Collabor8: (Re-) Engaging female secondary cohorts in STEM subjects

Demand for skilled professionals in science, technology, engineering and mathematics (STEM) is projected to increase significantly with 75% of the fastest growing occupations requiring STEM skills (Australian Industry Group, 2013). Yet, over the past 20 years, Australia has seen significant decline in the number of secondary students - particularly girls - electing to study science and advanced mathematics (Office of Chief Scientist, 2014). A 2014 national STEM strategy from the Office of the Chief Scientist recommended support for `high levels of participation and success in STEM [education] for all Australians, including women, Indigenous students and students from disadvantaged and marginalised backgrounds’. Recent research builds on previous work (e.g. Fine et al, 2010; Lyons et al, 2012; Sikora, 2012; Mills et al, 2010). Zecharia et al identify three key factors found to be influencing young women’s participation in STEM subjects: 1. Relevance of STEM to sense of identity and future aspirations. 2. Perceived actual and relative ability in STEM subjects. 3. ‘Science capital’ - or experience of STEM, including formal and informal exposure to STEM subjects and careers through the curriculum, schooling, media, culture, family and personal connections’ (Zecharia et al., 2014 p.9). This paper introduces Collabor8, an engineering and IT outreach program for junior female students from high schools serving low socio-economic communities. Collabor8 will test the relative importance of Zecharia et al’s three key factors for participants’ interest in STEM; intention to select STEM subjects in senior high school and tertiary study, and evaluate the chosen outreach model

A hybrid spatiotemporal model of PCa dynamics and insights into optimal therapeutic strategies

Using a hybrid cellular automaton with stochastic elements, we investigate the effectiveness of multiple drug therapies on prostate cancer (PCa) growth. The ability of Androgen Deprivation Therapy to reduce PCa growth represents a milestone in prostate cancer treatment, nonetheless most patients eventually become refractory and develop castration-resistant prostate cancer. In recent years, a “second generation” drug called enzalutamide has been used to treat advanced PCa, or patients already exposed to chemotherapy that stopped responding to it. However, tumour resistance to enzalutamide is not well understood, and in this context, preclinical models and in silico experiments (numerical simulations) are key to understanding the mechanisms of resistance and to assessing therapeutic settings that may delay or prevent the onset of resistance. In our mathematical system, we incorporate cell phenotype switching to model the development of increased drug resistance, and consider the effect of the micro-environment dynamics on necrosis and apoptosis of the tumour cells. The therapeutic strategies that we explore include using a single drug (enzalutamide), and drug combinations (enzalutamide and everolimus or cabazitaxel) with different treatment schedules. Our results highlight the effectiveness of alternating therapies, especially alternating enzalutamide and cabazitaxel over a year, and a comparison is made with data taken from TRAMP mice to verify our findings

Full NLO QCD predictions for Higgs-pair production in the 2-Higgs-doublet model

After the discovery of the Higgs boson in 2012 at the CERN Large Hadron Collider (LHC), the study of its properties still leaves room for an extended Higgs sector with more than one Higgs boson. 2-Higgs doublet models (2HDMs) are well-motivated extensions of the Standard Model (SM) with five physical Higgs bosons: two CP-even states h and H, one CP-odd state A, and two charged states $H^{\pm}$. In this letter, we present the calculation of the full next-to-leading order (NLO) QCD corrections to hH and AA production at the LHC in the 2HDM at small values of the ratio of the vacuum expectation values, $tan\space\beta$, including the exact top-mass dependence everywhere in the calculation. Using techniques applied in the NLO QCD SM Higgs pair production calculation, we present results for the total cross section as well as for the Higgs-pair-mass distribution at the LHC. We also provide the top-quark scale and scheme uncertainties which are found to be sizeable

Molecular Profiling of Lymphatic Endothelial Cell Activation In Vitro

The lymphatic vascular system plays a key role in cancer progression. Indeed, the activation of lymphatic endothelial cells (LECs) through the lymphangiogenic process allows for the formation of new lymphatic vessels (LVs) that represent the major route for the dissemination of solid tumors. This process is governed by a plethora of cancer-derived and microevironmental mediators that strictly activate and control specific molecular pathways in LECs. In this work we used an in vitro model of LEC activation to trigger lymphangiogenesis using a mix of recombinant pro-lymphangiogenic factors (VFS) and a co-culture system with human melanoma cells. Both systems efficiently activated LECs, and under these experimental conditions, RNA sequencing was exploited to unveil the transcriptional profile of activated LECs. Our data demonstrate that both recombinant and tumor cell-mediated activation trigger significant molecular pathways associated with endothelial activation, morphogenesis, and cytokine-mediated signaling. In addition, this system provides information on new genes to be further investigated in the lymphangiogenesis process and open the possibility for further exploitation in other tumor contexts where lymphatic dissemination plays a relevant role

Matrigel plug assay: evaluation of the angiogenic response by reverse transcription-quantitative PCR

The subcutaneous Matrigel plug assay in mice is a method of choice for the in vivo evaluation of pro- and anti-angiogenic molecules. However, quantification of the angiogenic response in the plug remains a problematic task. Here we report a simple, rapid, unbiased and reverse transcription-quantitative PCR (RT-qPCR) method to investigate the angiogenic process occurring in the Matrigel plug in response to fibroblast growth factor-2 (FGF2). To this purpose, a fixed amount of human cells were added to harvested plugs at the end of the in vivo experimentation as an external cell tracer. Then, mRNA levels of the panendothelial cell markers murine CD31 and vascular endothelial-cadherin were measured by species-specific RT-qPCR analysis of the total RNA and data were normalized for human GAPDH or b-actin mRNA levels. RTqPCR was used also to measure the levels of expression in the plug of various angiogenesis/inflammation-related genes. The procedure allows the simultaneous, quantitative evaluation of the newly-formed endothelium and of nonendothelial/ inflammatory components of the cellular infiltrate in the Matrigel implant, as well as the expression of genes involved in the modulation of the angiogenesis process. Also, the method consents the quantitative assessment of the effect of local or systemic administration of anti-angiogenic compounds on the neovascular response triggered by FGF

Three-Dimensional Bioprinting for Cartilage Tissue Engineering: Insights into Naturally-Derived Bioinks from Land and Marine Sources

In regenerative medicine and tissue engineering, the possibility to: (I) customize the shape and size of scaffolds, (II) develop highly mimicked tissues with a precise digital control, (III) manufacture complex structures and (IV) reduce the wastes related to the production process, are the main advantages of additive manufacturing technologies such as three-dimensional (3D) bioprinting. Specifically, this technique, which uses suitable hydrogel-based bioinks, enriched with cells and/or growth factors, has received significant consideration, especially in cartilage tissue engineering (CTE). In this field of interest, it may allow mimicking the complex native zonal hyaline cartilage organization by further enhancing its biological cues. However, there are still some limitations that need to be overcome before 3D bioprinting may be globally used for scaffolds' development and their clinical translation. One of them is represented by the poor availability of appropriate, biocompatible and eco-friendly biomaterials, which should present a series of specific requirements to be used and transformed into a proper bioink for CTE. In this scenario, considering that, nowadays, the environmental decline is of the highest concerns worldwide, exploring naturally-derived hydrogels has attracted outstanding attention throughout the scientific community. For this reason, a comprehensive review of the naturally-derived hydrogels, commonly employed as bioinks in CTE, was carried out. In particular, the current state of art regarding eco-friendly and natural bioinks' development for CTE was explored. Overall, this paper gives an overview of 3D bioprinting for CTE to guide future research towards the development of more reliable, customized, eco-friendly and innovative strategies for this field of interest

Namib Desert dune/interdune transects exhibit habitat-specific edaphic bacterial communities.

The sand dunes and inter-dune zones of the hyper-arid central Namib Desert represent heterogeneous soil habitats. As little is known about their indigenous edaphic bacterial communities, we aimed to evaluate their diversity and factors of assembly and hypothesized that soil physicochemistry gradients would strongly shape dune/interdune communities. We sampled a total of 125 samples from 5 parallel dune/interdune transects and characterized 21 physico-chemical edaphic parameters coupled with 16S rRNA gene bacterial community fingerprinting using T-RFLP and 454 pyrosequencing. Multivariate analyses of T-RFLP data showed significantly different bacterial communities, related to physico-chemical gradients, in four distinct dune habitats: the dune top, slope, base and interdune zones. Pyrosequencing of 16S rRNA gene amplicon sets showed that each dune zone presented a unique phylogenetic profile, suggesting a high degree of environmental selection. The combined results strongly infer that habitat filtering is an important factor shaping Namib Desert dune bacterial communities, with habitat stability, soil texture and mineral and nutrient contents being the main environmental drivers of bacterial community structures

The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors.

The FDA-approved anti-DNA virus agent cidofovir (CDV) is being evaluated in phase II/III clinical trials for the treatment of human papillomavirus (HPV)-associated tumors. However, previous observations had shown that CDV also inhibits the growth of vascular tumors induced by fibroblast growth factor-2 (FGF2)-transformed FGF2-T-MAE cells. Here, we demonstrate that CDV inhibits metastasis induced by FGF2-driven, virus-independent tumor cells. Pre-treatment of luciferase-expressing FGF2-T-MAE cells with CDV reduced single cell survival and anchorage-independent growth in vitro and lung metastasis formation upon intravenous inoculation into SCID mice. This occurred in the absence of any effect on homing of FGF2-T-MAE cells to the lungs and on the growth of subconfluent cell cultures or subcutaneous tumors in mice. Accordingly, CDV protected against lung metastasis when given systemically after tumor cell injection. Lung metastases in CDV-treated mice showed reduced Ki67 expression and increased nuclear accumulation of p53, indicating that CDV inhibits metastasis by affecting single cell survival properties. The anti-metastatic potential of CDV was confirmed on B16-F10 melanoma cells, both in zebrafish embryos and mice. These findings suggest that CDV may have therapeutic potential as an anti-metastatic agent and warrants further study to select those tumor types that are most likely to benefit from CDV therapy

Full NLO QCD corrections to Higgs-pair production in the Standard Model and beyond

Higgs-pair production is one of the targets of the high-luminosity LHC and of future hadron colliders, as it allows for a direct probe of the trilinear Higgs coupling and hence of the mechanism behind electroweak symmetry breaking. This contribution focuses on the impact of the full next- to-leading order QCD corrections to Higgs-pair production via gluon fusion, the main production mechanism at hadron colliders, in the Standard Model and in Two-Higgs-Doublet models. The uncertainties due to the top-mass scale-and-scheme choice will be discussed

NLO QCD corrections to Higgs boson pair production

In this contribution the next-to-leading (NLO) QCD corrections to Higgs boson pair production are discussed. A brief sketch of the calculation is given. The differential cross section as a function of the invariant Higgs pair mass and the total hadronic cross section are presented. Furthermore, the uncertainties not only from the renormalisation and factorisation scales but also the uncertainties due to the scheme-and-scale choice of the top mass are shown. In addition, the effects of varying the Higgs self-coupling strength on the cross section are investigated