Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline

Rationale: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. Objective: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Methods: Attentional function in mice haploinsufficient for Map2k7 (Map2k7+/− mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Results: Once stable performance had been achieved, Map2k7+/− mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline—a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia—signs of improvement in attentional performance were detected. Conclusions: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline

Studies relating to protein expression in the uterus of the cow

End of project reportEmbryo loss is a major cause of reproductive wastage in the cow. The majority of embryo loss occurs in the first 16 days after fertilisation when the embryo is critically dependent on the maternal uterine environment for survival. Despite the central role of uterine fluid in the normal growth and development of the embryo, there is limited information on the protein composition of these fluids. The main objectives of the studies in this thesis were to examine the protein composition of the bovine uterus during the oestrous cycle and to examine the relationship between the concentration of systemic progesterone and uterine protein expression in the cow. In the first study, the concentration of retinol-binding protein (RBP) in the bovine uterus was found to vary across the cycle and was 5-15-fold higher (P0.05) of the cycle, which was surprising given that previous studies have indicated that uterine RBP gene expression was positively associated with the concentration of systemic progesterone. In the second study, IGF binding protein 2 (IGFBP-2), IGFBP-3, IGFBP-4 and IGFBP-5 were identified in uterine fluid on days 3, 7, 11 and 15 of the oestrous cycle. There was a local effect on the concentration of IGFBPs where the concentration was greater on the ipsilateral side than that on the contralateral side for IGFBP-2 (P<0.05), 3 (P<0.01) and 5 (P<0.01) on day 15. This difference is a further indication of a local controlling mechanism regulating proteins between the uterine horns. Similar to RBP expression this study could find no significant relationship between the concentration of systemic progesterone and IGFBP concentrations on Day 7 of the oestrous cycle. In the third study, changes in the global pattern of uterine proteins between Days 3 and Day 15 of the oestrous cycle were examined using two-dimensional electrophoresis (2-DE). Six proteins were found to be upregulated on Day 15 compared to Day 3. Three proteins of these were identified as aldose reductase, plakoglobin and heat shock protein 27 while the other three proteins were identified as bovine serum albumin. Aldose reductase, an enzyme directly involved in the production of sorbitol and indirectly of fructose, was 10-fold higher (P<0.0001) on Day 15 compared to Day 3. Plakoglobin (Pg) was upregulated 2.3-fold (P<0.0001) on Day 15 compared to Day 3. Pg is a component of cellular junctions and its up-regulation may have a role in the uterine glandular epithelium. Heat shock protein 27 (Hsp27) was higher on Day 15 than on Day 3 (P<0.01) and Hsp27 was 1.4-fold higher in the ipsilateral compared to the contralateral uterine horn (P<0.01). Hsp27 may be secreted in response to potential stresses in the uterus or act as a molecular chaperone. On Day 7 there was no difference (P<0.05) in the pattern of proteins secreted between cows with low (2.7±0.10ng/ml) and high (4.8±0.13 ng/ml) concentrations of systemic progesterone on Day 7. The results of these studies have shown that dramatic changes occur in protein expression across the bovine oestrous cycle. Additionally, it emphasises the need for gene studies to be followed with protein studies as an adjunct or complementary tool. Proteins have a wide range of essential roles in the uterus and together these studies provide novel information on protein expression in the uterus of the cow

Advanced Technologies in Energy-Economy Models for Climate Change Assessment

Considerations regarding the roles of advanced technologies are crucial in energy-economic modeling, as these technologies, while usually not yet commercially viable, could substitute for fossil energy when relevant policies are in place. To improve the representation of the penetration of advanced technologies, we present a formulation that is parameterized based on observations, while capturing elements of rent and real cost increases if high demand suddenly appears due to large policy shock. The formulation is applied to a global economy-wide model to study the roles of low carbon alternatives in the power sector. While other modeling approaches often adopt specific constraints on expansion, our approach is based on the assumption and observation that these constraints are not absolute—the rate at which advanced technologies will expand is endogenous to economic incentives. The policy simulations are designed to illustrate the response under sudden increased demand for the advanced technologies, and are not intended to represent necessarily realistic price paths for greenhouse gas emissions.The authors gratefully acknowledge the financial support for this work provided by the MIT Joint Program on the Science and Policy of Global Change through a consortium of industrial sponsors and Federal grants. Suggestions and feedback from participants of the MIT EPPA meeting and Jamie Bartholomay are highly appreciated

Biotechnology in Cattle Reproduction.

End of Project ReportTeagasc acknowledges support from the European Union 3rd and 4th Framework Programmes (CT-92-0163 and CT-95-0190)Over the next decade the Irish agri-food industry will have to compete in a rapidly changing world environment arising from increased competitiveness, decreased world market prices and increased consumer demands for higher quality, healthier and safer food. To become competitive in this environment the scale and efficiency of production at both farm and factory level will have to increase significantly and this must be achieved with due regard for the protection of the environment and the welfare of animals. New technologies will be needed to achieve this. Biotechnology will be central to the development of these new technologies. This project has been concerned with the identification and evaluation of biotechnology developments that have the potential to increase reproductive efficiency in cattle. This includes a range of technologies relating to the in vitro production, manipulation, cryopreservation and transfer of cattle embryos. The potential of other emerging technologies such as embryo and sperm sexing, cloning and biopharming or the production of commercially desirable proteins in cows milk are also addressed in this report.European Unoi

Viability of in vitro produced cattle embryos.

End of Project ReportEmbryo transfer is being increasingly used in the cattle industry. As well as direct embryo transfers, many embryo-based biotechnologies have the potential to improve cattle production efficiency through enhanced breeding strategies, by facilitating the introduction of desirable traits such as disease resistance and through the production of desirable medical or pharmaceutical products in the milk. These biotechnologies are, however, dependent on a supply of viable in vitro produced (IVP) embryos. While the in vitro fertilization rate is high (80%) in cattle, only about 30 transferable embryos, or blastocysts, are produced from every 100 fertilized oocytes. A major factor affecting the viability of IVP embryos is their failure, in a high proportion of cases, to undergo normal development to the blastocyst stage in the manner of in vivo embryos. The major problem relates to a failure of the cells of IVP embryos to form a compact cell mass when they are 5 - 6 days old. This ultimately leads to developmental problems and compromised viability. Cell compaction is recognized as a critical event in early embryo development and has been associated with marked changes in protein synthesis and phosphorylation in the embryos of some species. This report is the first, to our knowledge, to describe the rate and pattern of protein synthesis and phosphorylation before, during and after compaction in both in vivo and in IVP cattle embryos. The main results are summarised below.European Union 4th Framework Programmes (Contract CT-95-0032

Renormalization group flows for gauge theories in axial gauges

Gauge theories in axial gauges are studied using Exact Renormalisation Group flows. We introduce a background field in the infrared regulator, but not in the gauge fixing, in contrast to the usual background field gauge. It is shown how heat-kernel methods can be used to obtain approximate solutions to the flow and the corresponding Ward identities. Expansion schemes are discussed, which are not applicable in covariant gauges. As an application, we derive the one-loop effective action for covariantly constant field strength, and the one-loop beta-function for arbitrary regulator

Students' decisions to use an eLearning system: a structural equation modelling analysis

This research investigates and identifies some of the major factors affecting studentsâ?? adoption of an e-learning system at Arab Open University in Jordan. E-learning adoption is approached from the information systems acceptance point of view. An extended version of the Technology Acceptance Model (TAM) was developed to investigate the underlying factors that influence studentsâ?? decisions to use an e-learning system. The proposed model uses the actual use of an e-learning system. It is different from most of the prior TAM studies, which only used a single dependent variable (intention to use). The model was estimated using Structural Equation Modelling (SEM). The final models derived from this study indicated that beliefs of usefulness and ease of use partially mediate the relationship between external factors and intention to use and actual use of e-learning systems

Holographic renormalisation group flows and renormalisation from a Wilsonian perspective

From the Wilsonian point of view, renormalisable theories are understood as submanifolds in theory space emanating from a particular fixed point under renormalisation group evolution. We show how this picture precisely applies to their gravity duals. We investigate the Hamilton-Jacobi equation satisfied by the Wilson action and find the corresponding fixed points and their eigendeformations, which have a diagonal evolution close to the fixed points. The relevant eigendeformations are used to construct renormalised theories. We explore the relation of this formalism with holographic renormalisation. We also discuss different renormalisation schemes and show that the solutions to the gravity equations of motion can be used as renormalised couplings that parametrise the renormalised theories. This provides a transparent connection between holographic renormalisation group flows in the Wilsonian and non-Wilsonian approaches. The general results are illustrated by explicit calculations in an interacting scalar theory in AdS space

Calibration of the Neutron Detection Efficiency of the COMPTEL NE213 Detector

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

The MIT EPPA6 Model: Economic Growth, Energy Use, and Food Consumption

The MIT Economic Projection and Policy Analysis (EPPA) model has been broadly applied on energy and climate policy analyses. In this paper, we provide an updated version of the model based on the most recent global economic database with the base year data of 2007. Also new in this version of the model are non-homothetic preferences, a revised capital vintaging structure, separate accounting of residences, and an improved model structure that smooths its functioning and makes future extensions easier. We compare reference (“business-as-usual”) and policy results for the latest model to the previous version. We also present how projections for the final consumption of food and agricultural products are improved with non-homothetic preferences, and how various assumptions for reference GDP growth, elasticity of substitution between energy and non-energy input, and autonomous energy efficiency improvement may change CO2 emissions and prices.We gratefully acknowledge the financial support for this work provided by the MIT Joint Program on the Science and Policy of Global Change through a consortium of industrial sponsors and Federal grants