Effect of farnesyltransferase inhibitor R115777 on mitochondria of plasmodium falciparum

The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (Delta psi m) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.1133Ysciescopu

Current Treatment Strategies for Intracranial Aneurysms: An Overview

Intracranial aneurysm is a leading cause of stroke. Its treatment has evolved over the past 2 decades. This review summarizes the treatment strategies for intracranial aneurysms from 3 different perspectives: open surgery approach, transluminal treatment approach, and new technologies being used or trialed. We introduce most of the available treatment techniques in detail, including contralateral clipping, wrapping and clipping, double catheters assisting coiling and waffle-cone technique, and so on. Data from major trials such as Analysis of Treatment by Endovascular approach of Non-ruptured Aneurysms (ATENA), Internal Subarachnoid Trial (ISAT), Clinical and Anatomical Results in the Treatment of Ruptured Intracranial Aneurysms (CLARITY), and Barrow Ruptured Aneurysm Trial (BRAT) as well as information from other clinical reports and local experience are reviewed to suggest a clinical pathway for treating different types of intracranial aneurysms. It will be a valuable supplement to the current existing guidelines. We hope it could help assisting real-time decision-making in clinical practices and also encourage advancements in managing the disease

Agile at scale : a summary of the 8th International Workshop on Large-Scale Agile Development

The Large-Scale Agile Development workshop explored the main research challenges in large-scale software development. We considered multi-site organisations with large-scale projects that include a large number of teams adopting agile methods. Such topics include inter-team coordination, knowledge sharing, large project organisation, agile transformation, agile teamwork quality, project models that facilitate several self-organising teams, and practices for scaling agile methods. We accepted five full research papers, which are included in this volume. The accepted papers report empirical research studies using surveys, observations and case studies. Also, an interactive online discussion session was conducted to compare the two approaches, SAFe and Spotify. The workshop participants, which were around a hundred people, joined this discussion to compare the two approaches and suggest some future research questions about the hybridisation of SAFe and Spotify. This workshop summary contributes as a current snapshot of research along with some results from an interactive discussion about SAFe and Spotify

Effect of false twist on the structure of low-twist ring spun yarns

2007-2008 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

The role of interfacial properties on the intralaminar and interlaminar damage behaviour of unidirectional composite laminates: Experimental characterization and multiscale modelling

The development of the latest generation of wide-body passenger aircraft has heralded a new era in the utilisation of carbon-fibre composite materials. One of the primary challenges facing future development programmes is the desire to reduce the extent of physical testing, required as part of the certification process, by adopting a ‘certification by simulation’ approach. A hierarchical bottom-up multiscale simulation scheme can be an efficient approach that takes advantage of the natural separation of length scales between different entities (fibre/matrix, ply, laminate and component) in composite structures. In this work, composites with various fibre/matrix and interlaminar interfacial properties were fabricated using an autoclave under curing pressures ranging from 0 to 0.8 MPa. The microstructure (mainly void content and spatial distribution) and the mechanical properties of the matrix and fibre/matrix interface were measured, the latter by means of nanoindentation tests in matrix pockets, and fibre push-in tests. In addition, the macroscopic interlaminar shear strength was determined by means of three-points bend tests on short beams. To understand the influence of interfacial properties on the intralaminar failure behaviour, a high-fidelity microscale computational model is presented to predict homogenized ply properties under shear loading. Predicted ply material parameters are then transferred to a mesoscale composite damage model to reveal the interaction between intralaminar and interlaminar damage behaviour of composite laminates

Birth, life and survival of Tidal Dwarf Galaxies

Advances on the formation and survival of the so-called Tidal Dwarf Galaxies (TDGs) are reviewed. The understanding on how objects of the mass of dwarf galaxies may form in debris of galactic collisions has recently benefited from the coupling of multi-wavelength observations with numerical simulations of galaxy mergers. Nonetheless, no consensual scenario has yet emerged and as a matter of fact the very definition of TDGs remains elusive. Their real cosmological importance is also a matter of debate, their presence in our Local Group of galaxies as well. Identifying old, evolved, TDGs among the population of regular dwarf galaxies and satellites may not be straightforward. However a number of specific properties (location, dark matter and metal content) that objects of tidal origin should have are reminded here. Examples of newly discovered genuine old TDGs around a nearby elliptical galaxy are finally presented.Comment: 9 pages, 5 figures, invited talk at JENAM 2010 symposium on "Dwarf Galaxies", v2:reference and acknowledgements update

Using standard typing algorithms incrementally

Modern languages are equipped with static type checking/inference that helps programmers to keep a clean programming style and to reduce errors. However, the ever-growing size of programs and their continuous evolution require building fast and efficient analysers. A promising solution is incrementality, aiming at only re-typing the diffs, i.e. those parts of the program that change or are inserted, rather than the entire codebase. We propose an algorithmic schema that drives an incremental usage of existing, standard typing algorithms with no changes. Ours is a grey-box approach: just the shape of the input, that of the results and some domain-specific knowledge are needed to instantiate our schema. Here, we present the foundations of our approach and the conditions for its correctmess. We show it at work to derive two different incremental typing algorithms. The first type checks an imperative language to detect information flow and non-interference, and the second infers types for a functional language. We assessed our proposal on a prototypical imple- mentation of an incremental type checker. Our experiments show that using the type checker incrementally is (almost) always rewardin

Using Standard Typing Algorithms Incrementally

Modern languages are equipped with static type checking/inference that helps programmers to keep a clean programming style and to reduce errors. However, the ever-growing size of programs and their continuous evolution require building fast and efficient analysers. A promising solution is incrementality, so one only re-types those parts of the program that are new, rather than the entire codebase. We propose an algorithmic schema driving the definition of an incremental typing algorithm that exploits the existing, standard ones with no changes. Ours is a grey-box approach, meaning that just the shape of the input, that of the results and some domain-specific knowledge are needed to instantiate our schema. Here, we present the foundations of our approach and we show it at work to derive three different incremental typing algorithms. The first two implement type checking and inference for a functional language. The last one type-checks an imperative language to detect information flow and non-interference. We assessed our proposal on a prototypical implementation of an incremental type checker. Our experiments show that using the type checker incrementally is (almost) always rewarding.Comment: corrected and updated; experimental results adde

Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption. Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks. Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD. Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring