NeuroBox: Computational Mathematics in Multiscale Neuroscience.

The brain is a complex organ operating on multiple scales. From molecular events that inform electrical and biochemical cellular responses, the brain interconnects processes all the way up to the massive network size of billions of brain cells. This strongly coupled, nonlinear, system has been subject to research that has turned increasingly multidisciplinary. The seminal work of Hodgkin and Huxley in the 1950s made use of experimental data to derive a coherent physical model of electrical signaling in neurons, which can be solved using mathematical and computational methods, thus bringing together neuroscience, physics, mathematics, and computer science. Over the last decades numerous projects have been dedicated to modeling and simulation of specific parts of molecular dynamics, neuronal signaling, and neural network behavior. Simulators have been developed around a specific objective and scale, in order to cope with the underlying computational complexity. Often times a dimension reduction approach allows larger scale simulations, this however has the inherent drawback of losing insight into structure-function interplay at the cellular level. This paper gives an overview of the project NeuroBox that has the objective of integrating multiple brain scales and associated physical models into one unified framework. NeuroBox hosts geometry and anatomical reconstruction methods, such that detailed three-dimensional domains can be integrated into numerical simulations of models based on partial differential equations. The project further focusses on deriving numerical methods for handling complex computational domains, and to couple multiple spatial dimensions. The latter allows the user to specify in which parts of the biological problem high-dimensional representations are necessary and where low-dimensional approximations are acceptable. NeuroBox offers workflow user interfaces that are automatically generated with VRL-Studio and can be controlled by non-experts. The project further uses uG4 as the numerical backend, and therefore accesses highly advanced discretization methods as well as hierarchical and scalable numerical solvers for very large neurobiological problems.

Laryngeal chondronecrosis after radiation therapy in a dog.

A 5-year-old pug presented with a soft tissue swelling on the ventral neck and moderate stridor with associated respiratory effort. This patient received hypofractionated radiotherapy for metastatic upper lip mast cell tumour and to the submandibular lymph nodes 6 months before presentation. Oral examination showed moderate elongation of the soft palate, stage III laryngeal collapse with only the right laryngeal saccule mildly everted and exuberant pale epiglottal and left pharyngeal mucosa. Staphylectomy, resection of the epiglottal mucosa and left arytenoid lateralisation were performed. One day after surgery, temporary tracheostomy was performed after respiratory distress due to the severe laryngeal and pharyngeal oedema. A third oral exam showed pale and redundant caudal pharyngeal mucosa obstructing the rima glottis, soft and collapsible arytenoid cartilage with pale mucosa and bilateral everted laryngeal saccules. Permanent tracheostomy was elected and laryngeal cartilage biopsies were taken. Histologic diagnosis showed cartilage necrosis and abundant tissue oedema. The patient was euthanased 1 week later.

DMSP--Database for Modeling Signaling Pathways. Combining biological and mathematical modeling knowledge for pathways.

OBJECTIVES: Presently, the protein interaction information concerning different signaling pathways is available in a qualitative manner in different online protein interaction databases. The challenge here is to derive a quantitative way of modeling signaling pathways from qualitative way of modeling signaling pathways from a qualitative level. To address this issue we developed a database that includes mathematical modeling knowledge and biological knowledge about different signaling pathways. METHODS: The database is part of an integrative environment that includes environments for pathway design, visualization, simulation and a knowledge base that combines biological and modeling information concerning pathways. The system is designed as a client-server architecture. It contains a pathway designing environment and a simulation environment as upper layers with a relational knowledge base as the underlying layer. RESULTS: DMSP--Database for Modeling Signaling Pathways incorporates biological datasets from online databases like BIND, DIP, PIP, and SPiD. The modeling knowledge that has been incorporated is based on a literature study. Pathway models can be designed, visualized and simulated based on the knowledge stored in the DMSP. The user can download the whole dataset and build pathway models using the knowledge stored in our database. As an example, the TNFalpha pathway model was implemented and tested using this approach. CONCLUSION: DMSP is an initial step towards the aim of combining modeling and biological knowledge concerning signaling pathways. It helps in understanding pathways in a qualitative manner from a qualitative level. Simulation results enable the interpretation of a biological system from a quantitative and system-theoretic point of view.

Ultrafast dynamics of coherences in a quantum Hall system.

Using three-pulse four-wave-mixing optical spectroscopy, we study the ultrafast dynamics of the quantum Hall system. We observe striking differences as compared to an undoped system, where the 2D electron gas is absent. In particular, we observe a large off-resonant signal with strong oscillations. Using a microscopic theory, we show that these are due to many-particle coherences created by interactions between photoexcited carriers and collective excitations of the 2D electron gas. We extract quantitative information about the dephasing and interference of these coherences.

A comparison of three nocturnal enuresis treatment methods.

To evaluate the efficacy of an operant approach that includes the bell and pad for the treatment of enuresis (Tangible Rewards with Fading), it was compared with an established operant method that includes the bell and pad (the Dry Bed method) and to a conventional Bell and Pad method. Although there were no overall statistically significant differences among the three methods, individual pairwise comparisons were of interest; the Dry Bed method had no advantage, but the Tangible Rewards with Fading method tended to have more patients reach a 14-day dryness criterion (p less than 0.10) and tended to have fewer patients relapse after treatment (p less than 0.08) than the Bell and Pad method.

Jealousy: interventions in couples therapy.

Jealousy is a ubiquitous phenomenon that often needs to be addressed in couples therapy. Eleven treatment interventions, with case examples, are discussed, ranging from traditional, direct, straightforward approaches to indirect, paradoxical solutions. Criteria are offered for determining which interventions to use.

Separation anxiety in mothers of latency-age fearful children.

The hypothesis that mothers of children who have symptoms indicative of separation anxiety are themselves separation-anxious was tested by scoring mothers' TAT themes for separation concerns. The stories of 15 mothers of fearful children were compared to the stories of 26 mothers of children manifesting behavior disorders and 21 mothers of children having had no psychiatric contact. Different kinds of separation concerns were found to differentiate the groups of mothers. The stories of mothers of fearful children expressed significantly more concerns about abandonment and rejection and more often expressed a desire to stay near the loved one; the mothers of children expressed significantly more concerns about abandonment and rejection and more often expressed a desire to stay near the loved one; the mothers of children with behavior disorders were found to tell significantly more stories with nurturance-succorance themes. The results lend support to the theory of anxious attachment in that mothers of fearful children seem to share the same concerns that have been ascribed to their children. On the other hand, it seems that separation anxiety may not be a unidimensional construct as different components seem to be more relevant to some symptom clusters than to others.