Modelling molecular interaction pathways using a two-stage identification algorithm

In systems biology, molecular interactions are typically modelled using white-box methods, usually based on mass action kinetics. Unfortunately, problems with dimensionality can arise when the number of molecular species in the system is very large, which makes the system modelling and behavior simulation extremely difficult or computationally too expensive. As an alternative, this paper investigates the identification of two molecular interaction pathways using a black-box approach. This type of method creates a simple linear-in-the-parameters model using regression of data, where the output of the model at any time is a function of previous system states of interest. One of the main objectives in building black-box models is to produce an optimal sparse nonlinear one to effectively represent the system behavior. In this paper, it is achieved by applying an efficient iterative approach, where the terms in the regression model are selected and refined using a forward and backward subset selection algorithm. The method is applied to model identification for the MAPK signal transduction pathway and the Brusselator using noisy data of different sizes. Simulation results confirm the efficacy of the black-box modelling method which offers an alternative to the computationally expensive conventional approach

Effectiveness of student response systems in terms of learning environment, attitudes and achievement

In order to investigate the effectiveness of using Student Response Systems (SRS) among grade 7 and 8 science students in New York, the How Do You Feel About This Class? (HDYFATC) questionnaire was administered to 1097 students (532 students did use SRS and 565 students who did not use SRS). Data analyses attested to the sound factorial validity and internal consistency reliability of the HDYFATC, as well as its ability to differentiate between the perceptions of students in different classrooms. Very large differences between users and non-users of SRS, ranging from 1.17 to 2.45 standard deviations for various learning environment scales, attitudes and achievement, supported the efficacy of using SRS

Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

Biogenic amines are important signaling molecules in the central nervous system of both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, biogenic amines take part in the regulation of various vital physiological processes such as feeding, learning/memory, locomotion, sexual behavior, and sleep/arousal. Consequently, several morphological studies have analyzed the distribution of aminergic neurons in the CNS. Previous descriptions, however, did not determine the exact spatial location of aminergic neurite arborizations within the neuropil. The release sites and pre-/postsynaptic compartments of aminergic neurons also remained largely unidentified. We here used gal4-driven marker gene expression and immunocytochemistry to map presumed serotonergic (5-HT), dopaminergic, and tyraminergic/octopaminergic neurons in the thoracic and abdominal neuromeres of the Drosophila larval ventral ganglion relying on Fasciclin2-immunoreactive tracts as three-dimensional landmarks. With tyrosine hydroxylase- (TH) or tyrosine decarboxylase 2 (TDC2)-specific gal4-drivers, we also analyzed the distribution of ectopically expressed neuronal compartment markers in presumptive dopaminergic TH and tyraminergic/octopaminergic TDC2 neurons, respectively. Our results suggest that thoracic and abdominal 5-HT and TH neurons are exclusively interneurons whereas most TDC2 neurons are efferent. 5-HT and TH neurons are ideally positioned to integrate sensory information and to modulate neuronal transmission within the ventral ganglion, while most TDC2 neurons appear to act peripherally. In contrast to 5-HT neurons, TH and TDC2 neurons each comprise morphologically different neuron subsets with separated in- and output compartments in specific neuropil regions. The three-dimensional mapping of aminergic neurons now facilitates the identification of neuronal network contacts and co-localized signaling molecules, as exemplified for DOPA decarboxylase-synthesizing neurons that co-express crustacean cardioactive peptide and myoinhibiting peptides

Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells

Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned

Development and validation of the motivations for selection of medical study (MSMS) questionnaire in India

Background and Objective Understanding medical students' motivation to select medical studies is particularly salient to inform practice and policymaking in countries-such as India-where shortage of medical personnel poses crucial and chronical challenges to healthcare systems. This study aims to develop and validate a questionnaire to assess the motivation of medical students to select medical studies. Methods A Motivation for Selection of Medical Study (MSMS) questionnaire was developed using extensive literature review followed by Delphi technique. The scale consisted of 12 items, 5 measuring intrinsic dimensions of motivations and 7 measuring extrinsic dimensions. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), validity, reliability and data quality checks were conducted on a sample of 636 medical students from six medical colleges of three North Indian states. Results The MSMS questionnaire consisted of 3 factors (subscales) and 8 items. The three principal factors that emerged after EFA were the scientific factor (e.g. research opportunities and the ability to use new cutting edge technologies), the societal factor (e.g. job security) and the humanitarian factor (e.g. desire to help others). The CFA conducted showed goodnessof-fit indices supporting the 3-factor model. Conclusion The three extracted factors cut across the traditional dichotomy between intrinsic and extrinsic motivation and uncover a novel three-faceted motivation construct based on scientific factors, societal expectations and humanitarian needs. This validated instrument can be used to evaluate the motivational factors of medical students to choose medical study in India and similar settings and constitutes a powerful tool for policymakers to design measures able to increase selection of medical curricula