Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus)

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN is the site of the endogenous biological clock that generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity and is responsible for the transmission of non-photic information to the SCN, thus participating in the integration between photic and non-photic stimuli. Both the SCN and IGL receive projections of retinal ganglion cells and the IGL is connected to the SCN through the geniculohypothalamic tract. Little is known about these structures in the primate brain and the pregeniculate nucleus (PGN) has been suggested to be the primate equivalent of the rodent IGL. The aim of this study was to characterize the PGN of a primate, the common marmoset (Callithrix jacchus), and to analyze its retinal afferents. Here, the marmoset PGN was found to be organized into three subsectors based on neuronal size, pattern of retinal projections, and the distribution of neuropeptide Y-, GAD-, serotonin-, enkephalin- and substance P-labeled terminals. This pattern indicates that the marmoset PGN is equivalent to the IGL. This detailed description contributes to the understanding of the circadian timing system in this primate species considering the importance of the IGL within the context of circadian regulation. (C) 2012 Elsevier B.V. All rights reserved.

MATHEMATICAL MODELS AND POLYHEDRAL STUDIES FOR INTEGRAL SHEET METAL DESIGN

We deal with the optimization of the production of branched sheet metal products. New forming techniques for sheet metal give rise to a wide variety of possible profiles and possible ways of production. In particular, we show how the problem of producing a given profile geometry can be modeled as a discrete optimization problem. We provide a theoretical analysis of the model in order to improve its solution time. In this context we give the complete convex hull description of some substructures of the underlying polyhedron. Moreover, we introduce a new class of facet-defining inequalities that represent connectivity constraints for the profile and show how these inequalities can be separated in polynomial time. Finally, we present numerical results for various test instances, both real-world and academic examples.

Modeling the Emergence of Circadian Rhythms in a Clock Neuron Network

Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.

An in-depth analysis of the HIV-1/AIDS dynamics by comprehensive mathematical modeling

This work presents major results from a novel dynamic model intended to deterministically represent the complex relation between HIV-1 and the human immune system. The novel structure of the model extends previous work by representing different host anatomic compartments under a more in-depth cellular and molecular immunological phenomenology. Recently identified mechanisms related to HIV-1 infection as well as other well known relevant mechanisms typically ignored in mathematical models of HIV-1 pathogenesis and immunology, such as cell-cell transmission, are also addressed. (C) 2011 Elsevier Ltd. All rights reserved.

Three time-based scale formulations for the two-stage lot sizing and scheduling in process industries

In this paper, we propose three novel mathematical models for the two-stage lot-sizing and scheduling problems present in many process industries. The problem shares a continuous or quasi-continuous production feature upstream and a discrete manufacturing feature downstream, which must be synchronized. Different time-based scale representations are discussed. The first formulation encompasses a discrete-time representation. The second one is a hybrid continuous-discrete model. The last formulation is based on a continuous-time model representation. Computational tests with state-of-the-art MIP solver show that the discrete-time representation provides better feasible solutions in short running time. On the other hand, the hybrid model achieves better solutions for longer computational times and was able to prove optimality more often. The continuous-type model is the most flexible of the three for incorporating additional operational requirements, at a cost of having the worst computational performance. Journal of the Operational Research Society (2012) 63, 1613-1630. doi:10.1057/jors.2011.159 published online 7 March 2012

Sleep disorders in climacteric women

Introduction: This paper examines the various factors that contribute to the occurrence of sleep alterations during peri and post climacteric and thus produce significant imperil to women's quality of life. Among the probable causes of insomnia or sleep disorders associated to climacteric stand out the occurrence of vasomotor symptoms, depressive state and respiratory distress during sleep, such as sleep apnea, along with chronic pain, although psychosocial factors related to the climacteric bear major influence on such clinical status. Method: The bibliographic analysis was carried out using several electronic data base namely: Cochrane, Medline, Embase, Bni Plus, Biological Abstracts, Psycinfo, Web Of Science, Sigle, Dissertation Abstracts and ZETOC published in English, Spanish and Poruguese. The key terms used were: sleep, REM sleep, slow wave sleep polysomnography; electroencephalogram; sleep disturbances; disturbances of sleep onset and maintenance; excessive somnolence disturbances; climacteric; menopause; depression; neurobiology; biologic models; circadian rhythm; mental health and epidemiology. Case studies and letters to the editor were excluded. The summaries of the identified studies found in the data base were analyzed and assessed, and the data analyzed separately according to the subjective or objective criteria for data collection. Results: The climacteric transition constitutes a period of major risk for the development of depressive, vasomotor and insomnia symptoms although not caused solely by hypoestrogenism. The diagnostic methods used in the study of sleep disorders range from subjective assessment by means of response to specific questionnaires to the objective analysis of actigraphic or polissonographic daytime and nocturnal reports. Polissonographic studies of the whole night, performed at the laboratory, are the golden method of choice for diagnostic of sleep disorders. Studies point to the high prevalence of sleep disorders in the climacteric, especially insomnia, apnea and periodic movement of legs and also to the fact that this phase of life presents decrease in the quality of sleep. Women in peri and post climacteric show higher sleep latency and difficulty in its maintenance and refer being less satisfied with its quality even when compared to those who are not climacteric. Exception made to the vasomotor symptomatology, the other climacteric complaints such as mood disturbances, libido alterations, cognitive deficit, articular pain and sleep disorders are markedly associated to psychosocial factors, lifestyle and especially to women's perception of what the climacteric means to their lives. Conclusion: The analysis of the available studies revealed a proneness to deterioration of quality of life of climacteric women markedly in the sleep disturbances, depressed mood and anxiety domains and should not to be basically attributed to the climacteric. It is necessary that the professionals consider the need of assessment of such pathologies as complex phenomena and the literature lacks studies contemplating such dimensions.

An integrated approach to remanufacturing: model of a remanufacturing system

Remanufacturing is the process of rebuilding used products that ensures that the quality of remanufactured products is equivalent to that of new ones. Although the theme is gaining ground, it is still little explored due to lack of knowledge, the difficulty of visualizing it systemically, and implementing it effectively. Few models treat remanufacturing as a system. Most of the studies still treated remanufacturing as an isolated process, preventing it from being seen in an integrated manner. Therefore, the aim of this work is to organize the knowledge about remanufacturing, offering a vision of remanufacturing system and contributing to an integrated view about the theme. The methodology employed was a literature review, adopting the General Theory of Systems to characterize the remanufacturing system. This work consolidates and organizes the elements of this system, enabling a better understanding of remanufacturing and assisting companies in adopting the concept.

Multimodality and flexibility of stochastic gene expression

We consider a general class of mathematical models for stochastic gene expression where the transcription rate is allowed to depend on a promoter state variable that can take an arbitrary (finite) number of values. We provide the solution of the master equations in the stationary limit, based on a factorization of the stochastic transition matrix that separates timescales and relative interaction strengths, and we express its entries in terms of parameters that have a natural physical and/or biological interpretation. The solution illustrates the capacity of multiple states promoters to generate multimodal distributions of gene products, without the need for feedback. Furthermore, using the example of a three states promoter operating at low, high, and intermediate expression levels, we show that using multiple states operons will typically lead to a significant reduction of noise in the system. The underlying mechanism is that a three-states promoter can change its level of expression from low to high by passing through an intermediate state with a much smaller increase of fluctuations than by means of a direct transition.