971 resultados para SMALL MOLECULES


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Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

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This study responds to calls for research on work-family aspects in entrepreneurship research. Our study examined the role of work-family conflict and enhancement on small business owners’ (SBOs) wellbeing. We found work-family has negative direct effect on mental health, job and family satisfactions. Furthermore, we found that under high level of work-family conflict condition, SBOs who perceive a greater level of work-family enhancement would feel more satisfy with their life, job as well as family aspects. Interestingly, under high level of conflict, even SBOs perceive greater level of enhancement, it would not lessen the negative impact of the conflict on their mental health. These results suggest that once psychological health is harmed by work-family conflict, its negative consequences remain unchanged.

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Effective fuel injector operation and efficient combustion are two of the most critical aspects when Diesel engine performance, efficiency and reliability are considered. Indeed, it is widely acknowledged that fuel injection equipment faults lead to increased fuel consumption, reduced power, greater levels of exhaust emissions and even unexpected engine failure. Previous investigations have identified fuel injector related acoustic emission activity as being caused by mechanisms such as fuel line pressure build-up; fuel flow through injector nozzles, injector needle opening and closing impacts and premixed combustion related pulses. Few of these investigations however, have attempted to categorise the close association and interrelation that exists between fuel injection equipment function and the acoustic emission generating mechanisms. Consequently, a significant amount of ambiguity remains in the interpretation and categorisation of injector related AE activity with respect to the functional characteristics of specific fuel injection equipment. The investigation presented addresses this ambiguity by detailing a study in which AE signals were recorded and analysed from two different Diesel engines employing the two commonly encountered yet fundamentally different types of fuel injection equipment. Results from tests in which faults were induced into fuel injector nozzles from both indirect-injection and direct-injection engines show that functional differences between the main types of fuel injection equipment results in acoustic emission activity which can be specifically related to the type of fuel injection equipment used.

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Background A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles of a malaria DNA vaccine is presented. A 40 kHz ultrasonic atomization device was used to create the microparticles from a feedstock containing 5 volumes of 0.5% w/v PLGA in acetone and 1 volume of condensed DNA which was fed at a flow rate of 18ml h-1. The plasmid DNA vectors encoding a malaria protein were condensed with a cationic polymer before atomization. Results High levels of gene expression in vitro were observed in COS-7 cells transfected with condensed DNA at a nitrogen to phosphate (N/P) ratio of 10. At this N/P ratio, the condensed DNA exhibited a monodispersed nanoparticle size (Z-average diameter of 60.8 nm) and a highly positive zeta potential of 38.8mV. The microparticle formulations of malaria DNA vaccine were quality assessed and it was shown that themicroparticles displayed high encapsulation efficiencies between 82-96% and a narrow size distribution in the range of 0.8-1.9 μm. In vitro release profile revealed that approximately 82% of the DNA was released within 30 days via a predominantly diffusion controlledmass transfer system. Conclusions This ultrasonic atomization technique showed excellent particle size reproducibility and displayed potential as an industrially viable approach for the formulation of controlled release particles.

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Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

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In the current regulatory climate, there is increasing expectation that law schools will be able to demonstrate students’ acquisition of learning outcomes regarding collaboration skills. We argue that this is best achieved through a stepped and structured whole-of-curriculum approach to small group learning. ‘Group work’ provides deep learning and opportunities to develop professional skills, but these benefits are not always realised for law students. An issue is that what is meant by ‘group work’ is not always clear, resulting in a learning regime that may not support the attainment of desired outcomes. This paper describes different types of ‘group work', each associated with distinct learning outcomes. It suggests that ‘group work’ as an umbrella term to describe these types is confusing, as it provides little indication to students and teachers of the type of learning that is valued and is expected to take place. ‘Small group learning’ is a preferable general descriptor. Identifying different types of small group learning allows law schools to develop and demonstrate a scaffolded, sequential and incremental approach to fostering law students’ collaboration skills. To support learning and the acquisition of higherorder skills, different types of small group learning are more appropriate at certain stages of the program. This structured approach is consistent with social cognitive theory, which suggests that with the guidance of a supportive teacher, students can develop skills and confidence in one type of activity which then enhances motivation to participate in another.

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There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6×6 to 98×98 mm2. Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the full diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26%, for the “very small” fields smaller than 15 mm, and 0.18% for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within 1.6%. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2% to the very small field output factors. The overall uncertainties in the field output factors were 1.8% for the very small fields and 1.1% for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.

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On 21 September 1999 Division 152 was inserted into the Income Tax Assessment Act (1997) (ITAA 1997). Division 152 contains the small business CGT concessions, which enables eligible small business taxpayers to reduce the amount of tax payable on capital gains arising from certain CGT events that occur after 11:45 am on 21 September 1999. One of the principal objectives of the legislation is to provide a concessionary regime for small business owners who do not have the same ability to access the concessionary superannuation regime generally available to employees. When announcing the introduction of the concessions the then Federal Treasurer, Mr Peter Costello, specifically stated that the objective of Division 152 was to provide ‘small business people with access to funds for retirement or expansion’. The purpose of this article is to: one, assess the extent to which small business taxpayers understand the CGT small business concessions, particularly when considering the sale of their business; two, determine which of the four small business CGT concessions are most commonly adopted and/or recommended by tax practitioners to clients; and three, to determine whether the superannuation changes in relation to the capping of the concessional superannuation thresholds have had an impact on the use of the small business retirement concession.

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Deoxyribonucleic acid molecules are heralding a new generation of reverse - engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This presentation will discuss the potential applications of pDNA molecules in vaccine development and gene therapy, pilot-scale production of pDNA-based biopharmaceuticals and the controlled delivery of therapeutic sequences in biodegradable polymers to different target cells via the nasal route.

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The detailed system design of a small experimental autonomous helicopter is described. The system requires no ground-to-helicopter communications and hence all automation hardware is on-board the helicopter. All elements of the system are described including the control computer, the flight computer (the helicopter-to-control-computer interface), the sensors and the software. A number of critical implementation issues are also discussed.

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While the economic and environmental benefits of fisheries management are well accepted, the costs of effective management in low value fisheries, including the research necessary to underpin such management, may be considerable relative to the total economic benefits they may generate. Co-management is often seen as a panacea in low value fisheries. Increasing fisher participation increases legitimacy of management decision in the absence of detailed scientific input. However, where only a small number of operators exist, the potential benefits of co-management are negated by the high transaction cost to the individual fishers engaging in the management process. From an economic perspective, sole ownership has been identified as the management structure which can best achieve biological and economic sustainability. Moving low value fisheries with a small number of participants to a corporate-cooperative management model may come close to achieving these sole ownership benefits, with lower transaction costs. In this paper we look at the applicability of different management models with industry involvement to low value fisheries with a small number of participants. We provide an illustration as to how a fishery could be transitioned to a corporate-cooperative management model that captures the key benefits of sole management at a low cost and is consistent with societal objectives.

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Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.