A semi-classical field method for the equilibrium Bose gas and application to thermal vortices in two dimensions

We develop a semi-classical field method for the study of the weakly interacting Bose gas at finite temperature, which, contrarily to the usual classical field model, does not suffer from an ultraviolet cut-off dependence. We apply the method to the study of thermal vortices in spatially homogeneous, two-dimensional systems. We present numerical results for the vortex density and the vortex pair distribution function. Insight in the physics of the system is obtained by comparing the numerical results with the predictions of simple analytical models. In particular, we calculate the activation energy required to form a vortex pair at low temperature.Comment: 19 page

A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.Galupa et al. uncover elements important for Xist regulation in its neighboring TAD and reveal that these elements can influence gene regulation both within and between topological domains. These findings, in a context where dynamic, developmental expression is necessary, challenge current models for TAD-based gene-regulatory landscapes

Non-Cooperative Interactions Between Transcription Factors and Clustered DNA Binding Sites Enable Graded Transcriptional Responses To Environmental Inputs

A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we show that NF-κB, a TF controlling inflammation and immunity, is conversely an analog transcriptional regulator that uses clustered binding sites noncooperatively. We observed that increasing concentrations of NF-κB are translated into gradual increments in gene transcription. We provide a thermodynamic interpretation of the experimental observations by combining quantitative measurements and a minimal physical model of an NF-κB-dependent promoter. We demonstrate that NF-κB binds independently to adjacent sites to promote additive RNA Pol II recruitment and graded transcriptional outputs. These findings reveal an alternative mode of operation of clustered TF binding sites, which might function in biological conditions where the transcriptional output is proportional to the strength of an environmental input

Respiratory distress syndrome in preterm infants of less than 32 weeks: What difference does giving 100 or 200 mg/kg of exogenous surfactant make?

Background: Surfactant dosing and effective delivery could affect continuous positive airways pressure (CPAP)-failure. Nevertheless, information on exogenous surfactant dosing with current administration methods is limited. Objective: To describe the effect of 100 or 200 mg/kg of surfactant as first-line treatment of respiratory distress syndrome in preterm infants of less than 32 weeks gestation. Study design: A retrospective single-center cohort study comparing two epochs, before and after switching from 100 to 200 mg/kg surfactant therapy. Results: Six hundred and fifty-eight of the 1615 infants of less than 32 weeks were treated with surfactant: 282 received 100 mg/kg (S-100) and 376 received 200 mg/kg (S-200). There were no differences between S-100 and S-200 in perinatal data including prenatal corticosteroids, medication use, age at first surfactant administration and respiratory severity before surfactant. The S-200 vs. S-100 had fewer retreatments (17.0% vs. 47.2%, p < 0.001) and a shorter duration of oxygen therapy and mechanical ventilation (315 vs. 339 h, p = 0.018; 37 vs. 118 h, p = 0.000, respectively). There was no difference in postnatal corticosteroid use (S-200 10.0% vs. S-100 11.0%, p = 0.361). Bronchopulmonary dysplasia (BPD) was significantly lower in S-200 vs. S-100 when comparing either the 4 and 6-year periods before and after the dose switch (29.4% vs. 15.7%, p = 0.003, and 18.7% vs. 27.3%, p = 0.024, respectively) CONCLUSIONS: The switch from 100 to 200 mg/kg was associated with a marked reduction in the need for surfactant redosing, respiratory support, and BPD. This information could be important when designing a study in the modern era of less invasive administration as surfactant dosing and its effective delivery may affect the outcome