Thermodynamics predicts how confinement modifies hard-sphere dynamics

We study how confining the equilibrium hard-sphere fluid to restrictive one- and two-dimensional channels with smooth interacting walls modifies its structure, dynamics, and entropy using molecular dynamics and transition-matrix Monte Carlo simulations. Although confinement strongly affects local structuring, the relationships between self-diffusivity, excess entropy, and average fluid density are, to an excellent approximation, independent of channel width or particle-wall interactions. Thus, thermodynamics can be used to predict how confinement impacts dynamics.Comment: 4 pages, 4 figure

Five-dimensional Nernst branes from special geometry

We construct Nernst brane solutions, that is black branes with zero entropy density in the extremal limit, of FI-gauged minimal five-dimensional supergravity coupled to an arbitrary number of vector multiplets. While the scalars take specific constant values and dynamically determine the value of the cosmological constant in terms of the FI-parameters, the metric takes the form of a boosted AdS Schwarzschild black brane. This metric can be brought to the Carter-Novotny-Horsky form that has previously been observed to occur in certain limits of boosted D3-branes. By dimensional reduction to four dimensions we recover the four-dimensional Nernst branes of arXiv:1501.07863 and show how the five-dimensional lift resolves all their UV singularities. The dynamics of the compactification circle, which expands both in the UV and in the IR, plays a crucial role. At asymptotic infinity, the curvature singularity of the four-dimensional metric and the run-away behaviour of the four-dimensional scalar combine in such a way that the lifted solution becomes asymptotic to AdS5. Moreover, the existence of a finite chemical potential in four dimensions is related to fact that the compactification circle has a finite minimal value. While it is not clear immediately how to embed our solutions into string theory, we argue that the same type of dictionary as proposed for boosted D3-branes should apply, although with a lower amount of supersymmetry.Comment: 59 pages, 1 figure. Revised version: references added, typos corrected. Final version, accepted by JHEP: two references adde

Cofinement, entropy, and single-particle dynamics of equilibrium hard-sphere mixtures

We use discontinuous molecular dynamics and grand-canonical transition-matrix Monte Carlo simulations to explore how confinement between parallel hard walls modifies the relationships between packing fraction, self-diffusivity, partial molar excess entropy, and total excess entropy for binary hard-sphere mixtures. To accomplish this, we introduce an efficient algorithm to calculate partial molar excess entropies from the transition-matrix Monte Carlo simulation data. We find that the species-dependent self-diffusivities of confined fluids are very similar to those of the bulk mixture if compared at the same, appropriately defined, packing fraction up to intermediate values, but then deviate negatively from the bulk behavior at higher packing fractions. On the other hand, the relationships between self-diffusivity and partial molar excess entropy (or total excess entropy) observed in the bulk fluid are preserved under confinement even at relatively high packing fractions and for different mixture compositions. This suggests that the partial molar excess entropy, calculable from classical density functional theories of inhomogeneous fluids, can be used to predict some of the nontrivial dynamical behaviors of fluid mixtures in confined environments.Comment: submitted to JC

Stereotype and skew: Quantifying gender bias in pre-trained and fine-tuned language models

This paper proposes two intuitive metrics, skew and stereotype, that quantify and analyse the gender bias present in contextual language models when tackling the WinoBias pronoun resolution task. We find evidence that gender stereotype correlates approximately negatively with gender skew in out-of-the-box models, suggesting that there is a trade-off between these two forms of bias. We investigate two methods to mitigate bias. The first approach is an online method which is effective at removing skew at the expense of stereotype. The second, inspired by previous work on ELMo, involves the fine-tuning of BERT using an augmented gender-balanced dataset. We show that this reduces both skew and stereotype relative to its unaugmented fine-tuned counterpart. However, we find that existing gender bias benchmarks do not fully probe professional bias as pronoun resolution may be obfuscated by cross-correlations from other manifestations of gender prejudice. Our code is available online

Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens

PURPOSE: Selection of the most appropriate chemotherapy dosing regimens for neonates treated within the first weeks of life represents a significant clinical dilemma. Due to a lack of information relating to the clinical pharmacology of anticancer drugs in these challenging patients, current dosing guidelines are based on limited scientific rationale. In the current study, we investigate the utilisation of therapeutic drug monitoring approaches in neonates with localised hepatoblastoma, Wilms' tumour and stage 4S neuroblastoma, being treated with widely used anticancer drugs. METHODS: Plasma concentrations of cisplatin, vincristine, etoposide and carboplatin were quantified in two neonates being treated within the first 3 weeks of life and in a 32-week preterm infant treated at a gestational age of 40 weeks. Therapeutic drug monitoring was carried out where appropriate, based on the pharmacokinetic data obtained in conjunction with clinical response and toxicity. RESULTS: Treatment of a child aged 2 weeks with a recommended cisplatin dose reduction for weight to 1.8 mg/kg resulted in achievement of unbound cisplatin plasma concentrations of 0.01-0.08 µg/mL, markedly lower than exposures previously reported in infants and older children. A dose increase to 2.7 mg/kg was implemented, leading to the achievement of levels more in-line with those previously reported. This increased dose level was well tolerated over six courses of treatment, resulting in a good response to cisplatin monotherapy and the patient remains in remission at 3.5 years. In contrast, a 50 % vincristine dose reduction for weight in a 3-week-old neonate resulted in plasma concentrations comparable to levels observed in older children, leading to successful treatment and continued remission at 2 years. In a third patient, etoposide and carboplatin clearance values normalised to body weight were comparable to those reported in older children, resulting in comparatively lower exposures following reduced dosing. CONCLUSIONS: The current report provides unique data on the pharmacokinetics of several widely used anticancer drugs in neonates treated within the first few weeks of life. The provision of these data acts as a useful reference point to support future dosing decisions to be made by clinicians in the treatment of these challenging patients

By design : negotiating flexible learning in the built environment discipline

The term ‘flexible education’ is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning ‘matching’ tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher’s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

Characterization of the Ebola virus nucleoprotein–RNA complex

When Ebola virus nucleoprotein (NP) is expressed in mammalian cells, it assembles into helical structures. Here, the recombinant NP helix purified from cells expressing NP was characterized biochemically and morphologically. We found that the recombinant NP helix is associated with non-viral RNA, which is not protected from RNase digestion and that the morphology of the helix changes depending on the environmental salt concentration. The N-terminal 450 aa residues of NP are sufficient for these properties. However, digestion of the NP-associated RNA eliminates the plasticity of the helix, suggesting that this RNA is an essential structural component of the helix, binding to individual NP molecules via the N-terminal 450 aa. These findings enhance our knowledge of Ebola virus assembly and understanding of the Ebola virus life cycle