Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance

Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease.     

Young's modulus of cement paste at elevated temperatures

Calcium silicate hydrate is a porous hydrate that is sensitive to temperature and readily loses strength at elevated temperatures. Mechanical and chemical changes in the microstructure, due to escaping water, can significantly affect the mechanical properties, but these changes occur over different temperature ranges. By measuring Young's modulus as a function of temperature using the dynamic mechanical analyzer, the temperature range in which the greatest change in stiffness occurs can be identified. Additional mineralogy, pore size distribution, and composition analysis from high temperature X-ray diffraction, nitrogen sorption, and thermogravimetric analysis will demonstrate the changes in the microstructure. The results demonstrate that over 90% of the loss in stiffness occurs below 120 °C. Therefore, the damage is due to microcracking caused by pore water expansion and evaporation and not the change in mineralogy or composition. More damage, as indicated by greater loss in stiffness, occurs in stiffer and less permeable samples where higher stresses can develop.     

Learning perceptually grounded word meanings from unaligned parallel data

In order for robots to effectively understand natural language commands, they must be able to acquire meaning representations that can be mapped to perceptual features in the external world. Previous approaches to learning these grounded meaning representations require detailed annotations at training time. In this paper, we present an approach to grounded language acquisition which is capable of jointly learning a policy for following natural language commands such as “Pick up the tire pallet,” as well as a mapping between specific phrases in the language and aspects of the external world; for example the mapping between the words “the tire pallet” and a specific object in the environment. Our approach assumes a parametric form for the policy that the robot uses to choose actions in response to a natural language command that factors based on the structure of the language. We use a gradient method to optimize model parameters. Our evaluation demonstrates the effectiveness of the model on a corpus of commands given to a robotic forklift by untrained users.     

Crystallization kinetics of low‐density polyethylene and polypropylene melt‐blended with a low‐Tg tin‐based phosphate glass

The nonisothermal and isothermal crystallizations of low‐density polyethylene (LDPE) and polypropylene (PP) in phosphate glass (Pglass)–polymer hybrid blends were studied through differential scanning calorimetry (DSC). As the Pglass volume fraction was increased, the percentage crystallinity decreased. The half‐time for crystallization decreased as the propagation rate constant rose, for both of the polymer matrices, with increasing Pglass concentrations. The Pglass was observed to be a nucleating agent for formation of two‐ or three‐dimensional spherulites in the hybrids. Tensile modulus improved for both of the Pglass–polymer hybrids up to 40% Pglass, but the energy to break decreased. Tensile strength changed slightly with the addition of Pglass to the LDPE matrix, exhibiting a larger value than that of pure LDPE at 30%. The tensile strength decreased as more Pglass was added to the PP matrix. The observed differences between tensile properties of the Pglass–PP and Pglass–LDPE hybrids at identical Pglass volume concentration were found to be consistent with that of the crystallization behavior of the hybrids. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3445–3456, 2003     

A new batch solvent-extraction pilot plant

Summary and Conclusions A new improved batch solvent extraction plant and its versatility of design have been described. Data have been given on the cost and initial test operations. The performance of the plant has been tested, and its value as a research tool has been demonstrated by the production of free gossypol and meals low in gossypol for use in research. Simplicity of operation is borne out by the fact that only one operator is needed. A limited number of detail drawings of the plant are available on written request from the Southern Regional Research Laboratory. Presented at the fall meeting, American Oil Chemists’ Society, Nov. 2–4, 1953, in Chicago, Ill. One of the laboratories of the Southern Utilization Research Branch, Agricultural Research Service, U. S. Department of Agriculture.     

Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease

Proteomic analysis of cerebrospinal fluid (CSF) holds great promise in understanding the progression of neurodegenerative diseases, including Alzheimer's disease (AD). As one of the primary reservoirs of neuronal biomolecules, CSF provides a window into the biochemical and cellular aspects of the neurological environment. CSF can be drawn from living participants allowing the potential alignment of clinical changes with these biochemical markers. Using cutting-edge mass spectrometry technologies, we perform a streamlined proteomic analysis of CSF. We quantify greater than 700 proteins across 10 pairs of age- and sex-matched participants in approximately one hour of analysis time each. Using the paired participant study structure, we identify a small group of biologically relevant proteins that show substantial changes in abundance between cognitive normal and AD participants, which were then analyzed at the peptide level using parallel reaction monitoring experiments. Our findings suggest the utility of fractionating a single sample and using matching to increase proteomic depth in cerebrospinal fluid, as well as the potential power of an expanded study.     

Transparent,methacrylate-based polymer networks with controlled crosslinker ductility

A series of transparent methacrylate-based crosslinked polymer networks are prepared in which the crosslinker length is controlled as a means to investigate the effects of network ductility on mechanical and ballistic properties. In each network the optical clarity of pure poly(methyl methacrylate) (PMMA) is retained, as well as a low value of haze. Both the glass transition temperature (T_g) and the tensile modulus of the networks are highly tunable, with network values both above and well below that of pure PMMA or the pure crosslinker network. The ballistic performance is likewise affected, with performance values of up to 400% greater than neat PMMA. We examine the effects of the crosslinker molecular weight on the impact performance, finding that, in these systems, the molecular weight between crosslinks is not a driving factor for the impact performance, and this may broadly translate to polymer networks in general. We find that improvements in ballistic performance can be realized at low molecular weight between crosslinks, provided the crosslinking agent is of sufficient ductility.     

An investigation of phase transformation behavior in sputter-deposited PtMn thin films

Sputter-deposited, equiatomic PtMn thin films have application in giant magnetoresistive spin valves, tunneling magnetoresistive spin valves, and magnetic random access memory. However, the as-deposited films are found to be a disordered A1 phase in a paramagnetic state rather than an antiferromagnetic phase with L1₀ structure, which is needed for device operation. Therefore, a postannealing step is required to induce the phase transformation from the asdeposited A1 face-centered-cubic phase to the antiferromagnetic L1₀ phase. The A1 to L1₀ metastable transformation was studied by x-ray diffraction and differential-scanning calorimetry. An exothermic transformation enthalpy of −12.1 kJ/mol of atoms was determined. The transformation kinetics were simulated using the Johnson-Mehl-Avrami analysis.     

Proactive privacy for a driverless age

Autonomous vehicles are on the cusp of disrupting the entire transportation industry and current privacy legislation is not yet equipped to deal with the changes being spurred by this innovation. This paper enumerates and elucidates on the various privacy concerns that are specific autonomous vehicles. It also proposes the principles of “Privacy-by-Design”, an industry trend pertaining to other arenas of privacy, be adapted and used for regulating privacy around autonomous vehicles. It calls for the NHTSA (National Highway Transportation Safety Administration), with guidance from the FCC, and the FTC, to use their expertise in creating administrative rules that will protect the privacy of the public. Having learned valuable lessons from recent privacy concerns in the mobile device industry, the Privacy-by-Design approach would help ease the transition into this useful, but potentially intrusive technology. Currently, privacy is receiving significant attention in publications, but with autonomous vehicles being a nascent industry, there is very little being said about the privacy concerns specifically pertaining to these technology autonomous vehicles. Recent strides in the technology and the legislative acceptance of these vehicles have made them a widely discussed topic, and thus makes a thorough discussion of privacy related specifically to this technology both timely and relevant. This paper provides an early assessment of an area of concern that is growing as rapidly as are autonomous vehicles. The technology is being proven effective and safe, so the real focus will shift to use concerns, like privacy. The autonomous vehicle industry is still early in its development, and there is imminent opportunity to anchor privacy into the fundamentals of autonomous vehicles, preempting numerous potential infringements.