Five minutes with Timothy Gowers: “academics can publish journals of the highest quality without a commercial entity”

Fields Medal-winning Cambridge mathematician Sir Timothy Gowers and a team of colleagues have recently launched a new editor-owned Open Access (OA) journal for mathematics. Discrete Analysis is an arXiv overlay journal, which means articles are submitted and hosted via the preprint server arXiv first. The journal coordinates peer-review and publishes via Scholastica with no cost to reader or author. Gowers reflects here on his vision for the future of editor-owned journals

How Craig Barton wishes he’d taught maths

A couple of months ago, I can’t remember precisely how, I became aware of a book called How I Wish I’d Taught Maths, by Craig Barton, that seemed to be highly thought of. The basic idea was that Craig Barton is an experienced, and by the sound of things very good, maths teacher who used to take a number of aspects of teaching for granted, until he looked into the mathematics-education literature and came to realize that many of his cherished beliefs were completely wrong. Since I’ve always been interested in the question of how best to teach mathematics, both because of my own university teaching and because from time to time I like to pontificate about school-level teaching, I decided to order the book. More surprisingly, given my past history of buying books that I felt I ought to read, I read it from cover to cover, all 450 pages of it

Sequoidal Categories and Transfinite Games:A Coalgebraic Approach to Stateful Objects in Game Semantics

The non-commutative sequoid operator $\oslash$ on games was introduced to capture algebraically the presence of state in history-sensitive strategies in game semantics, by imposing a causality relation on the tensor product of games. Coalgebras for the functor $A \oslash \_$ - i.e. morphisms from $S$ to $A \oslash S$ - may be viewed as state transformers: if $A \oslash \_$ has a final coalgebra, $!A$, then the anamorphism of such a state transformer encapsulates its explicit state, so that it is shared only between successive invocations. We study the conditions under which a final coalgebra $!A$ for $A \oslash \_$ is the carrier of a cofree commutative comonoid on $A$. That is, it is a model of the exponential of linear logic in which we can construct imperative objects such as reference cells coalgebraically, in a game semantics setting. We show that if the tensor decomposes into the sequoid, the final coalgebra $!A$ may be endowed with the structure of the cofree commutative comonoid if there is a natural isomorphism from $!(A \times B)$ to $!A \otimes !B$. This condition is always satisfied if $!A$ is the bifree algebra for $A \oslash \_$, but in general it is necessary to impose it, as we establish by giving an example of a sequoidally decomposable category of games in which plays will be allowed to have transfinite length. In this category, the final coalgebra for the functor $A \oslash \_$ is not the cofree commutative comonoid over A: we illustrate this by explicitly contrasting the final sequence for the functor $A \oslash \_$ with the chain of symmetric tensor powers used in the construction of the cofree commutative comonoid as a limit by Melli\'es, Tabareau and Tasson.Comment: Accepted for publication in the proceedings of CALCO 2017, published in the Dagstuhl LIPIcs series. 15pp + 2pp bibliography + 12 pp Appendix (the appendix is not part of the conference version

Engineering a Model Cell for Rational Tuning of GPCR Signaling.

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose response. Using five different GPCRs, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites, and hormones relevant to human health. This work enables rational tuning of cell sensing while providing a framework to guide reprogramming of GPCR-based signaling in other systems.BBSR

Fractional exhaled nitric oxide in the assessment of exercise- induced bronchoconstriction: A multicenter retrospective analysis of UK- based athletes

Introduction: Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes. Method: Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds—that is, intermediate (≥25ppb) and high FeNO (≥40ppb and≥50ppb)—and were evaluated against objective evidence of EIB (≥10% fall in FEV1). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Results: Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25ppb, ≥40ppb, and≥50ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25ppb was 55%, which decreased to 37% and 27% at ≥40ppb and≥50ppb, respectively. The specificity of FeNO ≥25ppb, ≥40ppb, and≥50ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656. Conclusions: FeNO ≥40ppb provides good specificity, that is, the ability to rulein a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes

Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response

The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization

“There was something very peculiar about Doc…”: Deciphering Queer Intimacy in Representations of Doc Holliday

This is an Accepted Manuscript of an article published by Taylor & Francis in American Nineteenth-Century History on 8-12-14, available online: http://dx.doi.org/10.1080/14664658.2014.971481This essay discusses representations of male intimacy in life-writing about consumptive gunfighter John Henry “Doc” Holliday (1851-1887). I argue that twentieth-century commentators rarely appreciated the historical specificity of Holliday’s friendships in a frontier culture that not only normalized but actively celebrated same-sex intimacy. Indeed, Holliday lived on the frayed edges of known nineteenth-century socio-sexual norms, and his interactions with other men were further complicated by his vicious reputation and his disability. His short life and eventful afterlife exposes the gaps in available evidence – and the flaws in our ability to interpret it. Yet something may still be gleaned from the early newspaper accounts of Holliday. Having argued that there is insufficient evidence to justify positioning him within modern categories of hetero/homosexuality, I analyze the language used in pre-1900 descriptions of first-hand encounters with Holliday to illuminate the consumptive gunfighter’s experience of intimacy, if not its meaning