939 resultados para Oracle of Release
Resumo:
Billfish movements relative to the International Commission for the Conservation of Atlantic Tunas management areas, as well as U.S. domestic data collection areas within the western North Atlantic basin, were investigated with mark-recapture data from 769 blue marlin, Makaira nigricans, 961 white marlin, Tetrapturus albidus, and 1,801 sailfish, Istiophorus platypterus. Linear displacement between release and recapture locations ranged from zero (all species) to 15,744 km (mean 575, median 119, SE 44) for blue marlin, 6,523 km (mean 719, median 216, SE 33) for white marlin, and 3,845 km (mean 294, median 98, SE 13) for sailfish. In total, 2,824 (80.0%) billfish were recaptured in the same management area of release. Days at liberty ranged from zero (all species) to 4,591 (mean 619, median 409, SE 24) for blue marlin, 5,488 (mean 692, median 448, SE 22) for white marlin, and 6,568 (mean 404, median 320, SE 11) for sailfish. The proportions (per species) of visits were highest in the Caribbean area for blue marlin and white marlin, and the Florida East Coast area for sailfish. Blue marlin and sailfish were nearly identical when comparing the percent of individuals vs. the number of areas visited. Overall, white marlin visited more areas than either blue marlin or sailfish. Seasonality was evident for all species, with overall results generally reflecting the efforts of the catch and release recreational fishing sector, particularly in the western North Atlantic. This information may be practical in reducing the uncertainties in billfish stock assessments and may offer valuable insight into management consideration of time-area closure regulations to reduce bycatch mortality of Atlantic billfishes.
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Extensive mark-recapture studies using internal ferromagnetic tags have been conducted on Atlantic menhaden, Brevoortia tyrannus, and Gulf menhaden, B. patronus. From 1966 through 1969, 1,066,357 adult Atlantic menhaden were tagged; subsequently, from 1970 through 1987, 428,272 juveniles of this species were tagged. Similarly, from 1969 through 1971, 75,673 adult Gulf menhaden were tagged; concurrently from 1970 through 1985, 236,936 juveniles were tagged and released. This report provides an overview of the history of the tagging program, methodologies for both release and recovery activities, a summary of release areas and number of fish tagged within each area, and a review of assumptions necessary for the analysis of this type of mark-recovery data. The resulting data sets have proven to be highly useful for a variety of analyses ranging from determination of migratory patterns and population structure to estimating mortality rates. The relatively wide range of acceptance of tagging results by laymen, industry, and analysts alike have made these data extremely useful for management-oriented analyses.
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The purpose of this study was to validate aging results of juvenile Shortfin Mako (Isurus oxyrinchus) by vertebral band counts. Vertebrae of 29 juvenile Shortfin Mako marked with oxytetracycline (OTC) were obtained from tag-recapture activities to determine centrum growth-band deposition. Tagging occurred off southern California from 1996 to 2010, and time at liberty of the 29 sharks ranged from 4 months to 4.4 years (mean=1.3 years). Growth information also was obtained from length-frequency modal analyses (MULTIFAN and MIXDIST) by using a 29-year data set of commercial and research catch data, in addition to a tag-recapture growth model (e.g, the GROTAG model). For vertebrae samples used for age validation, shark size at time of release ranged from 79 to 142 cm fork length (FL) and from 98 to 200 cm FL at recapture. Results from band counts of vertebrae distal to OTC marks indicate 2 band pairs (2 translucent and 2 opaque) are formed each year for Shortfin Mako of the size range examined. Length-frequency analyses identified 3 age class modes. Growth rate estimates from 26.5 to 35.5 cm/year were calculated for the first age-class mode (85 cm FL) and from 22.4 to 28.6 cm/year for the second age-class mode (130 cm FL). Results from the tag-recapture growth model revealed fast growth during time at liberty for tagged fish of the 2 youngest age classes. Collectively, these methods suggest rapid growth of juvenile Shortfin Mako in the southern California study area and indicate biannual deposition of growth bands in vertebrae for the first 5 years.
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From 2003 to 2006, 44,882 Yellowtail Flounder (Limanda ferruginea) were captured and released with conventional disc tags in the western North Atlantic as part of a cooperative Yellowtail Flounder tagging study. From these releases, 3767 of the tags were recovered. The primary objectives of this tagging program were to evaluate the mortality and large-scale movement of Yellowtail Flounder among 3 stock areas in New England. To explore mortality, survival and recovery rate were estimated from traditional Brownie tag-recovery models fitted to the data with Program MARK. Models were examined with time and sex-dependent parameters over several temporal scales. The models with a monthly scale for both survival and recovery rate had the best overall fit and returned parameter estimates that were biologically reasonable. Estimates of survival from the tag-recovery models confirm the general magnitude of total mortality derived from age-based stock assessments but indicate that survival was greater for females than for males. In addition to calculating mortality estimates, we examined the pattern of release and recapture locations and revealed frequent movements within stock areas and less frequent movement among stock areas. The collaboration of fishermen and scientists for this study successfully resulted in independent confirmation of previously documented patterns of movement and mortality rates from conventional age-based analyses.
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Increasing interest in the use of stock enhancement as a management tool necessitates a better understanding of the relative costs and benefits of alternative release strategies. We present a relatively simple model coupling ecology and economic costs to make inferences about optimal release scenarios for summer flounder (Paralichthys dentatus), a subject of stock enhancement interest in North Carolina. The model, parameterized from mark-recapture experiments, predicts optimal release scenarios from both survival and economic standpoints for varyious dates-of-release, sizes-at-release, and numbers of fish released. Although most stock enhancement efforts involve the release of relatively small fish, the model suggests that optimal results (maximum survival and minimum costs) will be obtained when relatively large fish (75–80 mm total length) are released early in the nursery season (April). We investigated the sensitivity of model predictions to violations of the assumption of density-independent mortality by including density-mortality relationships based on weak and strong type-2 and type-3 predator functional responses (resulting in depensatory mortality at elevated densities). Depending on postrelease density, density-mortality relationships included in the model considerably affect predicted postrelease survival and economic costs associated with enhancement efforts, but do not alter the release scenario (i.e. combination of release variables) that produces optimal results. Predicted (from model output) declines in flounder over time most closely match declines observed in replicate field sites when mortality in the model is density-independent or governed by a weak type-3 functional response. The model provides an example of a relatively easy-to-develop predictive tool with which to make inferences about the ecological and economic potential of stock enhancement of summer flounder and provides a template for model creation for additional species that are subjects of stock enhancement interest, but for which limited empirical data exist.
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On 10 July 1999, vertebrae bearing an oxytetracycline (OTC) time mark were retrieved from a tagged leopard shark (Triakis semifasciata) recaptured in San Francisco Bay, CA, after being at liberty for almost 20 years. An additional long-term leopard shark tag return was received in June 2001, for which growth information (but not vertebrae) was obtained. The first recapture is significant in that it represents the longest at-liberty period for an age-validated (OTC-injected) shark, extends and completes age validation for this species, spanning all age classes up to its estimated average maximum age, and provides an example of the persistence of the OTC time mark in an elasmobranch at liberty for almost 20 years. The recaptured leopard shark made in 2001 also provides valuable information on long-term growth from time of release to time of recapture. Findings are documented here so that other researchers are aware that validation is complete for this species, to present pertinent evidence of considerable interannual variability in growth in this species, and to report observations on processing difficulties relating to the ephemeral nature of the 20-yr-old OTC mark.
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An outbreak of saprolegniasis in Catla catla in composite carp culture ponds were recorded during winter season. The typical cotton wool growths were observed on whole body surfaces of catla along with sporadic mortality. The fungal invasion was only restricted to skin and no fungal elements were visible in any internal organs after periodic acid schiff staining. On histology, periportal accumulation of mononuclear cells in liver, presence of myxosporidean cysts in antieror kidney, eosinophilic granular cells reaction in submucosa of stomach and intestine, dilated and engorged blood vessels of brain along with sloughing of epidermis and hyperplasia at gill lamellar base were pronounced changes. The possible role of release of Saprolegnia toxin in producing internal organs pathology has been discussed.
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Experimental sediments and water from shallow, eutrophic Dianchi Lakes were treated in a controlled laboratory microcosm using different chemicals under different anoxic levels. This study revealed that the polyaluminum chloride (PAC) was able to inhibit the phosphorus release and decrease the UV254 value at any anoxic level. When the DO concentrations were between 0.76-0.95 mg(.) L-1, the UV(254)value, total phosphorus (TP), and total dissolved phosphorus (TDP) in the water column were decreased by 71.93%, 87.12% and 64.24% respectively. The UV254, TP, and TDP were also decreased by 72.94%, 70.87% and 50.76% respectively at the levels of 4.56-5.32mg(.)L(-1) of DO concentrations. The treatment effects of TP and TDP in the water column using copper sulfate however were not as efficient as the PAC treatment. The UV254 value was increased with the addition of copper sulfate at every anoxic level tested but the chlorophyll-a (Chl-a) content was decreased rapidly and efficiently by copper sulfate more than the treatment by PAC. When the DO concentrations were 0.76-0.86mg(.)L(-1) and 4.75-5.14mg(.)L(-1), the Chl-a concentrations were decreased by 84.87% and 75.07% respectively through copper sulfate treatment. With additions of PAC and copper sulfate, the phosphorus fractions in sediments were shifted forward to the favorable shapes that have little ability of release. The TP concentrations in sediments were increased after treatment via PAC and copper sulfate. Under anoxic conditions, most of the BD-P (Fe-P) to NaOH-P (Al-P) was converted using the recommended PAC dose in BD-P rich sediment. Similar to the PAC, the copper sulfate also could flocculate the exchange phosphorus from sediment to overlying water. Overall though, the effects of copper sulfate treatment were not better than that of the PAC.
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Drug delivery systems influence the various processes of release, absorption, distribution and elimination of drug. Conventional delivery methods administer drug through the mouth, the skin, transmucosal areas, inhalation or injection. However, one of the current challenges is the lack of effective and targeted oral drug administration. Development of sophisticated strategies, such as micro- and nanotechnology that can integrate the design and synthesis of drug delivery systems in a one-step, scalable process is fundamental in advancing the limitations of conventional processing techniques. Thus, the objective of this thesis is to evaluate novel microencapsulation technologies in the production of size-specific and target-specific drug-loaded particles. The first part of this thesis describes the utility of PDMS and silicon microfluidic flow focusing devices (MFFDs) to produce PLGA-based microparticles. The formation of uniform droplets was dependent on the surface of PDMS remaining hydrophilic. However, the durability of PDMS was limited to no more than 1 hour before wetting of the microchannel walls with dichloromethane and subsequent swelling occurred. Critically, silicon MFFDs revealed very good solvent compatibility and was sufficiently robust to withstand elevated fluid flow rates. Silicon MFFDs facilitated experiments to run over days with continuous use and re-use of the device with a narrower microparticle size distribution, relative to conventional production techniques. The second part of this thesis demonstrates an alternative microencapsulation technology, SmPill® minispheres, to target CsA delivery to the colon. Characterisation of CsA release in vitro and in vivo was performed. By modulating the ethylcellulose:pectin coating thickness, release of CsA in-vivo was more effectively controlled compared to current commercial CsA formulations and demonstrated a linear in-vitro in-vivo relationship. Coated minispheres were shown to limit CsA release in the upper small intestine and enhance localised CsA delivery to the colon.
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BACKGROUND: Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. METHODS: We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. RESULTS: We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine. CONCLUSIONS: Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.
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Purpose: To study the impact of powder flow properties on dosator filling systems, with particular focus on improvements in dose weight accuracy and repeatability. Method: This study evaluates a range of critical powder flow properties such as: flow function, cohesion, wall friction, adhesion to wall surfaces, density/compressibility data, stress ratio “K” and gas permeability. The characterisations of the powders considered in this study were undertaken using an annular shear cell using a sample size of 0.5 litres. This tester also incorporated the facility to measure bed expansion during shear in addition to contraction under consolidation forces. A modified Jenike type linear wall friction tester was used to develop the failure loci for the powder sample in conjunction with multiple wall samples (representing a variety of material types and surface finishes). Measurements of the ratio of applied normal stress versus lateral stress were determined using a piece of test equipment specifically designed for the purpose. Results: The correct characterisation of powders and the incorporation of this data into the design of process equipment are recognised as critical for reliable and accurate operation. An example of one aspect of this work is the stress ratio “K”. This characteristic is not well understood or correctly interpreted in many cases – despite its importance. Fig 1 [Omitted] (illustrates a sample of test data. The slope of the line gives the stress ratio in a uniaxial compaction system – indicating the behaviour of the material under compaction during dosing processes. Conclusions: A correct assessment of the bulk powder properties for a given formulation can allow prediction of: cavity filling behaviour (and hence dosage), efficiency of release from dosator, and strength and stability of extruded dose en route to capsule filling Influences over the effectiveness of dosator systems have been shown to be impacted upon by: bed pre-compaction history, gas permeability in the bed (with respect to local density effects), and friction effects for materials of construction for dosators
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The aim of the current study was to evaluate the potential of the dynamic lipolysis model to simulate the absorption of a poorly soluble model drug compound, probucol, from three lipid-based formulations and to predict the in vitro-in vivo correlation (IVIVC) using neuro-fuzzy networks. An oil solution and two self-micro and nano-emulsifying drug delivery systems were tested in the lipolysis model. The release of probucol to the aqueous (micellar) phase was monitored during the progress of lipolysis. These release profiles compared with plasma profiles obtained in a previous bioavailability study conducted in mini-pigs at the same conditions. The release rate and extent of release from the oil formulation were found to be significantly lower than from SMEDDS and SNEDDS. The rank order of probucol released (SMEDDS approximately SNEDDS > oil formulation) was similar to the rank order of bioavailability from the in vivo study. The employed neuro-fuzzy model (AFM-IVIVC) achieved significantly high prediction ability for different data formations (correlation greater than 0.91 and prediction error close to zero), without employing complex configurations. These preliminary results suggest that the dynamic lipolysis model combined with the AFM-IVIVC can be a useful tool in the prediction of the in vivo behavior of lipid-based formulations.
Resumo:
TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients incorporated into the IVRs.
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To give the first demonstration of neighboring group-controlled drug delivery rates, a series of novel, polymerizable ester drug conjugates was synthesized and fully characterized. The monomers are suitable for copolymerization in biomaterials where control of drug release rate is critical to prophylaxis or obviation of infection. The incorporation of neighboring group moieties differing in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate of ester hydrolysis, and hence drug liberation, to be rationally and widely controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according to first-order kinetics, with rate constants between 3.00 ( 0.12 10-5 s -1 (fastest) and 4.50 ( 0.31 10- 6 s-1 (slowest). The hydrolysis was characterized using UV-visible spectroscopy. When copolymerized with poly(methyl methacrylate), free drug was shown to elute from the resulting materials, with the rate of release being controlled by the nature of the conjugate, as in solution. The controlled molecular architecture demonstrated by this system offers an attractive class of drug conjugate for the delivery of drugs from polymeric biomaterials such as bone cements in terms of both sustained, prolonged drug release and minimization of mechanical compromise as a result of release. We consider these results to be the rationale for the development of 'designer' drug release biomaterials, where the rate of required release can be controlled by predetermined molecular architecture.
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The recent judgment of the Grand Chamber of the European Court of Human Rights (ECtHR) in Vinter and others v United Kingdom provides a much needed clarification of the parameters of the prohibition on inhuman and degrading punishment under Article 3 of the European Convention on Human Rights (ECHR) as it applies to whole life orders of imprisonment under mandatory life sentences – essentially, life imprisonment without parole. The Grand Chamber’s judgment refines Strasbourg doctrine on life imprisonment and the prospect of release and illuminates key principles concerning inhuman and degrading punishment under Article 3 of the ECHR. This article considers the judgment’s profound significance in relation to both human rights and penology.