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.     

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     

Quantum annealing for combinatorial clustering

Clustering is a powerful machine learning technique that groups “similar” data points based on their characteristics. Many clustering algorithms work by approximating the minimization of an objective function, namely the sum of within-the-cluster distances between points. The straightforward approach involves examining all the possible assignments of points to each of the clusters. This approach guarantees the solution will be a global minimum; however, the number of possible assignments scales quickly with the number of data points and becomes computationally intractable even for very small datasets. In order to circumvent this issue, cost function minima are found using popular local search-based heuristic approaches such as k-means and hierarchical clustering. Due to their greedy nature, such techniques do not guarantee that a global minimum will be found and can lead to sub-optimal clustering assignments. Other classes of global search-based techniques, such as simulated annealing, tabu search, and genetic algorithms, may offer better quality results but can be too time-consuming to implement. In this work, we describe how quantum annealing can be used to carry out clustering. We map the clustering objective to a quadratic binary optimization problem and discuss two clustering algorithms which are then implemented on commercially available quantum annealing hardware, as well as on a purely classical solver “qbsolv.” The first algorithm assigns N data points to K clusters, and the second one can be used to perform binary clustering in a hierarchical manner. We present our results in the form of benchmarks against well-known k-means clustering and discuss the advantages and disadvantages of the proposed techniques.     

Electrospinning of linear homopolymers of poly(methyl methacrylate): exploring relationships between fiber formation, viscosity, molecular weight and concentration in a good solvent

A series of seven linear homopolymers of poly(methylmethacrylate) ranging from 12,470 to 365,700 g/mol M_w, were utilized to further explore scaling relationships between viscosity and concentration in a good solvent at 25 °C and to investigate the impact of these relationships on fiber formation during electrospinning. For each of the polymers investigated, chain dimensions (hydrodynamic radius and radius of gyration) were measured by dynamic light scattering to determine the critical chain overlap concentration, c^*. The experimentally determined c^*, was found to be in good agreement with the theoretically determined value that was calculated by the criteria c^*∼1/[η], where the intrinsic viscosity was estimated from the Mark-Houwink parameters, K and a (at 25 °C in dimethyl formamide) obtained from the literature. The plot of the zero shear viscosity vs. c/c^* distinctly separated into different solution regimes, viz. dilute (c/c^*<1), semidilute unentangled (1<c/c^*<3) and semidilute entangled (c/c^*>3). The crossover between semidilute unentangled and semidilute entangled regimes in the present investigation occurred at c/c^*∼3, which, therefore, marked the onset of the critical chain entanglement concentration, c_e, according to the procedure utilized by Colby and co-workers [Colby RH, Rubinstein M, Daoud M. J de Phys II 1994;4(8):1299-310. [52]]. Electrospinning of all solutions was carried out at identical conditions to ascertain the effects of solution concentration, molecular weight, molecular weight distribution and viscosity on fiber formation and morphological features of the electrospun material. Only polymer droplets were observed to form from electrospinning of solutions in the dilute concentration regime due to insufficient chain overlap. As the concentration was increased, droplets and beaded fibers were observed in the semidilute unentangled regime; and beaded as well as uniform fibers were observed in the semidilute entangled regime. Uniform fiber formation was observed at c/c^*∼6 for all the narrow MWD polymers (M_w of 12,470-205,800 g/mol) but for the relatively broad MWD polymers (M_w of 34,070 and 95,800 g/mol), uniform fibers were not formed until higher concentrations, c/c^*∼10, were utilized. Dependence of fiber diameter on concentration and viscosity was also determined, viz. fiber dia∼(c/c^*)^3.1 and respectively. These scaling relationships were in general agreement with that observed by Mckee et al. [McKee MG, Wilkes GL, Colby RH, Long TE. Macromolecules 2004;37(5):1760-67. [33]].     

Type of milk consumed can influence plasma concentrations of fatty acids and minerals and body composition in infant and weanling pigs

Two experiments using 42 crossbred neonatal pigs to compare the effects of caprine and bovine milk on growth, apparent nutrient digestibility and body composition were conducted. At age 72 h, pigs were removed from their dams and randomly divided into two groups, housed separately in stainless steel metabolism cages and were fed a predetermined amount (300 mL/kg body weight) of pasteurized, nonfortified whole, caprine or bovine milk. Body composition was determined using dual energy X-ray absorptiometry (DXA). In Experiment 1, 22 intact male pigs were used for a 31-d experimental period. There was no significant (P > 0.05) dietary effect on growth, apparent nutrient digestibility or body composition. Significant differences (P < 0.05), however, were observed in plasma of C 8:0, C 10:0 and C 12:0 concentrations. In Experiment 2, 20 pigs (10 intact males and 10 females) were used in a 2 x 2 factorial experiment for 52 d. Pigs fed caprine milk had higher (P < 0.05) plasma concentrations of C10:0 and C12:0 as well as Na, Mg and Zn than those fed bovine milk. At Day 52, pigs fed caprine milk had less body fat (P < 0.001) and higher (P < 0.06) bone mineral density than those fed bovine milk. Drymatter, N and total mineral intake of male pigs was higher (P < 0.05) than female pigs. Also, male pigs had higher (P < 0.05) plasma concentrations of C12:0 than females. This study demonstrates that the type of milk consumed can influence plasma concentrations of fatty acids, minerals and body composition in pigs.     

木质鸡胸肉生肉品质表征及检测方法研究

目的探索木质肉(woody/wooden breast,WB)生肉品质特性差异及客观检测方法。方法对不同木质鸡胸肉等级样本的重量、挤压力(CF Probe、CF TA-25)进行检测,同时在剪切实验中以剪切力(MORSF)、剪切做功(MORSE)及剪切峰值个数(PC-MORS)作为生肉质构分析指标。结果重量、CF Probe、CF TA-25、MORSF、MORSE、PC-MORS随着WB等级的递增而显著增大,2种硬度检测探头均可用于鸡胸肉的硬度检测。PC-MORS在MORSF和MORSE的基础上可有效区分WB等级,同时可显示鸡胸肉肌肉内部的层状结构信息。各测量指标之间存在不同程度的相关性,其中重量、CF Probe、MORSE、PC-MORS与WB等级之间存在极显著相关。建立的BP神经网络模型区分正常肉和木质肉的总体识别率达90.6%。结论本研究确定了木质鸡胸肉生肉硬度检测方法、质构分析的特征参数,并研究其木质化等级判定模型,研究结果可为后续木质鸡胸肉在线检测分级装置的研发提供一定的理论支撑。     

Fuel injection characteristics of diesel‐stimulated natural gas combustion

Although dual‐fuel (DF) engines using a low cetane number primary fuel such as natural gas (NG) ignited by a pilot diesel spray have been the subject of much investigation over years, there are still many unknown problems related to the fundamental combustion process of two fuels. In this work, a quiescent constant volume combustion bomb and a 3‐D numerical model have been used to study the effects of injection nozzle characteristics on the combustion of pre‐mixed NG/air with pilot distillate spray. Experimental tests were conducted on combustion process of pre‐mixed natural gas/air with pilot injection pressure of 30 and 20 MPa with a 4 hole injector, and also with injector nozzle of 8 and 4 holes. The global results obtained from computations compared well with the experimental results. Copyright © 1999 John Wiley & Sons, Ltd.     

In situ optical variability and relationships in the Santa Barbara Channel: implications for remote sensing

Relationships and variability of bio-optical properties in coastal waters are investigated. Optical proxies indicate that these coastal waters are optically complex and highly variable and are categorized as follows: (1) relatively clear and dominated by high index of refraction, biogenic particles, (2) more turbid, consisting of mostly inorganic particles and little phytoplankton, (3) extremely turbid with high concentrations of inorganic particles, and (4) more turbid and dominated by biogenic particles. We present a method, alternative to traditional remote-sensing algorithms, of classifying coastal waters [the Spectral Angle Mapper (SAM)] and utilize the SAM to successfully isolate plume conditions in time series of downwelling irradiance and total absorption coefficient. We conclude with a discussion of the use of the SAM for coastal management operations.