Despite widespread interest, ultrathin and highly flexible light-emitting devices that can be seamlessly integrated and used for flexible displays, wearables, and as bioimplants remain elusive. ...Organic light-emitting diodes (OLEDs) with µm-scale thickness and exceptional flexibility have been demonstrated but show insufficient stability in air and moist environments due to a lack of suitable encapsulation barriers. Here, we demonstrate an efficient and stable OLED with a total thickness of ≈ 12 µm that can be fully immersed in water or cell nutrient media for weeks without suffering substantial degradation. The active layers of the device are embedded between conformal barriers formed by alternating layers of parylene-C and metal oxides that are deposited through a low temperature chemical vapour process. These barriers also confer stability of the OLED to repeated bending and to extensive postprocessing, e.g. via reactive gas plasmas, organic solvents, and photolithography. This unprecedented robustness opens up a wide range of novel possibilities for ultrathin OLEDs.
Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the ...factors most critically required for response to two classes of estrogen receptor-alpha (ER) antagonists. In this context, SWI/SNF-specific gene deletion resulted in drug resistance. Unexpectedly, ARID1A was also the top candidate in regard to response to the bromodomain and extraterminal domain inhibitor JQ1, but in the opposite direction, with loss of ARID1A sensitizing breast cancer cells to bromodomain and extraterminal domain inhibition. We show that ARID1A is a repressor that binds chromatin at ER cis-regulatory elements. However, ARID1A elicits repressive activity in an enhancer-specific, but forkhead box A1-dependent and active, ER-independent manner. Deletion of ARID1A resulted in loss of histone deacetylase 1 binding, increased histone 4 lysine acetylation and subsequent BRD4-driven transcription and growth. ARID1A mutations are more frequent in treatment-resistant disease, and our findings provide mechanistic insight into this process while revealing rational treatment strategies for these patients.
Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to ...develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved.
Prostate cancer (PCa) is one of the most prominent causes of cancer-related mortality in the male population. A highly impactful prognostic factor for patients diagnosed with PCa is the presence or ...absence of bone metastases. The formation of secondary tumours at the bone is the most commonly observed site for the establishment of PCa metastases and is associated with reduced survival of patients in addition to a cohort of life-debilitating symptoms, including mobility issues and chronic pain. Despite the prevalence of this disease presentation and the high medical relevance of bone metastases, the mechanisms underlying the formation of metastases to the bone and the understanding of what drives the osteotropism exhibited by prostate tumours remain to be fully elucidated. This lack of in-depth understanding manifests in limited effective treatment options for patients with advanced metastatic PCa and culminates in the low rate of survival observed for this sub-set of patients. The present review aims to summarise the most recent promising advances in the understanding of how and why prostate tumours metastasise to the bone, with the ultimate aim of highlighting novel treatment and prognostic targets, which may provide the opportunity to improve the diagnosis and treatment of patients with PCa with bone metastases.
Liquid crystalline materials possess great potential as emitters in organic light‐emitting diodes (OLEDs) due to their self‐assembling property, which may lead to anisotropic films and improved ...charge transport. Here, the key photophysical properties of the columnar liquid crystalline emitter perylene‐3,4,9,10‐tetracarboxylic tetraethyl ester (PTCTE) are investigated and the material is implemented into OLEDs. It is found that vacuum‐deposited PTCTE films exhibit preferential horizontal orientation of the transition dipole moment. Embedding the emitter into different host materials leads to increased photoluminescence quantum yield but reduces molecular orientation compared to the neat film. OLEDs containing PTCTE doped into an exciplex‐forming co‐host achieve very high luminance exceeding 10 000 cd m−2 at 5.7 V, which is among the best performances of OLEDs based on columnar liquid crystalline emitters reported so far.
The potential of liquid crystalline emitters for organic light‐emitting diodes (OLEDs) is explored by studying the columnar perylene‐3,4,9,10‐tetracarboxylic tetraethyl ester. Photophysical measurements reveal preferential horizontal orientation of the transition dipole moment on the substrate. The emitter is doped into an exciplex‐forming co‐host and implemented in OLEDs, which reach among the highest luminance reported for columnar liquid crystalline emitters so far.
A series of four 1,3,4-oxadiazole-based thermally activated delayed fluorescence (TADF) derivatives are reported as emitters for organic light emitting diodes (OLEDs). As a function of the nature of ...the substituent on the weak 1,3,4-oxadiazole acceptor, their emission color could be tuned from sky-blue to blue. The highly twisted conformation between carbazoles and oxadiazoles results in effective separation of the highest occupied and the lowest unoccupied molecular orbitals resulting in a small singlet–triplet splitting. The corresponding singlet–triplet energy gaps (ΔE ST) range from 0.22 to 0.28 eV resulting in an efficient reverse intersystem crossing (RISC) process and moderate to high photoluminescence quantum yields (ΦPL), ranging from 35 to 70% in a DPEPO matrix. OLEDs based on i-2CzdOXD4CF3Ph achieve maximum external quantum efficiency (EQEmax) of up to 12.3% with a sky-blue emission at CIE of (0.18, 0.28), while the device based on i-2CzdOXDMe shows blue emission at CIE of (0.17, 0.17) with a maximum EQE of 11.8%.
Background: Intracytoplasmic sperm injection (ICSI) usage (
∼
64% of autologous cycles) has increased in Australia as an attempt to avoid low fertilisation and total fertilisation failure after ...standard in vitro fertilization (IVF). ICSI and to a lesser extent IVF, bypass key sperm maturation (hyperactivation, capacitation/acrosome reaction) events that naturally occur in the female tract and are vital for successful fertilisation. Current commercial sperm preparation media are not fully designed to induce these changes in sperm prior to insemination.
Aim: To improve fertilisation rates following IVF by increasing sperm capacitation and hyperactivation between sperm preparation and insemination ultilising a new sperm medium (SpermFAST).
Method: Sperm from 12 consenting normospermic men were incubated in either G-IVF+ (Vitrolife) or SpermFAST (UoA/Monash IVF) following a direct swim-up. Measures of capacitation, hyperactivation, sperm binding, acrosome reaction and oxidative DNA damage were assessed. Further, sperm from male CBAF1 mice (N=8) were incubated in either G-IVF+ or SpermFAST prior to IVF insemination. Fertilisation rates, embryo development, blastocyst cell numbers and DNA damage were assessed.
Results: Incubation of human sperm in SpermFAST increased tyrosine phosphorylation (15.8% vs 9.5%, P
<
0.05), hyperactive motility (38.3% vs 14.9%, P
<
0.01), sperm binding (73.1% vs 47.7%, P
<
0.01), while having no impact on sperm acrosomal status or oxidative DNA damage levels. Following IVF in the mouse, sperm incubated in SpermFAST increased fertilisation rates (94% vs 88%, P
<
0.05), blastocyst total cell (92.2% vs 77.4%, P
<
0.05), inner cell mass (14.9% vs 18.9%, P
<
0.01) and epiblast cell numbers (3.7% vs 1.6%, P
<
0.01), while the proportion of DNA damaged cells decreased in blastocysts (2.3% vs 4.8%, P
<
0.001).
Conclusion: Sperm function and fertilisation rates are improved when the sperm medium better mimics the environment of the female reproductive tract during natural conception. Improving IVF culture media to better meet the physiological needs of sperm could potentially improve outcomes following IVF.
Three novel donor-acceptor molecules comprising the underexplored pyridazine (Pydz) acceptor moiety have been synthesized and their structural, electrochemical and photophysical properties thoroughly ...characterized. Combining Pydz with two phenoxazine donor units linked via a phenyl bridge in a
configuration (
) leads to high reverse intersystem crossing rate
= 3.9 · 10
s
and fast thermally activated delayed fluorescence (TADF) with <500 ns delayed emission lifetime. Efficient triplet harvesting via the TADF mechanism is demonstrated in OLEDs using
as the emitter but does not occur for compounds bearing weaker donor units.
Abstract Validation of a dual cycle ethylene oxide (EO) approach to removing DNA contamination from consumables has been undertaken. The limits of the technique were investigated resulting in ...evidence that the DNA from up to 50 μl of blood and saliva can be removed to a level where the consumable can be considered DNA free. DNA from semen was more resilient and some allelic peaks remained that would have prevented the consumable being classed as suitable for use in low template DNA analysis. No residual effect on consumables resulting in inhibition of subsequent DNA analysis was noted. However, if consumables had been previously treated with gamma or electron beam irradiation then slight inhibition of the downstream STR process was observed. Dual cycle EO treatment was effective at removing recoverable DNA from swabs and stain cards and consideration should be given to the suitability of EO treatment for use on critical consumables used in the forensic laboratory.
Polycaprolactone (PCL) is a biodegradable polyester that has advantages over other biopolymers, making it an extensively researched polymer. PCL is a hydrophobic, slow-degrading, synthetic polymer ...making it particularly interesting for the preparation of long-term implantable devices and a variety of drug delivery systems. Recently, PCL has been used for additional applications including food packaging and tissue engineering. In this chapter, the processing methods and characterization of PCL will be discussed. The chapter will summarize the synthesis of poly(
-hydroxy acid) and the ring-opening polymerization of PCL. Discussion on the biodegradability of PCL will be reviewed. The biomedical applications of PCL, such as, drug-delivery systems, medical devices, and tissue engineering will be also summarized. Finally, the chapter will conclude with a characterization section outlining recent studies focusing on PCL based composites and films.
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