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1.
During early-stage drug development, drug and metabolite distribution studies are carried out in animal tissues using a range of techniques, particularly whole body autoradiography (WBA). While widely employed, WBA has a number of limitations, including the following: expensive synthesis of radiolabeled drugs and analyte specificity and identification. WBA only images the radiolabel. MALDI MSI has been shown previously to be advantageous for imaging the distribution of a range of drugs and metabolites in whole body sections. Ion mobility separation (IMS) adds a further separation step to imaging experiments; demonstrated here is MALDI-IMS-MS whole body imaging of rats dosed at 6 mg/kg i.v. with an anticancer drug, vinblastine and shown is the distribution of the precursor ion m/z 811.4 and several product ions including m/z 793, 751, 733, 719, 691, 649, 524, and 355. The distribution of vinblastine within the ventricles of the brain is also depicted. Clearly demonstrated in these data are the removal of interfering isobaric ions within the images of m/z 811.4 and also of the transition m/z 811-751, resulting in a higher confidence in the imaging data. Within this work, IMS has shown to be advantageous in both MS and MS/MS imaging experiments by separating vinblastine from an endogenous isobaric lipid.  相似文献   
2.
The multiscale structure, materials properties, and mechanical responses of the turtle shell (Terrapene carolina) were studied to understand the fundamental knowledge of naturally occurring biological penetrator-armor systems. The structure observation and chemical analysis results revealed that the turtle shell carapace comprises a multiphase sandwich composite structure of functionally graded material having exterior bone layers and a foam-like bony network of closed-cells between the two exterior bone layers. Although the morphology was quite different, the exterior bone layers and interior bony network possessed comparable hardness and elastic modulus values of ~ 1 GPa and ~ 20 GPa, respectively. Compression and flexure test results showed a typical nonlinear deformation behavior recognizant of man-made foams. The mechanical test results revealed that the interior closed-cell foam layer plays a significant role on the overall deformation behavior of the turtle shell. The finite element analysis simulation results showed comparable agreement with the actual experimental test data. This systematic study could provide fundamental understanding for structure-property phenomena and biological pathways to design bio-inspired synthetic composite materials.  相似文献   
3.
The author presents a brief review of the historical developments which have resulted in the emergence of secondary surveillance radar (SSR) and, most recently, of Mode S as the principal radar sensor worldwide for civil air traffic control. The essential technical characteristics of both SSR and of Mode S are described  相似文献   
4.
The effects of selected methods of size reduction, holding periods and drying on elimination of cyanide from cassava roots of variety MCol 1684 were investigated. Drying at 50°C eliminated approximately 50% of the total cyanide from mechanically prepared chips, and 25% from manually prepared chips. Mechanical chipping and drying at 50°C eliminated 65% of the total cyanide from small chips and 47% from large chips. Mincing of whole roots completely degraded the glucoside, and rasping and mechanical chipping degraded 70–80% and 30% of the initial glucoside respectively. The results indicate that the method of size reduction and particle size control the rate of glucoside degradation, and that the drying rate limits the quantity of glucosidic cyanide eliminated. The results are compared with those of other researchers.  相似文献   
5.
Alcohol-related cognitions, particularly expectancies for drinking and nondrinking and motives for nondrinking, are involved in the initiation, maintenance, and cessation of alcohol use and are hypothesized to play key roles in adolescent decision making. This study explored (a) the relationships between alcohol use expectancies, nondrinking expectancies, and nondrinking motives; (b) the roles of these cognitions across hypothesized developmental stages of adolescent alcohol use; and (c) the relationships between these cognitions and recent or intended future changes in drinking behavior in a cross-sectional sample. Surveys assessing alcohol use behaviors and attitudes were administered to 1,648 high school students. Heavier drinkers reported more positive alcohol use expectancies and fewer nondrinking motives than did lighter drinkers or nondrinkers; however, nondrinking expectancies only differed between nondrinkers and rare drinkers and all subsequent drinking classes. Alcohol use expectancies, nondrinking expectancies, and nondrinking motives differentiated students who recently initiated alcohol from those who had not, while nondrinking expectancies and nondrinking motives differentiated binge-drinking students who had made recent efforts to reduce/stop their drinking from those who had not. Intentions to initiate or reduce drinking in the coming month were also associated with these alcohol-related cognitions. Drinking and nondrinking expectancies and motives for not drinking may play critical roles in decisions to alter alcohol-use behavior during adolescence. Future exploration of temporal relationships between changes in alcohol-related cognitions and behavioral decision making will be useful in the refinement of effective prevention and intervention strategies. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   
6.
The present study examined the role of adolescent substance use and its antecedent behavioral and familial risk factors in the prediction of young adult internalizing symptoms 10 years later, using a community sample of children of alcoholics (n = 194) and demographically matched controls (n = 209). Using growth curve modeling, the authors found that initial levels of adolescent alcohol and drug use (μage = 13) and growth in drug use during adolescence predicted higher levels of internalizing symptoms in young adulthood, even after including in the models shared risk factors for both internalizing symptoms and adolescent substance use. These effects remained significant after including concurrent substance use in adulthood, suggesting that adolescent substance use exerts a long-term impact on young adult internalizing symptoms over and above the effects of persistent substance use over time. The present investigation further revealed that initial levels of alcohol and drug use in adolescence mediate the relation between parental alcoholism and young adult internalizing symptoms. Findings provide evidence for the long-term effects of adolescent substance use on young adult functioning and can help inform both etiological and prevention research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
7.
The manufacture of cassava starch in medium — scale factories requires large volumes of water and produces equivalent volumes of effluent. The use of hydrocyclones to concentrate starch milk and thereby reduce water consumption in the extraction of cassava starch was investigated. Basic performance data with selected hydrocyclone configurations were obtained in the laboratory and the results showed conclusively that high and efficient levels of starch separation are possible with considerable potential for water conservation and effluent reduction in starch factories.  相似文献   
8.
Some of the most remarkable materials in terms of energy absorption and impact resistance are not found through human processing but in nature. Solutions to the continuing problems of improved composite technologies may lie in replicating naturally occurring systems. In this review, we examine several mammalian structural materials: bones (bovine femur and elk antler), teeth and tusks from various taxa, horns from the desert big horn sheep, and equine hooves. We establish the relationships between structural and mechanical properties for these materials, with an emphasis on energy absorption mechanisms. We also identify the energy absorbing strategies utilized in these materials. Implementation of these bioinspired design strategies can serve as a basis for the design of new energy absorbent synthetic composite materials. Synthetic constituent materials arranged according to the principles outlined in this work will achieve the same synergistic effects as nature and no longer be confined to the limitations imposed by a mixture law.  相似文献   
9.
Energy efficient refurbishment can have benefits beyond a saving on heating costs and Trim describes how energy efficient measures can be integrated with other non-energy measures when a major refurbishment of high-rise housing is planned.  相似文献   
10.
Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.  相似文献   
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