The NMDA receptor GluN2C subunit controls cortical excitatoryinhibitory balance, neuronal oscillations and cognitive function

Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2Ccontaining NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs. In addition a greater number of perisomatic GAD67 puncta was observed suggesting a potential increase in parvalbumin interneuron inputs. At a network level the GluN2C knockout mice were found to have a more robust increase in power of oscillations in response to NMDAR blocker MK- 801. Furthermore, GluN2C heterozygous and knockout mice exhibited abnormalities in cognition and sensorimotor gating. Our results demonstrate that loss of GluN2C subunit leads to cortical excitatoryinhibitory imbalance and abnormal neuronal oscillations associated with neurodevelopmental disorders

The all-pay-auction with complete information

In a (first price) all-pay auction, bidders simultaneously submit bids for an item. All players forfeit their bids, and the high bidder receives the item. This auction is widely used in economics to model rent seeking, R&D races, political contests, and job promotion tournaments. We fully characterize equilibrium for this class of games, and show that the set of equilibria is much larger than has been recognized in the literature. When there are more than two players, for instance, we show that even when the auction is symmetric there exists a continuum of asymmetric equilibria. Moreover, for economically important configurations of valuations, there is no revenue equivalence across the equilibria; asymmetric equilibria imply higher expected revenues than the symmetric equilibrium

Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

BACKGROUND: We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. METHODS: The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. RESULTS: In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. CONCLUSION: Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more effective and safer therapeutic approach as the tumor growth and progression are inhibited both in the primary and metastatic sites

Domestication as innovation : the entanglement of techniques, technology and chance in the domestication of cereal crops

The origins of agriculture involved pathways of domestication in which human behaviours and plant genetic adaptations were entangled. These changes resulted in consequences that were unintended at the start of the process. This paper highlights some of the key innovations in human behaviours, such as soil preparation, harvesting and threshing, and how these were coupled with genetic ‘innovations’ within plant populations. We identify a number of ‘traps’ for early cultivators, including the needs for extra labour expenditure on crop-processing and soil fertility maintenance, but also linked gains in terms of potential crop yields. Compilations of quantitative data across a few different crops for the traits of nonshattering and seed size are discussed in terms of the apparently slow process of domestication, and parallels and differences between different regional pathways are identified. We highlight the need to bridge the gap between a Neolithic archaeobotanical focus on domestication and a focus of later periods on crop-processing activities and labour organization. In addition, archaeobotanical data provide a basis for rethinking previous assumptions about how plant genetic data should be related to the origins of agriculture and we contrast two alternative hypotheses: gradual evolution with low selection pressure versus metastable equilibrium that prolonged the persistence of ‘semi-domesticated’ populations. Our revised understanding of the innovations involved in plant domestication highlight the need for new approaches to collecting, modelling and integrating genetic data and archaeobotanical evidence

Optimizing the vertebrate vestibular semicircular canal: could we balance any better?

The fluid-filled semicircular canals (SCCs) of the vestibular system are used by all vertebrates to sense angular rotation. Despite masses spanning seven decades, all mammalian SCCs are nearly the same size. We propose that the SCC represents a sensory organ that evolution has `optimally designed'. Four geometric parameters are used to characterize the SCC, and `building materials' of given physical properties are assumed. Identifying physical and physiological constraints on SCC operation, we find that the most sensitive SCC has dimensions consistent with available data.Comment: 4 pages, 3 figure

Combinatorial nuclear level density by a Monte Carlo method

We present a new combinatorial method for the calculation of the nuclear level density. It is based on a Monte Carlo technique, in order to avoid a direct counting procedure which is generally impracticable for high-A nuclei. The Monte Carlo simulation, making use of the Metropolis sampling scheme, allows a computationally fast estimate of the level density for many fermion systems in large shell model spaces. We emphasize the advantages of this Monte Carlo approach, particularly concerning the prediction of the spin and parity distributions of the excited states, and compare our results with those derived from a traditional combinatorial or a statistical method. Such a Monte Carlo technique seems very promising to determine accurate level densities in a large energy range for nuclear reaction calculations.Comment: 30 pages, LaTex, 7 figures (6 Postscript figures included). Fig. 6 upon request to the autho

Foreign Intravascular Object Embolization and Migration: Bullets, Catheters, Wires, Stents, Filters, and More

Foreign intravascular object embolization (FIOE) is an important, yet underreported occurrence that has been described in a variety of settings, from penetrating trauma to intravascular procedures. In this chapter, the authors will review the most common types of FIOEs, including bullet or “projectile” embolism (BPE), followed by intravascular catheter or wire embolization (ICWE), and conclude with intravascular noncatheter object (e.g., coil, gelatin, stent, and venous filter) migration (INCOM). In addition to detailed topic-based summaries, tables highlighting selected references and case scenarios are also presented to provide the reader with a resource for future research in this clinical area

"Driven to distraction?" Children's experiences of car travel

This is an Author's Accepted Manuscript of an article published in volume, 4, issue 1, pages 59-76 in Mobilities 2009. Copyright @ 2009 Taylor & Francis, available online at: http://www.tandfonline.com/doi/abs/10.1080/17450100802657962.Cars have become increasingly significant features in the lives of many children and adults in the UK and elsewhere. Whilst there is a growing body of research considering how adults experience automobility, that is the increasingly central role of cars within societies, there has been little equivalent research exploring children's perspectives. Drawing upon a variety of methods including personal diaries, photographs, in‐depth interviews and surveys amongst schools within Buckinghamshire and North London, the paper contributes to filling this gap in existing research through exploring how cars are not only journey spaces for children, but are also sites for play, relaxation, homework, companionship, technology and the consumption of commodities. Using a Foucauldian analysis of power, insights into wider familial processes relating to mobility are provided by exploring how cars are sites of conflicting power relations between parents and children. The paper also explores how children's everyday experiences of cars were framed by wider sets of power relations, including car corporations which design and manufacture these spaces, and the role of capital which commodifies everyday activities in cars. In doing so, the paper challenges existing research on automobility for only focusing upon adults' experiences of cars and begins to theorise a more inclusive account of automobility which incorporates children and young people

Learning and developing science capital through citizen science

Citizen science, the active participation of the public in scientific research projects, is a rapidly expanding field in open science and open innovation. It provides an integrated model of public knowledge production and engagement with science. As a growing worldwide phenomenon, it is invigorated by evolving new technologies that connect people easily and effectively with the scientific community. Catalysed by citizens’ wishes to be actively involved in scientific processes, as a result of recent societal trends, it also offers contributions to the rise in tertiary education. In addition, citizen science provides a valuable tool for citizens to play a more active role in sustainable development. This book identifies and explains the role of citizen science within innovation in science and society, and as a vibrant and productive science-policy interface. The scope of this volume is global, geared towards identifying solutions and lessons to be applied across science, practice and policy. The chapters consider the role of citizen science in the context of the wider agenda of open science and open innovation, and discuss progress towards responsible research and innovation, two of the most critical aspects of science today