Nonlinear decision-making with enzymatic neural networks.

Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.

Microscopic agents programmed by DNA circuits.

Information stored in synthetic nucleic acids sequences can be used in vitro to create complex reaction networks with precisely programmed chemical dynamics. Here, we scale up this approach to program networks of microscopic particles (agents) dispersed in an enzymatic solution. Agents may possess multiple stable states, thus maintaining a memory and communicate by emitting various orthogonal chemical signals, while also sensing the behaviour of neighbouring agents. Using this approach, we can produce collective behaviours involving thousands of agents, for example retrieving information over long distances or creating spatial patterns. Our systems recapitulate some fundamental mechanisms of distributed decision making and morphogenesis among living organisms and could find applications in cases where many individual clues need to be combined to reach a decision, for example in molecular diagnostics.

Estudio del comportamiento reológico in vitro de las fórmulas antirregurgitación / Thickened infant formula, rheological study of the “in vitro” properties

Introducción: La adición de espesantes a las fórmulas denominadas fórmulas antirregurgitación (F-AR) tiene como objetivo aumentar la viscosidad para el tratamiento del reflujo gastroesofágico no complicado. Objetivo: Determinar la viscosidad y el comportamiento reológico de las diferentes F-AR de inicio del mercado español, y compararlas con una fórmula de inicio estándar y tras su espesamiento con cereales sin gluten (10g/100ml). Método: La viscosidad de las muestras se determinó con un reómetro Bohlim CS de estrés controlado en condiciones basales (25°C, pH 7) y tras 30 y 60min de incubación en condiciones de simulación de fisiología gástrica (FG) (37°C, pH 4 y 10g/100ml de pepsina); la viscosidad se expresó en centipoises (cP). Resultados: Todas las fórmulas demostraron un aumento de la viscosidad tanto en condiciones basales como en condiciones de FG. Las fórmulas que contenían harina de semilla de algarrobo con una concentración de 2,9g/100g y un cociente de proteínas similar al de la leche de vaca (80% de caseína/20% de lactosuero) mostraron la viscosidad más alta y mantenida (70 y 90cP), con diferencias significativas con respecto a la fórmula de inicio en todas las mediciones. Cuando este espesante estaba en fórmulas con un cociente proteico similar al de la leche materna (40% de caseína/60% de lactosuero), la viscosidad alcanzada fue menor, y sólo con una concentración de 4,7g/100g se alcanzaron viscosidades superiores a 50cP, con diferencias significativas versus la fórmula de inicio. Las fórmulas que contenían almidones (arroz, patata y maíz) alcanzaron una viscosidad menor de 50cP y menos mantenida, y no alcanzaron una diferencia significativa. La viscosidad alcanzada tras la adición de cereales tanto en condiciones basales como en condiciones de FG fue similar a la alcanzada con las fórmulas más efectivas con espesantes. La concentración lipídica no se implicó en el distinto comportamiento reológico de las fórmulas. Conclusión: La viscosidad de las F-AR depende del agente empleado, la concentración de éste y el cociente proteico. No todas alcanzan una viscosidad de 50cP, valor hipotético por conseguir, dado que representaría doblar la viscosidad de la fórmula de inicio. Futuros estudios son necesarios para determinar el grado de viscosidad ideal y cómo conseguirlo (AU)

Introduction: Thickened infant formulas, specially formulated to increase the viscosity, are commonly used in the treatment of regurgitation in the non-complicated gastroesophageal reflux. Objective: To analyse viscosity and the rheological behaviour of different thickened standard formulas on the Spanish market compared to a standard formula with or without the addition of 10g/100mL of gluten-free cereals. Methods: Viscosity of the samples was evaluated in a Bohlim CS-1o controlled-stress rheometer and was performed at basal conditions (25°C, pH 7) and at simulated gastric conditions (37°C, pH 4 and 10g/100mL of pepsin) at time 0, 30 and after 60min of incubation. Values were expressed as centipoises (cp) (1cp=1/100p). Results: All formulas show a viscosity increase both in basal conditions and in gastric simulated conditions but the behaviour is very heterogeneous. Formulas containing bean gum (carob seed flour) with 2.9g/100g and a protein ratio similar to cow's milk (80 casein/20 whey) showed the highest and consistent viscosity (70cp and 90cp), with significant differences compared to the standard formula in all the measurements. When this thickener is in formulas with a protein ratio similar to breast milk (40 casein/60 whey) the viscosity was lower and reached 50cp only with the thickener at a concentration of 4.7gr/100g, achieving significant differences versus standard formula. The formulas with starch thickeners (rice, potatoes and corn) achieved a lower and less consistent viscosity, with no significant difference. The viscosity reached after the addition of cereals both in basal conditions and in gastric simulated conditions was similar to that achieved with more effective thickeners. Lipid concentration is not involved in viscosity and rheological behavior. Conclusion: The viscosity of the thickened infant formula depends on the agent used, concentration and protein ratio. Not all reach a viscosity of 50cp, hypothetical value to reach, since it doubles the viscosity of a standard formula. The ideal viscosity to be reached and the role of other components of the formula in the viscosity and rheological behaviour is still unclear (AU)

[Thickened infant formula, rheological study of the "in vitro" properties]. / Estudio del comportamiento reológico in vitro de las fórmulas antirregurgitación.

INTRODUCTION: Thickened infant formulas, specially formulated to increase the viscosity, are commonly used in the treatment of regurgitation in the non-complicated gastroesophageal reflux. OBJECTIVE: To analyse viscosity and the rheological behaviour of different thickened standard formulas on the Spanish market compared to a standard formula with or without the addition of 10 g/100mL of gluten-free cereals. METHODS: Viscosity of the samples was evaluated in a Bohlim CS-1o controlled-stress rheometer and was performed at basal conditions (25 degrees C, pH 7) and at simulated gastric conditions (37 degrees C, pH 4 and 10 g/100mL of pepsin) at time 0, 30 and after 60 min of incubation. Values were expressed as centipoises (cp) (1 cp=1/100 p). RESULTS: All formulas show a viscosity increase both in basal conditions and in gastric simulated conditions but the behaviour is very heterogeneous. Formulas containing bean gum (carob seed flour) with 2.9 g/100g and a protein ratio similar to cow's milk (80 casein/20 whey) showed the highest and consistent viscosity (70 cp and 90 cp), with significant differences compared to the standard formula in all the measurements. When this thickener is in formulas with a protein ratio similar to breast milk (40 casein/60 whey) the viscosity was lower and reached 50 cp only with the thickener at a concentration of 4.7 gr/100g, achieving significant differences versus standard formula. The formulas with starch thickeners (rice, potatoes and corn) achieved a lower and less consistent viscosity, with no significant difference. The viscosity reached after the addition of cereals both in basal conditions and in gastric simulated conditions was similar to that achieved with more effective thickeners. Lipid concentration is not involved in viscosity and rheological behaviour. CONCLUSION: The viscosity of the thickened infant formula depends on the agent used, concentration and protein ratio. Not all reach a viscosity of 50 cp, hypothetical value to reach, since it doubles the viscosity of a standard formula. The ideal viscosity to be reached and the role of other components of the formula in the viscosity and rheological behaviour is still unclear.

Arthritis self-management. A five-year history of a patient education program.

There are several lessons to be learned from the ASM experience. First, and most outstanding, is the willingness of large numbers of people across the United States to participate in both the ASM course and the research. Second, we have found that lay leaders can be trained to offer a rather complex arthritis course. They have proved to be reliable and, most important, are acceptable to the public and most health professionals. When their acceptance has been questioned, it is usually by persons with little or no experience with either the course or the lay leaders. Third, a national organization, in this case the Arthritis Foundation, has been able to disseminate the course widely and, to some extent, to conduct evaluations. From the national evaluation experience, we have learned that local areas are much more interested in service than evaluation and almost too readily accept an unproven yet hopeful arthritis education program. However, this acceptance of a new innovation before thorough testing is no different than that seen with other new medical technologies from medication to coronary bypass. Finally and most intriguing, we have found that such standard arthritis treatments as exercise and relaxation seem to directly contribute only slightly to the reductions in pain experienced by ASM participants. This unexpected lack of correlation has led us to begin studying other mediating factors such as self-efficacy, depression or both.(ABSTRACT TRUNCATED AT 250 WORDS)