Nanoformulated cell-penetrating survivin mutant and its dual actions

In this study, we investigated the differential actions of a dominant-negative survivin mutant (SurR9-C84A) against cancerous SK-N-SH neuroblastoma cell lines and differentiated SK-N-SH neurons. In both the cases, the mutant protein displayed dual actions, where its effects were cytotoxic toward cancerous cells and proliferative toward the differentiated neurons. This can be explained by the fact that tumorous (undifferentiated SK-N-SH) cells have a high endogenous survivin pool and upon treatment with mutant SuR9-C84A causes forceful survivin expression. These events significantly lowered the microtubule dynamics and stability, eventually leading to apoptosis. In the case of differentiated SK-N-SH neurons that express negligible levels of wild-type survivin, the mutant indistinguishably behaved in a wild-type fashion. It also favored cell-cycle progression, forming the chromosome-passenger complex, and stabilized the microtubule-organizing center. Therefore, mutant SurR9-C84A represents a novel therapeutic with its dual actions (cytotoxic toward tumor cells and protective and proliferative toward neuronal cells), and hence finds potential applications against a variety of neurological disorders. In this study, we also developed a novel poly(lactic-co-glycolic acid) nanoparticulate formulation to surmount the hurdles associated with the delivery of SurR9-C84A, thus enhancing its effective therapeutic outcome.

Validation of a multiplex reverse transcription and pre-amplification method using TaqMan(®) MicroRNA assays.

Since the discovery of microRNAs (miRNAs), different approaches have been developed to label, amplify and quantify miRNAs. The TaqMan(®) technology, provided by Applied Biosystems (ABIs), uses a stem-loop reverse transcription primer system to reverse transcribe the RNA and amplify the cDNA. This method is widely used to identify global differences between the expression of 100s of miRNAs across comparative samples. This technique also allows the quantification of the expression of targeted miRNAs to validate observations determined by whole-genome screening or to analyze few specific miRNAs on a large number of samples. Here, we describe the validation of a method published by ABIs on their web site allowing to reverse transcribe and pre-amplify multiple miRNAs and snoRNAs simultaneously. The validation of this protocol was performed on human muscle and plasma samples. Fast and cost efficient, this method achieves an easy and convenient way to screen a relatively large number of miRNAs in parallel.

Numerical modeling of dual phase microstructure behavior under deformation conditions on the basis of digital material representation

Development of a digital material representation (DMR) model of dual phase steel is presented within the paper. Subsequent stages involving generation of a reliable representation of microstructure morphology, assignment of material properties to component phases and incorporation of the model into the commercial finite element software are described within the paper. Different approaches used to recreate dual phase morphology in a digital manner are critically assessed. However, particular attention is placed on innovative identification of phase properties at the micro scale by using micro-pillar compression tests. The developed DMR model is finally applied to model influence of micro scale features on failure initiation and propagation under loading conditions.

Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome

 Objective: To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays aff ected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. Design, patients and setting: A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. Main outcome measures: Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. Results: 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically signifi cant diff erence in allhospital admission rates (95% CI for the diff erence, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the diff erence, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the diff erence, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the diff erence, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically signifi cant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the diff erence, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change signifi cantly (95% CI for the diff erence, - 1.5% to 0.8%; P = 0.43). Conclusion: The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no signifi cant change in rates of invasive treatment or inhospital mortality.

Modeling dual role preferences for trust-aware recommendation

Unlike in general recommendation scenarios where a user has only a single role, users in trust rating network, e.g. Epinions, are associated with two different roles simultaneously: as a truster and as a trustee. With different roles, users can show distinct preferences for rating items, which the previous approaches do not involve. Moreover, based on explicit single links between two users, existing methods can not capture the implicit correlation between two users who are similar but not socially connected. In this paper, we propose to learn dual role preferences (truster/trustee-specific preferences) for trust-aware recommendation by modeling explicit interactions (e.g., rating and trust) and implicit interactions. In particular, local links structure of trust network are exploited as two regularization terms to capture the implicit user correlation, in terms of truster/trustee-specific preferences. Using a real-world and open dataset, we conduct a comprehensive experimental study to investigate the performance of the proposed model, RoRec. The results show that RoRec outperforms other trust-aware recommendation approaches, in terms of prediction accuracy. Copyright 2014 ACM.

Strain partitioning in dual-phase steels containing tempered martensite

Tempering has been used as a method to develop a range of dual phase steels with the same martensite morphology and volume fraction, but containing phases with different relative strengths. These steels were used to examine the strain partitioning between the two constituent phases experimentally through mechanical testing and numerically through finite element modelling. It was found that increasing the differential in strength between the two phases not only produces regions of high strain, but also regions of low strain. On average, a larger difference in strength between the phases increased the strain carried by the softer phase. There was no discernible preferential strain localisation to the ferrite/martensite interface, with the regions of strain localisation being determined by the morphology of the microstructure. A direct correlation between the average strain in the ferrite, and the measured ductility has been found. © 2014 Elsevier B.V.