288 research outputs found
The external benefits of higher education
The private market benefits of education are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood. In this paper the macroeconomic effects of external benefits of higher education are estimated using the “micro-to-macro” simulation approach. Two types of externalities are explored: technology spillovers and productivity spillovers in the labour market. These links are illustrated and the results suggest they could be very large. However, this is qualified by the dearth of microeconomic evidence, for which we hope to encourage further work
Biophysical Modeling of Mangrove Seedling Establishment and Survival Across an Elevation Gradient With Forest Zones
Mangrove forest development critically depends on the establishment and survival of seedlings. Mechanistic insights into how water levels, waves and bed level dynamics influence the establishment process of individual mangrove seedlings are increasing. However, little is known about how spatial and temporal changes in water levels, waves and bed level dynamics across elevation gradients in mangrove forests facilitate/limit seedling dynamics. For this study, a new seedling establishment and growth model was integrated into a process-based hydrodynamic and morphodynamic numerical model. This biophysical model was applied to a fringing mangrove forest located in the southern Firth of Thames, Aotearoa, New Zealand. This study quantifies the increasing establishment density and survival probability of mangrove seedlings from the lower-elevated unvegetated intertidal flat toward the higher-elevated mature mangrove forest. Three cross-shore zones with distinctive seedling dynamics were identified: (a) a zone with daily tidal inundation where seedling dynamics are episodic and limited by the dispersal of individual propagules that rapidly anchor to the substrate by root growth, (b) a zone with daily to bi-weekly tidal inundation where seedling dynamics respond to variations in spring-neap tidal cycles and, (c) a zone with less than bi-weekly inundation where seedling dynamics are governed by high propagule supply and seedling survival probability. The seedling establishment density and survival probability are dominated by annual extremes in tidal hydroperiod and bed shear stresses, respectively. The obtained parameterizations can be used to incorporate seedling dynamics in decadal-timescale mangrove forest development models that are instrumental for mangrove management and restoration
Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging
Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported
Mass spectrometry imaging of cassette-dosed drugs for higher throughput pharmacokinetic and biodistribution analysis
Cassette dosing of compounds for preclinical drug plasma pharmacokinetic analysis has been shown to be a powerful strategy within the pharmaceutical industry for increasing throughput while decreasing the number of animals used. Presented here for the first time is data on the application of a cassette dosing strategy for label-free tissue distribution studies. The aim of the study was to image the spatial distribution of eight nonproprietary drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxifloxacin) in multiple tissues after oral and intravenous cassette dosing (four compounds per dose route). An array of mass spectrometry imaging technologies, including matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), liquid extraction surface analysis tandem mass spectrometry (LESA-MS/MS), and desorption electrospray ionization mass spectrometry (DESI-MS) was used. Tissue analysis following intravenous and oral administration of discretely and cassette-dosed compounds demonstrated similar relative abundances across a range of tissues indicating that a cassette dosing approach was applicable. MALDI MSI was unsuccessful in detecting all of the target compounds; therefore, DESI MSI, a complementary mass spectrometry imaging technique, was used to detect additional target compounds. In addition, by adapting technology used for tissue profiling (LESA-MS/MS) low spatial resolution mass spectrometry imaging (∼1 mm) was possible for all targets across all tissues. This study exemplifies the power of multiplatform MSI analysis within a pharmaceutical research and development (R&D) environment. Furthermore, we have illustrated that the cassette dosing approach can be readily applied to provide combined, label-free pharmacokinetic and drug distribution data at an early stage of the drug discovery/development process while minimizing animal usage
Age and growth of longfinned eels (Anguilla dieffenbachii) in pastoral and forested streams in the Waikato River basin, and in two hydro-electric lakes in the North Island, New Zealand
Growth rates of New Zealand endemic longfinned eels (Anguilla dieffenbachii) from streams in pasture and indigenous forest, and from two hydroelectric lakes (Lakes Karapiro and Matahina), were estimated by otolith examination. Habitat-specific growth was further investigated with measurement of widths of annual bands in otoliths. Longfinned eels 170-1095 mm in length ranged between 4 and 60 years old (N=252). Eels in pastoral streams grew faster (mean annual length increment ±95% CL = 24 ± 3 mm to 36 ± 7 mm) than eels in streams in indigenous forest (annual length increment 12 ± 2 mm to 15 ± 3 mm). Eels from the hydro-electric lakes had growth rates (annual length increments 19 ± 4 and 19 + 7 mm) similar to eels from pastoral streams. Otoliths of most eels showed annual band widths that indicated growth in several different habitats, corresponding to growth during upstream migration, and limited movement among adult habitats. Estimated age at marketable size (220 g) ranged between 7 and 26 years. The particularly slow growth of longfinned eels in streams in indigenous forest has considerable implications for management. The fast growth rates of eels in hydro-electric lakes provides evidence for the potential of increased eel production by stocking. The probable selective production of female eels in these lakes may be nationally important to allow enhancement of breeding stocks
Nuclear receptors in vascular biology
Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology
Econometric estimation of Armington import elasticities for a regional CGE model of the Illinois economy
One of the main concerns associated with the development and use of regional CGE models is the determination of key parameter values, particularly substitution and other price elasticities. A common problem is the lack of appropriate regional data for econometric estimation. Consequently, it is important to identify key parameters that are likely to be important in determining quantitative results and then to prioritize these for estimation where appropriate data are available. In this paper, the focus is on the estimation of the regional trade (import) substitution parameters, which tend to be important in analysis for regional economies (given their openness to trade). Here, commodity import elasticities for the Illinois economy are estimated and tested in a single region CGE model of the Illinois economy. In our econometric estimation, we apply a model that takes account of market size and distance in estimating the substitutability between commodities produced in Illinois and other US states
Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages
RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD
How much does a single graduation cohort from further education colleges contribute to an open regional economy?
This paper combines elements of growth accounting and numerical general equilibrium analysis to produce an alternative micro-to-macro modelling approach. This is used to evaluate the macroeconomic impact on the Scottish economy of the human capital generated by a single graduation cohort from further education colleges. The macroeconomic impact is found to be significant and larger than growth accounting would suggest due to the associated endogenous investment, employment and competitiveness effects. From a policy perspective this identifies the importance of the conventional teaching role of education institutions and the key function played by further education colleges in this process
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