In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Anaerobic co-digestion of food waste and FOG with sewage sludge – realising its potential in Ireland

The severe environmental pollution in many countries is caused by indiscriminate discharge of large quantities of food waste (FW), fat oil and grease (FOG) and sewage sludge (SS) to the environment. There are many possible treatment routes, but anaerobic digestion (AD) is now well accepted for treating several kinds of organic wastes. But AD of FW alone presents some operational challenges because of substrates and variability. Anaerobic co-digestion of two or more substrates is better than single substrate digestion. This can use a plant’s unused capacity, in line with the trend to renewable energy. Co-digestion technology, although well established in many European countries, is still in its infancy in Ireland. There are problems with different regulatory arrangements. They should be resolved. The paper reviews anaerobic co-digestion technology is reviewed, with special focus on possible application in Ireland.     

Corrosion of hot-dip-galvanised steel and zinc alloy-coated steel in ammonia and ammonium chloride

There are many potential causes of corrosion in animal buildings. Animals exhale large quantities of moisture into the air creating high relative humidity in the building if the moisture is not properly vented. High humidity increases the potential for condensation. In addition, ammonia may be found in large quantities in animal buildings. Ammonia is released from manure and urine. In addition, ammonium chloride is used as a nitrogen source in fertilisers. In this study, the atmospheric corrosion of hot-dip-galvanised steel and zinc alloy-coated steel such as zinc–aluminium and zinc–aluminium–magnesium has been studied in atmospheres containing different levels of ammonia. Investigations have also been conducted at different levels of ammonium chloride. The results are discussed in view of the mechanisms of corrosion of zinc and zinc alloy-coated steel in ammonia and ammonium chloride-containing environments.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Visceral Obesity and Its Shared Role in Cancer and Cardiovascular Disease: A Scoping Review of the Pathophysiology and Pharmacological Treatments

The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT’s role and ways to manage or prevent it are needed.     

Pilot Plant Study of Simultaneous Sewage Sludge Digestion and Metal Leaching

This research is related to a preindustrial pilot scale study of the performance of the simultaneous sewage sludge digestion and metal leaching (SSDML) process for decontamination and stabilization of sewage sludge. Ten batch tests were carried out in two 4?m3 bioreactors under various conditions of operation. Results indicated that the addition of 1.0 to 1.5?g?S0/L, which is the equivalent of approximately 30 to 50?kg?S0 per tons dry sludge, is sufficient to obtain conditions of acidity (pH<2.5) and oxido-reduction potential greater than 500 mV necessary for an effective solubilization of toxic metals. The final average of metal solubilization in the output sludge during the SSDML process varied in the following ranges: 25–78% Cd, 9–32% Cr, 48–100% Cu, 77–99% Mn, 15–53% Ni, 12–47% Pb, and 66–100% Zn. The N, P, and K contents were also preserved in the decontaminated sludge. Moreover, the use of low concentrations of elemental sulfur makes it possible to obtain decontaminated sludge with a low total sulfur content (1.4–1.5% S) compatible with agricultural use. The suspended solids removal calculated for the SSDML process was slightly lower, (2.5±0.4)% volatile suspended solids per day, than those reached using standard aerobic digestion. Finally, the SSDML process was found to be effective in removing bad odors and in the destruction (99–100%) of indicator bacteria.     

Sensitive Mother-to-Adolescent Disclosures After Divorce: Is the Experience of Sons Different From That of Daughters?

This study addressed two main questions: (a) Are adolescent sons and daughters exposed to sensitive maternal disclosures after divorce with similar frequency and in similar detail? and (b) Does gender act as a moderator in the association between maternal disclosures and adolescent adjustment difficulties? Forced-choice and open-ended data were collected from 194 adolescents within 2 years after their parents' divorce. Quantitative analyses revealed that although the majority of adolescents experience some level of maternal disclosure, neither frequency nor detail of maternal disclosure differed as a function of adolescent gender. Frequent and detailed maternal disclosures were associated with adolescent adjustment difficulties, primarily psychological distress. Gender did not moderate that significant association. Qualitative analysis shed light on the link between maternal disclosures and adolescent distress, suggested the importance of how disclosures are made, and revealed several gender differences in reactions to maternal disclosures. Implications of the findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimating local mean signal strength of indoor multipathpropagation

We explore techniques for the measurement of local mean signal strength at 900 MHz and 2 GHz. In particular, we characterize the impact of transmitter and receiver antenna rotation on the estimated local mean. Then, we explore the collection of high resolution data while moving along a linear trajectory and using linear averaging techniques to estimate the local mean. With this information, the best measurement techniques can be chosen depending on the required speed versus accuracy tradeoff. Finally, we use a ray tracing propagation model to evaluate different methods of calculating the local mean signal strength for indoor environments     

Progress in the development of polymer cholesteric liquid crystal flakes for display applications

Polymer cholesteric liquid crystal (PCLC) flake technology is being developed as an alternative display technology for flexible, reflective particle displays. The motion of PCLC flakes suspended in a host fluid can be controlled with an electric field, creating a way to electrically control the flakes' ability to brightly reflect light that is circularly polarized. The PCLC flake/host fluid dispersion has been successfully microencapsulated both in a polymer matrix and in gelatin micro-capsules. Microencapsulation will not only expand the applications scope of the technology, but also may aid in addressing some potential problem areas that are inherent to many forms of particle display technology. A second important development in PCLC flake technology involves the manufacture of shaped flakes based on soft lithography techniques. The size and shape of a flake impact its reorientation, and uniformly shaped flakes respond in a similar manner. The unique reflective properties of PCLC flakes also provide possible applications in areas such as optics and photonics, switchable ‘smart windows’ or conformal coatings, and information displays such as ‘electronic paper.’     

Experience, Context, and the Visual Perception of Human Movement.

Why are human observers particularly sensitive to human movement? Seven experiments examined the roles of visual experience and motor processes in human movement perception by comparing visual sensitivities to point-light displays of familiar, unusual, and impossible gaits across gait-speed and identity discrimination tasks. In both tasks, visual sensitivity to physically possible gaits was superior to visual sensitivity to physically impossible gaits, supporting perception-action coupling theories of human movement perception. Visual experience influenced walker-identity perception but not gait-speed discrimination. Thus, both motor experience and visual experience define visual sensitivity to human movement. An ecological perspective can be used to define the conditions necessary for experience-dependent sensitivity to human movement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)