Engaging teachers of the future through ‘opening real science: Authentic mathematics and science education for Australia’

Opening Real Science is a 3-year Australian Government project of the Office for Learning and Teaching. Led by Macquarie University, the project is a unique collaboration between teacher educators, scientists, mathematicians and ICT designers to bring, relevant, authentic science into teacher education programs. The partnership includes seven Australian universities and global experts in science, mathematics and technology. The project will develop innovative teacher education program modules in mathematics and science education and a unique professional experience model. An innovative ‘real science’ approach will be developed including assessing learning using rich scientific investigations related to specific areas: • Mathematics (e.g., Financial Literacy, Statistics and data modelling) • Earth and space sciences (e.g., Conceptions of weather and climate) • Astronomy (e.g., Indigenous astronomy, Planetary Nebulae) • Physics (e.g., Sound, Light) • Chemical Sciences (e.g., Pseudo Science, Visual Chemistry) • Biological sciences (e.g., Biology in Action, Big Theories in Biology) The professional experience (practicum) model will enable groups of pre-service teachers to work collaboratively with trained school-based teacher mentors and practising scientists. Evaluation data will include empirical evidence of the project’s impact on pre-service teacher knowledge, pedagogy and attitudes

Development of efficient docking strategies and structure-activity relationship study of the c-Met type II inhibitors

c-Met is a transmembrane receptor tyrosine kinase and an important therapeutic target for anticancer drugs. In the present study, we systematically investigated the influence of a range of parameters on the correlation between experimental and calculated binding free energies of type II c-Met inhibitors. We especially focused on evaluating the impact of different force fields, binding energy calculation methods, docking protocols, conformation sampling strategies, and conformations of the binding site captured in several crystallographic structures. Our results suggest that the force fields, the protein flexibility, and the selected conformation of the binding site substantially influence the correlation coefficient, while the sampling strategies and ensemble docking only mildly affect the prediction accuracy. Structure-activity relationship study suggests that the structural determinants to the high binding affinity of the type II inhibitors originate from its overall linear shape, hydrophobicity, and two conserved hydrogen bonds. Results from this study will form the basis for establishing an efficient computational docking approach for c-Met type II inhibitors design

Power and endurance in Hong Kong professional football players

Background The purpose of this study was to investigate the power and endurance characteristics of Hong Kong professional football players. Training recommendations can be deduced based on the comparison between Hong Kong and international football players. Methods Eighty-eight Hong Kong professional football players (height, 177.2 ± 6.4 cm; weight, 70.6 ± 7.6 kg; age, 25.6 ± 5.0 years) in the first division league participated in a battery of tests, which included: (1) height, (2) weight, (3) countermovement jump, (4) 30-m sprinting, and (5) Yo-Yo Intermittent Recovery Test Level 2. Results Compared with the test results of the first division players in other countries as reported in the literature (Norway, France, and Scandinavian countries), Hong Kong players were shorter in height (0.1–2.1%), lighter in weight (5.5–8.3%), fair in vertical jump height (−4.8 –17%), slower in acceleration (4.2–5.1%) and maximum speed (3–14.2%), and had poorer aerobic and anaerobic endurance (22.9%). Conclusion The present study suggests that Hong Kong football players (or players with similar physique and ability) need to improve their power and endurance

Aurora-A down-regulates IkappaBα via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival

<p>Abstract</p> <p>Background</p> <p>The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated.</p> <p>Results</p> <p>Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBα expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBα, these changes were accompanied by nuclear translocation of nuclear factor-κB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBα reduction was abrogated by suppression of Akt either chemically or genetically.</p> <p>Conclusion</p> <p>Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-κB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.</p

R-loops and regulatory changes in chronologically ageing fission yeast cells drive non-random patterns of genome rearrangements

Aberrant repair of DNA double-strand breaks can recombine distant chromosomal breakpoints. Chromosomal rearrangements compromise genome function and are a hallmark of ageing. Rearrangements are challenging to detect in non-dividing cell populations, because they reflect individually rare, heterogeneous events. The genomic distribution of de novo rearrangements in non-dividing cells, and their dynamics during ageing, remain therefore poorly characterized. Studies of genomic instability during ageing have focussed on mitochondrial DNA, small genetic variants, or proliferating cells. To characterize genome rearrangements during cellular ageing in non-dividing cells, we interrogated a single diagnostic measure, DNA breakpoint junctions, using Schizosaccharomyces pombe as a model system. Aberrant DNA junctions that accumulated with age were associated with microhomology sequences and R-loops. Global hotspots for age-associated breakpoint formation were evident near telomeric genes and linked to remote breakpoints elsewhere in the genome, including the mitochondrial chromosome. Formation of breakpoint junctions at global hotspots was inhibited by the Sir2 histone deacetylase and might be triggered by an age-dependent de-repression of chromatin silencing. An unexpected mechanism of genomic instability may cause more local hotspots: age-associated reduction in an RNA-binding protein triggering R-loops at target loci. This result suggests that biological processes other than transcription or replication can drive genome rearrangements. Notably, we detected similar signatures of genome rearrangements that accumulated in old brain cells of humans. These findings provide insights into the unique patterns and possible mechanisms of genome rearrangements in non-dividing cells, which can be promoted by ageing-related changes in gene-regulatory proteins

Molecular Prognostic Prediction for Locally Advanced Nasopharyngeal Carcinoma by Support Vector Machine Integrated Approach

BACKGROUND:Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. CONCLUSIONS/SIGNIFICANCE:Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways

Characterising a World Within the Hot Neptune Desert: Transit Observations of LTT 9779 b with HST WFC3

We present an atmospheric analysis of LTT 9779 b, a rare planet situated in the hot Neptune desert, that has been observed with HST WFC3 G102 and G141. The combined transmission spectrum, which covers 0.8 - 1.6 $\mu$m, shows a gradual increase in transit depth with wavelength. Our preferred atmospheric model shows evidence for H$_{\rm 2}$O, CO$_{\rm 2}$ and FeH with a significance of 3.1 $\sigma$, 2.4 $\sigma$ and 2.1 $\sigma$, respectively. In an attempt to constrain the rate of atmospheric escape for this planet, we search for the 1.083 $\mu$m Helium line in the G102 data but find no evidence of excess absorption that would indicate an escaping atmosphere using this tracer. We refine the orbital ephemerides of LTT 9779 b using our HST data and observations from TESS, searching for evidence of orbital decay or apsidal precession, which is not found. The phase-curve observation of LTT 9779 b with JWST NIRISS should provide deeper insights into the atmosphere of this planet and the expected atmospheric escape might be detected with further observations concentrated on other tracers such as Lyman $\alpha$.Comment: Accepted for publication in A

Characterizing a World Within the Hot-Neptune Desert: Transit Observations of LTT 9779 b with the Hubble Space Telescope/WFC3

We present an atmospheric analysis of LTT 9779 b, a rare planet situated in the hot-Neptune desert, that has been observed with Hubble Space Telescope (HST)/WFC3 with G102 and G141. The combined transmission spectrum, which covers 0.8–1.6 μm, shows a gradual increase in transit depth with wavelength. Our preferred atmospheric model shows evidence for H2O, CO2, and FeH with a significance of 3.1σ, 2.4σ, and 2.1σ, respectively. In an attempt to constrain the rate of atmospheric escape for this planet, we search for the 1.083 μm helium line in the G102 data but find no evidence of excess absorption that would indicate an escaping atmosphere using this tracer. We refine the orbital ephemerides of LTT 9779 b using our HST data and observations from TESS, searching for evidence of orbital decay or apsidal precession, which are not found. The phase-curve observation of LTT 9779 b with JWST NIRISS should provide deeper insights into the atmosphere of this planet and the expected atmospheric escape might be detected with further observations concentrated on other tracers such as Lyα

Planet Formation Imager (PFI): Science vision and key requirements

The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the Hill Sphere of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction