The olfactory placodes generate the primary sensory neurons of the olfactory sensory system. Additionally, the olfactory placodes have been proposed to generate a class of neuroendocrine cells containing gonadotropin-releasing hormone (GnRH). GnRH is a multifunctional decapeptide essential for the development of secondary sex characteristics in vertebrates as well as a neuromodulator within the central nervous system. Here, we show that endocrine and neuromodulatory GnRH cells arise from two separate, nonolfactory regions in the developing neural plate. Specifically, the neuromodulatory GnRH cells of the terminal nerve arise from the cranial neural crest, and the endocrine GnRH cells of the hypothalamus arise from the adenohypophyseal region of the developing anterior neural plate. Our findings are consistent with cell types generated by the adenohypophysis, a source of endocrine tissue in vertebrate animals, and by neural crest, a source of cells contributing to the cranial nerves. The adenohypophysis arises from a region of the anterior neural plate flanked by the olfactory placode fields at early stages of development, and premigratory cranial neural crest lies adjacent to the caudal edge of the olfactory placode domain [Development 127 (2000), 3645]. Thus, the GnRH cells arise from tissue closely associated with the developing olfactory placode, and their different developmental origins reflect their different functional roles in the adult animal.

Digital technologies are considered to be an essential enabler of the circular economy in various industries. However, to date, very few studies have investigated which digital technologies could enable the circular economy in the built environment. This study specifically focuses on the built environment as one of the largest, most energy- and material-intensive industries globally, and investigates the following question: which digital technologies potentially enable a circular economy in the built environment, and in what ways? The research uses an iterative stepwise method: (1) framework development based on regenerating, narrowing, slowing and closing resource loop principles; (2) expert workshops to understand the usage of digital technologies in a circular built environment; (3) a literature and practice review to further populate the emerging framework with relevant digital technologies; and (4) the final mapping of digital technologies onto the framework. This study develops a novel Circular Digital Built Environment framework. It identifies and maps ten enabling digital technologies to facilitate a circular economy in the built environment. These include: (1) additive/robotic manufacturing, (2) artificial intelligence, (3) big data and analytics, (4) blockchain technology, (5) building information modelling, (6) digital platforms/marketplaces, (7) digital twins, (8) the geographical information system, (9) material passports/databanks, and (10) the internet of things. The framework provides a fruitful starting point for the novel research avenue at the intersection of circular economy, digital technology and the built environment, and gives practitioners inspiration for sustainable innovation in the sector.

The process of cancer invasion and metastasis is associated with tissue remodeling (Aznavoorian et al., 1993). It is now widely believed that this process is controlled by different proteases released from the primary cancer. The proteases implicated in cancer progression include urokinase-plasminogen activator (uPA), cathepsins B, D and L and various matrix metalloproteases (MMPs) (for review, see DufFy, 1992;Birkedal-Hansen, 1995). One MMP that may be involved in cancer progression is stromelysin-3 (ST3). ST3 was originally identified using subtractive hybridization of a cDNA library prepared from a human breast cancer (Basset et a/., 1990). In breast and other cancers, ST3 is specifically expressed in fibroblast-like cells immediately surrounding cancer cells (for review, see Basset et al., 1993;Rouyer et al., 1994). While almost all invasive breast carcinomas express mRNA for ST3, expression of this gene was found in only 5% of 21 fibroadenomas, 31% of in situ ductal carcinomas of the non-comedo type and in 61% of in situ ductal carcinomas of the comedo type (Wolf et al., 1993). The latter are the most aggressive sub-type of in situ ductal carcinoma and are characterized by high nuclear grade and necrosis. Furthermore, ST3 expression has been shown to promote the tumor take of breast-cancer cells in nude mice . These findings taken together suggest that ST3 may contribute to breast-cancer progression.

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Over 300 researchers gathered at the 2013 International Brain-Computer Interface (BCI) Meeting to discuss current practice and future goals for BCI research and development. The authors organized the Virtual Users’ Forum at the meeting to provide the BCI community with feedback from users. We report on the Virtual Users’ Forum, including initial results from ongoing research being conducted by two BCI groups. Online surveys and in-person interviews were used to solicit feedback from people with disabilities who are expert and novice BCI users. For the Virtual Users’ Forum, their responses were organized into four major themes: current (non-BCI) communication methods, experiences with BCI research, challenges of current BCIs, and future BCI developments. Two authors with severe disabilities gave presentations during the Virtual Users’ Forum, and their comments are integrated with the other results. While participants’ hopes for BCIs of the future remain high, their comments about available systems mirror those made by consumers about conventional assistive technology. They reflect concerns about reliability (e.g. typing accuracy/speed), utility (e.g. applications and the desire for real-time interactions), ease of use (e.g. portability and system setup), and support (e.g. technical support and caregiver training). People with disabilities, as target users of BCI systems, can provide valuable feedback and input on the development of BCI as an assistive technology. To this end, participatory action research (PAR) should be considered as a valuable methodology for future BCI research.

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We-Met(Window 13nvirontnent-Meeting Enhancement Tools) is a prototype pen-based tool designed to support both the communication and information retrieval needs of stnall group meetings.The first part of this paper describes We-Met and the rationale for its design, the second discusses findings from an empirical study of the use of We-Met for group communication, ami the third discusses findings from a study of the search and retrieval of information from non-computer based meetings conducted to provide insight into how to facilitate these activities in We-Met. 'Ile paper identifies potential comtnunication process gains due to the pen-based interface style, opportunities for the facilitation of information retrieval in a pen-based tool, and functionality/interface challenges in the design of a tool to support small group mwt i rigs.

In Parkinson’s disease (PD), dopaminergic therapies are often associated with the development of motor complications. Attention has therefore been focused on the use of non-dopaminergic drugs. This study developed a new behavioural method capable of demonstrating the added value of combining adenosinergic and glutamatergic receptor antagonists in unilateral 6-OHDA lesioned rats. Rats were dosed orally with Tozadenant, a selective A2A receptor antagonist, and three different doses of Radiprodil, an NR2B-selective NMDA receptor antagonist. The drugs were given alone or in combination and rats were placed in an open-field for behavioural monitoring. Video recordings were automatically analysed. Five different behaviours were scored: distance traveled, ipsi- and contraversive turns, body position, and space occupancy. The results show that A2A or NR2B receptor antagonists given alone or in combination did not produce enhanced turning as observed with an active dose of L-Dopa/benserazide. Instead the treated rats maintained a straight body position, were able to shift from one direction to the other and occupied a significantly larger space in the arena. The highest “Tozadenant/Radiprodil” dose combination significantly increased all five behavioural parameters recorded compared to rats treated with vehicle or the same doses of the drugs alone. Our data suggest that the A2A/NR2B antagonist combination may be able to stimulate motor activity to a similar level as that achieved by L-Dopa but in the absence of the side-effects that are associated with dopaminergic hyperstimulation. If these results translate into the clinic, this combination could represent an alternative symptomatic treatment option for PD.