Combining Cloud-Based Free Energy Calculations, Synthetically Aware Enumerations and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization

**space**can be extended to the hit-to-lead process. In this work, we augment that approach by coupling large scale enumeration and cloud-based FEP profiling with goal-directed generative machine learning, which results in a higher enrichment of potent ideas compared to large scale enumeration alone, while simultaneously staying within the bounds of a predefined drug-like property

**space**. We are able to achieve this by building the molecular distribution for generative machine learning from the PathFinder rules-based enumeration and optimizing for a weighted sum QSAR based multi-parameter optimization function. We examine the utility of this combined approach by designing potent inhibitors of cyclin-dependent kinase 2 (CDK2) and demonstrate a coupled workflow that can: (1) provide a 6.4 fold enrichment improvement in identifying < 10nM compounds over random selection, and a 1.5 fold enrichment in identifying < 10nM compounds over our previous method (2) rapidly explore relevant chemical

**space**outside the bounds of commercial reagents, (3) use generative ML approaches to “learn” the SAR from large scale in silico enumerations and generate novel idea molecules for a flexible receptor site that are both potent and within relevant physicochemical

**space**and (4) produce over 3,000,000 idea molecules and run 2153 FEP simulations, identifying 69 ideas with a predicted IC50 < 10nM and 358 ideas with a predicted IC50

5/10 relevant

chemRxiv

Stocktaking the environmental coverage of a continental ecosystem observation network

**space**(Tukey HSD of mean dispersion, p .001). Expand abstract.

**space**represented via multi-dimensional scaling). Ausplots outperformed systematic grid, simple random and GRTS in coverage of environmental

**space**(Tukey HSD of mean dispersion, p .001). GRTS site selection obtained similar coverage to Ausplots when employing the same bioregional stratification. Stratification by climatic zones generated the highest environmental coverage (p .001), but the resulting sampling densities over-represented mesic coastal habitats. The Ausplots stratification by bioregions implemented under practical constraints represented complex environments well compared to statistically oriented or spatially even samples. However, potential statistical inference and power also depend on spatial and temporal replication, unbiased site selection, and accurate field measurements relative to the magnitude of change. A key conclusion is that environmental, rather than spatial, stratification is required to maximise ecological coverage across continental ecosystem observation networks.

4/10 relevant

bioRxiv

Advocating for Transgender and Non-Binary Affirmative **Spaces** in Graduate Education

5/10 relevant

PsyArXiv

The Cerebral Cortex Realizes a Universal Probabilistic Model of Computation in Complex Hilbert **Spaces**

**spaces**; second, normalization is a canonical neural computation, specifically,... Expand abstract.

5/10 relevant

PsyArXiv

Is Aligning Embedding **Spaces** a Challenging Task? An Analysis of the
Existing Methods

**spaces**representing entity-entity and entity-word. Expand abstract.

**spaces**along with its applications to many real-world scenarios have recently gained momentum. In order to make use of multiple KG embeddings for knowledge-driven applications such as question answering, named entity disambiguation, knowledge graph completion, etc., alignment of different KG embedding

**spaces**is necessary. In addition to multilinguality and domain-specific information, different KGs pose the problem of structural differences making the alignment of the KG embeddings more challenging. This paper provides a theoretical analysis and comparison of the state-of-the-art alignment methods between two embedding

**spaces**representing entity-entity and entity-word. This paper also aims at assessing the capability and short-comings of the existing alignment methods on the pretext of different applications.

6/10 relevant

arXiv

Generalized Kazdan-Warner equations associated with a linear action of a
torus on a complex vector **space**

**space**. We show the existence and the uniqueness of the solution of the equation on any compact Riemannian manifold. As an application, we give a direct proof of the Hitchin-Kobayashi correspondence for the solutions of the Abelian vortex equations on a compact K\"ahler manifold which are associated with a linear action of a torus on a complex vector

**space**. Our generalized Kazdan-Warner equations for a special action of a torus give rise to the $tt^\ast$ equations.

6/10 relevant

arXiv

Properties of Set-Valued Stochastic Integrals and Differential Equations
with Poisson Jump in a Banach **Space**

**space**, we explore some properties of set-valued stochastic integrals with respect to Poisson point processes. Expand abstract.

5/10 relevant

arXiv

Disjointness-preserving operators and isospectral Laplacians

**spaces**of continuous functions and on $L^2$-spaces.

4/10 relevant

arXiv

Gradual transitivity in orthogonality **spaces** of finite rank

**space**is a set together with a symmetric and irreflexive binary relation. Any linear

**space**equipped with a reflexive and anisotropic inner product provides an example: the set of one-dimensional subspaces together with the usual orthogonality relation is an orthogonality

**space**. We present simple conditions to characterise the orthogonality

**spaces**that arise in this way from finite-dimensional Hermitian

**spaces**. Moreover, we investigate the consequences of the hypothesis that an orthogonality

**space**allows gradual transitions between any pair of its elements. More precisely, given elements $e$ and $f$, we require a homomorphism from a divisible subgroup of the circle group to the automorphism group of the orthogonality

**space**to exist such that one of the automorphisms maps $e$ to $f$, and any of the automorphisms leaves the elements orthogonal to $e$ and $f$ fixed. We show that our hypothesis leads us to positive definite quadratic

**spaces**. By adding a certain simplicity condition, we furthermore find that the field of scalars is Archimedean and hence a subfield of the reals.

6/10 relevant

arXiv

Master equation for the finite state **space** planning problem

**space**case, in the presence of a common noise. Expand abstract.

**space**case, in the presence of a common noise. The results hold under monotonicity assumptions, which are used crucially in the different proofs of the paper. We also make a link with the trajectories induced by the solution of the master equation and start a discussion on the case of boundary conditions.

5/10 relevant

arXiv