A chain rule in the calculus of homotopy functors

We formulate and prove a chain rule for the derivative, in the sense of Goodwillie, of compositions of weak homotopy functors from simplicial sets to simplicial sets. The derivative spectrum dF(X) of such a functor F at a simplicial set X can be equipped with a right action by the loop group of its domain X, and a free left action by the loop group of its codomain Y = F(X). The derivative spectrum d(E o F)(X)$ of a composite of such functors is then stably equivalent to the balanced smash product of the derivatives dE(Y) and dF(X), with respect to the two actions of the loop group of Y. As an application we provide a non-manifold computation of the derivative of the functor F(X) = Q(Map(K, X)_+).Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol6/paper25.abs.htm

Pro-environmental beliefs and behaviors: two levels of response to environmental social norms

One of the ways to tackle the current environmental crisis is by trying to change beliefs and behaviors through the issuance of new laws. But laws and formal norms only become effective once they are also informally valued. This paper aims at determining whether law-regulated pro-environmental beliefs and behaviors (a) have acquired social value in Brazil, as they have in Europe and (b) pertain to two different construal levels, which could help explain the persistent belief-behavior gap in the environmental field. These two objectives are addressed in two studies using self-presentation and hetero-judgment paradigms. Results confirm the proposed hypotheses and are discussed in terms of social change for sustainability

Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedicationThe gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSH alpha subunit that are critical for biochemical function, plus two sites in the beta subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSH beta hypo-glycosylation seems to confer advantages toward reproductive fertility of childbearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5-10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR.This research was supported by National Institute of Health Grant P01 AG-029531 to GRB. LiS Consulting provided support in the form of a salary for GHL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the 'author contributions' section

GlycomicsDB - A Data Integration Platform for Glycans and their Strucutres

Glycomics is a discipline of biology that deals with the structure and function of glycans (or carbohydrates). Analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are having a significant impact on the field of glycomics. However, effective progress in glycomics research requires collaboration between laboratories to share experimental data, structural information of glycans, and simulation results. Herein we report the development of a web-based data management system that can incorporate large volumes of data from disparate sources and organize them into a uniform format for users to store and access. This system enables participating laboratories to set up a shared data repository which members of interdisciplinary teams can access. The system is able to manage and share raw MS data and structural information of glycans

Nerves and classifying spaces for bicategories

This paper explores the relationship amongst the various simplicial and pseudo-simplicial objects characteristically associated to any bicategory C. It proves the fact that the geometric realizations of all of these possible candidate `nerves of C' are homotopy equivalent. Any one of these realizations could therefore be taken as the classifying space BC of the bicategory. Its other major result proves a direct extension of Thomason's `Homotopy Colimit Theorem' to bicategories: When the homotopy colimit construction is carried out on a diagram of spaces obtained by applying the classifying space functor to a diagram of bicategories, the resulting space has the homotopy type of a certain bicategory, called the `Grothendieck construction on the diagram'. Our results provide coherence for all reasonable extensions to bicategories of Quillen's definition of the `classifying space' of a category as the geometric realization of the category's Grothendieck nerve, and they are applied to monoidal (tensor) categories through the elemental `delooping' construction.Comment: 42 page

Follicle-Stimulating Hormone Biological Products: Does Potency Predict Clinical Efficacy?

Follicle-stimulating hormone (FSH), together with luteinizing hormone (LH) and human chorionic gonadotropin (hCG), plays a fundamental role in human reproduction. The discovery of FSH and other gonadotropins was a defining moment in our understanding of reproduction and led to the development of many treatments for infertility. In this regard, exogenous FSH has been used to treat infertility in women for decades. Today, several recombinant and highly purified urinary forms of FSH are used in medically assisted reproduction (MAR). However, differences in the macro- and micro-heterogeneity of FSH result in a variety of FSH glycoforms, with glycoform composition determining the bioactivity (or potency), pharmacokinetic/pharmacodynamic (PK/PD) profiles, and clinical efficacy of the different forms of FSH. This review illustrates how the structural heterogeneity of FSH glycoforms affects the biological activity of human FSH products, and why potency does not predict effects in humans in terms of PK, PD, and clinical response

Synthesis of amides from acid chlorides and amines in the bio-based solvent Cyrene™

Cyrene™ as a bio-alternative dipolar aprotic solvent: a waste minimizing and molar efficient protocol for the synthesis of amides from acid chlorides and primary amines in the bio-available solvent Cyrene™ is disclosed. This protocol removed the use of toxic solvents, such as dimethylformamide and dichloromethane. A simple aqueous work-up procedure for the removal of the high boiling solvent Cyrene™ resulted in up to a 55-fold increase in molar efficiency (Mol E.%) versus standard operating procedures. In order to rapidly compare the molar efficiency of this process against other methodologies an Excel based Mol. E% calculator was developed that automates many of the calculations. An investigation into the hydration of Cyrene™ found that it readily hydrates to form a geminal diol in the presence of water and that this process is exothermic

BV-structures on the homology of the framed long knot space

We introduce BV-algebra structures on the homology of the space of framed long knots in $\mathbb{R}^n$ in two ways. The first one is given in a similar fashion to Chas-Sullivan's string topology. The second one is defined on the Hochschild homology associated with a cyclic, multiplicative operad of graded modules. The latter can be applied to Bousfield-Salvatore spectral sequence converging to the homology of the space of framed long knots. Conjecturally these two structures coincide with each other.Comment: 13 pages, 3 figures, to appear in Journal of Homotopy and Related Structure