Natural, engineered and synthetic inhibitors of kallikrein-related peptidases

There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.

Natural and engineered plasmin inhibitors : applications and design strategies

Plasmin is the primary enzyme responsible for dissolution of fibrin in the circulatory system. Plasminogen, the zymogen of plasmin is expressed ubiquitously in the human body [1], with the predominant source being the liver [2, 3]. Plasminogen is produced as an 810 amino acid protein with a 19 amino acid leader peptide, which is cleaved during secretion to produce the mature 791 amino acid one-chain zymogen. This is converted to plasmin by cleavage of the Arg561 - Val562 scissile bond [4], resulting in an active protease consisting of two disulfide linked chains. The amino-terminal heavy chain (residues Glu1-Arg561) is comprised of a plasminogen/apple/nematode (PAN) domain [5] and five kringle domains of approximately equal size [6] while the light chain (residues Val562-Asn791) contains a serine protease domain homologous to trypsin with a catalytic triad comprising His603, Asp646 and Ser741 [7]. Both plasmin and plasminogen occur in two forms, full length and a Lys77-Lys78 activated variant produced through self catalysis (Figure 1). The former exists in a tight conformation through binding of Lys50 and/or Lys62 to kringle domain 5 [8, 9] while Lys78-plasminogen assumes a more relaxed conformation rendering it more susceptible to plasmin conversion [10, 11].

Implementing natural PWM digitally

For dynamic closed loop control of a multilevel converter with a low switching frequency, natural sampled PWM is the best form of modulation. However previous natural sampled PWM implementations have generally been analog. A digital implementation has advantages, particularly for a multilevel converter. Re-sampled uniform PWM, a modulation technique which approaches the performance of natural PWM, is implemented both in software and hardware. Results demonstrating the improvement over uniformPWM techniques are presented.

More naturalness, less control: The effect of natural mapping on the co-located player experience

In the past years, there has been a surge in game controllers that allow players to play in a more physical, more natural way. In this paper we present an experimental study of the effect of gaming using these naturally mapped controllers on the player experience in a social setting. Results support the hypothesis that more naturally mapped controllers augment spatial presence. Furthermore, the results suggest that gaming with more naturally mapped controllers augment social presence for female players, but not for male players. However, gaming via naturally mapped controllers decreases perceived control and actual performance. Hence, users with high performance expectations might not benefit from gaming via naturally mapped controllers.

Critical factors for sustainable reconstruction of post natural disasters

While scientists are still debating the level of climate change impact to new weather patterns, there have been some devastating natural disasters worldwide in the last decade. From cyclones to earthquakes and from Tsunamis to landslides, these disasters occur with formidable forces and crushing effects. As one of the most important arrangements to erase the negative influence of natural disasters and help with the recovery and redevelopment of the hit area, reconstruction is of utmost importance in light of sustainable objectives. However, current reconstruction practice confronts quite a lot of criticisms for focusing on providing short-term necessities. How to conduct the post disaster reconstruction in a long-term perspective and achieve sustainable development is thereby a highlight for industry practice and research. This paper introduced an on-going research project which is aimed at establishing an operational framework for improving sustainability performance of post disaster reconstruction by identifying critical sustainable factors and exploring their internal relationships. The research reported in this paper is part of the project. After a comprehensive literature review, 17 potential critical sustainability factors for post disaster reconstruction were identified. Preliminary examination and discussion of the factors was conducted.

A rapid and sensitive UPLC-ESI MS method for analysis of isofraxidin, a natural antistress compound, and its metabolites in rat plasma

Isofraxidin is one of the main bioactive constituents in the root of Acanthopanax senticosus, which has antifatigue, antistress, and immuno-accommondating effects. In this study, an ultraperformance LC (UPLC)-ESI MS method was developed for analyzing isofraxidin and its metabolites in rat plasma. The analysis was performed on a UPLC coupled with ESI MS (quadropole MS tandem TOF MS). The lower LOD (LLOD) for isofraxidin was 0.25 ng/mL, the intraday precision was less than 10%, the interday precision was less than 10%, and the extraction recovery was more than 80%. Isofraxidin and two metabolites (M1 and M2) were detected in rat plasma after oral administration of isofraxidin, and the molecular polarities of M1 and M2 were both increased compared to isofraxidin. The metabolites were identified as 5,6-dihydroxyl-7-methoxycoumarin and 5-hydroxyl-6,7-dimethoxycoumarin when subjected to parent ion spectra, product ion spectra, and extract mass and element composition analyses.

Effect of an adiabatic fin on natural convection heat transfer in a triangular enclosure

Natural convection thermal boundary layer adjacent to the heated inclined wall of a right angled triangle with an adiabatic fin attached to that surface is investigated by numerical simulations. The finite volume based unsteady numerical model is adopted for the simulation. It is revealed from the numerical results that the development of the boundary layer along the inclined surface is characterized by three distinct stages, i.e. a start-up stage, a transitional stage and a steady stage. These three stages can be clearly identified from the numerical simulations. Moreover, in presence of adiabatic fin, the thermal boundary layer adjacent to the inclined wall breaks initially. However, it is reattached with the downstream boundary layer next to the fin. More attention has been given to the boundary layer development near the fin area.

Exit polls, turnout, and bandwagon voting : evidence from a natural experiment

We exploit a voting reform in France to estimate the causal effect of exit poll information on turnout and bandwagon voting. Before the change in legislation, individuals in some French overseas territories voted after the election result had already been made public via exit poll information from mainland France. We estimate that knowing the exit poll information decreases voter turnout by about 12 percentage points. Our study is the first clean empirical design outside of the laboratory to demonstrate the effect of such knowledge on voter turnout. Furthermore, we find that exit poll information significantly increases bandwagon voting; that is, voters who choose to turn out are more likely to vote for the expected winner.

Exploring information literacy during a natural disaster: The 2011 Brisbane Flood

This chapter presents the preliminary results of a phenomenographic study aimed at exploring people’s experience of information literacy during the 2011 flood in Brisbane, Queensland. Phenomenography is a qualitative, interpretive and descriptive approach to research that explores the different ways in which people experience various phenomena and situations in the world around them. In this study, semi-structured interviews with seven adult residents of Brisbane suggested six categories that depicted different ways people experienced information literacy during this natural disaster. Access to timely, accurate and credible information during a natural disaster can save lives, safeguard property, and reduce fear and anxiety, however very little is currently known about citizens’ information literacy during times of natural disaster. Understanding how people use information to learn during times of crisis is a new terrain for community information literacy research, and one that warrants further attention by the information research community and the emergency management sector.

Crisis Communication in Natural Disasters : The Queensland Floods and Christchurch Earthquakes

Over the past decade, social media have gone through a process of legitimation and official adoption, and they are now becoming embedded as part of the official communications apparatus of many commercial and public-sector organisations— in turn, providing platforms like Twitter with their own sources of legitimacy. Arguably, the demonstrated utility of social media platforms and tools in times of crisis—from civil unrest and violent crime through to natural disasters like bushfires, earthquakes, and floods—has been a crucial driver of this newfound legitimacy. In the mid-2000s, user-created content and ‘Web 2.0’ platforms were known to play a role in crisis communication; back then, the involvement of extra-institutional actors in providing and sharing information around such events involved distributed, ad hoc, or niche platforms (like Flickr), and was more likely to be framed as ‘citizen journalism’ or ‘crowdsourcing’ (see, for example, Liu, Palen, Sutton, Hughes, & Vieweg, 2008, on the then-emerging role of photo-sharing in disasters). Since then, the dramatically increased take-up of mainstream social media platforms like Facebook and Twitter means that the pool of potential participants in online crisis communication has broadened to include a much larger proportion of the general population, as well as traditional media and official emergency response organisations.

Design, synthesis and spectroscopic characterisation of a focused library based on the polyandrocarpamine natural product scaffold

A focused library based on the marine natural products polyandrocarpamines A (1) and B (2) has been designed and synthesised using parallel solution-phase chemistry. In silico physicochemical property calculations were performed on synthetic candidates in order to optimise the library for drug discovery and chemical biology. A library of ten 2-aminoimidazolone products (3–12) was prepared by coupling glycocyamidine and a variety of aldehydes using a one-step stereoselective aldol condensation reaction under microwave conditions. All analogues were characterised by NMR, UV, IR and MS. The library was evaluated for cytotoxicity towards the prostate cancer cell lines, LNCaP, PC-3 and 22Rv1.

Datasets for the evaluation of multi-sensor perception in natural environments with challenging conditions

This paper presents large, accurately calibrated and time-synchronised datasets, gathered outdoors in controlled environmental conditions, using an unmanned ground vehicle (UGV), equipped with a wide variety of sensors. It discusses how the data collection process was designed, the conditions in which these datasets have been gathered, and some possible outcomes of their exploitation, in particular for the evaluation of performance of sensors and perception algorithms for UGVs.

Reflections on talk about natural disasters by early childhood educators and directors

Facilitated discussion with early childhood staff working with children and families affected by natural disasters in Queensland, Australia, raises issues regarding educational communication in emergencies. This paper reports on these discussions as ‘reflections on talk’. It examines discrepancies between the literature and staff talk, gaps in the literature, and the inaccessible style of some literature-demanded collaborative debate and information re-interpretation. Reframing of the discourse style was used to support staff de-briefing, mutual encouragement, and sharing of insights on promoting resilience in children and families. Formal investigation is required regarding effective emergency-situation talk between staff, as well as with children and families.

The Marulan data sets: multi-sensor perception in a natural environment with challenging conditions

In this paper we present large, accurately calibrated and time-synchronized data sets, gathered outdoors in controlled and variable environmental conditions, using an unmanned ground vehicle (UGV), equipped with a wide variety of sensors. These include four 2D laser scanners, a radar scanner, a color camera and an infrared camera. It provides a full description of the system used for data collection and the types of environments and conditions in which these data sets have been gathered, which include the presence of airborne dust, smoke and rain.

The emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of natural disasters in Queensland, Australia 2011

The following research reports the emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of disasters and the ensuing clean up in Queensland, Australia during 2011. For the 12 month period (1 January to 31 December) L. borgpetersenii serovar Arborea accounted for over 49% of infections. In response to a flooding event public health officials need to issue community wide announcements warning the population about the dangers of leptospirosis and other water borne diseases. Communication with physicians working in the affected community should also be increased to update physicians with information such as clinical presentation of leptospirosis and other waterborne diseases. These recommendations will furnish public health officials with considerations for disease management when dealing with future disaster management programs.