New physical insights into the supporting subspace factorization of XMS-CASPT2 and generalization to multiple spin states via spin-free formulation

This paper introduces a spin-free formulation of the supporting subspace factorization [C. Song and T. J. Martínez, J. Chem. Phys. 149, 044108 (2018)], enabling a reduction in the computational scaling of the extended multi-state complete active space second-order perturbation (XMS-CASPT2) method for arbitrary spins. Compared to the original formulation that is defined in the spin orbitals and is limited to singlet states, the spin-free formulation in this work treats different spin states equivalently, thus naturally generalizing the idea beyond singlet states. In addition, we will present a new way of deriving the supporting subspace factorization with the purpose of understanding its physical interpretation. In this new derivation, we separate the sources that make CASPT2 difficult into the "same-site interactions" and "inter-site interactions." We will first show how the Kronecker sum can be used to remove the same-site interactions in the absence of inter-site interactions, leading to MP2 energy in dressed orbitals. We will then show how the inter-site interactions can be exactly recovered using Löwdin partition, where the supporting subspace concept will naturally arise. The new spin-free formulation maintains the main advantage of the supporting subspace factorization, i.e., allowing XMS-CASPT2 energies to be computed using highly optimized MP2 energy codes and Fock build codes, thus reducing the scaling of XMS-CASPT2 to the same scaling as MP2. We will present and discuss results that benchmark the accuracy and performance of the new method. To demonstrate how the new method can be useful in studying real photochemical systems, the supporting subspace XMS-CASPT2 is applied to a photoreaction sensitive to magnetic field effects. The new spin-free formulation makes it possible to calculate the doublet and quartet states required in this particular photoreaction mechanism

Severing telicity from result

This paper investigates the peculiar behaviors of resultative compound verbs in Dongying Mandarin, a previously unstudied Mandarin Chinese variety. Data from multiple syntactic contexts (e.g. completive, negation, future/irrealis, potential) show that resultative complements in this variety fall in two contrasting categories: atelic and telic. Atelic resultatives have full lexical tones and require a grammati- calized telic marker (liu) in various [+TELIC] contexts, whereas telic resultatives assume the neutral tone and prohibit liu in the same contexts. The theoretical dis- cussion begins with an evaluation of two neo-constructionist approaches, featuring event decomposition and Inner Aspect, and ends with a middle-way model combin- ing and adapting the two. The main proposal is that in Dongying Mandarin, telicity is not encoded in the resultative complement itself, but in a Low Inner Aspect position between the action and the result verbs, which turns the state denoted by the resultative complement into a telos of the complex event. I derive the surface compound verb via the Defective Goal theory (Roberts 2010) and analyze the tonal variation as Root allomorphy

Bond-Order Time Series Analysis for Detecting Reaction Events in Ab Initio Molecular Dynamics Simulations.

Ab initio molecular dynamics is able to predict novel reaction mechanisms by directly observing the individual reaction events that occur in simulation trajectories. In this article, we describe an approach for detecting reaction events from simulation trajectories using a physically motivated model based on time series analysis of ab initio bond orders. We found that applying a threshold to the bond order was insufficient for accurate detection, whereas peak finding on the first time derivative resulted in significantly improved accuracy. The model is trained on a reference set of reaction events representing the ideal result given unlimited computing resources. Our study includes two model systems: a heptanylium carbocation that undergoes hydride shifts and an unsaturated iron carbonyl cluster that features CO ligand migration and bridging behavior. The results indicate a high level of promise for this analysis approach to be used in mechanistic analysis of reactive AIMD simulations more generally

A Polarizable QM/MM Model That Combines the State-Averaged CASSCF and AMOEBA Force Field for Photoreactions in Proteins

This study presents the polarizable quantum mechanics/molecular mechanics (QM/MM) embedding of the state-averaged complete active space self-consistent field (SA-CASSCF) in the atomic multipole optimized energetics for biomolecular applications (AMOEBA) force field for the purpose of studying photoreactions in protein environments. We describe two extensions of our previous work that combine SA-CASSCF with AMOEBA water models, allowing it to be generalized to AMOEBA models for proteins and other macromolecules. First, we discuss how our QM/MM model accounts for the discrepancy between the direct and polarization electric fields that arises in the AMOEBA description of intramolecular polarization. A second improvement is the incorporation of link atom schemes to treat instances in which the QM/MM boundary goes through covalent bonds. A single-link atom scheme and double-link atom scheme are considered in this work, and we will discuss how electrostatic interaction, van der Waals interaction, and various kinds of valence terms are treated across the boundary. To test the accuracy of the link atom scheme, we will compare QM/MM with full QM calculations and study how the errors in ground state properties, excited state properties, and excitation energies change when tuning the parameters in the link atom scheme. We will also test the new SA-CASSCF/AMOEBA method on an elementary reaction step in NanoLuc, an artificial bioluminescence luciferase. We will show how the reaction mechanism is different when calculated in the gas phase, in polarizable continuum medium (PCM), versus in protein AMOEBA models

On the Formal Flexibility of Syntactic Categories

This dissertation explores the formal flexibility of syntactic categories. The main proposal is that Universal Grammar (UG) only provides templatic guidance for syntactic category formation and organization but leaves many other issues open, including issues internal to a single category and issues at the intercategorial, system level: these points that UG "does not care about" turn out to enrich the categorial ontology of human language in important ways. The dissertation consists of seven chapters. After a general introduction in Chapter 1, I lay out some foundational issues regarding features and categories in Chapter 2 and delineate a featural metalanguage comprising four components: specification, valuation, typing, and granularity. Based on that I put forward a templatic definition for syntactic categories, which unifies the combinatorial and taxonomic perspectives under the notion mergeme. Then, a detailed overview of the "categorial universe" I work with is presented, which shows that the syntactic category system (SCS) is an intricate web structured by five layers of abstraction divided into three broad levels of concern: the individual level (layers 1–2), the global level (layers 3–4), and the supraglobal level (layer 5). In the subsequent chapters I explore the template-flexibility pairs at each abstraction layer, with Chapters 3–4 focusing on the first layer, Chapter 5 on the second layer, and Chapter 6 on the third and fourth layers; the fifth layer is not in the scope of this dissertation. Chapter 3 examines a special type of category defined by an underspecified mergeme, the defective category, which behaves like a "chameleon" in that it gets assimilated into whatever nondefective category it merges with. This characteristic makes it potentially useful in analyzing certain adjunction structures, and I explore this potential by two case studies, one focusing on modifier-head compounds and the other on sentence-final particles. Chapter 4 examines another special type of category defined by the absence of a mergeme, the Root category. Deductive reasoning leads me to propose a generalized root syntax, according to which roots are not confined to lexical categorial environments but may legally merge with and hence "support" any non-Root category. I demonstrate the empirical consequences of this theory by a comprehensive study of the half-lexical–half-functional vocabulary items in Chinese. Chapter 5 ascends to the second abstraction layer and raises the question of whether the categorial sequences (or projection hierarchies) in human language are necessarily totally ordered, as certain analytical devices (e.g., "flavored" categories) can only be theoretically maintained if we also allow categorial sequences to be partially ordered. After a diachronic study of the flavored verbalizer $v_{BE}$ (stative) in Chinese resultative compounds, I conclude that while "flavoring" is indeed a possible type of flexibility in the SCS, it is the deviation rather than the norm due to non-UG or "third" factors and hence should be cautiously used in syntactic analyses. Chapter 6 ascends even higher on the ladder of abstraction and examines the global interconnection in the SCS ontology with the aid of mathematical Category theory. I formalize the functional parallelism across major parts of speech and the inheritance-based relations across granularity levels as Category-theoretic structures, which reveal further and more abstract templates and flexibility types in the SCS. A crucial mathematical concept in the formalization is epi-Adjunction. Finally, in Chapter 7 I summarize the main results of this dissertation and briefly discuss some potential directions of future research.My PhD is funded by Cambridge Trust and China Scholarship Council. I have also received travel grants and financial aids from Gonville and Caius College and the Faculty of Modern and Medieval Languages

From text to effectiveness:Quantifying green industrial policies in China

The evolution of green industrial policy in China is deeply embedded within a unique political, economic, cultural, and social milieu. The intricacies and complexities inherent in this context present challenges for quantitative policy research. In the existing literature, the study of thematic clustering of green industry policy instruments and their effectiveness measures in large-scale policy text repositories remains a relatively unexplored area. To fill this research gap, this study provides an analysis of China's green industrial policies from 1994 to 2022. By adopting the Latent Dirichlet Allocation (LDA) topic model, implicit and optimal themes are identified, and key policy instruments are systematically and comprehensively parsed. Based on this, the cutting-edge Policy Modeling Consistency-Text Encoder (PMC-TE) index model was used to conduct an in-depth quantitative evaluation of various policy tools. The findings reveal 15 policy instruments from 7891 Chinese green industry policy documents. Notably, technical support, information resource demonstration project policies emerged as the most frequently deployed and efficacious. Conversely, government procurement and service outsourcing policies, while showing incremental growth year-on-year, lagged in utilization and effectiveness. These policy instruments can be broadly categorized into three primary archetypes: supply-type, demand-type, and environment-type. The supply-type instruments dominate, while environment-type instruments remain underutilized. Additionally, this study delineates the four chronological phases of China's green industrial policy evolution, illuminating China's strategic pivots-transitioning from resource allocation, to market dynamics, and ultimately to environmental governance trajectories

Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation

Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca2+-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain

Cost-Effective Incentive Allocation via Structured Counterfactual Inference

We address a practical problem ubiquitous in modern marketing campaigns, in which a central agent tries to learn a policy for allocating strategic financial incentives to customers and observes only bandit feedback. In contrast to traditional policy optimization frameworks, we take into account the additional reward structure and budget constraints common in this setting, and develop a new two-step method for solving this constrained counterfactual policy optimization problem. Our method first casts the reward estimation problem as a domain adaptation problem with supplementary structure, and then subsequently uses the estimators for optimizing the policy with constraints. We also establish theoretical error bounds for our estimation procedure and we empirically show that the approach leads to significant improvement on both synthetic and real datasets

Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models

Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX