Modified protein expression in the tectorial membrane of the cochlea reveals roles for the striated sheet matrix

The tectorial membrane (TM) of the mammalian cochlea is a complex extracellular matrix which, in response to acoustic stimulation, displaces the hair bundles of outer hair cells (OHCs), thereby initiating sensory transduction and amplification. Here, using TM segments from the basal, high-frequency region of the cochleae of genetically modified mice (including models of human hereditary deafness) with missing or modified TM proteins, we demonstrate that frequency-dependent stiffening is associated with the striated sheet matrix (SSM). Frequency-dependent stiffening largely disappeared in all three TM mutations studied where the SSM was absent either entirely or at least from the stiffest part of the TM overlying the OHCs. In all three TM mutations, dissipation of energy is decreased at low (<8 kHz) and increased at high (>8 kHz) stimulus frequencies. The SSM is composed of polypeptides carrying fixed charges, and electrostatic interaction between them may account for frequency-dependent stiffness changes in the material properties of the TM. Through comparison with previous in vivo measurements, it is proposed that implementation of frequency-dependent stiffening of the TM in the OHC attachment region facilitates interaction among tones, backward transmission of energy, and amplification in the cochlea

Early changes in rpS6 phosphorylation and BH3 profiling predict response to chemotherapy in AML cells

Blasts from different patients with acute myeloid leukemia (AML) vary in the agent(s) to which they are most responsive. With a myriad of novel agents to evaluate, there is a lack of predictive biomarkers to precisely assign targeted therapies to individual patients. Primary AML cells often survive poorly in vitro, thus confounding conventional cytotoxicity assays. The purpose of this work was to assess the potential of two same-day functional predictive assays in AML cell lines to predict long-term response to chemotherapy. (i) Ribosomal protein S6 (rpS6) is a downstream substrate of PI3K/akt/mTOR/ kinase and MAPK kinase pathways and its dephosphorylation is also triggered by DNA double strand breaks. Phospho-rpS6 is reliably measurable by flow cytometry and thus has the potential to function as a biomarker of responsiveness to several therapeutic agents. (ii) A cell’s propensity for apoptosis can be interrogated via a functional assay termed “Dynamic BH3 Profiling” in which mitochondrial outer membrane permeabilization in drug-treated cells can be driven by pro-apoptotic BH3 domain peptides such as PUMA-BH3. The extent to which a particular cell is primed for apoptosis by the drug can be determined by measuring the amount of cytochrome C released on addition of BH3 peptide. We demonstrate that phospho-rpS6 expression and PUMA-BH3 peptide-induced cytochrome C release after 4 hours both predict long term chemoresponsiveness to tyrosine kinase inhibitors and DNA double strand break inducers in AML cell lines. We also describe changes in expression levels of the prosurvival BCL-2 family member Mcl-1 and the pro-apoptotic protein BIM after short term drug culture

Comparative Study of 3-Dimensional Woven Joint Architectures for Composite Spacecraft Structures

The National Aeronautics and Space Administration (NASA) Exploration Systems Mission Directorate initiated an Advanced Composite Technology (ACT) Project through the Exploration Technology Development Program in order to support the polymer composite needs for future heavy lift launch architectures. As an example, the large composite structural applications on Ares V inspired the evaluation of advanced joining technologies, specifically 3D woven composite joints, which could be applied to segmented barrel structures needed for autoclave cured barrel segments due to autoclave size constraints. Implementation of these 3D woven joint technologies may offer enhancements in damage tolerance without sacrificing weight. However, baseline mechanical performance data is needed to properly analyze the joint stresses and subsequently design/down-select a preform architecture. Six different configurations were designed and prepared for this study; each consisting of a different combination of warp/fill fiber volume ratio and preform interlocking method (Z-fiber, fully interlocked, or hybrid). Tensile testing was performed for this study with the enhancement of a dual camera Digital Image Correlation (DIC) system which provides the capability to measure full-field strains and three dimensional displacements of objects under load. As expected, the ratio of warp/fill fiber has a direct influence on strength and modulus, with higher values measured in the direction of higher fiber volume bias. When comparing the Z-fiber weave to a fully interlocked weave with comparable fiber bias, the Z-fiber weave demonstrated the best performance in two different comparisons. We report the measured tensile strengths and moduli for test coupons from the 6 different weave configurations under study

An analysis of Australia's carbon pollution reduction scheme

The authors review the decision-making since the Labour Government came into office (November 2007). The Australian Government’s ‘Carbon Pollution Reduction Scheme’ White Paper (15 December 2008) proposes that an Australian Emissions Trading Scheme (AETS) be implemented in mid-2010. Acknowledging that the scheme is comprehensive, the paper finds that in many cases, Australia will take a softer approach to climate change through the AETS than the European Union ETS(EUETS). The paper assesses key issues in the White Paper such as emissions reduction targets, GHG coverage, sectoral coverage, inclusion of unlimited quantities of offsets from Kyoto international markets and exclusion of deforestation activities

Facial Cosmetics and Attractiveness: Comparing the Effect Sizes of Professionally-Applied Cosmetics and Identity

Forms of body decoration exist in all human cultures. However, in Western societies, women are more likely to engage in appearance modification, especially through the use of facial cosmetics. How effective are cosmetics at altering attractiveness? Previous research has hinted that the effect is not large, especially when compared to the variation in attractiveness observed between individuals due to differences in identity. In order to build a fuller understanding of how cosmetics and identity affect attractiveness, here we examine how professionally-applied cosmetics alter attractiveness and compare this effect with the variation in attractiveness observed between individuals. In Study 1, 33 YouTube models were rated for attractiveness before and after the application of professionally-applied cosmetics. Cosmetics explained a larger proportion of the variation in attractiveness compared with previous studies, but this effect remained smaller than variation caused by differences in attractiveness between individuals. Study 2 replicated the results of the first study with a sample of 45 supermodels, with the aim of examining the effect of cosmetics in a sample of faces with low variation in attractiveness between individuals. While the effect size of cosmetics was generally large, between-person variability due to identity remained larger. Both studies also found interactions between cosmetics and identity-more attractive models received smaller increases when cosmetics were worn. Overall, we show that professionally- applied cosmetics produce a larger effect than self-applied cosmetics, an important theoretical consideration for the field. However, the effect of individual differences in facial appearance is ultimately more important in perceptions of attractiveness

Sex Differences in the Perceived Dominance and Prestige of Women With and Without Cosmetics

Human social status has long been of interest to evolutionary and social psychologists. The question of who gets to control resources and be a leader has garnered a lot of attention from these and other fields, and this thesis examines evidence for there being two different mechanisms of achieving high status, and their correlates. The mechanisms are 1) Dominance: being aggressive, manipulative and forcing others to follow you, and 2) Prestige: possessing qualities which make others freely follow you. Chapter 1 is an introductory chapter in which I explain selection pressures, group formation, and the need for social hierarchies; I then describe the two proposed methods of attaining social status and how facial characteristics can give clues as to an individual’s social status. In Chapter 2, my first experimental chapter, I examined how faces created to appear either high in dominance or high in prestige were judged with respect to those traits as well as personality characteristics. Taking this further, in Chapter 3, I looked at how natural variation in real faces would reflect differences in other- and self-perceived ratings of dominance and prestige. Chapter 4 served to examine whether, given a set of words related to social status, I would find differences in what words were placed into dominant or prestige categories. Findings within these chapters are consistent with dominance and prestige being separable methods of attaining high status, from differences in facial appearance (Chapter 2 and 3), to personality characteristics (Chapter 2), to word usage (Chapter 4). Once I had established that these were two distinct routes to achieving high status, I chose to focus on dominance in Chapter 5 and explored the conceptual relationships between dominance and facial expressions. I found that manipulating perceptions of dominance affected how intense expressions of anger, sadness, and fear were perceived (Chapter 5). As there has been a paucity of research in the area of women’s social status, in Chapter 6, I went on to explore what effects cosmetics use in women would have on their perceived social status. I found differences in how men and women perceived women wearing cosmetics, which again points to a distinction between dominance and prestige. My thesis then presents a broad view of the two different mechanisms for attaining high status. Using new methods not otherwise used in exploring dominance and prestige I was able to explore correlates and indicators, as well as perceptions of both strategies. These findings will allow us to determine who might be capable of attaining social status, which of the two methods they might use, as well as what implicit associations we hold about each. They will also open doors for future research into the two strategies, and even help interpret previous research, as many previous studies simply relate to high status and do not distinguish between dominance and prestige

Single cell analysis identifies <em>CRLF2</em> rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL. Using fluorescence in situ hybridisation, we were able to track up to four structural variants in single cells from 47 CRLF2-r B-ALL patients, which in association with our multiplex single cell analysis of a further four patients, permitted simultaneous tracking of copy number alterations, structural and single nucleotide variants within individual cells. We observed CRLF2-r arising as both early and late events in DS and non-DS-ALL patients. Parallel evolution of discrete clones was observed in the development of CRLF2-r B-ALL, either involving the CRLF2-r or one of the other tracked abnormalities. In depth single cell analysis identified both linear and branching evolution with early clones harbouring a multitude of abnormalities, including the CRLF2-r in DS-ALL patients

Radio and X-ray monitoring of the accreting millisecond X-ray pulsar IGR J17591-2342 in outburst

IGR J17591$-$2342 is a new accreting millisecond X-ray pulsar (AMXP) that was recently discovered in outburst in 2018. Early observations revealed that the source's radio emission is brighter than that of any other known neutron star low-mass X-ray binary (NS-LMXB) at comparable X-ray luminosity, and assuming its likely $\gtrsim 6$ kpc distance. It is comparably radio bright to black hole LMXBs at similar X-ray luminosities. In this work, we present the results of our extensive radio and X-ray monitoring campaign of the 2018 outburst of IGR J17591$-$2342. In total we collected 10 quasi-simultaneous radio (VLA, ATCA) and X-ray (Swift-XRT) observations, which make IGR J17591$-$2342 one of the best-sampled NS-LMXBs. We use these to fit a power-law correlation index $\beta = 0.37^{+0.42}_{-0.40}$ between observed radio and X-ray luminosities ( $L_\mathrm{R}\propto L_\mathrm{X}^{\beta}$). However, our monitoring revealed a large scatter in IGR J17591$-$2342's radio luminosity (at a similar X-ray luminosity, $L_\mathrm{X} \sim 10^{36}$ erg s$^{-1}$, and spectral state), with $L_\mathrm{R} \sim 4 \times 10^{29}$ erg s$^{-1}$ during the first three reported observations, and up to a factor of 4 lower $L_\mathrm{R}$ during later radio observations. Nonetheless, the average radio luminosity of IGR J17591$-$2342 is still one of the highest among NS-LMXBs, and we discuss possible reasons for the wide range of radio luminosities observed in such systems during outburst. We found no evidence for radio pulsations from IGR J17591$-$2342 in our Green Bank Telescope observations performed shortly after the source returned to quiescence. Nonetheless, we cannot rule out that IGR J17591$-$2342 becomes a radio millisecond pulsar during quiescence.Comment: 12 pages, 3 figures, 2 tables, accepted for publication in MNRA