A Potent,Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K_d of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.     

Damage evolution around white etching layer during uniaxial loading

Rolling contact fatigue cracks and thermally induced defects are common problems in the railway industry especially as demands for increasing loads, speeds, and safety continue to rise. Often, the two types of defects are found together in the field, however, whether one causes the other to occur is not completely agreed upon. The effect of thermal damage, in the form of a martensite spot on pearlitic steel test bars, on the fatigue life in uniaxial low cycle fatigue experiments was investigated by the authors. However, the focus of the current work was to characterize the damage evolution from the low cycle fatigue (LCF) tests and correlate the crack initiation and propagation with the initial thermal damage. Residual stress measurements, digital image correlation, and X‐ray tomography were used to characterize the effects of the thermal damage before, during, and after fatigue testing, respectively. It was found that the thermal damage causes strain accumulation and crack initiation at the interface between the two materials. The strain evolution was visualized using digital image correlation (DIC), clearly showing the strain concentrations at the top and bottom of the white etching layers (WEL), where the residual stresses are also most tensile. X‐ray tomography confirmed the planar crack growth from the martensite spot.     

Retardation of Crystallization through the Addition of Dairy Phospholipids

The objective of this work was to identify the effects that milk phospholipids (PL) have on crystallization of anhydrous milk fat (AMF). Three mixtures were prepared by adding 0%, 0.01%, and 0.1% PL to AMF. Each mixture was crystallized for 90 min at 24, 26, and 28 °C. The solid fat content was measured as a function of time and fitted to the Avrami equation. Melting point, thermal behavior, viscoelastic properties, and crystal morphology were all measured at 90 min. All assays were repeated, as well as hardness, after being stored at 5 °C for 48 hours. Samples containing PL showed slower crystallization as concentration increased especially at higher temperatures (26 and 28 °C). The addition of PL caused a difference in crystal morphology resulting in visibly larger crystals at 90 min. The elasticity and hardness at 90 min were influenced by the addition of PL at 24 °C with lower values obtained in samples with PL compared to the AMF alone. No differences in hardness nor in elasticity was observed for samples crystallized at 26 and 28 °C. A decrease in melting enthalpy was observed in samples with PL indicating a reduction in crystallization at all temperatures, which was supported by crystal morphology.     

Influence of Ni and Process Parameters in Medium Mn Steels Heat Treated by High Partitioning Temperature Q&P Cycles

In this work, two medium Mn steels (5.8 and 5.7 wt pct Mn) were subjected to a quenching and partitioning (Q&P) treatment employing a partitioning temperature which corresponded to the start of austenite reverse transformation (ART). The influence of a 1.6 wt pct Ni addition in one of the steels and cycle parameters on austenite stability and mechanical properties was also studied. High contents of retained austenite were obtained in the lower quenching temperature (QT) condition, which at the same time resulted in a finer microstructure. The addition of Ni was effective in stabilizing higher contents of austenite. The partitioning of Mn and Ni from martensite into austenite was observed by TEM–EDS. The partitioning behaviour of Mn depended on the QT condition. The lower QT condition facilitated Mn enrichment of austenite laths during partitioning and stabilization of a higher content of austenite. The medium Mn steel containing Ni showed outstanding values of the product of tensile strength (TS) and total elongation (TEL) in the lower QT condition and a higher mechanical stability of the austenite.

     

Enhanced efficiency fertilisers: a review of formulation and nutrient release patterns

Fertilisers are one of the most important elements of modern agriculture. The application of fertilisers in agricultural practices has markedly increased the production of food, feed, fuel, fibre and other plant products. However, a significant portion of nutrients applied in the field is not taken up by plants and is lost through leaching, volatilisation, nitrification, or other means. Such a loss increases the cost of fertiliser and severely pollutes the environment. To alleviate these problems, enhanced efficiency fertilisers (EEFs) are produced and used in the form of controlled release fertilisers and nitrification/urease inhibitors. The application of biopolymers for coating in EEFs, tailoring the release pattern of nutrients to closely match the growth requirement of plants and development of realistic models to predict the release pattern of common nutrients have been the foci of fertiliser research. In this context, this paper intends to review relevant aspects of new developments in fertiliser production and use, agronomic, economic and environmental drives for enhanced efficiency fertilisers and their formulation process and the nutrient release behaviour. Application of biopolymers and complex coacervation technique for nutrient encapsulation is also explored as a promising technology to produce EEFs. © 2014 Society of Chemical Industry     

A Multifunctional Nanoplatform for Imaging,Radiotherapy, and the Prediction of Therapeutic Response

Gold nanoparticles have garnered interest as both radiosensitzers and computed tomography (CT) contrast agents. However, the extremely high concentrations of gold required to generate CT contrast is far beyond that needed for meaningful radiosensitization, which limits their use as combined therapeutic–diagnostic (theranostic) agents. To establish a theranostic nanoplatform with well‐aligned radiotherapeutic and diagnostic properties for better integration into standard radiation therapy practice, a gold‐ and superparamagnetic iron oxide nanoparticle (SPION)‐loaded micelle (GSM) is developed. Intravenous injection of GSMs into tumor‐bearing mice led to selective tumoral accumulation, enabling magnetic resonance (MR) imaging of tumor margins. Subsequent irradiation leads to a 90‐day survival of 71% in GSM‐treated mice, compared with 25% for irradiation‐only mice. Furthermore, measurements of the GSM‐enhanced MR contrast are highly predictive of tumor response. Therefore, GSMs may not only guide and enhance the efficacy of radiation therapy, but may allow patients to be managed more effectively.     

Liquid marbles,formation and locomotion using external fields and forces

Liquid marbles may be traditionally formed by rolling a droplet on a bed of non-wetting particles resulting in encapsulation and stabilisation. Particles used in this process may range from nanometre to millimetre if handled with sufficient care. This method, however, runs the risk of droplet coalescence and is limited to non-wetting particles. Currently there exist some alternative methods of formulation including using electrostatics to either deliver a particle bed to the droplet or pull the droplet to the particles. The former has shown some promise in potential batch processes but is hindered by interparticle forces. Additional production methods include a form of blender, but this has shown to be unable to produce marbles of a narrow size distribution. Once formed, liquid marbles have demonstrated value as potential blood typing devices, as micro-reaction vessels due to the inherent barrier between the internal phase and the substrate whilst maintaining gas permeability, and as contaminant sensors. Liquid marbles also demonstrate a remarkable level of elasticity under compressive force and reduced evaporation rates when compared to bare water droplets, a function of the size and composition of the stabilising particles. In addition to this, liquid marbles have been proposed as actuators. Locomotion may easily be induced in these structures, using electrostatics, sound, magnetism or light depending on the particle/liquid combinations used in formation, and the environment of deployment. This review seeks to present and summarise recent advances in the field of liquid marble manufacture and methods for actuation. We also aim to highlight potential future avenues of further study within this arena.     

The effect of fertilizer nitrogen input to grass-clover swards and calving date on the productivity of pasture-based dairy production

The objective of this systems-scale study was to investigate grazing season timeframes on pasture and milk production and on milk processability of dairy systems with compact spring-calving dairy cows grazing white clover (Trifolium repens L.) based grassland. Fifty-four primiparous and multiparous Holstein-Friesian dairy cows were used in a one-factor study with 3 systems (n = 18) and repeated over 2 yr (2008/09 and 2009/10). The 3 systems were: early spring calving with annual fertilizer N input of 100 kg·ha^?1 applied in spring (ES100N; 2.1 cows·ha^?1; grazing February to November), early spring calving without fertilizer N (ES0N; 1.6 cows·ha^?1; grazing February to November) and late spring calving without fertilizer N (LS0N; 1.53 cows·ha^?1; grazing April to January). Annual pasture production was affected by an interaction between grazing system and year: Mean annual pasture yields for 2008 and 2009 were ES100N; 10.35 and 9.88, ES0N; 8.88 and 8.63, LS0N; 9.18 and 10.31 t of dry matter (DM)·ha^?1 (SEM 0.39). LS0N had higher pasture DM yield in 2009 due to higher clover DM production and biological N fixation compared with the other systems. Clover stolon and root mass in the following February was correlated with stolon and root mass in the previous November with 64% of stolon mass present on LS0N in February (R² = 0.84). There were no detectable differences in per-lactation milk yield (6,335 kg·cow^?1), fat, protein and lactose yields (271, 226, 297 kg·cow^?1, respectively), cow liveweight (585 kg) or body condition score (3.02). Although winter grazing favored subsequent clover DM production, biological N fixation and pasture DM production, delaying calving date in spring and extending lactation into the following winter led to inefficient use of this pasture by the grazing herd and lowered the quality of late-lactation milk for processing purposes. Hence, a mean calving date in mid- to late-February is recommended for zero-fertilizer N input clover-based grassland.