The realization of regional synergies in industrial areas with intensive minerals processing provides a significant avenue toward sustainable resource processing. This article provides an overview of past and current synergy developments in two of Australia's major heavy industrial regions, Kwinana (Western Australia) and Gladstone (Queensland), and includes a comparative review and assessment of the drivers, barriers, and trigger events for regional synergies initiatives in both areas. Kwinana and Gladstone compare favorably with well‐known international examples in terms of the current level and maturity of industry involvement and collaboration and the commitment to further explore regional resource synergies. Kwinana stands out with regard to the number, diversity, complexity, and maturity of existing synergies. Gladstone is remarkable with regard to unusually large geographic boundaries and high dominance of one industry sector. Many diverse regional synergy opportunities still appear to exist in both industrial regions (particularly in Kwinana), mostly in three broad areas: water, energy, and inorganic by‐product reuse. To enhance the further development of new regional synergies, the Centre for Sustainable Resource Processing (CSRP), a joint initiative of Australian minerals processing companies, research providers, and government agencies, has undertaken several collaborative projects. These include research to facilitate the process of identifying and evaluating potential synergy opportunities and assistance for the industries with feasibility studies and implementation of selected synergy projects in both regions. The article also reports on the progress to date from this CSRP research. 相似文献
Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a major roadblock to making it a curable malignancy. Ganetespib, an Hsp90 (Heat shock protein 90) small molecule inhibitor, shows preferential efficacy in HER2-positive breast cancer, including therapy-refractory cases, and has an excellent safety profile in ongoing clinical trials (38 in total, six on breast cancer). However, Ganetespib itself evokes acquired resistance, which is a significant obstacle to its clinical advancement. Here, we show that Ganetespib potently, albeit temporarily, suppresses HER2-positive breast cancer in genetic mouse models, but the animals eventually succumb via acquired resistance. We found that Ganetespib-resistant tumors upregulate several compensatory HSPs, as well as a wide network of phospho-activated receptor tyrosine kinases (RTKs), many of which are HSP clients. Downstream of p-RTKs, the MAPK pathway remains suppressed in the resistant tumors, as is HER2 itself. In contrast, the p-RTK effector Akt is stabilized and phospho-activated. Notably, pharmacological inhibition of Akt significantly delays acquired Ganetespib resistance, by 50%. These data establish Akt as a unifying actionable node downstream of the broadly upregulated HSP/p-RTK resistance program and suggests that Akt co-targeting with Ganetespib may be a superior therapeutic strategy in the clinic.Subject terms: Breast cancer, Cancer therapeutic resistance相似文献
While pregnancy is known to reduce a woman’s life-long risk of breast cancer, clinical data suggest that it can specifically promote HER2 (human EGF receptor 2)-positive breast cancer subtype (HER2+ BC). HER2+ BC, characterized by amplification of HER2, comprises about 20% of all sporadic breast cancers and is more aggressive than hormone receptor-positive breast cancer (the majority of cases). Consistently with human data, pregnancy strongly promotes HER2+ BC in genetic mouse models. One proposed mechanism of this is post-pregnancy accumulation of PIMECs (pregnancy-identified mammary epithelial cells), tumor-initiating cells for HER2+ BC in mice. We previously showed that p63, a homologue of the tumor suppressor p53, is required to maintain the post-pregnancy number of PIMECs and thereby promotes HER2+ BC. Here we set to test whether p63 also affects the intrinsic tumorigenic properties of PIMECs. To this end, we FACS-sorted YFP-labeled PIMECs from p63+/−;ErbB2 and control p63+/+;ErbB2 females and injected their equal amounts into immunodeficient recipients. To our surprise, p63+/− PIMECs showed increased, rather than decreased, tumorigenic capacity in vivo, i.e., significantly accelerated tumor onset and tumor growth, as well as increased self-renewal in mammosphere assays and proliferation in vitro and in vivo. The underlying mechanism of these phenotypes seems to be a specific reduction of the tumor suppressor TAp63 isoform in p63+/− luminal cells, including PIMECs, with concomitant aberrant upregulation of the oncogenic ΔNp63 isoform, as determined by qRT-PCR and scRNA-seq analyses. In addition, scRNA-seq revealed upregulation of several cancer-associated (Il-4/Il-13, Hsf1/HSP), oncogenic (TGFβ, NGF, FGF, MAPK) and self-renewal (Wnt, Notch) pathways in p63+/−;ErbB2 luminal cells and PIMECs per se. Altogether, these data reveal a complex role of p63 in PIMECs and pregnancy-associated HER2+ BC: maintaining the amount of PIMECs while suppressing their intrinsic tumorigenic capacity.Subject terms: Breast cancer, Mechanisms of disease相似文献
GaAs has excellent optical, electrical, and mechanical properties and shows promise to be used in the fabrication of novel
devices. However, the unprotected GaAs surface can release heavy metal compounds such as AsOx, which are toxic to living cells.
A promising approach to reduce or eliminate this release relies on the passivation of the GaAs surface using different chemical
approaches. In this work, we compared three different passivation methods aimed at enhancing the viability of cells on GaAs.
Protective layers composed of self-assembled alkyl thiols, polypeptides, thick polymer layers, and shells of polyelectrolytes
were tested. We confirmed that the GaAs surface can be made biocompatible for several days based on in vitro tests with HeLa
and KB cells. In addition, we compared the cell spreading behavior on the GaAs substrates modified by different chemical approaches.
Our results suggest that when the toxicity of the GaAs surface is reduced or eliminated, the cells’viability and spreading
depend on the chemical and topographical nature of the surface. 相似文献
The production of activated oxygen species (AOS) by neutrophils (PMNL) is thought to play a key role in the host defence against invading microorganisms. However, the oxygen metabolites are toxic not only to the invading bacteria but also to the surrounding tissue. The oxidative metabolites production can be evaluated by means of chemiluminescent methods. In this study, the possibility of a new analytical approach for quantitative assessment of chemiluminescent kinetics (AOS generation) of isolated PMNL was estimated.
Based on the assumption that the kinetics of luminol-amplified chemiluminescence (LCL) of stimulated PMNL possesses a time-probabilistic nature, this kinetics was described with three components. These components, obtained from different investigated systems, were analyzed and a conclusion was made that the first and the second component represent the processes resulting in extra-and intracellular myeloperoxidase (MPO)-dependent light emission (AOS generation), respectively. The second component was found to be completely dependent on the stimulus ingestion. The third component was not completely MPO-dependent and complicated for interpretation. This component was weakly dependent on the stimulus ingestion, and presents at least some intracellular processes different from those presented by the second component.
A conclusion is made that the examined approach for analysis of LCL kinetics allows an assessment of extra-and intracellularly generated quantities of AOS by stimulated PMNL. The assessment could be done for emitting systems in which no additional modificators are used. 相似文献