Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis

The extracellular calcium (Ca(2+)(o))-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca(2+)(o) concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca(2+)(o) homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH). However, CASR mutations are only detected in ≤70% of FHH and ADH cases, referred to as FHH type 1 and ADH type 1, respectively, and studies in other FHH and ADH kindreds have revealed these disorders to be genetically heterogeneous. Thus, loss- and gain-of-function mutations of the GNA11 gene on chromosome 19p13.3, which encodes the G-protein α-11 (Gα(11)) subunit, lead to FHH type 2 and ADH type 2, respectively; whilst loss-of-function mutations of AP2S1 on chromosome 19q13.3, which encodes the adaptor-related protein complex 2 sigma (AP2σ) subunit, cause FHH type 3. These studies have demonstrated Gα(11) to be a key mediator of downstream CaSR signal transduction, and also revealed a role for AP2σ, which is involved in clathrin-mediated endocytosis, in CaSR signalling and trafficking. Moreover, FHH type 3 has been demonstrated to represent a more severe FHH variant that may lead to symptomatic hypercalcaemia, low bone mineral density and cognitive dysfunction. In addition, calcimimetic and calcilytic drugs, which are positive and negative CaSR allosteric modulators, respectively, have been shown to be of potential benefit for these FHH and ADH disorders

Utilising semantic technologies for intelligent indexing and retrieval of digital images

The proliferation of digital media has led to a huge interest in classifying and indexing media objects for generic search and usage. In particular, we are witnessing colossal growth in digital image repositories that are difficult to navigate using free-text search mechanisms, which often return inaccurate matches as they in principle rely on statistical analysis of query keyword recurrence in the image annotation or surrounding text. In this paper we present a semantically-enabled image annotation and retrieval engine that is designed to satisfy the requirements of the commercial image collections market in terms of both accuracy and efficiency of the retrieval process. Our search engine relies on methodically structured ontologies for image annotation, thus allowing for more intelligent reasoning about the image content and subsequently obtaining a more accurate set of results and a richer set of alternatives matchmaking the original query. We also show how our well-analysed and designed domain ontology contributes to the implicit expansion of user queries as well as the exploitation of lexical databases for explicit semantic-based query expansion

Developing Feedback Based Robotic Manufacturing Method for Earth-Based Materials

Although earth-based materials have the advantage of being locally sourced and have low embodied emissions, they can have an unpredictable material behavior due to their heterogeneous composition which potentially limits their use in manufacturing. As a result, it becomes challenging to standardise and maintain quality outcomes. Moreover, current industry methods are labour-intensive and require a high level of traditional knowledge. This research explores and develops a fabrication methodology for earthen materials that is location-agnostic. It involves an array of fabrication approaches, including the development of a robotic 'Impact Printing' setup using a UR10 robot and a custom tool to pick, place, and mechanically compact earth blocks. The 'Feedback System' employs Kinect 2.0 to scan the deformation of earth materials observed during fabrication and a computational algorithm to generate accurate and adapted toolpaths for the position and compaction of earthen blocks in real-time. To push the boundaries of architectural design for traditional building materials, the study investigates the construction of a closed Nubian vault using the aforementioned techniques and tools. Through the optimization of material behavior and manufacturing processes, the research opens up a pathway for automated onsite earth construction

Self-medication amongst pregnant women in a tertiary care teaching hospital in India

Background: Self-medication is a popular practice in developing countries where there is no strict regulation of drugs sold in local pharmacies. General public is usually unaware of the adverse effects of drugs used for common illness and continue using them without prescription during pregnancy. This study was carried out to know the extent of self-medication practised by pregnant women and various factors associated with it.Methods: A questionnaire based, cross-sectional study of pregnant women visiting the OB GYN-OPD of a tertiary care teaching hospital was conducted. 303 eligible subjects were questioned and statistical analysis was carried out.Results: Total 16.5% women were found to be self-medicating during pregnancy for common conditions like headache (26%), fever (23%) and common cold (19%). Odds Ratio between the self-medicating and non-self-medicating groups for variables like age (<25 years; ≥25 years), education (illiterate; literate) and gestational age (<20 weeks; ≥20 weeks) are 1.6, 2 and 1.73 respectively. Women with a history of self-medicating before pregnancy were significantly more likely to continue doing so during pregnancy (p value <0.00001).Conclusions: A significant proportion of pregnant women have been found to self-medicate without knowing the adverse effects of the drug used. Thus, spreading awareness against this health-predicament is necessary

The role of the central stellar cluster in active galactic nuclei. I. Semi-analytical model

The subject of the paper is the role of the massive stellar cluster in the activity phenomenon and in the structure of active galactic nuclei. We introduce a simple model of stellar dynamics in the internal part of the cluster, which allows us to include both the star-disk and the star-star interactions. It is shown that the properties of the distribution of stars in the vicinity of the black hole are determined both by the interaction of the stars with the accretion disk and by the pair gravitational and contact interaction between the stars. We calculate the distribution of stars in the central parts of the cluster and we discuss possible effects of stellar mass-loss due to the star-disk interaction. Finally, we study the implications of the central cluster for active galactic nuclei activity. We model the broad line region assuming that the gaseous wakes, following stars after each disk crossing, play the role of the broad line region clouds, and we calculate the corresponding line profiles. We also analyze the contribution of star-star and star-disk collisions to active galactic nuclei variability.Comment: Accepted for publication in Astronomy and Astrophysic