Using a Fragment‐Based Approach To Target Protein–Protein Interactions

The ability to identify inhibitors of protein–protein interactions represents a major challenge in modern drug discovery and in the development of tools for chemical biology. In recent years, fragment‐based approaches have emerged as a new methodology in drug discovery; however, few examples of small molecules that are active against chemotherapeutic targets have been published. Herein, we describe the fragment‐based approach of targeting the interaction between the tumour suppressor BRCA2 and the recombination enzyme RAD51; it makes use of a screening pipeline of biophysical techniques that we expect to be more generally applicable to similar targets. Disruption of this interaction in vivo is hypothesised to give rise to cellular hypersensitivity to radiation and genotoxic drugs. We have used protein engineering to create a monomeric form of RAD51 by humanising a thermostable archaeal orthologue, RadA, and used this protein for fragment screening. The initial fragment hits were thoroughly validated biophysically by isothermal titration calorimetry (ITC) and NMR techniques and observed by X‐ray crystallography to bind in a shallow surface pocket that is occupied in the native complex by the side chain of a phenylalanine from the conserved FxxA interaction motif found in BRCA2. This represents the first report of fragments or any small molecule binding at this protein–protein interaction site.     

Modelling methodology for thermal analysis of hot solder dip process

The shift of electronics industry towards the use of lead-free solders in components manufacturing brought also the challenge of addressing the problem of tin whiskers. Manufacturers of high reliability and safety critical equipment in sectors such as defence and aerospace rely increasingly on the use of commercial-of-the-shelf (COTS) electronic components for their products and systems. The use of COTS components with lead-free solder plated terminations comes with the risks for their long term reliability associated with tin whisker growth related failures. In the case of leaded type electronic components such as Quad Flat Package (QFP) and Small Outline Package (SOP), one of the promising solutions to this problem is to “re-finish” the package terminations by replacing the lead-free solder coatings on the leads with conventional tin–lead solder. This involves subjecting the electronic components to a post-manufacturing process known as Hot Solder Dip (HSD). One of the main concerns for adopting HSD (refinishing) as a strategy to the tin whisker problem is the potential risk for thermally induced damage in the components when subjected to this process.     

The depth profiling of TiO2 pigmented coil coatings using step scan phase modulation photoacoustic FTIR

The depth distribution of a TiO₂ pigment within the polyurethane (PU) coil coatings is investigated using step scan phase modulation photoacoustic (SS-PM-PA) FTIR. Coil coatings with different pigment contents were prepared and the modulation frequency (MF) of the SS-PM-PA FTIR varied to record the depth distribution of the pigment within the coating. The TiO₂ pigment was shown to contribute significantly to the SS-PM-PA FTIR signal. A TiO₂ aggregated region within the topcoat is found close to the topcoat-primer interface and further away from the topcoat surface. A deeper TiO₂ aggregated region can be identified when pigment content is relatively low. The SS-PM-PA FTIR signal shows a considerable contribution from the primer originated signal, provided the TiO₂ pigment content is sufficiently high and the modulation frequency applied is relatively low. SEM cross-section imaging results show a strong correlation of the TiO₂ depth distribution with SS-PM-PA FTIR results, which confirms the applicability of the SS-PM-PA FTIR technique to the depth profiling study of TiO₂ pigmented coil coatings.     

Production worthy method to structure platinum electrodes for ferroelectric devices elisabeth

Abstract

Platinum (Pt) is a viable electrode material for use with ferroelectric films to form FeRAM cells. Due to the chemical stability of Pt etching at low-temperature, drawbacks like tapered Pt profiles with poor CD control and low mean time between cleans are resulting.

In this work plasma etching of sub-micron Pt electrodes with vertical and veil-free profiles was successfully demonstrated. This was obtained by maintaining substrate temperatures >250°C, assisting etch by-product volatility and promotion of necessary chemical reactions.

The production worthiness of high-temperature Pt etching was evaluated by a marathon run on simulated product material while monitoring the process parameter stability. Production was successfully simulated by 950 product like substrates for more than 34 plasma hours. Stable wafer-to-wafer performance in all monitored parameters demonstrated the production worthiness of this platinum electrode structuring method for applications in FeRAM manufacturing.     

Advances in Etching High-Density Embedded FRAM Structures

The development of ferroelectric random access memories (FRAM) has been a sustained endeavor among semiconductor manufacturers over the past decade in response to the growing communications and consumer electronics demand for nonvolatile memories capable of high-speed/low-voltage operation. Process technology and materials performance improvements have refined cell structure, device density, operating voltage, endurance, and data retention. Similarly, advances are being made in etch technology to enable the patterning of true high-density, electrically sound FRAM capacitor arrays. This paper addresses enhancements in chamber design and etch chemistry that have significantly improved electrical performance of the capacitors and achieved sustained stability of the etch process.     

Voltage jump during polarization of a PEM fuel cell operated at low relative humidities

A PEM fuel cell with a Nafion 211 membrane-based membrane electrode assembly (MEA) was tested with an H₂/air stoichiometry of 2/4 at 25%, 50%, 75%, and 100% relative humidities. A voltage jump on the polarization curve was observed when the cell was operated at a lower humidity. This phenomenon may be explained by the water back-diffusion from the cathode into the membrane resulting in both a non-uniform water distribution in the membrane and a liquid-equilibrated interface between the membrane and the anode catalyst layer. Experimental results obtained by AC impedance spectroscopy measuring the MEA resistance (membrane+catalyst ionomer layers) at different current densities as well as collected polarization data at high feed-gas flow rates (or at low backpressures) and high temperatures all confirmed the validity of the proposed water back-diffusion hypothesis.     

A fourth empirically derived cluster of chronic pain patients based on the Multidimensional Pain Inventory: Evidence for repression within the dysfunctional group.

The authors proposed that chronic pain patients with repressive defenses are not represented in current 3-cluster solutions of the Multidimensional Pain Inventory and that such a group can be distinguished by using a measure of defensiveness together with subscales of the MPI. For 178 pain patients, hierarchical cluster analyses were performed on the MPI and Balanced Inventory of Desirable Responding. Profile analysis of validation measures showed that repressors scored comparably with dysfunctional patients on somatic symptoms of depression, pain severity, and perceived disability but significantly higher on these factors than the adaptive copers. Repressors scored comparably with adaptive copers on cognitive-affective symptoms of depression, anxiety, and anger but significantly lower on these variables than dysfunctional patients. Repressors also reported greater pain severity and perceived disability relative to their reports of negative affect, whereas dysfunctional and adaptive coper groups exhibited no such disparities. Without a measure of defensiveness, the MPI may misclassify a distinct group of patients as dysfunctional, but who readily endorse physical symptoms yet report low levels of emotional distress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)