Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

Investigation of the Structure and Corrosive Properties of Additively Manufactured Stainless Steel 316L by Binder Jetting and Supersolidus Liquid Phase Sintering

Additive Manufacturing(AM) has seen a great deal of growth and adaptation since its emergence in the 1970s. Through AM's constituent techniques freeform fabrication with an unprecedented degree of geometric freedom is possible. Originally reserved for small scale prototyping AM has recently seen a push for application in a production setting, it is of of particular flexibility in material and application is binder. One common material for use in AM is stainless steel 316L due to its wide use in bio-materials, automotive parts, nuclear reactors, and anywhere corrosion resistance in required. Despite is wide application across many materials; the complex interaction of as-printed structures with post-printing processing is not well understood. This is particularly true for complex post printing processes such as supersolidus liquid phase sintering of metals such as 316L with boron. As binder jetting (BJ) provides several potential advantages over other forms of AM further exploration of the effects of BJ on sintering and therefore resultant material properties, such as corrosion resistance, is a promising avenue for improvement of the process. In this study, a range of standard BJ process parameters were employed in order to print various sample geometries with pre-alloyed 316L Stainless steel powder. The resultant structure was then examined with particular attention given to porosity and microstructure. Samples were also subjected to corrosion testing in a sulfuric acid environment in order to clarify how the observed structure would affect the material's performance in extreme environments. It was found that that variation in printing parameters had a quantifiable effect on corrosion resistance.M.S., Materials Science and Engineering -- Drexel University, 201

The Millennium Galaxy Catalogue: The connection between close pairs and asymmetry; implications for the galaxy merger rate

We compare the use of galaxy asymmetry and pair proximity for measuring galaxy merger fractions and rates for a volume limited sample of 3184 galaxies with -21 < M(B) -5 log h < -18 mag. and 0.010 < z < 0.123 drawn from the Millennium Galaxy Catalogue. Our findings are that: (i) Galaxies in close pairs are generally more asymmetric than isolated galaxies and the degree of asymmetry increases for closer pairs. At least 35% of close pairs (with projected separation of less than 20 h^{-1} kpc and velocity difference of less than 500 km s^{-1}) show significant asymmetry and are therefore likely to be physically bound. (ii) Among asymmetric galaxies, we find that at least 80% are either interacting systems or merger remnants. However, a significant fraction of galaxies initially identified as asymmetric are contaminated by nearby stars or are fragmented by the source extraction algorithm. Merger rates calculated via asymmetry indices need careful attention in order to remove the above sources of contamination, but are very reliable once this is carried out. (iii) Close pairs and asymmetries represent two complementary methods of measuring the merger rate. Galaxies in close pairs identify future mergers, occurring within the dynamical friction timescale, while asymmetries are sensitive to the immediate pre-merger phase and identify remnants. (iv) The merger fraction derived via the close pair fraction and asymmetries is about 2% for a merger rate of (5.2 +- 1.0) 10^{-4} h^3 Mpc^{-3} Gyr^{-1}. These results are marginally consistent with theoretical simulations (depending on the merger time-scale), but imply a flat evolution of the merger rate with redshift up to z ~1.Comment: 10 pages, 10 figures, emulateapj format. ApJ, accepte

Assessing a Hydrodynamic Description for Instabilities in Highly Dissipative, Freely Cooling Granular Gases

An intriguing phenomenon displayed by granular flows and predicted by kinetic-theory-based models is the instability known as particle "clustering," which refers to the tendency of dissipative grains to form transient, loose regions of relatively high concentration. In this work, we assess a modified-Sonine approximation recently proposed [Garz\'o et al., Physica A 376, 94 (2007)] for a granular gas via an examination of system stability. In particular, we determine the critical length scale associated with the onset of two types of instabilities -vortices and clusters- via stability analyses of the Navier-Stokes-order hydrodynamic equations by using the expressions of the transport coefficients obtained from both the standard and the modified-Sonine approximations. We examine the impact of both Sonine approximations over a range of solids fraction \phi <0.2 for small restitution coefficients e=0.25--0.4, where the standard and modified theories exhibit discrepancies. The theoretical predictions for the critical length scales are compared to molecular dynamics (MD) simulations, of which a small percentage were not considered due to inelastic collapse. Results show excellent quantitative agreement between MD and the modified-Sonine theory, while the standard theory loses accuracy for this highly dissipative parameter space. The modified theory also remedies a (highdissipation) qualitative mismatch between the standard theory and MD for the instability that forms more readily. Furthermore, the evolution of cluster size is briefly examined via MD, indicating that domain-size clusters may remain stable or halve in size, depending on system parameters.Comment: 4 figures; to be published in Phys. Rev.

The series Bi2Sr2Ca(n-1) Cu(n)O(2n+4) (1 less than or equal to n less than or equal to 5): Phase stability and superconducting properties

Phase relations at 850 and 870 C, melting transitions in air, oxygen, and helium were studied for Bi(2.1)Sr(1.9) CuO6 and for the Bi2Sr2Ca(n-1) Cu(n)O(2n+4) for n = 1, 2, 3, 4, 5, and infinity (CaCuO2). Up to 870 C, the n = 2 composition resides in the compatibility tetrahedron bounded by Bi(2+x)(Sr,Ca)(3-y) Cu2O8, (Sr,Ca)14 Cu24O41, Ca2CuO3, and a Bi-Sr-Ca-O phase. The n is greater than or equal to 3 compositions reside in the compatibility tetrahedron Bi(2+x)(Sr,Ca)(3-y) Cu2O8 - (Sr,Ca)14 Cu24O41 - Ca2CuO3 - CuO up to 850 C. However, Bi(2+x)Sr(4-y) Cu3O10 forms for n is greater than or equal to 3 after extended heating at 870 C. Bi(2+x)Sr(2-y) CuO6 and Bi(2+x)(Sr,Ca)(3-y) Cu2O8 melt in air at 914 C and 895 C respectively. During melting, all of the compositions studied lose 1 to 2 percent by weight of oxygen from the reduction of copper. Bi(2+x)Sr(2-y) CuO6, Bi(2+n)(Sr,Ca)(3-y) Cu2O8, and Bi(2+x)(Sr,Ca)(4-y) Cu3O10 exhibit crystallographic alignment in a magnetic field, with the c-axes orienting parallel to the field

Probing visual consciousness with transcranial magnetic stimulation

This thesis explores the effects of transcranial magnetic stimulation (TMS) on conscious perception and visual processing. Chapter 1 addresses issues of experimental design. Two broad classes of TMS intervention were used and are reported in separate chapters. Chapter 2 involves repetitive ‘off-line’ TMS combined with neuroimaging techniques. Chapter 3 employs ‘on-line’ TMS applied with temporal specificity to track the passage of information through early visual cortex. Chapter 4 is a general discussion primarily concerned with the issues encountered experiments oriented towards consciousness

Eliminating the Racial Disparity in Classroom Exclusionary Discipline

Advocates call for schools with high suspension rates to receive technical assistance in adopting “proven-effective” systematic supports. Such supports include teacher professional development. This call is justified given evidence that good teaching matters. But what types of professional development should be funded? Increasingly, research points to the promise of programs that are sustained, rigorous, and focused on teachers’ interactions with students. The current study tests whether a professional development program with these three characteristics helped change teachers’ use of exclusionary discipline practices—especially with their African American students. Exclusionary discipline is when a classroom teacher sends a student to the administrators’ office for perceived misbehavior. Administrators then typically assign a consequence, usually in the form of suspension (in-school or out-of school). The My Teaching Partner-Secondary (MTP-S) aims to improve teachers’ interactions with their students when implementing instruction and managing behavior. MTP-S helps teachers offer clear routines, implement consistent rules, and monitor behavior in a proactive way. The program also supports teachers in developing warm, respectful relationships that recognize students’ needs for autonomy and leadership. Teachers are paired with a coach for an entire school year (sustained approach), they regularly reflect on videorecordings of their classroom instruction and carefully observe how they interact with students, and they apply the validated Classroom Assessment Scoring System (CLASS-S) to improve the quality of their interactions (rigorous approach). In the current study, a randomized controlled trial found that teachers receiving MTP-S relied less on exclusionary discipline compared to the control teachers. Specifically, MTP-S teachers issued fewer exclusionary discipline referrals to their African American students. This is the first study to show that programs like MTP-S that focus on teacher-student interactions in a sustained manner using a rigorous approach can actually reduce the disproportionate use of exclusionary discipline with African American students. More broadly, the findings offer policymakers direction in identifying types of professional development programs that have promise for reducing the racial discipline gap

A flavour of omics approaches for the detection of food fraud

Food fraud has been identified as an increasing problem on a global scale with wide-ranging economic, social, health and environmental impacts. Omics and their related techniques, approaches, and bioanalytical platforms incorporate a significant number of scientific areas which have the potential to be applied to and significantly reduce food fraud and its negative impacts. In this overview we consider a selected number of very recent studies where omics techniques were applied to detect food authenticity and could be implemented to ensure food integrity. We postulate that significant reductions in food fraud, with the assistance of omics technologies and other approaches, will result in less food waste, decreases in energy use as well as greenhouse gas emissions, and as a direct consequence of this, increases in quality, productivity, yields, and the ability of food systems to be more resilient and able to withstand future food shocks