Survivin : a target from brain cancer to neurodegenerative disease

Apoptosis is an important contributing factor during neuronal death in a variety of neurodegenerative disorders, including multiple sclerosis, Parkinson's disease and sciatic nerve injury. Whereas several clinical and preclinical studies have focused on the neuroprotective effects of caspase inhibitors, their clinical benefits are still unclear. Here, we discuss novel alternative strategies to protect neuronal cells from apoptotic death using members of the inhibitors of apoptosis (IAP) family. We specifically review the different roles of survivin, which is an important member of the IAP family that serves a dual role in the inhibition of apoptosis as well as a vital role in mitosis and cell division. Due to the various roles of survivin during cell division and apoptosis, targeting this protein illustrates a new therapeutic window for the treatment of neurodegenerative diseases.

Comparison between response surface models and artificial neural networks in hydrologic forecasting

Developing an efficient and accurate hydrologic forecasting model is crucial to managing water resources and flooding issues. In this study, response surface (RS) models including multiple linear regression (MLR), quadratic response surface (QRS), and nonlinear response surface (NRS) were applied to daily runoff (e.g., discharge and water level) prediction. Two catchments, one in southeast China and the other in western Canada, were used to demonstrate the applicability of the proposed models. Their performances were compared with artificial neural network (ANN) models, trained with the learning algorithms of the gradient descent with adaptive learning rate (ANN-GDA) and Levenberg-Marquardt (ANN-LM). The performances of both RS and ANN in relation to the lags used in the input data, the length of the training samples, long-term (monthly and yearly) predictions, and peak value predictions were also analyzed. The results indicate that the QRS and NRS were able to obtain equally good performance in runoff prediction, as compared with ANN-GDA and ANN-LM, but require lower computational efforts. The RS models bring practical benefits in their application to hydrologic forecasting, particularly in the cases of short-term flood forecasting (e.g., hourly) due to fast training capability, and could be considered as an alternative to ANN

Redefining teacher education through a `multiple space` model: examining the forgotten spaces that teachers work in

This paper maps the current debates surrounding school-based and university-based teacher education models, and presents a ‘multiple-space’ model of teacher education that both explores and values the many ‘forgotten’ spaces that teachers work in. It draws from a variety of research studies, including my own doctoral work, to argue for a new approach to teacher education programs. I suggest that in order for teacher education to move beyond separatist, binary models, we need to adopt a ‘multiple-space’ view of learning to be a teacher that embraces the notion that teachers do not learn about theory in a university space, nor do they simply work in a classroom space.

Suppression by ABA of salicylic acid and lignin accumulation and the expression of multiple genes, in Arabidopsis infected with Pseudomonas syringae pv. tomato

Abscisic acid (ABA) has been implicated in determining the outcome of interactions between many plants and their pathogens. We had previously shown that increased concentrations of ABA within leaves of Arabidopsis induced susceptibility towards an avirulent strain of Pseudomonas syringae pathovar (pv.) tomato. We now show that ABA induces susceptibility via suppression of the accumulation of components crucial for a resistance response. Lignin and salicylic acid concentrations in leaves were increased during a resistant interaction but reduced when plants were treated with ABA. The reduction in lignin and salicylic acid production was independent of the development of the hypersensitive response (HR), indicating that, in this host-pathogen system, HR is not required for resistance. Genome-wide gene expression analysis using microarrays showed that treatment with ABA suppressed the expression of many defence-related genes, including those important for phenylpropanoid biosynthesis and those encoding resistance-related proteins. Together, these results show that resistance induction in Arabidopsis to an avirulent strain of P. syringae pv. tomato is regulated by ABA.

Multiple urea transporter proteins in the kidney of holocephalan elephant fish (Callorhinchus milii)

Reabsorption of filtered urea by the kidney is essential for retaining high levels of urea in marine cartilaginous fish. Our previous studies on the shark facilitative urea transporter (UT) suggest that additional UT(s) comprising the urea reabsorption system could exist in the cartilaginous fish kidney. Here, we isolated three cDNAs encoding UTs from the kidney of elephant fish, Callorhinchus milii, and termed them efUT-1, efUT-2 and efUT-3. efUT-1 is orthologous to known elasmobranch UTs, while efUT-2 and efUT-3 are novel UTs in cartilaginous fish. Two variants were found for efUT-1 and efUT-2, in which the NH₂-terminal intracellular domain was distinct between the variants. Differences in potential phosphorylation sites were found in the variant-specific NH2-terminal domains. When expressed in Xenopus oocytes, all five UT transcripts including the efUT-1 and efUT-2 variants induced more than a 10-fold increase in [¹⁴C] urea uptake. Phloretin inhibited dose-dependently the increase of urea uptake, suggesting that the identified UTs are facilitative UTs. Molecular phylogenetic analysis revealed that efUT-1 and efUT-2 had diverged in the cartilaginous fish lineage, while efUT-3 is distinct from efUT-1 and efUT-2. The present finding of multiple UTs in elephant fish provides a key to understanding the molecular mechanisms of urea reabsorption system in the cartilaginous fish kidney.

Multiple vesicular morphologies in AB/AC diblock copolymer complexes through hydrogen bonding interactions

We report for the first time multiple vesicular morphologies in block copolymer complexes formed in aqueous media via hydrogen bonding interactions. A model AB/AC diblock copolymer system consisting of polystyrene-block- poly(acrylic acid) (PS-b-PAA) and polystyrene-block-poly(ethylene oxide) (PS-b-PEO) was examined using transmission electron microscopy, small-angle X-ray scattering, and dynamic light scattering. The complexation and morphological transitions were driven by the hydrogen bonding between the complementary binding sites on PAA and PEO blocks of the two diblock copolymers. Upon the addition of PS-b-PEO, a variety of bilayer aggregates were formed in PS-b-PAA/PS-b-PEO complexes including vesicles, multilamellar vesicles (MLVs), thick-walled vesicles (TWVs), interconnected compound vesicles (ICCVs), and irregular aggregates. Among these aggregates, ICCVs were observed as a new morphology. The morphology of aggregates was correlated with respect to the molar ratio of PEO to PAA. At [EO]/[AA] = 0.5, vesicles were observed, while MLVs were obtained at [EO]/[AA] = 1. TWVs and ICCVs were formed at [EO]/[AA] = 2 and 6, respectively. When [EO]/[AA] reached 8 and above, only irregular aggregates appeared. These findings suggest that complexation between two amphiphilic diblock copolymers is a viable approach to prepare polymer vesicles in aqueous media.

Design of multiple sequence alignment algorithms on parallel, distributed memory supercomputers

The challenge of comparing two or more genomes that have undergone recombination and substantial amounts of segmental loss and gain has recently been addressed for small numbers of genomes. However, datasets of hundreds of genomes are now common and their sizes will only increase in the future. Multiple sequence alignment of hundreds of genomes remains an intractable problem due to quadratic increases in compute time and memory footprint. To date, most alignment algorithms are designed for commodity clusters without parallelism. Hence, we propose the design of a multiple sequence alignment algorithm on massively parallel, distributed memory supercomputers to enable research into comparative genomics on large data sets. Following the methodology of the sequential progressiveMauve algorithm, we design data structures including sequences and sorted k-mer lists on the IBM Blue Gene/P supercomputer (BG/P). Preliminary results show that we can reduce the memory footprint so that we can potentially align over 250 bacterial genomes on a single BG/P compute node. We verify our results on a dataset of E.coli, Shigella and S.pneumoniae genomes. Our implementation returns results matching those of the original algorithm but in 1/2 the time and with 1/4 the memory footprint for scaffold building. In this study, we have laid the basis for multiple sequence alignment of large-scale datasets on a massively parallel, distributed memory supercomputer, thus enabling comparison of hundreds instead of a few genome sequences within reasonable time.

Detection of cross-channel anomalies from multiple data channels

We identify and formulate a novel problem: crosschannel anomaly detection from multiple data channels. Cross channel anomalies are common amongst the individual channel anomalies, and are often portent of significant events. Using spectral approaches, we propose a two-stage detection method: anomaly detection at a single-channel level, followed by the detection of cross-channel anomalies from the amalgamation of single channel anomalies. Our mathematical analysis shows that our method is likely to reduce the false alarm rate. We demonstrate our method in two applications: document understanding with multiple text corpora, and detection of repeated anomalies in video surveillance. The experimental results consistently demonstrate the superior performance of our method compared with related state-of-art methods, including the one-class SVM and principal component pursuit. In addition, our framework can be deployed in a decentralized manner, lending itself for large scale data stream analysis.

Online pattern classification with multiple neural network systems: an experimental study

In this paper, an empirical study of the development and application of a committee of neural networks on online pattern classification tasks is presented. A multiple classifier framework is designed by adopting an Adaptive Resonance Theory-based (ART) autonomously learning neural network as the building block. A number of algorithms for combining outputs from multiple neural classifiers are considered, and two benchmark data sets have been used to evaluate the applicability of the proposed system. Different learning strategies coupling offline and online learning approaches, as well as different input pattern representation schemes, including the "ensemble" and "modular" methods, have been examined experimentally. Benefits and shortcomings of each approach are systematically analyzed and discussed. The results are comparable, and in some cases superior, with those from other classification algorithms. The experiments demonstrate the potentials of the proposed multiple neural network systems in offering an alternative to handle online pattern classification tasks in possibly nonstationary environments.

An examination of the associations among multiple memory systems, past tense, and vocabulary in typically developing 5 year old children

Purpose: Considerable research has investigated the role of verbal working memory in language development in children with and without language problems. Much less is currently known about the relationship between language and the declarative and procedural memory systems. This study examined whether these 2 memory systems were related to typically developing children's past tense and lexical knowledge.

Method: Fifty-eight typically developing children approximately 5 years of age completed a battery of linguistic and nonlinguistic tasks, including tests of vocabulary, past tense production, and procedural and declarative memory.

Results: The results showed that declarative and procedural memory were not correlated with either regular or irregular past tense use. A significant correlation was observed between declarative memory and vocabulary.

Conclusions: The results of the study were not consistent with the view that the declarative and procedural memory systems support children's use of the regular and irregular past tense. However, evidence was found suggesting that declarative memory supports vocabulary in this age group.

Perceived benefits and barriers to exercise for recently treated patients with multiple myeloma: a qualitative study

Abstract
Background: Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM.
Methods: This was a qualitative study that used a grounded theory approach. Semi-structured interviews were conducted in Victoria, Australia by telephone from December 2011-February 2012 with patients who had been treated for MM within the preceding 2 – 12 months. Interviews were transcribed and analysed using the constant comparison coding method to reduce the data to themes. Gender differences and differences between treatment groups were explored.
Results: Twenty-four interviews were completed. The sample comprised 13 females (54%), with a mean age of 62 years (SD = 8.8). Sixteen (67%) participants had received an autologous stem cell transplant (ASCT). All participants currently engaged in a range of light to moderate intensity physical activity; walking and gardening were the most common activities. Recovery from the symptoms of MM and side effects of therapy, psychological benefits, social factors and enjoyment were important benefits of physical activity. Barriers to physical activity predominately related to the symptoms of MM and side effects of therapy, including pain, fatigue, and fear of infection. Low self- motivation was also a barrier. Women participated in a more diverse range of physical activities than men and there were gender differences in preferred type of physical activity. Women were more likely to report psychological and social benefits; whereas men reported physical activity as a way to keep busy and self- motivation was a barrier. Patients treated with an ASCT more often reported affective benefits of participation in physical activity and fatigue as a barrier. Patients treated with other therapies (e.g., chemotherapy, radiotherapy) were more likely to report pain as a barrier.
Conclusions: Patients with MM experience debilitating effects of their condition and therapy, which influences their level and intensity of physical activity participation. Physical activity programs should be individualised; take into consideration gender differences and the impact of different types of therapy on physical activity; and focus on meeting the psychological, coping and recovery needs of patients.

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

Online health information seeking: How people with multiple sclerosis find, assess and integrate treatment information to manage their health

Background and objective: The Internet is increasingly prominent as a source of health information for people with multiple sclerosis (MS). But there has been little exploration of the needs, experiences and preferences of people with MS for integrating treatment information into decision making, in the context of searching on the Internet. This was the aim of our study. Design: Sixty participants (51 people with MS; nine family members) took part in a focus group or online forum. They were asked to describe how they find and assess reliable treatment information (particularly online) and how this changes over time. Thematic analysis was underpinned by a coding frame. Results: Participants described that there was both too much information online and too little that applied to them. They spoke of wariness and scepticism but also empowerment. The availability of up-to-date and unbiased treatment information, including practical and lifestyle-related information, was important to many. Many participants were keen to engage in a 'research partnership' with health professionals and developed a range of strategies to enhance the trustworthiness of online information. We use the term 'self-regulation' to capture the variations in information seeking behaviour that participants described over time, as they responded to their changing information needs, their emotional state and growing expertise about MS. © 2014 John Wiley & Sons Ltd.

Multiple states of financially distressed companies: Tests using a competing-risks model

This study examines the determinants of multiple states of financial distress by applying a competing-risks model. It investigates the effect of financial ratios, market-based variables and company-specific variables, including company age, size and squared size on three different states of corporate financial distress: active companies; distressed external administration companies; and distressed takeover, merger or acquisition companies. A sample of 1,081 publicly listed Australian non-financial companies over the period 1989 to 2005 using a competing-risks model is used to determine the possible differences in the factors of entering various states of financial distress. It is found that specifically, distressed external administration companies have a higher leverage, lower past excess returns and a larger size; while distressed takeover, merger or acquisition companies have a lower leverage, a higher capital utilisation efficiency and a larger size compared to active companies. Comparing the results from both the single-risk model and the competing-risks model reveals the need to distinguish between financial distress states.

Multiple threats, or multiplying the threats? Interactions between invasive predators and other ecological disturbances

Invasive species have reshaped the composition of biomes across the globe, and considerable cost is now associated with minimising their ecological, social and economic impacts. Mammalian predators are among the most damaging invaders, having caused numerous species extinctions. Here, we review evidence of interactions between invasive predators and six key threats that together have strong potential to influence both the impacts of the predators, and their management. We show that impacts of invasive predators can be classified as either functional or numerical, and that they interact with other threats through both habitat- and community-mediated pathways. Ecosystem context and invasive predator identity are central in shaping variability in these relationships and their outcomes. Greater recognition of the ecological complexities between major processes that threaten biodiversity, including changing spatial and temporal relationships among species, is required to both advance ecological theory and improve conservation actions and outcomes. We discuss how novel approaches to conservation management can be used to address interactions between threatening processes and ameliorate invasive predator impacts.