Effects of piperaquine, chloroquine, and amodiaquine on drug uptake and of these in combination with dihydroartemisinin against drug-sensitive and -resistant Plasmodium falciparum strains.

Piperaquine is being developed as a long-acting component in artemisinin combination therapies. It was highly active in vitro and drug interaction studies showed that dihydroartemisinin combinations with piperaquine, chloroquine, and amodiaquine were indifferent tending toward antagonism. Competitive uptake of radiolabeled chloroquine and dihydroartemisinin in combination with other antimalarials was observed

Examining the Effect of Pore Size Distribution and Shape on Flow through Unsaturated Peat using Computer Tomography

The hydraulic conductivity of unsaturated peat soil is controlled by the air-filled porosity, pore size and geometric distribution as well as other physical properties of peat materials. This study investigates how the size and shape of pores affects the flow of water through peat soils. In this study we used X-ray Computed Tomography (CT), at 45μm resolution under 5 specific soil-water pressure head levels to provide 3-D, high-resolution images that were used to detect the inner pore structure of peat samples under a changing water regime. Pore structure and configuration were found to be irregular, which affected the rate of water transmission through peat soils. The 3-D analysis suggested that pore distribution is dominated by a single large pore-space. At low pressure head, this single large air-filled pore imparted a more effective flowpath compared to smaller pores. Smaller pores were disconnected and the flowpath was more tortuous than in the single large air-filled pore, and their contribution to flow was negligible when the single large pore was active. We quantify the pore structure of peat soil that affects the hydraulic conductivity in the unsaturated condition, and demonstrate the validity of our estimation of peat unsaturated hydraulic conductivity by making a comparison with a standard permeameter-based method. Estimates of unsaturated hydraulic conductivities were made for the purpose of testing the sensitivity of pore shape and geometry parameters on the hydraulic properties of peats and how to evaluate the structure of the peat and its affects on parameterization. We also studied the ability to quantify these factors for different soil moisture contents in order to define how the factors controlling the shape coefficient vary with changes in soil water pressure head. The relation between measured and estimated unsaturated hydraulic conductivity at various heads shows that rapid initial drainage, that changes the air-filled pore properties, creates a sharp decline in hydraulic conductivity. This is because the large pores readily lose water, the peat rapidly becomes less conductive and the flow path among pores, more tortuous

The co-production of value in digital, university–industry R&D collaborative projects

In the context of R&D collaborations between universities and industry, this study investigates the co-production process and the contextual elements that shape it. We develop a conceptual framework that builds on the service-dominant logic perspective that value propositions emerge from the interaction between co-producing parties and the integration of resources. Specifically, the framework explicates how individual, organizational, and external factors shape the type of interactions and the platforms used, the availability and use of operand and operant resources, and the organizational and individual outcomes sought in R&D collaborative projects. We investigate the interplay among these factors through group interviews with UK industry practitioners and university researchers in the context of digital research projects. The types of interaction, resources, and outcomes sought that characterize successful R&D collaboration are revealed, and the contextual aspects that enable, facilitate, block, or create barriers to successful R&D collaborations are identified. Finally, we propose five practical principles for the successful development of collaborative R&D projects within the university–industry context

Normal mucus formation requires cAMP-dependent HCO3- secretion and Ca2+-mediated mucin exocytosis.

  Evidence from the pathology in cystic fibrosis (CF) and recent results in vitro indicate that HCO3- is required for gel-forming mucins to form the mucus that protects epithelial surfaces. Mucus formation and release is a complex process that begins with an initial intracellular phase of synthesis, packaging and apical granule exocytosis that is followed by an extracellular phase of mucin swelling, transport and discharge into a lumen. Exactly where HCO3- becomes crucial in these processes is unknown, but we observed that in the presence of HCO3-, stimulating dissected segments of native mouse intestine with 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) induced goblet cell exocytosis followed by normal mucin discharge in wild-type (WT) intestines. CF intestines that inherently lack cystic fibrosis transmembrane conductance regulator (CFTR)-dependent HCO3- secretion also demonstrated apparently normal goblet cell exocytosis, but in contrast, this was not followed by similar mucin discharge. Moreover, we found that even in the presence of HCO3-, when WT intestines were stimulated only with a Ca2+-mediated agonist (carbachol), exocytosis was followed by poor discharge as with CF intestines. However, when the Ca2+-mediated agonist was combined with a cAMP-mediated agonist (isoproterenol (isoprenaline) or vasoactive intestinal peptide) in the presence of HCO3- both normal exocytosis and normal discharge was observed. These results indicate that normal mucus formation requires concurrent activation of a Ca2+-mediated exocytosis of mucin granules and an independent cAMP-mediated, CFTR-dependent, HCO3- secretion that appears to mainly enhance the extracellular phases of mucus excretion

Beyond hormone replacement: quality of life in women with congenital hypogonadotropic hypogonadism.

Little is known about how women with isolated GnRH deficiency cope with their condition. This study aimed to examine the health and informational needs of women with congenital hypogonadotropic hypogonadism (CHH) and evaluate if their experiences differ from women with more common forms of infertility. Cross-sectional, multiple methods study using web-based data collection to reach dispersed rare disease patients. A community-based participatory research framework was employed to develop an online survey and collect quantitative and qualitative data. Adult women diagnosed with CHH who had received at least one year of hormonal treatment completed the Morisky Medication Adherence Scale, Revised Illness Perception Questionnaire and Zung Self-Rating Depression Scale. Information on health care experiences, treatment outcomes and patient-reported challenges were also collected. Women (n = 55) were often diagnosed late (20.7 ± 7.4, range: 10-48 years) and 16/20 patients receiving fertility treatment conceived. Poor adherence was frequently observed (34/55) while more than half (27/49) reported a gap in treatment exceeding a year. Low adherence correlated with depressive symptoms (r = 0.3, P > 0.05). Negative illness perceptions were pervasive and 30/55 exhibited some depressive symptoms - significantly greater than women with common female factor infertility (P < 0.01). Symptoms were underappreciated by providers as only 15 of 55 patients had discussions about psychological services. Women identified isolation, need for information and finding expert care as challenges to living with CHH. Despite being a treatable form of female infertility, the presumable availability of treatment does not necessarily ensure adequate quality of life for women with isolated GnRH deficiency

Integer polyhedra for program analysis

Polyhedra are widely used in model checking and abstract interpretation. Polyhedral analysis is effective when the relationships between variables are linear, but suffers from imprecision when it is necessary to take into account the integrality of the represented space. Imprecision also arises when non-linear constraints occur. Moreover, in terms of tractability, even a space defined by linear constraints can become unmanageable owing to the excessive number of inequalities. Thus it is useful to identify those inequalities whose omission has least impact on the represented space. This paper shows how these issues can be addressed in a novel way by growing the integer hull of the space and approximating the number of integral points within a bounded polyhedron

Environmental Effects on Long Term Displacement Data of Woven Fabric Webbings Under Constant Load for Inflatable Structures

An experimental study of the effects of environmental temperature and humidity conditions on long-term creep displacement data of high strength Kevlar and VectranTM woven fabric webbings under constant load for inflatable structures is presented. The restraint layer of an inflatable structure for long-duration space exploration missions is designed to bear load and consists of an assembly of high strength webbings. Long-term creep displacement data of webbings can be utilized by designers to validate service life parameters of restraint layers of inflatable structures. Five groups of high-strength webbings were researched over a two year period. Each group had a unique webbing length, load rating, applied load, and test period. The five groups consisted of 1.) 6K Vectran webbings loaded to 49% ultimate tensile strength (UTS), 2.) 6K Vectran webbings loaded to 55% UTS, 3.) 12.5K Vectran webbings loaded to 22% UTS, 4.) 6K Kevlar webbings loaded to 40% and 43% UTS, and 5.) 6K Kevlar webbings loaded to 48% UTS. Results show that all webbing groups exhibit the initial two stages of three of a typical creep curve of an elastic material. Results also show that webbings exhibit unique local wave patterns over the duration of the test period. Data indicate that the local pattern is primarily generated by daily variations in relative humidity values within the test facility. Data indicate that after a three to six month period, where webbings reach a steady-state creep condition, an annual sinusoidal displacement pattern is exhibited, primarily due to variations in annual mean temperature values. Data indicates that variations in daily temperature values and annual mean humidity values have limited secondary effects on creep displacement behavior. Results show that webbings in groups 2 and 5 do not exhibit well defined annual displacement patterns because the magnitude of the applied loads cause large deformations, and data indicate that material yielding within a webbing tends to neutralize the annual sinusoidal displacement pattern. Study indicates that applied load, environmental effects, mechanical strength, coefficient of thermal expansion, and hygroscopic properties of webbings are fundamental requirements for quantifying accurate creep displacements and behaviors over multiple year time periods. Results from a study of the environmental effects on long-term creep displacement data of Kevlar and Vectran woven webbings are presented to increase the knowledge base of webbing materials and to enhance designs of inflatable space structures for long-duration space missions