A long-term field trial of membrane capacitive deionization (MCDI) was conducted in a remote community in the Northern Territory of Australia, with the aim of producing safe palatable drinking water from groundwater that contains high concentrations of salt and hardness ions and other contaminants. This trial lasted for 1.5 years, which, to our knowledge, is one of the longest reported studies of pilot-scale MCDI field trials.
View Article and Find Full Text PDFCytochrome P450 3A4 (CYP3A4) is the dominant P450 involved in human xenobiotic metabolism. Competition for CYP3A4 therefore underlies several adverse drug-drug interactions. Despite its clinical significance, the mechanisms CYP3A4 uses to bind diverse ligands remain poorly understood.
View Article and Find Full Text PDFIntegrated-optic components are being increasingly used in astrophysics, mainly where accuracy and precision are paramount. One such emerging technology is nulling interferometry that targets high contrast and high angular resolution. Two of the most critical limitations encountered by nullers are rapid phase fluctuations in the incoming light causing instability in the interference and chromaticity of the directional couplers that prevent a deep broadband interferometric null.
View Article and Find Full Text PDFThe shallow subsurface of Mars is extremely interesting as a possible microbial habitat because it becomes temporarily wet, it is shielded from radiation, and mixing by aeolian processes could provide the sources of energy and nutrients necessary for sustaining microbial life in it. The Modern Aqueous Habitat Reconnaissance Suite (MAHRS) was developed primarily to search for potentially habitable environments in the shallow subsurface of Mars and to study weathering, but it can also be used to search for potentially habitable environments in the shallow subsurface of other planetary bodies such as the Icy Worlds. MAHRS includes an instrument developed to measure regolith wetness and search for brine in the shallow subsurface of Mars, where it is most likely to be found.
View Article and Find Full Text PDFTo identify new therapeutic targets in acute myeloid leukemia (AML), we performed small-molecule and small-interfering RNA (siRNA) screens of primary AML patient samples. In 23% of samples, we found sensitivity to inhibition of colony-stimulating factor 1 (CSF1) receptor (CSF1R), a receptor tyrosine kinase responsible for survival, proliferation, and differentiation of myeloid-lineage cells. Sensitivity to CSF1R inhibitor GW-2580 was found preferentially in de novo and favorable-risk patients, and resistance to GW-2580 was associated with reduced overall survival.
View Article and Find Full Text PDFIn many malignancies, the tumor microenvironment includes CSF1R-expressing supportive monocyte/macrophages that promote tumor cell survival. For chronic lymphocytic leukemia (CLL), these supportive monocyte/macrophages are known as nurse-like cells (NLCs), although the potential effectiveness of selective small-molecule inhibitors of CSF1R against CLL is understudied. Here, we demonstrate the preclinical activity of two inhibitors of CSF1R, GW-2580 and ARRY-382, in primary CLL patient samples.
View Article and Find Full Text PDFBackground: Asthma is characterized by airway hyper-responsiveness and variable airflow obstruction, in part as a consequence of hyper-contractile airway smooth muscle, which persists in primary cell culture. One potential mechanism for this hyper-contractility is abnormal intracellular Ca(2+) handling.
Methods: We sought to compare intracellular Ca(2+) handling in airway smooth muscle cells from subjects with asthma compared to non-asthmatic controls by measuring: i) bradykinin-stimulated changes in inositol 1,4,5-trisphosphate (IP3) accumulation and intracellular Ca(2+) concentration, ii) sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) expression, iii) mechanisms of cytoplasmic Ca(2+) clearance assessed following instantaneous flash photolytic release of Ca(2+) into the cytoplasm.
The cause of airway smooth muscle (ASM) hypercontractility in asthma is not fully understood. The relationship of spontaneous intracellular calcium oscillation frequency in ASM to asthma severity was investigated. Oscillations were increased in subjects with impaired lung function abolished by extracellular calcium removal, attenuated by caffeine and unaffected by verapamil or nitrendipine.
View Article and Find Full Text PDFConsiderable resources have been spent developing and rigorously testing HIV prevention intervention models, but such models do not impact the AIDS pandemic unless they are implemented effectively by community-based organizations (CBOs) and health departments. The Mpowerment Project (MP) is being implemented by CBOs around the U.S.
View Article and Find Full Text PDFAs efforts to reduce the overpopulation and euthanasia of unwanted and unowned dogs and cats have increased, greater attention has been focused on spay-neuter programs throughout the United States. Because of the wide range of geographic and demographic needs, a wide variety of programs have been developed to increase delivery of spay-neuter services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, feral cat programs, and services provided through private practitioners. In an effort to ensure a consistent level of care, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs.
View Article and Find Full Text PDFThe apolipoprotein E epsilon4 allele contributes to the genetic susceptibility underlying a large proportion (~40-60%) of typical, sporadic Alzheimer disease. Apolipoprotein E deficient mice made transgenic for human apolipoprotein E epsilon4 accumulate excess cerebral amyloid when compared to similarly prepared mice expressing human apolipoprotein E epsilon3. Therefore, it is important to search for relevant interactions(s) between apolipoprotein E epsilon4 and Abeta in order to clarify the biological role for apolipoprotein E epsilon4 in Alzheimer disease.
View Article and Find Full Text PDFRecent work from our laboratory demonstrated that phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)), are required to maintain the structural integrity of the Golgi apparatus. To investigate the role of these lipids in regulating Golgi structure and function, we developed a novel assay to follow the release of post-Golgi vesicles. Isolated rat liver Golgi membranes were incubated with [(3)H]CMP sialic acid to radiolabel endogenous soluble and membrane glycoproteins present in the late Golgi and trans-Golgi network.
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