Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis

Myeloid leukaemias share the common characteristics of being stem cell-derived clonal diseases, characterised by excessive proliferation of one or more myeloid lineage. Chronic myeloid leukaemia (CML) arises from a genetic alteration in a normal haemopoietic stem cell (HSC) giving rise to a leukaemic stem cell (LSC) within the bone marrow (BM) ‘niche’. CML is characterised by the presence of the oncogenic tyrosine kinase fusion protein breakpoint cluster region-abelson murine leukaemia viral oncogene homolog 1 (BCR-ABL), which is responsible for driving the disease through activation of downstream signal transduction pathways. Recent evidence from our group and others indicates that important regulatory networks involved in establishing primitive and definitive haemopoiesis during development are reactivated in myeloid leukaemia, giving rise to an LSC population with altered self-renewal and differentiation properties. In this review, we explore the role the bone morphogenic protein (BMP) signalling plays in stem cell pluripotency, developmental haemopoiesis, HSC maintenance and the implication of altered BMP signalling on LSC persistence in the BM niche. Overall, we emphasise how the BMP and Wnt pathways converge to alter the Cdx–Hox axis and the implications of this in the pathogenesis of myeloid malignancies

Design of a 41.14-48.11 GHz triple frequency based VCO

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Growing deployment of more efficient communication systems serving electric power grids highlights the importance of designing more advanced intelligent electronic devices and communication-enabled measurement units. In this context, phasor measurement units (PMUs) are being widely deployed in power systems. A common block in almost all PMUs is a phase locked oscillator which uses a voltage controlled oscillator (VCO). In this paper, a triple frequency based voltage controlled oscillator is presented with low phase noise and robust start-up. The VCO consists of a detector, a comparator, and triple frequency. A VCO starts-up in class AB, then steadies oscillation in class C with low current oscillation. The frequency of the VCO, which is from 13.17 GHz to 16.03 GHz, shows that the frequency is tripling to 41.14-48.11 GHz. Therefore, its application is not limited to PMUs. This work has been simulated in a standard 0.18 µm CMOS process. The simulated VCO achieves a phase noise of -99.47 dBc/Hz at 1 MHz offset and -121.8 dBc/Hz at 10 MHz offset from the 48.11 GHz carrier

Chronic myeloid leukemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal

Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients

The Political Economy of Retailing Sustainable Food: Green Consumerism and Sustainability

In recent decades, the global impacts of unsustainable consumption and production patterns have become a leading topic of sustainability, and more recently, climate action discourse. At the policy level, green consumerism – an element of green capitalism – has been positioned as the pathway to more sustainable consumption and production (SCP) practices. Within this model, eco-labeling schemes are used to communicate various sustainability attributes, or conditions of production, to the consumer. This study set out to investigate whether SCP is achievable through green consumerism using a two-part case study that centers around the egg industry and specific hen welfare standards. The case study examines the effectiveness of egg eco-labeling schemes and related statements and images placed on egg packaging in informing consumers' purchasing decisions. It also examines the impacts of green consumerism on organic egg production in the presence of strong consumer demand for enhanced hen welfare standards. The results of the case study demonstrate that in the egg industry, green consumerism is not highly effective because consumers' purchasing decisions are often informed by vague and misleading information about conditions of production. Moreover, the presence of strong consumer demand has not resulted in enhanced hen welfare standards in organic production. In interpreting these findings through the lens of David Harvey's theory of the spatial fix, I argue that the true role of green consumerism is to facilitate a spatial fix to resolve the chronic crisis of overaccumulation in the conventional egg industry. Furthermore, that the limitations and contradictions within green consumerism (e.g. vague or insignificant eco-label claims) aid in removing the barrier of capital fixity so that the spatial fix can occur

Design Simulation and Assessment of Cellular Automata Based Improved Image Segmentation System

A variety of methods may be found in the numerous image segmentation techniques. Here a method of text retrieval conducted is typically to produce a collection of localized features. In computer science, object recognition is the problem of automatically "identifying", or classifying, an object. In certain instances, the awareness of artifacts is deeper into image in image segmentation through image processing. The algorithm used for image segmentation has a direct impact on the outcome of the whole approach, therefore it is important to choose carefully. It is important to choose a segmentation method appropriate for a certain framework. There are several ready-to-use segmentation methods, so one by one evaluate the tools to see which works best. Segmentation algorithms have reached such a level of complexity that a research employing them is often considered impractical. The given research undertakes the process of improved graph cut method to select the foreground and background of image through labelling and segmentation of the image. Results have been compared on the performance parameter to analyse the effectiveness of the proposed algorithm for segmentation of the images

Designing the Residential Places for Tourists Based on Environmental Factors and Green Architecture: A Case Study in Historical City of Masouleh

Masouleh is a mountain city and has many striking features. The city has a stepped structure and for many years has been considered as a destination for tourists. A mild climate, breathtaking landscape, newly architectural forms and fresh air are major characteristics of Masouleh. Unfortunately, nowadays many historical and natural textures are converted to touristic and residential areas in such a way that they jeopardize the environment and nature. Although some  may claim that these dramatic changes can help cities boom economically and bring many examples of flourishing cities, made by these changes, there are many real world examples showing  natural resource are consumed hugely for the sake of developments and moreover these changes are not sustainable. In this article, two important common trends in the architectural world are discussed such as sustainability and it is applied to Masouleh in order to protect and conserve the natural texture of the city and also it presents a solution that help city grow economically

Designing the Residential Places for Tourists Based on Environmental Factors and Green Architecture: A Case Study in Historical City of Masouleh

Masouleh is a mountain city and has many striking features. The city has a stepped structure and for many years has been considered as a destination for tourists. A mild climate, breathtaking landscape, newly architectural forms and fresh air are major characteristics of Masouleh. Unfortunately, nowadays many historical and natural textures are converted to touristic and residential areas in such a way that they jeopardize the environment and nature. Although some  may claim that these dramatic changes can help cities boom economically and bring many examples of flourishing cities, made by these changes, there are many real world examples showing  natural resource are consumed hugely for the sake of developments and moreover these changes are not sustainable. In this article, two important common trends in the architectural world are discussed such as sustainability and it is applied to Masouleh in order to protect and conserve the natural texture of the city and also it presents a solution that help city grow economically

Designing the Residential Places for Tourists Based on Environmental Factors and Green Architecture: A Case Study in Historical City of Masouleh

Masouleh is a mountain city and has many striking features. The city has a stepped structure and for many years has been considered as a destination for tourists. A mild climate, breathtaking landscape, newly architectural forms and fresh air are major characteristics of Masouleh. Unfortunately, nowadays many historical and natural textures are converted to touristic and residential areas in such a way that they jeopardize the environment and nature. Although some  may claim that these dramatic changes can help cities boom economically and bring many examples of flourishing cities, made by these changes, there are many real world examples showing  natural resource are consumed hugely for the sake of developments and moreover these changes are not sustainable. In this article, two important common trends in the architectural world are discussed such as sustainability and it is applied to Masouleh in order to protect and conserve the natural texture of the city and also it presents a solution that help city grow economically