Molecular Network Control Through Boolean Canalization

Boolean networks are an important class of computational models for molecular interaction networks. Boolean canalization, a type of hierarchical clustering of the inputs of a Boolean function, has been extensively studied in the context of network modeling where each layer of canalization adds a degree of stability in the dynamics of the network. Recently, dynamic network control approaches have been used for the design of new therapeutic interventions and for other applications such as stem cell reprogramming. This work studies the role of canalization in the control of Boolean molecular networks. It provides a method for identifying the potential edges to control in the wiring diagram of a network for avoiding undesirable state transitions. The method is based on identifying appropriate input-output combinations on undesirable transitions that can be modified using the edges in the wiring diagram of the network. Moreover, a method for estimating the number of changed transitions in the state space of the system as a result of an edge deletion in the wiring diagram is presented. The control methods of this paper were applied to a mutated cell-cycle model and to a p53-mdm2 model to identify potential control targets

The Returns to Health for Peruvian Urban Adults: Differentials Across Genders, the Life Cycle and the Wage Distribution

This report shows evidence on determinants of health status for urban adults and their effects on productivity. Accurate estimation of the effect of health on wages is always difficult to obtain due to endogeneity and measurement error of the health indicators that are available in household surveys for developing countries. The health measure used here is the number of days ill, which involves endogeneity and reporting error problems that are controlled for. The use of household sanitary infrastructure and proxies for health prices, measured by the distance to the health center and the average waiting time for attention at the district level, enabled the construction of an instrument variable estimator for the effects of health on wages. The instruments are statistically significant for all urban individuals. Schooling effects on health are positive and strong for urban males, and the positive effect of schooling on health is clearly increasing with age. The effect of health on wages is positive and robust, especially for urban males. The larger effects of an additional day sick are found among older self-employed males (-4. 3%) and those at the bottom of the hourly earnings distribution (-3. 8%), and those in the private sector (-1. 8%). These results suggest that health has a stronger impact on the wages of those jobs where productivity and health are closely connected, as in the private sector and the self-employed. The inconclusive results among females indicate the need to work on the development of a model that better expresses the way in which women fit into the labor market.

Vulnerability in consumption, education, and health - evidence from Moldova during the Russian crisis

The authors analyze the widespread effects of the financial crisis in Russia to explore the vulnerabilities of households in Moldova. They show that the crisis had differential impacts on households, affecting most the urban and better-off. Households'decisions about education and health resulted in decreased utilization and expenditures. The enrollment of young children from better-off households did not improve while others did. Secondary school enrollment of children from better-off households decreased after the crisis, in part because of the need to release labor supply. Health utilization decreased mainly for primary health care (not for hospitals), both for better-off households and in rural areas. Some of these changes are due to limited household resources (health), decreased public spending (health and education) or the need to increase households'labor supply (education of teenagers). Social benefits played a very limited role in mitigating these effects, solely in health care use. Households'assets helped to offset some of the negative effects of declining incomes.Environmental Economics&Policies,Health Monitoring&Evaluation,Housing&Human Habitats,Public Health Promotion,Economic Theory&Research,Health Monitoring&Evaluation,Housing&Human Habitats,Environmental Economics&Policies,Economic Theory&Research,Inequality

The effects of a fee-waiver program on health care utilization among the poor : evidence from Armenia

This study examines the impact of a fee-waiver program for basic medical services on health care utilization in Armenia. Because of the reduction in public financing of health services and decentralization and increased privatization of health care provision, private out-of-pocket contributions are increasingly becoming a significant component of health costs in Armenia. To help poor families cope with this constraint, the Armenian government provided a free-of-charge basic package service to eligible individuals in vulnerable groups, such as the disabled and children from single parent households. Drawing on the 1996 and 1998-99 Armenia Integrated Survey of Living Standards (AISLS), which allows the identification of eligible individuals under this program, the authors estimate the impact of the fee-waiver program on utilization of health services, particularly among the poor. Across the two survey rounds utilization rates have indeed declined despite comparable levels of income, and this decline has occurred among both the poor and the rich, with average utilization falling by 12 percent between the two surveys. But families with four or more children, the largest beneficiary group under the"vulnerable population"program, have decreased their use of health care services in a disproportionate manner-21 percent reduction in use between the two survey rounds. This precipitous drop in health care use by this vulnerable group, despite being eligible for free medical services, suggests that the program was inadequate in stemming the decline in the use of health services. The authors further present evidence to suggest that the free-of-charge eligibility program acts more like an income transfer mechanism, particularly to disabled individuals.Health Systems Development&Reform,Health Monitoring&Evaluation,Public Health Promotion,Early Child and Children's Health,Health Economics&Finance,Health Systems Development&Reform,Health Economics&Finance,Gender and Health,Regional Rural Development,Health Monitoring&Evaluation

Identification of control targets in Boolean molecular network models via computational algebra

Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. Experimentally, node manipulation requires technology to completely repress or fully activate a particular gene product while edge manipulations only require a drug that inactivates the interaction between two gene products. Results: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network.Comment: 12 pages, 4 figures, 2 table

The hidden costs of ethnic conflict - decomposing trends in educational outcomes of young Kosovars

The authors examine the impact of ethnic segmentation in education on educational outcomes. Between 1991 and the late 1990s, the Albanian Kosovar population received education services in an informal system parallel to the official one. Using the 2000 Kosovo LSMS Survey data, the authors exploit cohort differences in exposure to the parallel system to estimate its effects among Albanian youth. The first (untreated) cohort includes individuals who entered secondary education before 1991 when the"parallel"education system was initiated. The second (treated) cohort includes individuals who entered secondary school in the last ten years under the ethnically segmented education system. To disentangle the effects of the changing system and economic environment, and the changes in the characteristics of the population, a Oaxaca-type decomposition is used. The results suggest that the past decade of ethnic tension has claimed a substantial toll on the educational outcomes of young male Albanian Kosovars. In addition to declines in enrollment rates in secondary education, those who are enrolled are expected to complete one less year of education. However, secondary school enrollment for girls increased during the parallel system, but with a sharp decline in the expected number of years completed.Primary Education,Public Health Promotion,Teaching and Learning,Curriculum&Instruction,Health Monitoring&Evaluation,Primary Education,Curriculum&Instruction,Gender and Education,Teaching and Learning,Health Monitoring&Evaluation