Quantitative structure–activity relationship (QSAR) analysis of aromatic effector specificity in NtrC-like transcriptional activators from aromatic oxidizing bacteria

A quantitative structure–activity relationship (QSAR) approach was taken to provide mechanistic insights into the interaction between the chemical structure of inducing compounds and the transcriptional activation of aromatic monooxygenase operons among the XylR/DmpR subclass of bacterial NtrC-like transcriptional regulators. Compared to XylR and DmpR, a broader spectrum of effector compounds was observed for the TbuT system from Ralstonia pickettii PKO1. The results of QSAR analysis for TbuT suggested that a steric effect, rather than hydrophobic or electronic effects, may be the predominant factor in determining aromatic effector specificity, and the active site of the regulator may positively interact not only with the methyl moiety but also with the most electron-rich aryl side of an aromatic effector.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74885/1/S0378-1097_03_00400-2.pd

Predictors of Endocarditis in Isolates from Cultures of Blood Following Dental Extractions in Rats with Periodontal Disease

Rats with periodontitis and catheter-induced aortic valve vegetations underwent dental extractions. Cultures of blood obtained 1 min later showed polymicrobial bacteremia in 19 of 19 rats, mostly due to viridans streptococci (18 of 19), Morganella (15 of 19), group G streptococci (13 of 19), and Staphylococcus aureus (10 of 19). Viridans streptococci circulated in higher numbers than did group G streptococci and S. aureus (P < .01). Three days after dental extractions, 18 of 20 rats had endocarditis. Fifteen (83%) of 18 infections were due to group G streptococci, 9 (50%) of 18 were due to S. aureus, and 2 (11%) of 18 were due to viridans streptococci (P < .05). In vitro, adherence to platelet-fibrin matrices of endocarditis strain 8 of group G streptococcus was two times greater than that of endocarditis strain S. aureus 23 and three to four times greater than that of Streptococcus sanguis 44 and Morganella morganii 93 (P < 10−5). The inoculum size that produced endocarditis in 90% of rats after iv challenge was 105 cfu for group G streptococcus strain 8 and 107 for S. sanguis 4

Single-dose rifampin prophylaxis for experimental endocarditis induced by high bacterial inocula of viridans streptococci

In rats challenged with viridans streptococci poorly susceptible to antibiotic killing, single doses of antibiotics only prevent endocarditis induced by bacterial inoculum sizes that produce disease in 90% of control animals (ID90): additional doses are required to protect against inocula exceeding the ID90. We investigated whether single-dose rifampin would extend the efficacy of single-dose prophylaxis to inocula exceeding the ID90. We used two strains of viridans streptococci highly susceptible to killing by rifampin and two resistant strains. All rats were injected with 10-1,000 times the ID90 of the four strains. Single-dose rifampin successfully prevented endocarditis due to all four strains. A few prophylaxis failures were observed after challenge with the two poorly susceptible strains, but in vivo emergence of resistant variants did not account for these failures. Thus, rifampin was the first antibiotic given as a single dose that successfully prevented experimental streptococcus endocarditis after challenge with high bacterial inocula

A connectivist approach to smart city learning : Valletta city case-study

A connectivist approach will be adopted to design and evaluate learning in technology-enhanced open spaces in Valletta city. Learning is considered as a process of creating connections between learner’s inner cognitive and affective systems with the external physical and social worlds. These interactions are organised within a model comprising dimensions and levels of interactions. The experience for a learner in a technology-enhanced historical place will be designed considering interactions with the content domain (history, botany, art), the technological dimension (interaction between handheld devices and the available signals such as 3/4G, Wifi or GNSS) and the social dimension comprising interactions with fellow learners /citizens and domain experts. The levels of interactions are related to learner’s experience within the subject domain, with technology and one’s status or role in learning community or community of practice. Thus learning experiences have to be designed considering acquisition level for novice learners, participatory learning for more experience learners and contributory learning for highly competent learners. This connectivist model will be applied to identified places of historical or educational interest in Valletta city to design different modes of learning mediated through interactive technologies. The concept of Personal Learning Environments in Smart cities [1] will be used to provide technology-enhanced experiences in Playful learning, Seamless learning, Geo-learning, Citizen enquiry and Crowd learning. A number of these technology-enhanced learning experiences, developed in collaboration with CYBERPARKS ACTION’s WG1, will be contextualized in Valletta city. University of Malta will provide the domain content and resources, together with the pedagogical strategy for each learning experience. Researchers from WG1 will design and develop the technological model and infrastructure, mainly the Android-based Way-Cyberparks App that will integrate GNSS-based learning, Augmented Reality, Navigation tracing and other functionalities used for specific tasks and type of data collection. An interactions-based methodology will be used to evaluate learning along the identified dimensions.Funded by the Horizon 2020 Framework Programme of the European Union.peer-reviewe

The integration of an augmented reality module within the Way- Cyberparks app. : the case study of Valletta city

Latest improvements on mobile devices capabilities are changing the way people interact with their surroundings. Nowadays, devices are able to sense the environment and user’s location, enabling the user to experience improved digital services. This is a key aspect of public spaces enhancement, which plays a pivotal role for the improvement of public spaces; a key to make public locations more accessible, interactive and enjoyable. One of the most powerful technologies enabling this innovative set of services is known as Augmented Reality (AR). More in depth, AR allows users to visualise in real time virtual information about the physical objects of the real world, directly on the display of their own devices. AR provides innovative way-finding widgets and context-awareness services. Along with the aims of the COST Action Cyberparks, our aim is to improve the App delivered during the first stages of the project (Way-Cyberparks) with AR functionalities, by developing a location-based AR module tailored to be integrated within Way-Cyberparks. The AR section will link virtual geo-tagged annotations as an interface to (geo) spatial and attribute data, allowing users to quick access digital sensory inputs. The overarching idea is to populate the App with virtual signage fostering the fruition of public spaces by allowing users to experience new ways of moving within specific places. Thanks to that, on one hand, the App works as an interactive path-finder tool, heading visitors towards the most interesting locations or landmarks within a specific area (Points of Interest or POIs). On the other, users are enabled to create their own contents and upload them into the network of available POIs, enabling a true participative community. The city of Valletta has been chosen as first case study; here the AR module will be tested to identify historical locations and heritage buildings, acting as contextual objects for the Way- Cyberparks App.Funded by the Horizon 2020 Framework Programme of the European Union.peer-reviewe

A Survey of Augmented, Mixed and Virtual Reality for Cultural Heritage

A multimedia approach to the diffusion, communication, and exploitation of Cultural Heritage (CH) is a well-established trend worldwide. Several studies demonstrate that the use of new and combined media enhances how culture is experienced. The benefit is in terms of both number of people who can have access to knowledge and the quality of the diffusion of the knowledge itself. In this regard, CH uses augmented-, virtual-, and mixed-reality technologies for different purposes, including education, exhibition enhancement, exploration, reconstruction, and virtual museums. These technologies enable user-centred presentation and make cultural heritage digitally accessible, especially when physical access is constrained. A number of surveys of these emerging technologies have been conducted; however, they are either not domain specific or lack a holistic perspective in that they do not cover all the aspects of the technology. A review of these technologies from a cultural heritage perspective is therefore warranted. Accordingly, our article surveys the state-of-the-art in augmented-, virtual-, and mixed-reality systems as a whole and from a cultural heritage perspective. In addition, we identify specific application areas in digital cultural heritage and make suggestions as to which technology is most appropriate in each case. Finally, the article predicts future research directions for augmented and virtual reality, with a particular focus on interaction interfaces and explores the implications for the cultural heritage domain

The architecture of EMC reveals a path for membrane protein insertion

Approximately 25% of eukaryotic genes code for integral membrane proteins that are assembled at the endoplasmic reticulum. An abundant and widely conserved multi-protein complex termed EMC has been implicated in membrane protein biogenesis, but its mechanism of action is poorly understood. Here, we define the composition and architecture of human EMC using biochemical assays, crystallography of individual subunits, site-specific photocrosslinking, and cryo-EM reconstruction. Our results suggest that EMC’s cytosolic domain contains a large, moderately hydrophobic vestibule that can bind a substrate’s transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD. A gap between the cytosolic vestibule and intramembrane groove provides a potential path for substrate egress from EMC. These findings suggest how EMC facilitates energy-independent membrane insertion of TMDs, explain why only short lumenal domains are translocated by EMC, and constrain models of EMC’s proposed chaperone function

The architecture of EMC reveals a path for membrane protein insertion

Approximately 25% of eukaryotic genes code for integral membrane proteins that are assembled at the endoplasmic reticulum. An abundant and widely conserved multi-protein complex termed EMC has been implicated in membrane protein biogenesis, but its mechanism of action is poorly understood. Here, we define the composition and architecture of human EMC using biochemical assays, crystallography of individual subunits, site-specific photocrosslinking, and cryo-EM reconstruction. Our results suggest that EMC’s cytosolic domain contains a large, moderately hydrophobic vestibule that can bind a substrate’s transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD. A gap between the cytosolic vestibule and intramembrane groove provides a potential path for substrate egress from EMC. These findings suggest how EMC facilitates energy-independent membrane insertion of TMDs, explain why only short lumenal domains are translocated by EMC, and constrain models of EMC’s proposed chaperone function

The architecture of EMC reveals a path for membrane protein insertion

Approximately 25% of eukaryotic genes code for integral membrane proteins that are assembled at the endoplasmic reticulum. An abundant and widely conserved multi-protein complex termed EMC has been implicated in membrane protein biogenesis, but its mechanism of action is poorly understood. Here, we define the composition and architecture of human EMC using biochemical assays, crystallography of individual subunits, site-specific photocrosslinking, and cryo-EM reconstruction. Our results suggest that EMC’s cytosolic domain contains a large, moderately hydrophobic vestibule that can bind a substrate’s transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD. A gap between the cytosolic vestibule and intramembrane groove provides a potential path for substrate egress from EMC. These findings suggest how EMC facilitates energy-independent membrane insertion of TMDs, explain why only short lumenal domains are translocated by EMC, and constrain models of EMC’s proposed chaperone function