Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA

We report that tumor cells devoid of their mitochondrial genome (mtDNA) show delayed tumor growth and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory supercomplexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest a novel pathophysiological process for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.

Development and parameterization of a rain- and fire-driven model for exploring elephant effects in African savannas

We describe the development and parameterization of a grid-based model of African savanna vegetation processes. The model was developed with the objective of exploring elephant effects on the diversity of savanna species and structure, and in this formulation concentrates on the relative cover of grass and woody plants, the vertical structure of the woody plant community, and the distribution of these over space. Grid cells are linked by seed dispersal and fire, and environmental variability is included in the form of stochastic rainfall and fire events. The model was parameterized from an extensive review of the African savanna literature; when available, parameter values varied widely. The most plausible set of parameters produced long-term coexistence between woody plants and grass, with the tree-grass balance being more sensitive to changes in parameters influencing demographic processes and drought incidence and response, while less sensitive to fire regime. There was considerable diversity in the woody structure of savanna systems within the range of uncertainty in tree growth rate parameters. Thus, given the paucity of height growth data regarding woody plant species in southern African savannas, managers of natural areas should be cognizant of different tree species growth and damage response attributes when considering whether to act on perceived elephant threats to vegetation. © 2007 Springer Science+Business Media B.V.

Instance-driven TBox revision in DL-Lite

The development and maintenance of large and complex ontologies are often time-consuming and error-prone. Thus, automated ontology learning and revision have attracted intensive research interest. In data-centric applications where ontologies are designed or automatically learnt from the data, when new data instances are added that contradict to the ontology, it is often desirable to incrementally revise the ontology according to the added data. This problem can be intuitively formulated as the problem of revising a TBox by an ABox. In this paper we introduce a model-theoretic approach to such an ontology revision problem by using a novel alternative semantic characterisation of DL-Lite ontologies. We show some desired properties for our ontology revision. We have also developed an algorithm for reasoning with the ontology revision without computing the revision result. The algorithm is efficient as its computational complexity is in coNP in the worst case and in PTIME when the size of the new data is bounded.

Design of coreless PCB transformers for power and signal isolation in a modular ADC system for power quality data acquisition

Available industrial energy meters offer high accuracy and reliability, but are typically expensive and low-bandwidth, making them poorly suited to multi-sensor data acquisition schemes and power quality analysis. An alternative measurement system is proposed in this paper that is highly modular, extensible and compact. To minimise cost, the device makes use of planar coreless PCB transformers to provide galvanic isolation for both power and data. Samples from multiple acquisition devices may be concentrated by a central processor before integration with existing host control systems. This paper focusses on the practical design and implementation of planar coreless PCB transformers to facilitate the module's isolated power, clock and data signal transfer. Calculations necessary to design coreless PCB transformers, and circuits designed for the transformer's practical application in the measurement module are presented. The designed transformer and each application circuit have been experimentally verified, with test data and conclusions made applicable to coreless PCB transformers in general.

Curiosity driven reinforcement learning for motion planning on humanoids

Most previous work on artificial curiosity (AC) and intrinsic motivation focuses on basic concepts and theory. Experimental results are generally limited to toy scenarios, such as navigation in a simulated maze, or control of a simple mechanical system with one or two degrees of freedom. To study AC in a more realistic setting, we embody a curious agent in the complex iCub humanoid robot. Our novel reinforcement learning (RL) framework consists of a state-of-the-art, low-level, reactive control layer, which controls the iCub while respecting constraints, and a high-level curious agent, which explores the iCub's state-action space through information gain maximization, learning a world model from experience, controlling the actual iCub hardware in real-time. To the best of our knowledge, this is the first ever embodied, curious agent for real-time motion planning on a humanoid. We demonstrate that it can learn compact Markov models to represent large regions of the iCub's configuration space, and that the iCub explores intelligently, showing interest in its physical constraints as well as in objects it finds in its environment.

Initial design and physical characterization of a polymeric device for osmosis-driven delayed burst delivery of vaccines

Achieving the combination of delayed and immediate release of a vaccine from a delivery device without applying external triggers remains elusive in implementing single administration vaccination strategies. Here a means of vaccine delivery is presented, which exploits osmosis to trigger delayed burst release of an active compound. Poly(-caprolactone) capsules of 2 mm diameter were prepared by dip-coating, and their burst pressure and release characteristics were evaluated. Burst pressures (in bar) increased with wall thickness (t in mm) following Pburst = 131.t + 3.4 (R2 = 0.93). Upon immersion in PBS, glucose solution-filled capsules burst after 8.7 ± 2.9 days. Copolymers of hydrophobic  -caprolactone and hydrophilic polyethylene glycol were synthesized and their physico-chemical properties were assessed. With increasing hydrophilic content, the copolymer capsules showed increased water uptake rates and maximum weight increase, while the burst release was earlier: 5.6 ± 2.0 days and 1.9 ± 0.2 days for 5 and 10 wt% polyethylene glycol, respectively. The presented approach enables the reproducible preparation of capsules with high versatility in materials and properties, while these vaccine delivery vehicles can be prepared separately from, and independently of the active compound.

The impact of intense training on endogenous estrogen and progesterone concentrations and bone mineral acquisition in adolescent rowers

The effect of 18 months of training on the ovarian hormone concentrations and bone mineral density (BMD) accrual was assessed longitudinally in 14 adolescent rowers and 10 matched controls, aged 14–15 years. Ovarian hormone levels were assessed by urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) excretion rates, classifying the menstrual cycles as ovulatory or anovulatory. Total body (TB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) (L2–4) bone mass were measured at baseline and 18 months using dual-energy X-ray densitometry. Results were expressed as bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Five rowers had anovulatory menstrual cycles compared with zero prevalence for the control subjects. Baseline TB BMD was significantly higher in the ovulatory rowers, with PF BMD, FN BMD and LS BMD similar for all groups. At completion, the LS bone accrual of the ovulatory rowers was significantly greater (BMC 8.1%, BMD 6.2%, BMAD 6.2%) than that of the anovulatory rowers (BMC 1.1%, BMD 3.9%, BMAD 1.6%) and ovulatory controls (BMC 0.5%, BMD 1.1%, BMAD 1.1%). No difference in TB, PF or FN bone accrual was observed among groups. This study demonstrated an osteogenic response to mechanical loading, with the rowers accruing greater bone mass than the controls at the lumbar spine. However, the exercise-induced osteogenic benefits were less when rowing training was associated with low estrogen and progesterone metabolite excretion.

Data driven and practice-based evidence : design and development of efficient and effective clinical decision support system

Decision-making is such an integral aspect in health care routine that the ability to make the right decisions at crucial moments can lead to patient health improvements. Evidence-based practice, the paradigm used to make those informed decisions, relies on the use of current best evidence from systematic research such as randomized controlled trials. Limitations of the outcomes from randomized controlled trials (RCT), such as “quantity” and “quality” of evidence generated, has lowered healthcare professionals’ confidence in using EBP. An alternate paradigm of Practice-Based Evidence has evolved with the key being evidence drawn from practice settings. Through the use of health information technology, electronic health records (EHR) capture relevant clinical practice “evidence”. A data-driven approach is proposed to capitalize on the benefits of EHR. The issues of data privacy, security and integrity are diminished by an information accountability concept. Data warehouse architecture completes the data-driven approach by integrating health data from multi-source systems, unique within the healthcare environment.

Molecular analysis of asymptomatic bacteriuria escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

Exploring Environmental Stewardship Through Data-Driven Practices

What potential do artists working with environmental data in public space have for producing new forms of engagement with local environmental conditions? Operating on the edge of heavy bureaucracy, these types of data-driven artistic experiments probe the politics of environmental metrics and explore methods of engaging audiences with issues of environmental health. This discussion considers a small collection of cases studies representative of this growing field of practice. These are works by Natalie Jeremijenko and The Living, Tega Brain and Keith Deverell. The case studies considered are examples of strategic design, works that soften, reveal and potentially shift existing regulations and bureaucratic norms. In doing so they open up new possibilities and questions as to what the smart city is and how it might be realised.

User centred engineering in automotive design: A shift from technology-driven product development

The research assessed how best to transition engineering-based automotive firms towards more customer-orientated design and development approaches, whilst identifying the main barriers and concerns facing such a shift. The research investigates the ability of a firm to empower individual engineers with user centred design tools traditionally used by designers, whilst understanding the company-wide needs to facilitate their implementation.

Customer-driven innovation: Digital channels and community

This study investigates the role of digital channels in community-led businesses by exploring two case study companies, Uber and Airbnb. At present, these community-led businesses are disrupting traditional industries by connecting with customers via digital channels and facilitating transactions between two parties. A deductive structured qualitative content analysis approach utilising a predetermined categorization matrix was implemented to decipher the digital channels used by both companies. The results discovered that both company’s digital channels push the customer to their core channel, allowing, customers to create their own physical, largely self-governed communities. However, little research exists which explores and analyses the role of digital channels in forming community-led businesses. Therefore, this paper aims to instigate future research and discussion in this emerging area by concluding with future research agendas.

International regulation of large-scale land acquisition involving foreign entities

Outlines some of the potential risks or actual harms that result from large-scale land leases or acquisitions and the relevant human rights and environmental law principles.