408 research outputs found
Improved Ant Colony Optimization for Seafood Product Delivery Routing Problem
This paper deals with a real-life vehicle delivery routing problem, which is a seafood product delivery routing problem. Considering the features of the seafood product delivery routing problem, this paper formulated this problem as a multi-depot open vehicle routing problem. Since the multi-depot open vehicle routing problem is a very complex problem, a method is used to reduce the complexity of the problem by changing the multi-depot open vehicle routing problem into an open vehicle routing problem with a dummy central depot in this paper. Then, ant colony optimization is used to solve the problem. To improve the performance of the algorithm, crossover operation and some adaptive strategies are used. Finally, the computational results for the benchmark problems of the multi-depot vehicle routing problem indicate that the proposed ant colony optimization is an effective method to solve the multi-depot vehicle routing problem. Furthermore, the computation results of the seafood product delivery problem from Dalian, China also suggest that the proposed ant colony optimization is feasible to solve the seafood product delivery routing problem
Multi-scale Investigation of Weight-bearing Exercise on Bone Biomechanical Integrity in the Osteogenesis Imperfecta Model (oim) Mouse
Comparative Medicine - OneHealth and Comparative Medicine Poster SessionOsteogenesis imperfecta (OI), a heritable connective tissue disorder generally due to type I collagen defects, is characterized by small stature, reduced bone mineral density, and frequent fractures. Bone is inherently mechanosensitive, responding and adapting to its mechanical environment. Bone formation occurs in response to high mechanical loads; often changing its geometry to strengthen the skeleton. In humans, during the normal 2 year prepubertal/pubertal growth period normal children attain 26% of their peak bone mass, and children which are physically active accrue 10-40% more bone (region specific) than inactive children. This suggests that sedentary lifestyle choices of children with OI are particularly detrimental to their bone health. We postulate that even though the OI bone material is biomechanically weaker, the OI bone will respond to exercise (muscle loading and/or gravitational ground force), especially during pubertal growth by altering bone geometry, architecture, and/or mineral:matrix physiochemistry to generate an inherently stronger bone. The potential benefits of therapeutic exercise to OI patients are significant, but the risks are real. It is critical that we first demonstrate the feasibility and potential success of an exercise therapy in a mouse model of OI for it to be considered a viable therapy for patients. To address this need we combined the unique strengths of two University of Missouri Campuses (Columbia and Kansas City) to create a collaborative research team from the Departments of Biochemistry (UMC) and Veterinary Pathobiology (UMC) and Oral Biology (UMKC School of Dentistry) to determine if weight bearing exercise will improve bone biomechanical integrity in a mouse model of osteogenesis imperfecta (oim), and to investigate the molecular, biochemical, physiochemical, structural and biomechanical impact of exercise on bone at the macro-, ultra- and nano-structural levels. The relationship of whole bone biomechanical integrity and geometry to the mineral:matrix composition, architecture, crystal geometry, and the matrix:mineral interactions of bone is poorly understood. Therefore, we examined femurs of wildtype and oim mice by multi-scale analyses characterizing geometry (muCT) and biomechanics (torsional loading to failure) in relation to the bone mineral and matrix, physicochemical and mechanical properties (FTIR, Raman and scanning acoustic microscopy). By muCT and torsional loading to failure we defined the geometric structural properties and the whole bone biomechanical properties (torsional ultimate strength, torsional stiffness, and strain energy until failure), which are a function of both the geometry and bone biomechanical material properties (tensile strength and shear modulus of elasticity). We used FTIR and Raman microscopy in conjunction with scanning acoustic microscopy to correlate the chemical structure and composition with mechanical integrity. We then performed the same analyses on femoral bones from wildtype and oim mice that underwent moderate weight bearing exercise (running on a treadmill) to determine if weight bearing exercise could alter the molecular structure of bone mineral:matrix and improve bone physicochemical and biomechanical properties. Our preliminary findings support the hypothesis that weight bearing exercise induces an adaptive response in oim mouse bone to alter its matrix/mineral composition, physiochemical structure/ property, and geometry to increase bone quality and biomechanical strength
Preparation of fluorescence-encoded microspheres in a core-shell structure for suspension arrays
Fluorescence-encoded microspheres are widely used in the detection and analysis of biological molecules, especially in suspension arrays. Here, we report an efficient strategy for the preparation of fluorescence-encoded polystyrene microspheres with desirable optical and surface properties. The micron-sized, monodisperse polystyrene seed beads were first synthesized by dispersion polymerization. Then, dye molecules and carboxyl functional groups were copolymerized on the surface of the seed beads by forming a core-shell structure. Rhodamine 6G (R6G) was used as a model dye molecule to prepare the fluorescent beads, and the fluorescence intensity of the beads can be precisely controlled by adjusting the quantity of R6G. These fluorescent beads were characterized by environmental scanning electron microscopy, laser scanning confocal microscopy, and spectrofluorometry. The differences of the fluorescence spectra between fluorescent beads and R6G in solution were investigated. Twelve kinds of fluorescent beads encoded with different R6G fluorescence intensities were prepared, and they can be clearly distinguished on a conventional flow cytometer. Furthermore, the encoded beads are stable in water and resistant to photobleaching, which is crucial for their potential applications in diagnostic assays and imaging. Detection of human alpha fetoprotein antigen via a sandwich microsphere-based immunoassay yielded a detection limit of 80 pg mL(-1), demonstrating that the fluorescence-encoded microspheres synthesized herein are efficient in serving as the microcarriers in suspension arrays. As both the encoding and functionalizing procedures are made simultaneously, the newly designed technique is extremely simple and time-saving. Moreover, it could be readily applicable to the preparation of a wide size range of fluorescent particles made by polymerization.National Natural Science Foundation of China [20675070]; Program for New Century Excellent Talents in University [NCET-07-0729]; NFFTBS [J0630429]; Scientific Research Foundation ; State Education Ministr
Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146322/1/cpt971_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146322/2/cpt971.pd
Identification of Pharmacokinetic Markers for Guanxin Danshen Drop Pills in Rats by Combination of Pharmacokinetics, Systems Pharmacology, and Pharmacodynamic Assays
This paper reported a feasibility study strategy of identifying pharmacokinetic (PK) markers for a cardiovascular herbal medicine, Guanxin Danshen drop pill (GDDP). First, quantification analysis revealed the constituent composition in the preparation by high-performance liquid chromatography (HPLC). Subsequently, physiochemical property calculation predicted the solubility and intestinal permeability of the constituents in the preparation. Furthermore, HPLC–MS analysis ascertained the absorbable ingredients and their PK properties in rat plasma. The main effective substances from the ingredients absorbed into blood and their cardiovascular effects were also predicted by systems pharmacology study, and were further confirmed by in vivo protective effects on isoprenaline-induced myocardial injury in mice. Finally, the ingredients with high content, representative structure feature, favorable PK properties, high relevant degree to myocardial ischemia (MI) issues, and validated therapeutic effects were considered as the PK markers for the preparation. Ginsenosides Rg1, Rb1, and tanshinone (TS) IIA were identified originally as PK markers for representing PK properties of GDDP. In addition, integrated PK studies were carried out according to previous reports, viz. drug concentration sum method and the AUC weighting method, to understand the in vivo process of GDDP comprehensively. The present study maybe provide a reference approach to identify PK markers for cardiovascular herbal medicines
Effects of Moxibustion Stimulation on the Intensity of Infrared Radiation of Tianshu (ST25) Acupoints in Rats with Ulcerative Colitis
ST25 is a key acupoint used in the treatment of ulcerative colitis by moxibustion stimulation, but the biophysical mechanism underlying its effects is still unknown. The aim of the present study was to explore the biophysical properties of ST25 acupoint stimulated by moxibustion in a rat model of ulcerative colitis. The infrared radiation intensity of fourteen wavelengths of ST25 showed significant differences between the normal and model control groups. The intensity of infrared radiation of forty wavelengths showed significant differences compared with the corresponding control points in normal rats. The intensity of infrared radiation of twenty-eight wavelengths showed significant differences compared with the corresponding control points in model rats. The intensity of infrared radiation of nine wavelengths in the herb-partition moxibustion group, eighteen wavelengths in the ginger-partition moxibustion group, seventeen wavelengths in the garlic-partition moxibustion group, and fourteen wavelengths in the warming moxibustion group of the left ST25 showed significant differences compared with that of the model control group. For the right-hand-side ST25, these values were 33, 33, 2, and 8 wavelengths, respectively. This indicated that one possible biophysical mechanism of moxibustion on ST25 in ulcerative colitis model rats might involve changes in the intensity of infrared radiation of ST25 at different wavelengths
MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
Septic shock is a leading cause of morbidity and mortality. However, genetic factors predisposing to septic shock are not fully understood. Excessive production of proinflammatory cytokines, particularly tumor necrosis factor (TNF)-α, and the resultant severe hypotension play a central role in the pathophysiological process. Mitogen-activated protein (MAP) kinase cascades are crucial in the biosynthesis of proinflammatory cytokines. MAP kinase phosphatase (MKP)-1 is an archetypal member of the dual specificity protein phosphatase family that dephosphorylates MAP kinase. Thus, we hypothesize that knockout of the Mkp-1 gene results in prolonged MAP kinase activation, augmented cytokine production, and increased susceptibility to endotoxic shock. Here, we show that knockout of Mkp-1 substantially sensitizes mice to endotoxic shock induced by lipopolysaccharide (LPS) challenge. We demonstrate that upon LPS challenge, Mkp-1−/− cells exhibit prolonged p38 and c-Jun NH2-terminal kinase activation as well as enhanced TNF-α and interleukin (IL)-6 production compared with wild-type cells. After LPS challenge, Mkp-1 knockout mice produce dramatically more TNF-α, IL-6, and IL-10 than do wild-type mice. Consequently, Mkp-1 knockout mice develop severe hypotension and multiple organ failure, and exhibit a remarkable increase in mortality. Our studies demonstrate that MKP-1 is a pivotal feedback control regulator of the innate immune responses and plays a critical role in suppressing endotoxin shock
Sample size determination for bibliographic retrieval studies
<p>Abstract</p> <p>Background</p> <p>Research for developing search strategies to retrieve high-quality clinical journal articles from MEDLINE is expensive and time-consuming. The objective of this study was to determine the minimal number of high-quality articles in a journal subset that would need to be hand-searched to update or create new MEDLINE search strategies for treatment, diagnosis, and prognosis studies.</p> <p>Methods</p> <p>The desired width of the 95% confidence intervals (W) for the lowest sensitivity among existing search strategies was used to calculate the number of high-quality articles needed to reliably update search strategies. New search strategies were derived in journal subsets formed by 2 approaches: random sampling of journals and top journals (having the most high-quality articles). The new strategies were tested in both the original large journal database and in a low-yielding journal (having few high-quality articles) subset.</p> <p>Results</p> <p>For treatment studies, if W was 10% or less for the lowest sensitivity among our existing search strategies, a subset of 15 randomly selected journals or 2 top journals were adequate for updating search strategies, based on each approach having at least 99 high-quality articles. The new strategies derived in 15 randomly selected journals or 2 top journals performed well in the original large journal database. Nevertheless, the new search strategies developed using the random sampling approach performed better than those developed using the top journal approach in a low-yielding journal subset. For studies of diagnosis and prognosis, no journal subset had enough high-quality articles to achieve the expected W (10%).</p> <p>Conclusion</p> <p>The approach of randomly sampling a small subset of journals that includes sufficient high-quality articles is an efficient way to update or create search strategies for high-quality articles on therapy in MEDLINE. The concentrations of diagnosis and prognosis articles are too low for this approach.</p
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