A model-based approach for the rational design of the freeze-thawing of a protein-based formulation

Proteins are unstable molecules that may be severely injured by stresses encountered during freeze-thawing. Despite this, the selection of freeze-thaw conditions is currently empirical, and this results in reduced process control. Here we propose a mathematical model that takes into account the leading causes of protein instability during freeze-thawing, i.e. cold denaturation and surface-induced unfolding, and may guide the selection of optimal operating conditions. It is observed that a high cooling rate is beneficial for molecules that are extremely sensitive to cold denaturation, while the opposite is true when ice-induced unfolding is dominant. In all cases, a fast thawing rate is observed to be beneficial. The simulation outputs are confirmed by experimental data for myoglobin and lactate dehydrogenase, suggesting that the proposed modeling approach can reproduce the main features of protein behavior during freeze-thawing. This approach can therefore guide the selection of optimal conditions for protein-based formulations that are stored in a frozen or freeze-dried state

The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information’s (NCBI’s) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation

Issues in the Design of a Pilot Concept-Based Query Interface for the Neuroinformatics Information Framework

This paper describes a pilot query interface that has been constructed to help us explore a "concept-based" approach for searching the Neuroscience Information Framework (NIF). The query interface is concept-based in the sense that the search terms submitted through the interface are selected from a standardized vocabulary of terms (concepts) that are structured in the form of an ontology. The NIF contains three primary resources: the NIF Resource Registry, the NIF Document Archive, and the NIF Database Mediator. These NIF resources are very different in their nature and therefore pose challenges when designing a single interface from which searches can be automatically launched against all three resources simultaneously. The paper first discusses briefly several background issues involving the use of standardized biomedical vocabularies in biomedical information retrieval, and then presents a detailed example that illustrates how the pilot concept-based query interface operates. The paper concludes by discussing certain lessons learned in the development of the current version of the interface

Management of patients with Graves' disease and orbital involvement: role of spectral domain optical coherence tomography

PURPOSE: To investigate the role of choroidal thickness evaluation with spectral domain optical coherence tomography (SDOCT) and enhanced depth imaging (EDI) technique in the management of patients with Graves' disease and orbitopathy (GO). METHODS: Thirty-six eyes of 18 patients with GO and 36 eyes of 18 age-matched control subjects were included in this retrospective observational study. All the subjects underwent a complete ophthalmological evaluation, including clinical activity score (CAS) and exophthalmometry. The SDOCT images of the choroid were obtained by EDI modality. RESULTS: Choroidal thickness was significantly increased in GO than in control eyes (p < 0.01). A significant correlation was found between choroidal thickness and CAS, proptosis, and the duration of disease (p < 0.05). CONCLUSION: This study shows that choroidal thickness, evaluated with EDI-OCT, is significantly increased in patients with GO and correlates with the activity of the disease, proptosis, and duration of the disease. The choroidal thickening may reflect the ocular hemodynamic changes, and enhanced depth imaging optical coherence tomography may be a useful tool for the evaluation of orbital congestion and management of patients with Graves' disease and orbital involvement

A modified femtosecond laser technique for anterior capsule contraction syndrome

Anterior capsule contraction syndrome (ACCS) is a rare, late complication of cataract surgery, associated with impairment of visual function. In this paper, we describe a new surgical technique to treat ACCS by femtosecond laser procedure. The femtosecond laser was used to perform an anterior capsulotomy with a customized size, in order to avoid IOL damage. After ophthalmic viscosurgical device injection in the anterior chamber, the anterior capsule flap was separated from the IOL surface by gentle hydrodissection. This manoeuvre enabled an easy and safe removal of the fibrotic material by vitreal microscissors. Our technique allowed a complete removal of the fibrotic material and opening of the capsule, with immediate complete visual acuity recovery without IOL damage. In conclusion, femtosecond laser appears to be safe and effective for treatment of ACCS with long-lasting efficacy

Chromatic scheduling polytopes coming from the bandwidth allocation problem in point to multipoint radio access systems

Lo sistemas de radio punto a multipunto son conjuntos de antenas de radio que proveen acceso inalámbrico a redes de comunicación de voz y datos. Este tipo de sistemas debe ser operado utilizando un cierto espectro de frecuencia de radio, lo cual normalmente produce problemas de capacidad. Por lo tanto es necesario reutilizar frecuencias, pero este reuso no debe generar interferencia entre las señales. El problema de determinar las frecuencias para los enlaces se conoce como el problema de asignación de frecuencias, y en este tipo de sistemas es un caso especial de los problemas de planificación cromática. Estos problemas son NP-hard, y no existen algoritmos aproximados polinomiales con una garantía de calidad fija. Como los métodos de planos de corte han demostrado ser efectivos para muchos otros problemas de optimización combinatoria, el objetivo es aplicar estos métodos al problema de asignación de frecuencias en sistemas punto a multipunto. Para esto, es necesario estudiar previamente los politopos asociados con el problema. El presente trabajo contribuye a este estudio. Introducimos una formulación del problema de asignación de frecuencias en sistemas punto a multipunto como un problema de programación lineal entera, y definimos los politipos de planificación cromática asociados a esta formulación. Estudiamos en primer lugar la estructura combinatoria de estos politipos, analizando los distintos estados - vacuidad, no vacuidad pero dimensión incompleta, dimensión completa pero inestabilidad combinatoria, y estabilidad combinatoria - a medida que el ancho de banda disponible aumenta. Por otra parte, exploramos las relaciones de los politipos de planificación cromática con el politipo de ordenamiento lineal. Desde el punto de vista geométrico, los politipos de planificación cromática son de un interés particular debido a su simetría. como consecuencia de esta propiedad, desarrollamos una importante herramienta para identificar desigualdades que definen facetas sin requerir información sobre la dimensión del politipo. Esto nos permite identificar las restricciones del modelo de programación lineal entera que definen facetas del politipo asociado. Las restantes restricciones del modelo deben ser reforzadas mediante estructuras basadas en cliques del grafo de interferencia para obtener desigualdades que definen facetas. En particular, las desigualdades de clique en cubrimiento generan una gran familia de facetas, y además presentamos varias clases de facetas que provienen de generalizaciones y variaciones de estas desigualdades. Introducimos clases adicionales de facetas basadas en distintos conceptos, y estudiamos la complejidad de los problemas de separación asociados.Fil:Marenco, Javier L.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Horizontal and vertical structure of the Eyjafjallajökull ash cloud over the UK: a comparison of airborne lidar observations and simulations

During April and May 2010 the ash cloud from the eruption of the Icelandic volcano Eyjafjallajökull caused widespread disruption to aviation over northern Europe. The location and impact of the eruption led to a wealth of observations of the ash cloud were being obtained which can be used to assess modelling of the long range transport of ash in the troposphere. The UK FAAM (Facility for Airborne Atmospheric Measurements) BAe-146-301 research aircraft overflew the ash cloud on a number of days during May. The aircraft carries a downward looking lidar which detected the ash layer through the backscatter of the laser light. In this study ash concentrations derived from the lidar are compared with simulations of the ash cloud made with NAME (Numerical Atmospheric-dispersion Modelling Environment), a general purpose atmospheric transport and dispersion model. The simulated ash clouds are compared to the lidar data to determine how well NAME simulates the horizontal and vertical structure of the ash clouds. Comparison between the ash concentrations derived from the lidar and those from NAME is used to define the fraction of ash emitted in the eruption that is transported over long distances compared to the total emission of tephra. In making these comparisons possible position errors in the simulated ash clouds are identified and accounted for. The ash layers seen by the lidar considered in this study were thin, with typical depths of 550–750 m. The vertical structure of the ash cloud simulated by NAME was generally consistent with the observed ash layers, although the layers in the simulated ash clouds that are identified with observed ash layers are about twice the depth of the observed layers. The structure of the simulated ash clouds were sensitive to the profile of ash emissions that was assumed. In terms of horizontal and vertical structure the best results were obtained by assuming that the emission occurred at the top of the eruption plume, consistent with the observed structure of eruption plumes. However, early in the period when the intensity of the eruption was low, assuming that the emission of ash was uniform with height gives better guidance on the horizontal and vertical structure of the ash cloud. Comparison of the lidar concentrations with those from NAME show that 2–5% of the total mass erupted by the volcano remained in the ash cloud over the United Kingdom