Induced Förster resonance energy transfer by encapsulation of DNA-scaffold based probes inside a plant virus based protein cage

Insight into the assembly and disassembly of viruses can play a crucial role in developing cures for viral diseases. Specialized fluorescent probes can benefit the study of interactions within viruses, especially during cell studies. In this work, we developed a strategy based on Förster resonance energy transfer (FRET) to study the assembly of viruses without labeling the exterior of viruses. Instead, we exploit their encapsulation of nucleic cargo, using three different fluorescent ATTO dyes linked to single-stranded DNA oligomers, which are hybridised to a longer DNA strand. FRET is induced upon assembly of the cowpea chlorotic mottle virus, which forms monodisperse icosahedral particles of about 22 nm, thereby increasing the FRET efficiency by a factor of 8. Additionally, encapsulation of the dyes in virus-like particles induces a two-step FRET. When the formed constructs are disassembled, this FRET signal is fully reduced to the value before encapsulation. This reversible behavior makes the system a good probe for studying viral assembly and disassembly. It, furthermore, shows that multi-component supramolecular materials are stabilized in the confinement of a protein cage.</p

Identifying design criteria for urban system last-mile solutions -A multi-stakeholder perspective

This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/09537287.2016.1147099This study presents a novel approach to design and evaluate ‘last-mile’ solutions – encompassing the social and economic perspectives of key stakeholders. While urban system initiatives have been implemented in practice, theoretical gaps remain at the operational design level. A theoretical framework is developed, based on design criteria identified from a critical synthesis of supply chain and operations management literature, and ‘operationalised’ using an in-depth case study demonstrating implementation of a Consumer Choice Portal-Package Consolidation Centre solution, within a densely populated urban geography. Findings suggest that there is a need to re-define the role of institutional actors beyond that of the traditional governance task, to one of being able to facilitate performance outcomes. Similarly, industrial efficiency dimensions need to be reorientated to include consumer participation, social considerations and multi-stakeholder service outcomes. Finally, implications for operations theory and practising managers in city logistics are highlighted, with suggested directions for future research.TS

Pretenuring for Java

Pretenuring is a technique for reducing copying costs in garbage collectors. When pretenuring, the allocator places long-lived objects into regions that the garbage collector will rarely, if ever, collect. We extend previous work on profiling-driven pretenuring as follows. (1) We develop a collector-neutral approach to obtaining object lifetime profile information. We show that our collection of Java programs exhibits a very high degree of homogeneity of object lifetimes at each allocation site. This result is robust with respect to different inputs, and is similar to previous work on ML, but is in contrast to C programs, which require dynamic call chain context information to extract homogeneous lifetimes. Call-site homogeneity considerably simplifies the implementation of pretenuring and makes it more efficient. (2) Our pretenuring advice is neutral with respect to the collector algorithm, and we use it to improve two quite different garbage collectors: a traditional generational collector and an older-first collector. The system is also novel because it classifies and allocates objects into 3 categories: we allocate immortal objects into a permanent region that the collector will never consider, long-lived objects into a region in which the collector placed survivors of the most recent collection, and shortlived objects into the nursery, i.e., the default region. (3) We evaluate pretenuring on Java programs. Our simulation results show that pretenuring significantly reduces collector copying for generational and older-first collectors. 1

Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings

Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy, preoperative MRI leads to the detection of clinically relevant additional findings in a substantial percentage of patients, irrespective of the percentage of the lobular component. Detection of a small lobular component may however not be reproducible among pathologists. Loss of membrane expression of E-cadherin or p120 is useful biomarkers of ILC and may therefore support a more objective diagnosis. All patients diagnosed with breast cancer containing a lobular component of any percentage between January 2008 and October 2012 were prospectively offered preoperative MRI. Clinically relevant additional findings on MRI were verified by pathology evaluation. Expression patterns of E-cadherin and p120 were evaluated by immunohistochemistry on the core needle biopsy. MRI was performed in 109 patients. The percentage of lobular component was significantly increased in cases with aberrant E-cadherin or p120 expression (both p = <0.001). However, aberrant expression of E-cadherin and p120 was not related to the probability of detecting relevant additional MRI findings. E-cadherin and p120 did not appear to be useful objective biomarkers for predicting additional relevant findings on MRI in patients with a lobular component in the core needle of their breast cancer