Open source drug discovery- A new paradigm of collaborative research in tuberculosis drug development

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. (C) 2011 Elsevier Ltd. All rights reserved.

Digital image analysis around isotropic points for photoelastic pattern recognition

Fringe tracking and fringe order assignment have become the central topics of current research in digital photoelasticity. Isotropic points (IPs) appearing in low fringe order zones are often either overlooked or entirely missed in conventional as well as digital photoelasticity. We aim to highlight image processing for characterizing IPs in an isochromatic fringe field. By resorting to a global analytical solution of a circular disk, sensitivity of IPs to small changes in far-field loading on the disk is highlighted. A local theory supplements the global closed-form solutions of three-, four-, and six-point loading configurations of circular disk. The local theoretical concepts developed in this paper are demonstrated through digital image analysis of isochromatics in circular disks subjected to three-and four-point loads. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

Comportamiento prooxidante y antioxidante de hierbas aromáticas en queso

Los quesos de cabra, con mejores cualidades funcionales provienen de leche de cabras en pastoreo, esto obedece al mayor contenido de ácidos grasos ω-3 y ω-6 en una relación óptima para la salud, sumado a un menor contenido de grasa y colesterol. Saborizar quesos con especias, otorga beneficios sensoriales y saludables al producto. Las especias son usadas para realzar el flavor de los alimentos además presentan beneficios antioxidantes. Sin embargo, se reportaron evidencias del doble papel de los flavonoides como antioxidantes o prooxidantes en función de la concentración de uso. El objetivo del trabajo es evaluar el efecto de distintas concentraciones de especias aromáticas con capacidad antioxidante, frente a las reacciones de deterioro que ocurren en el almacenamiento de quesos de cabra. Se estudió la actividad antirradicalaria (AAR) de 18 especias. Para evaluar la actividad antioxidante (AA0) se usó la técnica de desaparición de un radical libre estable el 2,2-difenil-1-picril hidrazilo (DPPH) y se calculó la AAR porcentual. Definido el queso base estándar (control), se ensayaron tres variedades con especies, elegidas de entre las de mayor AAR (orégano, romero y tomillo) y se adicionaron con las concentraciones 0,4 – 1 % p/p. Estos, fueron madurados 30 días y almacenados 7 meses a 4 °C. Se analizaron cada 4 semanas. Se realizaron pruebas sensoriales de aceptabilidad con 60 consumidores de queso (condición), usando planillas, con escala hedónica. Se trabajó sobre los lípidos extraídos de los quesos. El rancidez y deterioro fueron evaluados con análisis de acidez; índice peróxido y sustancias reactivas al ácido TBA. Los resultados se compararon con el comportamiento sensorial del producto en el tiempo de almacenamiento. En los quesos adicionados al 1 %, la acidez se incrementó con el almacenamiento. El máximo valor corresponde al queso con orégano (3,72 % de ac. láctico a los 126 días). En el control, la acidez inicial fue inferior y alcanzó 1,05 g de ác. láctico % a los 166 días. El IP más alto corresponde a los quesos con orégano al 1% , resultado que se contrapone a la actividad antirradicalaria de esta especia. Al 0,4 %, tanto el IP como el número de TBA son menores en quesos adicionados, respecto del control. En los quesos de cabra analizados las especias agregadas al 1% ejercieron acción prooxidante, mientras que al ser agregadas al 0,4% la acción es antioxidante, lo que indica la importancia de la selección de concentraciones adecuadas.

Expanding adoption of drinking water treatment systems in developing countries: a case study from Tamil Nadu, India

Household-level water treatment and safe storage systems (HWTS) are simple, local, user-friendly, and low cost options to improve drinking water quality at the point of use. However, despite conclusive evidence of the health and economic benefits of HWTS, and promotion efforts in over 50 countries in the past 20 years, implementation outcomes have been slow, reaching only 5-10 million regular users. This study attempts to understand the barriers and drivers affecting HWTS implementation. Using a case study example of a biosand filter program in southern India, system dynamics modelling is shown to be a useful tool to map the inter-relationships of different critical factors and to understand the dissemination dynamics. It is found that the co-existence of expanding quickly and achieving financial sustainability appears to be difficult to achieve under the current program structure.

Teoría de la plusvalía en Marx

Resumen: El artículo presenta un recorrido por algunos de los postulados de la economía británica clásica, a fin de comprender acabadamente la teoría de la plusvalía de Carlos Marx. Así, el autor analiza algunos conceptos fundamentales para tal efecto. Define –entrecruzando los postulados de Adam Smith y David Ricardo– las nociones de: el valor de las cosas, el precio de los salarios, y el beneficio empresario. Luego, dedica una sección a describir las críticas de Adam Smith y Carlos Marx al capitalismo. Desarrolla cabalmente lo relativo a la obtención y magnitud de la plusvalía, y realiza una reflexión final que define a la teoría de la plusvalía como conceptualmente falsa.

A systems approach to characterise the dissemination process of household water treatment systems in developing countries

Abstract: Starting in the 1980s, household-level water treatment and safe storage systems (HWTS) have been developed as simple, local, user-friendly, and low cost options to improve drinking water quality at the point of use. However, despite conclusive evidence of the health and economic benefits of HWTS, and promotion efforts in over 50 countries in the past 20 years, implementation outcomes have been slow, reaching only 5-10 million regular users. This study attempts to understand the barriers and drivers affecting HWTS implementation. Although existing literature related to HWTS and innovation diffusion theories proposed ample critical factors and recommendations, there is a lack of holistic and systemic approach to integrate these findings. It is proposed that system dynamics modelling can be a promising tool to map the inter-relationships of different critical factors and to understand the structure of HWTS dissemination process, which may lead to identifying high impact, leveraged mitigation strategies to scale-up HWTS adoption and sustained use.

Robust multiplexed model predictive control

This paper extends the recently developed multiplexed model predictive control (MMPC) concept to ensure satisfaction of hard constraints despite the action of persistent, unknown but bounded disturbances. MMPC uses asynchronous control moves on each input channel instead of synchronised moves on all channels. It offers reduced computation, by dividing the online optimisation into a smaller problem for each channel, and potential performance improvements, as the response to a disturbance is quicker, albeit via only one channel. Robustness to disturbances is introduced using the constraint tightening approach, tailored to suit the asynchronous updates of MMPC and the resulting time-varying optimisations. Numerical results are presented, involving a simple mechanical example and an aircraft control example, showing the potential computational and performance benefits of the new robust MMPC.

Status of policies on fish hygiene in Nigeria

An examination is made of fish health policy formulation in Nigeria. Such policies are necessary to protect fish a living aquatic resources and also fish food at harvest because of the immense nutritional, social and economic benefits derivable by man from fish. Fish health policies must recognize the implications of aquatic environment pollution, the dangers of bad fishing methods and application of harmful fishing gears and appliances and post-mortem handling practices

Concerted action for successful coastal communities in Tanzania: Lessons from the Tanzania Coastal Management Partnership (TCMP) 2006-2009

The Tanzania Coastal Management Partnership (TCMP) works to implement the National Integrated Coastal Environmental Management Strategy (ICEMS) in Tanzania’s coastal landscapes and seascapes, funded in large measure by the U.S. Agency for International Development. The overarching goal of the Sustainable Coastal Communities and Ecosystems in Tanzania (SUCCESS Tanzania) initiative is to conserve coastal and marine biodiversity while improving the well being of coastal residents through implementation of the Tanzania ICEMS and related ICM policies and strategies. It does this by focusing on three key results: -Policies and Laws that Integrate Conservation and Development Applied -Participatory Landscape Scale Conservation Practiced -Conservation Enterprises Generate Increased and Equitable Benefits from Sustainable Use An additional result sought in the program is gender equity and HIV/AIDS preventive behaviors promoted through communicating HIV/AIDS, environment, and equity messages. (PDF contains 3 pages)

Utilization of some aquatic macrophytes in Nigeria in-land water bodies: a review

Aquatic vegetation is an essential component of the aquatic ecosystem with both positive and negative implications on the water body. Efforts are always made to curtail the excessive growth of aquatic plants in order to prevent them from becoming a nuisance in the ecosystem. One of the ways of solving such problem is the positive economic use of such plants. Utilization as a method of weed control within the aquatic ecosystem is considered to be one of the safest methods of weed control as this provides the riparian communities double advantages in terms of save environment and personal benefits of the plant. The flora diversity of freshwater and brackish environments posses a great potential to both man and higher animals alike. Due to this fact, this paper attempt to review the exploited and unexploited aquatic plants resources of many of our water bodies in Nigeria both economica/ly and socially, to the populace. Recommendations are also advanced for further studies that will enhance sound management of the resources for maximum benefits and sustainability

The logic of receptor-ligand interactions in the Notch signaling pathway

The Notch signaling pathway enables neighboring cells to coordinate developmental fates in diverse processes such as angiogenesis, neuronal differentiation, and immune system development. Although key components and interactions in the Notch pathway are known, it remains unclear how they work together to determine a cell's signaling state, defined as its quantitative ability to send and receive signals using particular Notch receptors and ligands. Recent work suggests that several aspects of the system can lead to complex signaling behaviors: First, receptors and ligands interact in two distinct ways, inhibiting each other in the same cell (in cis) while productively interacting between cells (in trans) to signal. The ability of a cell to send or receive signals depends strongly on both types of interactions. Second, mammals have multiple types of receptors and ligands, which interact with different strengths, and are frequently co-expressed in natural systems. Third, the three mammalian Fringe proteins can modify receptor-ligand interaction strengths in distinct and ligand-specific ways. Consequently, cells can exhibit non-intuitive signaling states even with relatively few components.

In order to understand what signaling states occur in natural processes, and what types of signaling behaviors they enable, this thesis puts forward a quantitative and predictive model of how the Notch signaling state is determined by the expression levels of receptors, ligands, and Fringe proteins. To specify the parameters of the model, we constructed a set of cell lines that allow control of ligand and Fringe expression level, and readout of the resulting Notch activity. We subjected these cell lines to an assay to quantitatively assess the levels of Notch ligands and receptors on the surface of individual cells. We further analyzed the dependence of these interactions on the level and type of Fringe expression. We developed a mathematical modeling framework that uses these data to predict the signaling states of individual cells from component expression levels. These methods allow us to reconstitute and analyze a diverse set of Notch signaling configurations from the bottom up, and provide a comprehensive view of the signaling repertoire of this major signaling pathway.

Enfrentando mudanças e valorizando a vida - uma referência para a enfermeira no cuidado à mulher submetida à cirurgia ginecológica

Diversos estudos que abordam as repercussões das cirurgias ginecológicas na vida da mulher apontam para uma relação existente com aspectos subjetivos, em virtude da construção social da identidade feminina, indicando que a perda de órgãos ginecológicos pode interferir na maneira da mulher se perceber e se relacionar com o mundo. O presente estudo tem como objeto o processo de interação da mulher no contexto das cirurgias ginecológicas. Para isso foram formulados os objetivos: Descrever os significados da cirurgia ginecológica para a mulher submetida a este procedimento e Analisar o processo de interação da mulher com ela mesma e com o seu núcleo social a partir dos significados por ela atribuídos à cirurgia ginecológica, considerando o fenômeno da mutilação. O estudo de natureza qualitativa, do tipo descritivo-exploratório, teve como referencial teórico-metodológico o Interacionismo Simbólico e a Grounded Theory, que subsidiaram uma interpretação da ação e das relações das mulheres no contexto da cirurgia ginecológica e da mutilação, baseados na definição e interpretação de significados por elas atribuídos. Dos resultados emergiram quatro categorias: Investigando a doença e decidindo aceitar a cirurgia, A passagem pela cirurgia: vivendo o processo de resolução do problema, Enfrentando as mudanças impostas pela cirurgia e Valorizando a vida. Evidenciou-se que ao receber o diagnóstico da doença, a mulher interage com dúvidas, medos, a busca por informação e pelos benefícios da cirurgia, e por fim decide aceitá-la. Ao passar pela cirurgia, vivencia incômodos, complicações, compreende que perdeu uma parte do corpo e procura conformar-se, tentando crer que foi o único caminho. As diversas mudanças que ocorrem fazem-na construir novos significados e mudar a percepção de si e do seu meio social, a partir da interação consigo mesma e com este meio, fazendo-a refletir sobre a sexualidade, seus relacionamentos, sua saúde, a diferença no corpo e em si mesma, nas funções que desempenha e sobre a mutilação provocada pela cirurgia. O desenvolvimento de mecanismos de enfrentamento, como comparar sua cirurgia e histórias com outras, identificar aprendizados com a experiência, buscar formas de superação e resignar-se resultaram na valorização da vida e na vontade de viver melhor. Percebe-se a importância da enfermeira estabelecer um cuidado multidimensional, que identifique as necessidades que vão além do corpo biológico, respeitando as particularidades e a individualidade no momento do cuidado e contribuindo para o bem-estar físico, psíquico, social e espiritual das mulheres.

Decarbonising urban transportation

18 p.

A dynamic CGE modelling approach for analyzing trade-offs in climate change policy options: the case of Green Climate Fund

38 p.

Relação da doença periodontal com a anticoagulação oral e os benefícios do tratamento periodontal em pacientes anticoagulados

Anticoagulantes orais são amplamente indicados para prevenção de eventos tromboembólicos. No entanto, nem sempre os pacientes atingem a faixa terapêutica recomendada. Os objetivos desse estudo foram avaliar a associação entre periodontite e níveis de anticoagulação (fase 1) e o efeito do tratamento periodontal nos níveis de anticoagulação (fase 2) em pacientes que faziam uso do anticoagulante oral varfarina. O exame clínico incluiu índice CPO-D, índice de placa, sangramento à sondagem, profundidade de bolsa e nível de inserção clínica. Coeficiente normalizado internacional (INR), níveis de albumina, proteína C-reativa (PCR) e fibrinogênio foram avaliados no dia zero e até 180 dias após tratamento periodontal. Na fase 1 do estudo foram examinados 62 pacientes (42 mulheres e 20 homens, com idade média de 50,8 9,2 anos). Observamos uma correlação negativa entre extensão e severidade da doença periodontal e índice de placa com valores de INR. Não houve associação entre diagnóstico periodontal e níveis de anticoagulação. Dentre os pacientes fora do alvo terapêutico, 87% apresentavam diagnóstico de periodontite, enquanto no grupo na faixa terapêutica apenas 56%. Participaram da fase 2 do estudo 26 pacientes com periodontite severa (15 mulheres e 11 homens, com idade média de 51,3 9,2 anos). O tratamento periodontal resultou em melhora significativa de todos os parâmetros periodontais e dos níveis de anticoagulação 30, 60 90 e 180 dias após conclusão da terapia periodontal. Não houve alteração significativa na dose semanal da varfarina. Foi observada redução significativa entre níveis séricos de albumina dos dia 90 e 180 após a terapia periodontal, quando comparado aos valores do dia 0 (p < 0,05). De acordo com o alvo terapêutico estabelecido, observamos que no dia 0 doze pacientes (46,15%) estavam fora dessa faixa. Esse percentual foi reduzido significativamente após tratamento periodontal, sendo 26,1% e 29,2% nos dias 60 e 90, respectivamente. Embora tenha ocorrido melhora nos níveis de anticoagulação, não houve alteração significativa nos níveis de PCR e fibrinogênio. Sendo assim, pacientes com periodontite severa podem apresentar dificuldade para atingir a faixa terapêutica e o tratamento periodontal pode resultar em benefícios na busca da anticoagulação plena. Novos estudos são necessários para avaliar se formas menos severas de doença periodontal também podem interferir com a varfarina.