Fisheries Exclusion Zones: Value and its sensitivity to data uncertainty

This paper focuses on the findings of the project that pertain particularly to the determination of the value of fisheries exclusion zones and the sensitivity of value estimation to data uncertainty. It necessarily draws on both the lite rature review and the case studies and in terms of its content extracts, presents and su mmarises the pertinent material therein covered. By collating this material a more directed consid eration of the topic of value is facilitated and the findings of the study as a whole more clear ly highlighted, and through consideration of uncertainty, also qualified

(3R,5S,7as)-(3,5-bis(4-Fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol: A Novel Neuroprotective Agent

Compounds that interact with microtubules, such as paclitaxel, have been shown to possess protective properties against β-amyloid (Aβ)-induced neurodegeneration associated with Alzheimer's disease. In this work, the novel agent (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol was investigated for effectiveness in protecting neurons against several toxic stimuli and its interaction with the microtubule network. Exposure of neuronal cultures to Aβ peptide in the presence of 5 nM (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol resulted in a 50% increase in survival. Neuronal cultures treated with other toxic stimuli such as staurosporine, thapsigargin, paraquat and H2O2 showed significantly enhanced survival in the presence of (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol. Microtubule binding and tubulin assembly studies revealed differences compared to paclitaxel, but confirmed the interaction of (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol with microtubules. Furthermore, in vitro studies using bovine brain microvessel endothelial cells experiments suggest that (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol can readily cross the blood-brain barrier in a passive manner

Poboljšanje fizičko-mehaničkih svojstava karbamazepina prekristalizacijom pri različitim pH

The morphology of crystals has an appreciable impact on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviors of drugs. The objective of this study was to achieve improved physicomechanical properties of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressures and measuring their hardness. SEM studies showed that carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle-shaped. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature or pH of crystallization media. The crushing strength of tablets indicated that all the recrystallized carbamazepine samples had better compactibility than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate of carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.Morfologija kristala ima značajan utjecaj na fizičko-mehanička svojstva lijekova. Kristaliničnost može utjecati na tečnost, oslobađanje, tvrdoću i bioraspoloživost lijekova. Cilj ovog rada bio je poboljšati fizičko-mehanička svojstva praha karbamazepina prekristalizacijom iz vodenih otopina pri različitim pH vrijednostima (1, 7 i 11). Fizičko-mehanička svojstva prekristaliziranog karbamazepina određivana su na sljedeći način: morfologija kristala ispitivana je pretražnom elektronskom mikroskopijom, polimorfi su identificirani rendgenskom difrakcijom praha (XRPD), a termodinamička svojstva analizirana su diferencijalnom pretražnom kalorimetrijom (DSC). Topljivost je određena pomoću aparata prema USP. Mehanička svojstva prekristaliziranog karbamazepina ispitivana su tijekom tabletiranja pri različitim tlakovima i mjerenjem tvrdoće nastalih tableta. SEM ispitivanja pokazala su da kristalizacija karbamazepina iz različitih medija utječe na morfologiju i veličinu kristala. Oblik kristala mijenjao se od pahuljastog ili pločastog do igličastog. Rezultati dobiveni XRPD i DSC metodama isključili su promjene kristaliničnosti zbog temperature ili pH medija. Mjerenjem lomljivosti tableta utvrđeno je da su svi prekristalizirani uzorci karbamazepina bili kompaktniji od polaznog praškastog uzorka. Ispitivanja topljivosti in vitro pokazala su da su kristali dobiveni iz otopine s pH 11 i 1 topljiviji. Uzorci karbamazepina dobiveni prekristalizacijom iz vodenih otopina različite pH vrijednosti imali su bolja mehanička svojstva od originalnog uzorka karbamazepina

Total Synthesis and Evaluation of c26-Hydroxyepothilone D Derivatives for Photoaffinity Labeling of β-Tubulin

Three photaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. The key step for the asymmetric synthesis of (S,E)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (R)-Me-CBS-oxazaborolidine. For the synthesis of (5S)-5,7-di-[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric Noyori reduction of a β-ketoester was employed. The C26 hydroxyepothilone D derivative was constructed following a well-established total synthesis strategy and the photoaffinity labels were attached to the C26 hydroxyl group. The photoaffinity analogues were tested in a tubulin assembly assay and for cytotoxicity against MCF-7 and HCT-116 cancer cell lines. The 3- and 4-azidobenzoic acid analogues were found to be as active as epothilone B in a tubulin assembly assay, but demonstrated significantly reduced cellular cytotoxicity compared to epothilone B. The benzophenone analogue was inactive in both assays. Docking and scoring studies were conducted that suggested that the azide analogues can bind to the epothilone binding site, but that the benzophenone analogue undergoes a sterically driven ligand rearrangement that interrupts all hydrogen bonding and therefore protein binding. Photoaffinity labeling studies with the 3-azidobenzoic acid derivative did not identify any covalently labeled peptide fragments, suggesting that the phenylazido side chain was predominantly solvent-exposed in the bound conformation

Why nature matters: A systematic review of intrinsic, instrumental, and relational values

\ua9 2023 The Author(s). Published by Oxford University Press on behalf of the American Institute of Biological Sciences. In this article, we present results from a literature review of intrinsic, instrumental, and relational values of nature conducted for the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, as part of the Methodological Assessment of the Diverse Values and Valuations of Nature. We identify the most frequently recurring meanings in the heterogeneous use of different value types and their association with worldviews and other key concepts. From frequent uses, we determine a core meaning for each value type, which is sufficiently inclusive to serve as an umbrella over different understandings in the literature and specific enough to help highlight its difference from the other types of values. Finally, we discuss convergences, overlapping areas, and fuzzy boundaries between different value types to facilitate dialogue, reduce misunderstandings, and improve the methods for valuation of nature\u27s contributions to people, including ecosystem services, to inform policy and direct future research

Associations of American Indian Children\u27s Screen-Time Behavior With Parental Television Behavior, Parental Perceptions of Children\u27s Screen Time, and Media-Related Resources in the Home

Introduction: American Indian children have high rates of overweight and obesity, which may be partially attributable to screen-time behavior. Young children\u27s screen-time behavior is strongly influenced by their environment and their parents\u27 behavior. We explored whether parental television watching time, parental perceptions of children\u27s screen time, and media-related resources in the home are related to scree time (ie, television, DVD/video, video game, and computer use) among Oglala Lakota youth residing on or near the Pine Ridge Reservation in South Dakota. Methods: We collected baseline data from 431 child and parent/caregiver pairs who participated in Bright Start, a group-randomized, controlled, school-based obesity prevention trial to reduce excess weight gain. Controlling for demographic characteristics, we used linear regression analysis to assess associations between children\u27s screen time and parental television watching time, parental perceptions of children\u27s screen time, and availability of media-related household resources. Results: The most parsimonious model for explaining children screen time included the children\u27s sex, parental body mass index, parental television watching time, how often the child watched television after school or in the evening, parental perception that the child spent too much time playing video games, how often the parent limited the child\u27s television time, and the presence of a VCR/DVD player or video game player in the home (F7,367 = 14.67; P \u3c .001; adjusted R2 = .37). The presence of a television in the bedroom did not contribute significantly to the model. Conclusion: Changes in parental television watching time, parental influence over children\u27s screen-time behavior, and availability of media-related resources in the home could decrease screen time and may be used as a strategy for reducing overweight and obesity in American Indian children

Height, adiposity and body fat distribution and breast density in young women

INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHOD: Associations of height, adiposity and body fat distribution with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25-29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy x-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging (MRI). Associations were evaluated using linear mixed effects models. All tests of statistical significance are 2-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percent fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) each was associated significantly with a 44.4% - 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. However, after adjustment for childhood BMI only the DXA measures percent fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8% - 19.6% decrease in ADBV . In mutually adjusted analysis, percent fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in A:G ratio was associated with a 18.5% decrease in ADBV. CONCLUSIONS: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations

Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

<p>Abstract</p> <p>Background</p> <p>Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.</p> <p>Methods</p> <p>rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.</p> <p>Results</p> <p>Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV₁and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.</p> <p>Conclusion</p> <p>Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.</p