Mathematical models of the transitions between endocrine therapy responsive and resistant states in breast cancer

Endocrine therapy, targeting the oestrogen receptor pathway, is the most common treatment for oestrogen receptor-positive breast cancers. Unfortunately, these tumours frequently develop resistance to endocrine therapies. Among the strategies to treat resistant tumours are sequential treatment (in which second-line drugs are used to gain additional responses) and intermittent treatment (in which a ‘drug holiday’ is imposed between treatments). To gain a more rigorous understanding of the mechanisms underlying these strategies, we present a mathematical model that captures the transitions among three different, experimentally observed, oestrogen-sensitivity phenotypes in breast cancer (sensitive, hypersensitive and independent). To provide a global view of the transitions between these phenotypes, we compute the potential landscape associated with the model. We show how this oestrogen response landscape can be reshaped by population selection, which is a crucial force in promoting acquired resistance. Techniques from statistical physics are used to create a population-level state-transition model from the cellular-level model. We then illustrate how this population-level model can be used to analyse and optimize sequential and intermittent oestrogen-deprivation protocols for breast cancer. The approach used in this study is general and can also be applied to investigate treatment strategies for other types of cancer.     

From Isonitriles to Unsaturated NHC Complexes of Gold,Palladium and Platinum

In a modular template synthesis, unsaturated NHC complexes of gold, palladium and platinum were synthesized from simple metal salts, isonitriles and amines with acetal or ketal groups. Upon the addition of amines with tethered acetal or ketal moieties to the metal‐activated isonitrile, first nitrogen acyclic carbene (NAC) complexes are formed. These undergo ring closure and elimination to the unsaturated NHC complexes upon addition of acid. This simple strategy opens an attractive and fast approach to NHC complexes of gold, palladium and platinum. The modular approach allows a fast modification and is well‐suited for the synthesis of unsymetrically and symmetrically substituted unsaturated NHC complexes.

     

Dynamic Control Over Electronic Transport in 3D Bulk Nanographene via Interfacial Charging

Electrochemical surface charge‐induced variation of physical properties in interface‐dominated bulk materials is a rapidly emerging field in material science. The recently developed three‐dimensional bulk nanographene (3D‐BNG) macro‐assemblies with ultra‐high surface area and chemical inertness offer new opportunities in this area. Here, the electronic transport in centimeter‐sized 3D‐BNG monoliths can be dynamically controlled via electrochemically induced surface charge density. Specifically, a fully reversible variation in macroscopic conductance up to several hundred percent is observed with ≤1 V applied gate potential. The observed conductivity change can be explained in the light of the electrochemically‐induced accumulation or depletion of charge carriers in combination with a large variation in the carrier mobility; the latter, being highly affected by the defect density modulations resulting from the interfacial charge injection, sharply decreases with an increase in defect concentrations. The phenomenon presented in this study is believed to open the door to novel applications of bulk graphene materials such as, for example, low voltage and high power tunable resistors.     

High performance polymer chemical hydrogel-based electrode binder materials for direct borohydride fuel cells

Novel, cost-effective, high-performance, and environment-friendly electrode binders, comprising polyvinyl alcohol chemical hydrogel (PCH) and chitosan chemical hydrogel (CCH), are reported for direct borohydride fuel cells (DBFCs). PCH and CCH binders-based electrodes have been fabricated using a novel, simple, cost-effective, time-effective, and environmentally benign technique. Morphologies and electrochemical performance in DBFCs of the chemical hydrogel binder-based electrodes have been compared with those of Nafion^® binder-based electrodes. Relationships between the performance of binders in DBFCs with structural features of the polymers and the polymer-based chemical hydrogels are discussed. The CCH binder exhibited better performance than a Nafion^® binder whereas the PCH binder exhibited comparable performance to Nafion^® in DBFCs operating at elevated cell temperatures. The better performance of CCH binder at higher operating cell temperatures has been ascribed to the hydrophilic nature and water retention characteristics of chitosan. DBFCs employing CCH binder-based electrodes and a Nafion^®-117 membrane as an electrolyte exhibited a maximum peak power density of about 589 mW cm⁻² at 70 °C.     

The effects of expected group longevity and expected task difficulty on learning and recall: Implications for the development of transactive memory.

[Correction Notice: An erratum for this article was reported in Vol 15(3) of Group Dynamics: Theory, Research, and Practice (see record 2011-14268-001). An error was introduced during the production process. On article page 8, column 1 line 6 through column 2 line 2, the statement “…the main effect of expected longevity was significant only in the same expertise condition…” is incorrect. The effect found was for expected difficulty, not expected longevity.] The ability to effectively coordinate with others is a vital component of group success. It is often useful to base this coordination on expectations derived from perceived expertise (transactive memory; Wegner, 1986). Yet, the value of coordination overall and specific coordination strategies vary by task. We argue that the benefit of applying a task-appropriate coordination strategy increases with the number of trials of the task performed (expected longevity), and that the most beneficial strategy varies by task difficulty. We, therefore, predict that coordination increases with expected longevity and that the form of coordination (increased or decreased duplication) depends on expected task difficulty. To test these predictions we manipulate expectations of longevity and difficulty among individuals expecting to work with a partner on a memory task. The predicted relationships are found for both learning and recall. The implications of these findings for the development of transactive memory are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Thin film lithium niobate for use in silicon based devices

The incorporation of a thin film of lithium niobate (LiNbO3) in a conventional MOS (metal-oxide-semiconductor) structure gives the possibility of two fundamentally different types of computer memory architectures. One, based on ferroelectric switching involves the reorganization of charge in the transistor channel to compensate for the change in polarization. Another, based on the bulk photovoltaic effect, involves a shift in the transistor threshold with exposure to differing intensities of incident light. With the use of a molybdenum liftoff process, transistors have been fabricated in which LiNbO3 replaces the usual gate oxide of an MOS transistor. Transistor parameters such as the transconductance, output conductance, and amplification for these devices are reported.     

The TRAPS Apparatus: Enhancing Target Density of Nanoparticle Beams in Vacuum for X-ray and Optical Spectroscopy

We present an experimental setup that allows the injection of charged nanoparticles in a diameter range of 3–15 nm into a vacuum chamber and their storage there in an electrodynamic cage. The nanoparticle density in the trap is limited by space charge and can be several orders of magnitude higher than in a free nanoparticle beam. The setup provides for the first time a tool for the application of advanced techniques of spectroscopy to free nanoparticles in this size range. It consists of a combination of (1) a plasma discharge nanoparticle source that generates a high density of nanoparticles of various composition suspended in helium carrier gas at a pressure of about 10–150 mbar, (2) an aerodynamic lens optimized for small particles (diameter 3–15 nm) that forms a well-collimated beam of charged nanoparticles and focuses it into (3) an octopole ion trap operated at low frequencies and filled with helium buffer gas at 10^?2 mbar in order to moderate and store the nanoparticles at densities of more than 10⁷ cm^?3.