Methodology for identifying alternative solutions in a population based data generation approach applied to synthetic biology

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonDesign is an essential component of sustainable development. Computational modelling has become a useful technique that facilitates the design of complex systems. Variables that characterises a complex system are encoded into a computational model using mathematical concepts and through simulation each of these variables alone or in combination are modified to observe the changes in the outcome. This allows the researchers to make predictions on the behaviour of the real system that is being studied in response to the changes. The ultimate goal of any design process is to come up with the best design; as resources are limited, to minimize the cost and resource consumption, and to maximize the performance, profits and efficiency. To optimize means to find the best solution, the best compromise among several conflicting demands subject to predefined requirements. Therefore, computational optimization, modelling and simulation forms an integrated part of the modern design practice. This thesis defines a data analytics driven methodology which enables the identification of alternative solutions of computational design by analysing the generational history of the population based heuristic search used to generate the templates. While optimisation is focused on obtaining the optimal solution this methodology focuses on alternative solutions which are sub optimal by fitness or solutions with similar fitness but different structures. When the optimal design solution is less robust, alternative solutions can offer a sufficiently good accuracy and an achievable resource requirement. The main advantage of the methodology is that it exploits the exploration process of the solution space during a single run, by focusing also on suboptimal solutions, which usually get neglected in the search for an optimal one. The history of the heuristic search is analysed for the emergence of alternative solutions and evolving of a solution. By examining how an initial solution converts to an optimal solution core design patterns are identified, and these were used to improve the design process. Further, this method limits the number of runs of the heuristic search as more solution space is covered. The methodology is generic because it can be used to any instance where a population based heuristic search is applied to generate optimal designs. The applicability of the methodology is demonstrated using three case studies from mathematics (building of a mathematical function for a set target) and biology (obtaining alternative designs for genomic metabolic models [GEM] and DNA walker circuits). In each case a different heuristic search method was used: Gene expression programming (mathematical expressions), genetic algorithms (GEM models) and simulated annealing (DNA walker circuits). Descriptive analytics, visual analytics and clustering was mainly used to build the data analytics driven approach in identifying alternative solutions. This data analytics driven methodology is useful in optimising the computational design of complex systems

Brasil y Portugal : análisis por contraste de los programas de transferencia de renta condicionada para la lucha contra la pobreza = Brazil and Portugal : contrast análisis of the conditioned income transfer programs in the fight against poverty

El presente artículo expone los resultados de una investigación realizada bajo el modelo de análisis por contraste y su discusión sobre las contribuciones e impactos de los Programas Sociales, específicamente del Programa de Transferencia Condicionada de Renta o Bolsa de Familia – PBF, implementado en Salvador, en el periodo 2008–2009, en Brasil y el Programa de Renta Social para la Inserción – RS I desarrollado en la ciudad de Coimbra, en el período 2009 – 2010, en Portugal. El objetivo es abordar la percepción de los programas desde y sobre las prácticas de los técnicos que intervienen en la gestión y operacionalización de éstos, así como desde la percepción de las familias socialmente vulnerables que son atendidas por el PBF en Brasil y el RS I en Portugal. La conclusión principal es que los programas de transferencia de renta son paliativos, movilizan recursos, más no generan riqueza; recrean una noción de ciudadanía, la ciudadanía del consumo y por lo tanto, del ciudadano-consumidor. La investigación plantea los límites y posibilidades de los programas sociales para asumir la complejidad de la injusticia social, de la dominación e invisibilidad de una pobreza que no es afrontada en su origen estructural y que por lo tanto, se sigue manifestando como generacional, polisémica y excluyente.____________________________________________The present article presents the results of a research conducted using the model of contrast analysis and its discussion on the contributions and impact of Social Programs—specifically the Conditioned Income or Family Purse Transfer Program—implemented in Salvador (2008-2009) in brazil, and the Social Income Insertion Program developed in coimbra (2009-2010) in Portugal. Its purpose is to explore the perception of such programs from and on the practices of professionals participating in their management and functionality, together with the perception of the socially vulnerable families that are asisted by such programs. The main conclusion is that income transfer programs are palliative, they mobilize resources but do not produce richness, they recreate a notion of consummerist citizenship and therefore, of the consumer-citizen. This research considers the limits and possibilities of social programs to assume the complexity of social injustice, dominance and invisibility of a poverty that is not faced in its structural origin and therefore, manifests itself as generational, polysemous and excluding

Design and spectral analysis of a six-axis shaker system

Shaker table assemblies can exhibit resonances within their frequency range of operation. The spectral analysis of a six-axis shaker system permits the identification and prediction of resonance frequencies. In the project described here, a small six-axis shaker was tested experimentally. In parallel with the experiments, Finite Element (FE) models of the shaker were generated, and their dynamic performance was simulated. Time data from experimental test series were compared with the responses from FE analysis obtained for identical test conditions. The comparison of the response spectra between experiments and simulation permits the assessment and validation of FE analysis as a predictive tool for designing larger multi-axis shakers. The power density and coherence frequency response spectra for the entire 6x6 control matrix are computed in Matlab, creating a detailed performance assessment for all aspects of the 6x6 control matrix. A new FE model of a larger 6-axis shaker table has been created. The design seeks to minimize the inertial table mass, while maintaining platform stiffness such that all eigenvalues are above the shaker table\u27s operational frequency range

A Study of Socio- Cultural factors and their influence on Rural Women Empowerment in Solar Power Sector in select states of India

Rural women’s participation in the formal economy is small and largely confined to domestic work and less payed low grade jobs in the economy due to social, economic, political and other factors. Therefore, this study is done to assess the socio cultural factors that influence the rural women empowerment in Solar Power Sector in select states of India. Basically, the study is exploratory in nature. Primary as well as secondary data is used for the study while including the Quantitative and qualitative techniques. For this study, 500 rural women respondents who were into solar business were taken from the states of Andhra Pradesh, Bihar, Orissa and Telangana. A structured questionnaire was used for data collection. Descriptive statistics was used to analyze the data collected. Also, SPSS software was used to further analyse the data. The findings of study revealed that the majority of the rural women respondents were interested to start the solar business. From the data it is further observed the socio-cultural attitudes of the rural women like: Social Empowerment- Participation in domestic decision making, Recognition in the society, Access to and visibility in Social spaces, Rural women and Political attitudes- Ability to exercise right to vote, Rural women and Psychological attitudes- Self- esteem. Thus, it is suggested that the government of India and other NGO’s should work together to bolster the rural women’s socio-cultural development by providing required skills training, diversification sources of women income, guidance with the procedures to procure the loans, creating business networks and so on

C-type natriuretic peptide-induced PKA activation promotes endochondral bone formation in hypertrophic chondrocytes

Longitudinal bone growth is achieved by a tightly controlled process termed endochondral bone formation. C-type natriuretic peptide (CNP) stimulates endochondral bone formation through binding to its specific receptor, guanylyl cyclase (GC)-B. However, CNP/GC-B signaling dynamics in different stages of endochondral bone formation have not been fully clarified, especially in terms of the interaction between the cyclic guanine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Here, we demonstrated that CNP activates the cAMP/protein kinase A (PKA) pathway and that this activation contributed to the elongation of the hypertrophic zone in the growth plate. Cells of the chondrogenic line ATDC5 were transfected with Förster resonance energy transfer (FRET)–based cGMP and PKA biosensors. Dual-FRET imaging revealed that CNP increased intracellular cGMP levels and PKA activities in chondrocytes. Further, CNP-induced PKA activation was enhanced following differentiation of ATDC5 cells. Live imaging of the fetal growth plate of transgenic mice, expressing a FRET biosensor for PKA, PKAchu mice, showed that CNP predominantly activates the PKA in the hypertrophic chondrocytes. Additionally, histological analysis of the growth plate of PKAchu mice demonstrated that CNP increased the length of the growth plate, but coadministration of a PKA inhibitor, H89, inhibited the growth-promoting effect of CNP only in the hypertrophic zone. In summary, we revealed that CNP-induced cGMP elevation activated the cAMP/PKA pathway, and clarified that this PKA activation contributed to the bone growth–promoting effect of CNP in hypertrophic chondrocytes. These results provide insights regarding the cross-talk between cGMP and cAMP signaling in endochondral bone formation and in the physiological role of the CNP/GC-B system

C-type Natriuretic Peptide–induced PKA Activation Promotes Endochondral Bone Formation in Hypertrophic Chondrocytes

Longitudinal bone growth is achieved by a tightly controlled process termed endochondral bone formation. C-type natriuretic peptide (CNP) stimulates endochondral bone formation through binding to its specific receptor, guanylyl cyclase (GC)-B. However, CNP/GC-B signaling dynamics in different stages of endochondral bone formation have not been fully clarified, especially in terms of the interaction between the cyclic guanine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Here, we demonstrated that CNP activates the cAMP/protein kinase A (PKA) pathway and that this activation contributed to the elongation of the hypertrophic zone in the growth plate. Cells of the chondrogenic line ATDC5 were transfected with Förster resonance energy transfer (FRET)–based cGMP and PKA biosensors. Dual-FRET imaging revealed that CNP increased intracellular cGMP levels and PKA activities in chondrocytes. Further, CNP-induced PKA activation was enhanced following differentiation of ATDC5 cells. Live imaging of the fetal growth plate of transgenic mice, expressing a FRET biosensor for PKA, PKAchu mice, showed that CNP predominantly activates the PKA in the hypertrophic chondrocytes. Additionally, histological analysis of the growth plate of PKAchu mice demonstrated that CNP increased the length of the growth plate, but coadministration of a PKA inhibitor, H89, inhibited the growth-promoting effect of CNP only in the hypertrophic zone. In summary, we revealed that CNP-induced cGMP elevation activated the cAMP/PKA pathway, and clarified that this PKA activation contributed to the bone growth–promoting effect of CNP in hypertrophic chondrocytes. These results provide insights regarding the cross-talk between cGMP and cAMP signaling in endochondral bone formation and in the physiological role of the CNP/GC-B system

Clinical Practice Changes After Post-Market Safety Reports on Desmopressin Orally Disintegrating Tablet in Japan: A Single-Center Retrospective Study

Background: Desmopressin orally disintegrating tablet (ODT) was approved in March 2012 in Japan; the post-market safety reports, which warned about adequate initial dose of desmopressin ODT, were published in 2014. However, it is unclear how the warning affected physician and patient behavior. Methods: We performed a retrospective single-center study to compare the clinical situation of Japanese central diabetes insipidus patients before and after the report. Results: Thirty-four patients before October 2014 and 16 patients after November 2014 switched from intranasal desmopressin to desmopressin ODT. The mean follow-up period after the switch to desmopressin ODT was 38 ± 3 months. Patients switching after November 2014 tended to have lower ratios of oral to nasal desmopressin dose at switching and 3 months after the switch (at switching; P = 0.20, 3 months; P = 0.42, respectively), and higher ratios from 6 to 12 months than before October 2014 (6 months; P = 0.93, 9 months; P = 0.52, 12 months; P = 0.80, respectively). Relative doses per initial desmopressin ODT at 9 and 12 months were significantly higher in patients switching after November 2014 than in patients switching before October 2014 (9 months; P = 0.02, 12 months; P = 0.04, respectively). Moreover, logistic regression analysis revealed that the incidence of hyponatremia was dependent on the ratio of nasal to oral desmopressin dose (P = 0.02). In addition, in four out of six patients who had serum sodium level reduced below 130 mEq/L, hyponatremia occurred within 1 month after the switch. Conclusions: A more gradual dose titration after the safety reports was performed, which involved the long-term safety of desmopressin ODT use. Vigilance of hyponatremia in early phase of desmopressin ODT use should be noted

イタリアの憲法改正国民投票論争 : 制度改革とポピュリスト的機運

The meaning of the referendum to amend the Italian constitution has been obscured by a gambling attempt of the prime minisiter Matteo Renzi to bet his office on the result. The amendment prospects that it corrects the leadership crisis continued after the 2013 election, however, the abolishment of the equality of both houses of the parliament is easy to invite criticism that Renzi prepares for the dominant position of his Democratic Party. Each amendment can be criticized by legalinquiries, but most of criticism comes from political intentions to compel Renzi to resign. Populist momentum may risk the Renzi\u27s political life and wash away the reforming process in Italy