At a high level, the tidyverse is a language for solving data science challenges with R code. Its primary goal is to facilitate a conversation between a human and a computer about data. Less abstractly, the tidyverse is a collection of R packages that share a high-level design philosophy and low-level grammar and data structures, so that learning one package makes it easier to learn the next.

The sole human cathelicidin peptide, LL-37, has been demonstrated to protect animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (≤1 μg/ml) were able to modulate inflammatory responses by inhibiting the release of the proinflammatory cytokine TNF-α in LPS-stimulated human monocytic cells. Microarray studies established a temporal transcriptional profile and identified differentially expressed genes in LPS-stimulated monocytes in the presence or absence of LL-37. LL-37 significantly inhibited the expression of specific proinflammatory genes up-regulated by NF-κB in the presence of LPS, including NFκB1 (p105/p50) and TNF-α-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-α-induced protein 3 (TNFAIP3) and the NF-κB inhibitor, NFκBIA, or certain chemokine genes that are classically considered proinflammatory. Nuclear translocation, in LPS-treated cells, of the NF-κB subunits p50 and p65 was reduced ≥50% in the presence of LL-37, demonstrating that the peptide altered gene expression in part by acting directly on the TLR-to-NF-κB pathway. LL-37 almost completely prevented the release of TNF-α and other cytokines by human PBMC following stimulation with LPS and other TLR2/4 and TLR9 agonists, but not with cytokines TNF-α or IL-1β. Biochemical and inhibitor studies were consistent with a model whereby LL-37 modulated the inflammatory response to LPS/endotoxin and other agonists of TLR by a complex mechanism involving multiple points of intervention. We propose that the natural human host defense peptide LL-37 plays roles in the delicate balancing of inflammatory responses in homeostasis as well as in combating sepsis induced by certain TLR agonists.

Neuroactive small molecules are indispensable tools for treating mental illnesses and dissecting nervous system function. However, it has been difficult to discover novel neuroactive drugs. Here, we describe a high—throughput (HT) behavior—based approach to neuroactive small molecule discovery in the zebrafish. We use automated screening assays to evaluate thousands of chemical compounds and find that diverse classes of neuroactive molecules cause distinct patterns of behavior. These `behavioral barcodes' can be used to rapidly identify novel psychotropic chemicals and to predict their molecular targets. For example, we identify novel acetylcholinesterase and monoamine oxidase inhibitors using phenotypic comparisons and computational techniques. By combining HT screening technologies with behavioral phenotyping in vivo, behavior—based chemical screens may accelerate the pace of neuroactive drug discovery and provide small—molecule tools for understanding vertebrate behavior.

The local Gromov-Witten theory of curves is solved by localization and degeneration methods. Localization is used for the exact evaluation of basic integrals in the local Gromov-Witten theory of P 1 \mathbb P^1 . A TQFT formalism is defined via degeneration to capture higher genus curves. Together, the results provide a complete and effective solution. The local Gromov-Witten theory of curves is equivalent to the local Donaldson-Thomas theory of curves, the quantum cohomology of the Hilbert scheme points of C 2 \mathbb C^2 , and the orbifold quantum cohomology of the symmetric product of C 2 \mathbb C^2 . The results of the paper provide the local Gromov-Witten calculations required for the proofs of these equivalences.

Given a smooth complex threefold X, we define the virtual motive [Hilb n (X)] vir of the Hilbert scheme of n points on X. In the case when X is Calabi-Yau, [Hilb n (X)] vir gives a motivic refinement of the n-point degree zero Donaldson-Thomas invariant of X. The key example is X = C 3 , where the Hilbert scheme can be expressed as the critical locus of a regular function on a smooth variety, and its virtual motive is defined in terms of the Denef-Loeser motivic nearby fiber. A crucial technical result asserts that if a function is equivariant with respect to a suitable torus action, its motivic nearby fiber is simply given by the motivic class of a general fiber. This allows us to compute the generating function of the virtual motives [Hilb n (C 3 )] vir via a direct computation involving the motivic class of the commuting variety. We then give a formula for the generating function for arbitrary X as a motivic exponential, generalizing known results in lower dimensions. The weight polynomial specialization leads to a product formula in terms of deformed MacMahon functions, analogous to Göttsche's formula for the Poincaré polynomials of the Hilbert schemes of points on surfaces..See §1.5 for the definition of Exp. While the above formula only applies when dim(X) = 3, it fits well with corresponding formulas for dim(X) < 3. In these cases, the Hilbert schemes are smooth and thus have canonical virtual motives which are easily expressed in terms of the ordinary classes [Hilb n (X)] in the Grothendieck group. The resulting partition functions have been computed for curves [17] and surfaces [15], and all these results can be expressed (Corollary 3.4) in the single formula Z X (T ) = Exp T [X] vir Exp T [P d−2 ] vir valid when d = dim(X) is 0, 1, 2, or 3. Hereand the class of a negative dimensional projective space is defined by (3.3). In particular, [P −1 ] vir = 0 and [P −2 ] vir = −1. There are some indications that the above formula has significance for dim X > 3; see Remarks 3.5 and 3.6. The weight polynomial specialization of the class of a projective manifold gives its Poincaré polynomial. For example, if X is a smooth 1 Note that the variable "t" has special meaning in the definition of "Exp"; in particular, one cannot simply substitute t for T in the above equation for Z X .1.3. Relative motivic weights. Given a reduced (but not necessarily irreducible) variety S, let K 0 (Var S ) be the Z-module generated by isomorphism classes of (reduced) S-varieties, under the scissor relation for S-varieties, and ring structure whose multiplication is given by fiber product over S. Elements of this ring will be denoted [X] S . A morphism f : S → T induces a ring homomorphism f * : K 0 (Var T ) → K 0 (Var S ) given by fiber product. In particular, K 0 (Var S ) is always a K 0 (Var C )-module. Thus we can let

Author summaryComputers are now essential in all branches of science, but most researchers are never taught the equivalent of basic lab skills for research computing. As a result, data can get lost, analyses can take much longer than necessary, and researchers are limited in how effectively they can work with software and data. Computing workflows need to follow the same practices as lab projects and notebooks, with organized data, documented steps, and the project structured for reproducibility, but researchers new to computing often don't know where to start. This paper presents a set of good computing practices that every researcher can adopt, regardless of their current level of computational skill. These practices, which encompass data management, programming, collaborating with colleagues, organizing projects, tracking work, and writing manuscripts, are drawn from a wide variety of published sources from our daily lives and from our work with volunteer organizations that have delivered workshops to over 11,000 people since 2010.

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ABSTRACT. For orbifolds admitting a crepant resolution and satisfying a hard Lefschetz condition, we formulate a conjectural equivalence between the GromovWitten theories of the orbifold and the resolution. We prove the conjecture for the equivariant Gromov-Witten theories of Sym n C 2 and Hilb n C 2 .