Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Early childhood education : the natural starting point for environmental education

Young children are most vulnerable to, and most at risk from, environmental and sustainability challenges. Early education investments aimed at addressing such issues, until recently however, have been neglected or under-rated. Fortunately, this is changing. A groundswell of practitioner interest in early childhood environmental education/ education for sustainability is emerging, in contrast to the ‘patches of green’ that have characterised previous decades. Indeed, an international coalition for early childhood education for sustainability (ECEfS) is beginning to develop, evidenced by The Gothenburg Recommendations on Education for Sustainable Development (2008) that identifies early childhood, within a framework of lifelong learning, as a ‘natural starting point’ for all ongoing education for sustainability. This document is important as it is the first international statement to explicitly identify ECEfS as contributing to education for sustainability. The next challenge for ECEfS is for practitioner mobilisation to be matched by research activity aimed at broadening and deepening practice-based responses. This is the next exciting frontier in the legitimisation of ECEfS.

Implementing design build project delivery system in Indonesian road infrastructure projects

Design-Build (DB) project delivery systems have increasingly been adopted by many private and public sector organizations worldwide due to its many advantages. However, many Indonesian road infrastructure projects are still delivered using the traditional design-bid-build (DBB) project delivery system. This paper reviews the existing literature to explore factors that can influence the successful implementation of DB project delivery system in Indonesian road infrastructure projects. It founds the lack of clarification in existing legislations as well as the lack of experiences, knowledge and skill as the main obstacles in implementing DB systems in Indonesia. To overcome these obstacles, this paper proposes (1) A relook at existing legislation in term of providing more guidance on determining projects appropriate for the DB, procedures for implementing DB, and the structure of builder entity; (2) To develop the skills and knowledge of DB to all stakeholders through communications, knowledge sharing and training. The outcome of this review can serve as a guide to development a framework for the implementation of the design-build project delivery system in Indonesian road infrastructure projects.

Gatekeeping, gatewatching, real-time feedback : new challenges for Journalism

How bloggers and other independent online commentators criticise, correct, and otherwise challenge conventional journalism has been known for years, but has yet to be fully accepted by journalists; hostilities between the media establishment and the new generation of citizen journalists continue to flare up from time to time. The old gatekeeping monopoly of the mass media has been challenged by the new practice of gatewatching: by individual bloggers and by communities of commentators which may not report the news first-hand, but curate and evaluate the news and other information provided by official sources, and thus provide an important service. And this now takes place ever more rapidly, almost in real time: using the latest social networks, which disseminate, share, comment, question, and debunk news reports within minutes, and using additional platforms that enable fast and effective ad hoc collaboration between users. When hundreds of volunteers can prove within a few days that a German minister has been guilty of serious plagiarism, when the world first learns of earthquakes and tsunamis via Twitter – how does journalism manage to keep up?

Designing and evaluating mobile multimedia user experiences in public urban places : Making sense of the field

The majority of the world’s population now lives in cities (United Nations, 2008) resulting in an urban densification requiring people to live in closer proximity and share urban infrastructure such as streets, public transport, and parks within cities. However, “physical closeness does not mean social closeness” (Wellman, 2001, p. 234). Whereas it is a common practice to greet and chat with people you cross paths with in smaller villages, urban life is mainly anonymous and does not automatically come with a sense of community per se. Wellman (2001, p. 228) defines community “as networks of interpersonal ties that provide sociability, support, information, a sense of belonging and social identity.” While on the move or during leisure time, urban dwellers use their interactive information communication technology (ICT) devices to connect to their spatially distributed community while in an anonymous space. Putnam (1995) argues that available technology privatises and individualises the leisure time of urban dwellers. Furthermore, ICT is sometimes used to build a “cocoon” while in public to avoid direct contact with collocated people (Mainwaring et al., 2005; Bassoli et al., 2007; Crawford, 2008). Instead of using ICT devices to seclude oneself from the surrounding urban environment and the collocated people within, such devices could also be utilised to engage urban dwellers more with the urban environment and the urban dwellers within. Urban sociologists found that “what attracts people most, it would appear, is other people” (Whyte, 1980, p. 19) and “people and human activity are the greatest object of attention and interest” (Gehl, 1987, p. 31). On the other hand, sociologist Erving Goffman describes the concept of civil inattention, acknowledging strangers’ presence while in public but not interacting with them (Goffman, 1966). With this in mind, it appears that there is a contradiction between how people are using ICT in urban public places and for what reasons and how people use public urban places and how they behave and react to other collocated people. On the other hand there is an opportunity to employ ICT to create and influence experiences of people collocated in public urban places. The widespread use of location aware mobile devices equipped with Internet access is creating networked localities, a digital layer of geo-coded information on top of the physical world (Gordon & de Souza e Silva, 2011). Foursquare.com is an example of a location based 118 Mobile Multimedia – User and Technology Perspectives social network (LBSN) that enables urban dwellers to virtually check-in into places at which they are physically present in an urban space. Users compete over ‘mayorships’ of places with Foursquare friends as well as strangers and can share recommendations about the space. The research field of Urban Informatics is interested in these kinds of digital urban multimedia augmentations and how such augmentations, mediated through technology, can create or influence the UX of public urban places. “Urban informatics is the study, design, and practice of urban experiences across different urban contexts that are created by new opportunities of real-time, ubiquitous technology and the augmentation that mediates the physical and digital layers of people networks and urban infrastructures” (Foth et al., 2011, p. 4). One possibility to augment the urban space is to enable citizens to digitally interact with spaces and urban dwellers collocated in the past, present, and future. “Adding digital layer to the existing physical and social layers could facilitate new forms of interaction that reshape urban life” (Kjeldskov & Paay, 2006, p. 60). This methodological chapter investigates how the design of UX through such digital placebased mobile multimedia augmentations can be guided and evaluated. First, we describe three different applications that aim to create and influence the urban UX through mobile mediated interactions. Based on a review of literature, we describe how our integrated framework for designing and evaluating urban informatics experiences has been constructed. We conclude the chapter with a reflective discussion on the proposed framework.

Early childhood education

Young children are the most vulnerable and most at risk of environmental challenges, current and future. Yet, early learning around environment and sustainability issues and topics has been neglected and underrated in early childhood education even though there is an expanding body of research literature – from economics, neuroscience, sociology and health – that shows that early investments in human capital offer substantial returns for individuals and for communities and have a long reach into the future. Early childhood education for sustainability (ECEfS) - a synthesis of early childhood education (ECE) and education for sustainability (EfS) - builds on groundings in play, outdoor learning and nature education, but takes a stronger focus on learning about, and engagement with, environmental and sustainability issues. Child participation and agency is central to ECEfS and can relate, for example, to local environmental problem-solving such as water and energy conservation or waste reduction in a childcare centre, kindergarten or preschool, or young children’s social learning for Indigenous Reconciliation and cultural inclusivity. While the ECE field has been much slower than other educational sectors in taking up the challenges of sustainability, this situation is rapidly changing as early childhood practitioners begin to engage – it is fast moving from the margins of early childhood curriculum and pedagogic decision-making into the mainstream. This presents challenges, however, as ECEfS is somewhat misunderstood and misrepresented and, as a new field, is under-researched and under-theorised.

M-ary trees for combinatorial asset management decision problems

A novel m-ary tree based approach is presented to solve asset management decisions which are combinatorial in nature. The approach introduces a new dynamic constraint based control mechanism which is capable of excluding infeasible solutions from the solution space. The approach also provides a solution to the challenges with ordering of assets decisions.

Review of the design-build market in the People’s Republic of China

Design-build (DB) system has been demonstrated as an effective delivery method and been widely used overseas. However it does not receive the same popularity in the People’s Republic of China (PRC). This paper first conducts a literature review on advantages and disadvantages of DB in general; then it gives an overview of the PRC construction industry. There are ample evidences that the DB system will theoretically bring benefits to the PRC construction industry. After a thorough investigation of the current DB market, it can be concluded that the development of the DB system is still at its infancy stage. The barriers to entry have been finally identified, which relate to the legal restraints, negative owner attitude, and high requirement of DB projects. These barriers constitute obstacles to the development of DB system in the PRC. However, with rapid growth of construction industry, new requirements in modern construction projects, and strong promotion from governments, it is believed that the domestic DB market will have great potential in the near future.

Scheduling a flow-shop with combined buffer conditions

In this paper, No-Wait, No-Buffer, Limited-Buffer, and Infinite-Buffer conditions for the flow-shop problem (FSP) have been investigated. These four different buffer conditions have been combined to generate a new class of scheduling problem, which is significant for modelling many real-world scheduling problems. A new heuristic algorithm is developed to solve this strongly NP-hard problem. Detailed numerical implementations have been analysed and promising results have been achieved.