Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia

To determine if NMDA receptor alterations are present in the cerebellum in schizophrenia, we measured NMDA receptor binding and gene expression of the NMDA receptor subunits in a post-mortem study of elderly patients with schizophrenia and non-affected subjects. Furthermore, we assessed influence of genetic variation in the candidate gene neuregulin-1 (NRG1) on the expression of the NMDA receptor in an exploratory study. Post-mortem samples from the cerebellar cortex of ten schizophrenic patients were compared with nine normal subjects. We investigated NMDA receptor binding by receptor autoradiography and gene expression of the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D by in situ hybridization. For the genetic study, we genotyped the NRG1 polymorphism rs35753505 (SNP8NRG221533). Additionally, we treated rats with the antipsychotics haloperidol or clozapine and assessed cerebellar NMDA receptor binding and gene expression of subunits to examine the effects of antipsychotic treatment. Gene expression of the NR2D subunit was increased in the right cerebellum of schizophrenic patients compared to controls. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of the NR2C subunit in the right cerebellum, compared to individuals homozygous for the T allele. Correlation with medication parameters and the animal model revealed no treatment effects. In conclusion, increased NR2D expression results in a hyperexcitable NMDA receptor suggesting an adaptive effect due to receptor hypofunction. The decreased NR2C expression in NRG1 risk variant may cause a deficit in NMDA receptor function. This supports the hypothesis of an abnormal glutamatergic neurotransmission in the right cerebellum in the pathophysiology of schizophrenia

Competitive Tendering In The Netherlands: Central Planning Or Functional Specifications?

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Strong simple policies for POMDP

The synthesis problem for partially observable Markov decision processes (POMDPs) is to compute a policy that provably adheres to one or more specifications. Yet, the general problem is undecidable, and policies require full (and thus potentially unbounded) traces of execution history. To provide good approximations of such policies, POMDP agents often employ randomization over action choices. We consider the problem of computing simpler policies for POMDPs, and provide several approaches to still ensure their expressiveness. Key aspects are (1) the combination of an arbitrary number of specifications the policies need to adhere to, (2) a restricted form of randomization, and (3) a light-weight preprocessing of the POMDP model to encode memory. We provide a novel encoding as a mixed-integer linear program as baseline to solve the underlying problems. Our experiments demonstrate that the policies we obtain are more robust, smaller, and easier to implement for an engineer than those obtained from state-of-the-art POMDP solvers

Examining the evolution education literature with a focus on teachers: major findings, goals for teacher preparation, and directions for future research

The theory of evolution is the fundamental backbone to the discipline of biology, yet many students possess misunderstandings. The teacher is the most important school-based factor in student learning, and therefore to improve students’ understandings of evolution, we must better prepare teachers. The purpose of this paper is three-fold. First, we reviewed empirical research studies focused on K-12 teachers regarding evolution education from 1993 to 2011 with the purpose of identifying major themes of research and corresponding findings. Second, we used our understandings of current findings to inform the development and articulation of five goals for teacher preparation. Third, we discuss implications of this work for teacher preparation initiatives and directions of future research. We found that current evolution education research specific to K-12 teachers falls within four major themes, which collectively inform the development of five goals for preparing teachers to teach evolution. We argue that teachers should: (1) develop content knowledge of evolution; (2) develop understandings of the nature of science related to evolution; (3) develop acceptance of evolution as valid within science; (4) develop knowledge of and strategies for handling the public controversy; and (5) develop pedagogical content knowledge for teaching evolution. Based on our review, evolution courses and professional development initiatives for K-12 teachers should integrate the five goals, with more attention to teaching evolution in the classroom. Investigating the nature of teachers’ acceptance of evolution and pedagogical content knowledge for teaching evolution are areas of research in need of continued pursuit