The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration

Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into various cell types and have been used widely in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with the activation of the PI3K/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functinalities. Biomaterials have been modified in their properties, surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

A comparison study on hydrogen sensing performance of Pt/MoO3 nanoplatelets coated with a thin layer of Ta2O5 or La2O3

In this work, we investigate how hydrogen sensing performance of thermally evaporated MoO3 nanoplatelets can be further improved by RF sputtering a thin layer of tantalum oxide (Ta2O5) or lanthanum oxide (La2O3). We show that dissociated hydrogen atoms cause the thin film layer to be polarised, inducing a measurable potential difference greater than that as reported previously. We attribute these observations to the presence of numerous traps in the thin layer; their states allow a stronger trapping of charge at the Pt-thin film oxide interface as compared to the MoO3 sensors without the coating. Under exposure to H2 (10 000 ppm) the maximum change in dielectric constant of 45.6 (at 260 °C) for the Ta2O5/MoO3 nanoplatelets and 31.6 (at 220 °C) for La2O3/MoO3 nanoplatelets. Subsequently, the maximum sensitivity for the Ta2O5/MoO3 is 16.87 (at 260 °C) and La2O3/MoO3 is 7.52 (at 300 °C).

Growing profitable or growing from profits : putting the horse in front of the cart?

Top lists of and praise for the economy's fastest growing firms abound in business media around the world. Similarly, in academic research there has been a tendency to equate firm growth with business success. This tendency appears to be particularly pronounced in-but not confined to­ entrepreneurship research. In this study we critically examine this tendency to portray firm growth as more or less universally favorable. While several theories suggest that growth drives profitability we first show that the available empirical evidence does not support the existence of a general, positive relation­ ship between growth and profitability. Using the theoretical lens of the Resource-Based View (RBV) we then argue that sound growth usually starts with achieving sufficient levels of profitability. In summary, our theoretical argument is as follows: In a population of SMEs, superior profitability is likely to be indicative of having built a resource-based competitive advantage. Building such a valuable and hard to-copy advantage may at first constrain growth. However, the underlying advantage itself and the financial resources generated through high profitability make it possible for firms in this situation to now achieve sound and sustainable growth - which may require building a series of temporary advantages- without having to sacrifice profitability. By contrast, when firms strive for high growth starting from low profitability, the latter often indicates lack of competitive advantage. Therefore growth must be achieved in head-to-head competition with equally attractive alternatives, leading to profitability deterioration rather than improvement. In addition, these low profitability firms are unlikely to be able to finance strategies toward building valuable and difficult-to-imitate advantages while growing.

Rock, paper, scissors : reflective practice for design process in the novice landscape architect

We describe a pedagogical approach that addresses challenges in design education for novices. These include an inability to frame new problems and limited-to-no design capability or domain knowledge. Such challenges can reduce student engagement with design practice, cause derivative design solutions as well as the inappropriate simplification of design assignments and assessment criteria by educators. We argue that a curriculum that develops the student’s design process will enable them to deal with the uncertain and dynamic situations that characterise design. We describe how this may be achieved and explain our pedagogical approach in terms of methods from Reflective Practice and theories of abstraction and creativity. We present a landscape architecture unit, recently taught, as an example. It constitutes design exercises that require little domain or design expertise to support the development of conceptual thinking and a design rationale. We show how this approach (a) leveraged the novice’s existing spatial and thinking skills while (b) retaining contextually-rich design situations. Examples of the design exercises taught are described along with samples of student work. The assessment rationale is also presented and explained. Finally, we conclude by reflecting on how this approach relates to innovation, sustainability and other disciplines.

A description of the Mei2-like protein family; structure, phylogenetic distribution and biological context

The Schizosaccharomyces pombe Mei2 gene encodes an RNA recognition motif (RRM) protein that stimulates meiosis upon binding a specific non-coding RNA and subsequent accumulation in a “mei2-dot” in the nucleus. We present here the first systematic characterization of the family of proteins with characteristic Mei2-like amino acid sequences. Mei2-like proteins are an ancient eukaryotic protein family with three identifiable RRMs. The C-terminal RRM (RRM3) is unique to Mei2-like proteins and is the most highly conserved of the three RRMs. RRM3 also contains conserved sequence elements at its C-terminus not found in other RRM domains. Single copy Mei2-like genes are present in some fungi, in alveolates such as Paramecium and in the early branching eukaryote Entamoeba histolytica, while plants contain small families of Mei2-like genes. While the C-terminal RRM is highly conserved between plants and fungi, indicating conservation of molecular mechanisms, plant Mei2-like genes have changed biological context to regulate various aspects of developmental pattern formation.

SECIS-binding protein 2 promotes cell survival by protecting against oxidative stress

Reactive oxygen species (ROS) are a primary cause of cellular damage that leads to cell death. In cells, protection from ROS-induced damage and maintenance of the redox balance is mediated to a large extent by selenoproteins, a distinct family of proteins that contain selenium in form of selenocysteine (Sec) within their active site. Incorporation of Sec requires the Sec-insertion sequence element (SECIS) in the 3'-untranslated region of selenoproteins mRNAs and the SECIS-binding protein 2 (SBP2). Previous studies have shown that SBP2 is required for the Sec-incorporation mechanism; however, additional roles of SBP2 in the cell have remained undefined. We herein show that depletion of SBP2 by using antisense oligonucleotides (ASOs) causes oxidative stress and induction of caspase- and cytochrome c-dependent apoptosis. Cells depleted of SBP2 have increased levels of ROS, which lead to cellular stress manifested as 8-oxo-7,8-dihydroguanine (8-oxo-dG) DNA lesions, stress granules, and lipid peroxidation. Small-molecule antioxidants N-acetylcysteine, glutathione, and α-tocopherol only marginally reduced ROS and were unable to rescue cells fully from apoptosis, indicating that apoptosis might be directly mediated by selenoproteins. Our results demonstrate that SBP2 is required for protection against ROS-induced cellular damage and cell survival. Antioxid. Redox Signal. 12, 797–808.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Permeability of high-performance concrete incorporating presoaked lightweight aggregates for internal curing

This paper presents an experimental study on the effect of presoaked lightweight aggregates (LWAs) for internal curing on water permeability, water absorption and resistance of concrete to chloride-ion penetration in comparison with those of a control concrete and a concrete with shrinkage reducing admixture (SRA) of similar water/cement ratios (w/c). In general, the concretes with LWA particles had initial water absorption, sorptivity and water permeability similar to or lower than those of the control concrete and the concrete with SRA. The charges passed, chloride migration coefficient and chloride diffusion coefficient of such concretes were in the same order as those of the control concrete and the concrete with SRA. However, the incorporation of the LWAs for internal curing reduced unit weight, compressive strength and elastic modulus of the concrete. Comparing the LWAs of different sizes for internal curing, finer particles were more efficient in reducing the shrinkage and generally resulted in less reduction in the unit weight, compressive strength, and elastic modulus. However, the increase in the more porous crushed LW particles in concrete seems to increase the penetration of chloride ions in the concrete. The concrete with SRA had initial water absorption, sorptivity, water permeability and resistance to chloride ion penetration comparable with those of the control concrete. The use of SRA in concrete does not affect the elastic modulus of the concrete, except for a minor influence on the compressive strength of the concrete.

Digital soapboxes : towards an interaction design agenda for situated civic innovation

We argue that there are at least two significant issues for interaction designers to consider when creating the next generation of human interfaces for civic and urban engagement: (1) The disconnect between citizens participating in either digital or physical realms has resulted in a neglect of the hybrid role that public place and situated technology can play in contributing to civic innovation. (2) Under the veneer of many social media tools, hardly any meaningful strategies or approaches are found that go beyond awareness raising and allow citizens to do more than clicking a ‘Like’ button. We call for an agenda to design the next generation of ‘digital soapboxes’ that contributes towards a new form of polity helping citizens not only to have a voice but also to appropriate their city in order to take action for change.

Urban agriculture : a growing field of research workshop at INTERACT 2013

Growing food presents diverse challenges and opportunities within the urban environment. As cities develop, population density rises, land prices rise, and the opportunity to use land for traditional farming and gardening diminishes. Counter to this trend there are a growing number of both community gardens, city farms, guerrilla gardening, rooftop and vertical gardens, pot plants, windowsill herbs, and other balcony or backyard gardens cropping up in different cities, all with a purpose to produce food. This workshop brings to-gether practitioners and researchers in the field of urban agriculture and Hu-man-Computer Interaction to explore and opportunities for technology design to support the different forms of growing practice and foster local food production in cities. This 1-day workshop will serve as an active forum for researchers and practi-tioners across various fields including, but not limited to, agriculture and gar-dening, education, urban planning, human-computer interaction, and communi-ty engagement. This workshop has three distinct points of focus: i) Individual and small-scale gardening and food production, and how to connect like minded people who are involved in these practices to share their knowledge ii) Com-munities involved in urban agriculture, either through community gardens, city farms, or grassroots movements, often dependant on volunteer participation, providing the challenge of managing limited resources iii) Environmental and sociocultural sustainability through urban agriculture. The participants will have an opportunity to present their own work. This will be followed by a visit to a nearby city farm, which will provide a local context for a group design exercise. Finally the workshop will conclude with panel dis-cussions to review opportunities for further research and collaborations beyond the conference. For more information, please visit the workshop website, at http://www.urbaninformatics.net/resources/interact2013cfp/

Establishment and characterisation of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model

Background A large animal model is required for assessment of minimally invasive, tissue engineering based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here we develop a novel open mini–thoracotomy approach in an ovine model of thoracic interbody fusion which allows assessment of various fusion constructs, with a focus on novel, tissue engineering based interventions. Methods The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances required of the study. Twelve male Merino sheep aged 4 to 6 years and weighing 35 – 45 kg underwent the abovementioned procedure and were divided into two groups of six sheep at survival timelines of 6 and 12 months. Each sheep underwent a 3-level discectomy (T6/7, T8/9 and T10/11) with randomly allocated implantation of a different graft substitute at each of the three levels; (i) polycaprolactone (PCL) based scaffold plus 0.54μg rhBMP-2, (ii) PCL-based scaffold alone or (iii) autograft. The sheep were closely monitored post- operatively for signs of pain (i.e. gait abnormalities/ teeth gnawing/ social isolation). Fusion assessments were conducted post-sacrifice using Computed Tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol has been approved by the Institute's committee on animal research. Results. All twelve sheep were successfully operated on and reached the allotted survival timelines, thereby demonstrating the feasibility of the surgical procedure and post-operative care. There were no significant complications and during the post-operative period the animals did not exhibit marked signs of distress according to the described assessment criteria. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluation of the respective groups. Conclusion. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method which can reproducibly form the platform for research into various spine tissue engineered constructs (TEC) and their fusion promoting properties.

EatChaFood : challenging technology design to slice food waste production

This paper presents work in progress of EatChaFood – a prototype app designed to increase user knowledge of the currently available domestic supply and location of food, with a view to reducing expired household food waste. In order to reap the benefits that EatChaFood can provide we explore ways to overcome manual data entry as a barrier to use. Our user study has to recognise the limitations of the prototype app, and conduct an evaluation of the interaction design built into the app to promote behaviour change. Innovations in the near future such as the automatic scanning of barcodes on food items or photo-recognition will close the gap between perceived prototype usability and usefulness.

TrainRoulette : promoting situated in-train social interaction between passengers

Travelling by public transport is usually regarded as boring and uninteresting. Refraining from talking to the stranger next to you may be due to limitations that are self-imposed and further corroborated by social expectations and cultural norms that govern behaviour in public space. Our design research into passenger interactions on board of urban commuter trains has informed the development of the TrainRoulette prototype – a mobile app for situated, real-time chats between train passengers. We study the impact of our design intervention on shaping perceptions of the train journey experience. Moreover, we are interested in the implications of such ICT-mediated interactions within train journeys for stimulating social offline interactions and new forms of passenger engagement.

Automatic object segmentation of unstructured scenes using colour and depth maps

This study presents a segmentation pipeline that fuses colour and depth information to automatically separate objects of interest in video sequences captured from a quadcopter. Many approaches assume that cameras are static with known position, a condition which cannot be preserved in most outdoor robotic applications. In this study, the authors compute depth information and camera positions from a monocular video sequence using structure from motion and use this information as an additional cue to colour for accurate segmentation. The authors model the problem similarly to standard segmentation routines as a Markov random field and perform the segmentation using graph cuts optimisation. Manual intervention is minimised and is only required to determine pixel seeds in the first frame which are then automatically reprojected into the remaining frames of the sequence. The authors also describe an automated method to adjust the relative weights for colour and depth according to their discriminative properties in each frame. Experimental results are presented for two video sequences captured using a quadcopter. The quality of the segmentation is compared to a ground truth and other state-of-the-art methods with consistently accurate results.

Copyright protections and disability rights : turning the page to a new international paradigm

This paper argues that governments around the world need to take immediate coordinated action to reverse the 'book famine.' There are over 129 million book titles in the world, but persons with print disabilities can obtain less than 7% of these titles in formats that they can read. The situation is most acute in developing countries, where less than 1% of books are accessible. Two recent international developments – the United Nations Convention on the Rights of Persons with Disabilities (‘CRPD’) and the new Marrakesh Treaty to Facilitate Access to Published Works for Persons who are Blind, Visually Impaired, or otherwise Print Disabled (somewhat ironically nicknamed the ‘VIP Treaty’) – suggest that nation states are increasingly willing to take action to reverse the book famine. The Marrakesh Treaty promises to level out some of the disparity of access between people in developed and developing nations and remove the need for each jurisdiction to digitise a separate copy of each book. This is a remarkable advance, and suggests the beginnings of a possible paradigm shift in global copyright politicsmade all the more remarkable in the face of heated opposition by global copyright industry representatives. Now that the Marrakesh Treaty has been concluded, however, we argue that a substantial exercise of global political will is required to (a) invest the funds required to digitise existing books; and (b) avert any further harm by ensuring that books published in the future are made accessible upon their release.