model-based and design-based approaches. Some more recent developments are examined next, namely history-friendly simulation and information-theory based approaches. Finally, in a constructive perspective, structural causal modeling (SCM) is presented, based on the concepts of mechanism and sub-mechanisms, and of recursive decomposition of the joint distribution of variables. This modeling strategy endeavors at representing the structure of the underlying data generating process. It operationalizes the concept of causation through the ordering and role-function of the variables in each of the intelligible sub-mechanisms

Time and Causality in the Social Sciences

This article deals with the role of time in causal models in the social sciences, in particular in structural causal modeling, in contrast to time-free models. The aim is to underline the importance of time-sensitive causal models. For this purpose, it also refers to the important discussion on time and causality in the philosophy of science, and examines how time is taken into account in demography and in economics as examples of social sciences. Temporal information is useful to the extent that it is placed in a correct causal structure, and thus further corroborating the causal mechanism or generative process explaining the phenomenon under consideration. Despite the fact that the causal ordering of variables is more relevant for explanatory purposes than the temporal order, the former should nevertheless take into account the time-patterns of causes and effects, as these are often episodes rather than single events. For this reason in particular, it is time to put time at the core of our causal models

Metabolism and hydrophilicity of the polarised 'Janus face' all-cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery

This work was supported by the Initial Training Network, FLUOR21, funded by the FP7 Marie Curie Actions of the European Commission (FP7-PEOPLE-2013-ITN-607787). JM is supported by a University Research Fellowship from the Royal Society. The research leading to these results has received funding from the European Research Council under the EU 7th Framework Programme (FP7/2007-2013)/ERC No 336289.The metabolism and polarity of the all-cis tetra-fluorocyclohexane motif is explored in the context of its potential as a motif for inclusion in drug discovery programmes. Biotransformations of phenyl all-cis tetra-, tri- and di- fluoro cyclohexanes with the human metabolism model organism Cunninghamella elegans illustrates various hydroxylated products, but limited to benzylic hydroxylation for the phenyl all-cis tetrafluorocyclohexyl ring system. Evaluation of the lipophilicities (Log P) indicate a significant and progressive increase in polarity with increasing fluorination on the cyclohexane ring system. Molecular dynamics simulations indicate that water associates much more closely with the hydrogen face of these Janus face cyclohexyl rings than the fluorine face owing to enhanced hydrogen bonding interactions with the polarised hydrogens and water.Publisher PDFPeer reviewe

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities

Molecular dynamics simulation of humic substances

© 2014, Orsi. Humic substances (HS) are complex mixtures of natural organic material which are found almost everywhere in the environment, and particularly in soils, sediments, and natural water. HS play key roles in many processes of paramount importance, such as plant growth, carbon storage, and the fate of contaminants in the environment. While most of the research on HS has been traditionally carried out by conventional experimental approaches, over the past 20 years complementary investigations have emerged from the application of computer modeling and simulation techniques. This paper reviews the literature regarding computational studies of HS, with a specific focus on molecular dynamics simulations. Significant achievements, outstanding issues, and future prospects are summarized and discussed

Current and emerging opportunities for molecular simulations in structure-based drug design

An overview of the current capabilities and limitations of molecular simulation of biomolecular complexes in the context of computer-aided drug design is provided. Steady improvements in computer hardware coupled with more refined representations of energetics are leading to a new appreciation of the driving forces of molecular recognition. Molecular simulations are poised to more frequently guide the interpretation of biophysical measurements of biomolecular complexes. Ligand design strategies emerge from detailed analyses of computed structural ensembles. The feasibility of routine applications to ligand optimization problems hinges upon successful extensive large scale validation studies and the development of protocols to intelligently automate computations

Variability of the Ross Gyre, Southern Ocean: Drivers and responses revealed by satellite altimetry

Year-round variability in the Ross Gyre (RG), Antarctica, during 2011–2015, is derived using radar altimetry. The RG is characterized by a bounded recirculating component and a westward throughflow to the south. Two modes of variability of the sea surface height and ocean surface stress curl are revealed. The first represents a large-scale sea surface height change forced by the Antarctic Oscillation. The second represents semiannual variability in gyre area and strength, driven by fluctuations in sea level pressure associated with the Amundsen Sea Low. Variability in the throughflow is also linked to the Amundsen Sea Low. An adequate description of the oceanic circulation is achieved only when sea ice drag is accounted for in the ocean surface stress. The drivers of RG variability elucidated here have significant implications for our understanding of the oceanic forcing of Antarctic Ice Sheet melting and for the downstream propagation of its ocean freshening footprint

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio