An analysis of the literature supporting the UN Decade of Education for Sustainable Development and a sample of its key products suggests that it failed to acknowledge or challenge neoliberalism as a ...hegemonic force blocking transitions towards genuine sustainability. The authors argue that the rationale for the Decade was idealistic and that global education for sustainability citizenship provides a more realistic focus for such an initiative. They anchor such education in appropriate social theory, outline its four dimensions and use these to review four key products from the Decade, before suggesting remedial measures to render ESD a more effective vehicle for promoting democratic global governance and sustainability.
We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The ...centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Molecular dispersions are a highly effective method of increasing bioavailability for a poorly soluble active pharmaceutical ingredient (API) and can be prepared on a large scale by hot melt ...extrusion (HME). Processing thermally labile active pharmaceutical ingredients (APIs) via HME is generally more difficult, with operating temperatures limited to below that of the API melting point. API melting is considered essential to facilitate the formation of a fully homogeneous amorphous system. Processing below the melting point renders the system much more susceptible to residual crystalline content; hence, HME is not suitable for APIs which degrade upon melting. In the following work, meloxicam (MEL) was used as a model API, possessing properties of high melting temperature and thermal lability. In this proof of concept work, a modified HME method, termed solvent-assisted HME, was used to overcome this issue and prepare an amorphous solid dispersion using HME, wherein a solvent was incorporated in the formulation blend during extrusion and removed post-processing. Formulations containing 10%wt meloxicam (MEL) and 90%wt polyvinylpyrrolidone vinyl acetate (PVPVA) copolymer were extruded using a twin-screw extruder at temperatures below the melting point of MEL. Dimethylformamide (DMF) solvent was added directly into the extruder barrel through a liquid addition port, resulting in extrudate products having a higher conversion of API to the amorphous form. The incorporation of solvent allowed a significant reduction in processing temperatures due to its increased mobility, while also driving the conversion of the API to its amorphous form. The solvent was successfully reduced through a secondary drying step using a vacuum oven. This advancement has demonstrated the potential for thermally labile APIs to be processed via HME expanding the applications of this technology.
Graphical Abstract
Radiance Simulations in Support of Climate Services Poli, P.; Roebeling, R.; John, V. O. ...
Earth and space science (Hoboken, N.J.),
October 2023, 2023-10-00, 20231001, 2023-10-01, Letnik:
10, Številka:
10
Journal Article
Recenzirano
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Climate services are largely supported by climate reanalyses and by satellite Fundamental (Climate) Data Records (F(C)DRs). This paper demonstrates how the development and the uptake of F(C)DR ...benefit from radiance simulations, using reanalyses and radiative transfer models. We identify three classes of applications, with examples for each application class. The first application is to validate assumptions during F(C)DR development. Hereto we show the value of applying advanced quality controls to geostationary European (Meteosat) images. We also show the value of a cloud mask to study the spatio‐temporal coherence of the impact of the Mount Pinatubo volcanic eruption between Advanced Very High Resolution Radiometer (AVHRR) and the High‐resolution Infrared Radiation Sounder (HIRS) data. The second application is to assess the coherence between reanalyses and observations. Hereto we show the capability of reanalyses to reconstruct spectra observed by the Spektrometer Interferometer (SI‐1) flown on a Soviet satellite in 1979. We also present a first attempt to estimate the random uncertainties from this instrument. Finally, we investigate how advanced bias correction can help to improve the coherence between reanalysis and Nimbus‐3 Medium‐Resolution Infrared Radiometer (MRIR) in 1969. The third application is to inform F(C)DR users about particular quality aspects. We show how simulations can help to make a better‐informed use of the corresponding F(C)DR, taking as examples the Nimbus‐7 Scanning Multichannel Microwave Radiometer (SMMR), the Meteosat Second Generation (MSG) imager, and the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave Water Vapor Profiler (SSM/T‐2).
Key Points
Radiance simulations can help characterize two essential inputs of climate services, satellite data records and reanalyses
Uncertainties in observations collected by the Spektrometer Interferometer‐1 flown on a Soviet satellite in 1979 were estimated
Radiance simulations of satellite instruments can provide information on the quality and realism of climate reanalyses
We report a second-generation gene annotation of human chromosome 22. Using expressed sequence databases, comparative sequence analysis, and experimental verification, we have extended genes, fused ...previously fragmented structures, and identified new genes. The total length in exons of annotation was increased by 74% over our previously published annotation and includes 546 protein-coding genes and 234 pseudogenes. Thirty-two potential protein-coding annotations are partial copies of other genes, and may represent duplications on an evolutionary path to change or loss of function. We also identified 31 non-protein-coding transcripts, including 16 possible antisense RNAs. By extrapolation, we estimate the human genome contains 29,000-36,000 protein-coding genes, 21,300 pseudogenes, and 1500 antisense RNAs. We suggest that our revised annotation criteria provide a paradigm for future annotation of the human genome.
Tylosis (focal non-epidermolytic palmoplantar keratoderma) is associated with the early onset of squamous cell oesophageal cancer in three families. Linkage and haplotype analyses have previously ...mapped the tylosis with oesophageal cancer ( TOC) locus to a 500-kb region on chromosome 17q25 that has also been implicated in sporadically occurring squamous cell oesophageal cancer. In the current study, 17 additional putative microsatellite markers were identified within this 500-kb region by using sequence data and seven of these were shown to be polymorphic in the UK and US families. In addition, our complete sequence analysis of the non-repetitive parts of the TOC minimal region identified 53 novel and six known single nucleotide polymorphisms (SNPs) in one or both of these families. Further fine mapping of the TOC disease locus by haplotype analysis of the seven polymorphic markers and 21 of the 59 SNPs allowed the reduction of the minimal region to 42.5 kb. One known and two putative genes are located within this region but none of these genes shows tylosis-specific mutations within their protein-coding regions. Alternative mechanisms of disease gene action must therefore be considered.
Pseudomonas strain NCIMB10586, in the P. fluorescens subgroup, produces the polyketide antibiotic mupirocin, and has potential as a host for industrial production of a range of valuable products. To ...underpin further studies on its genetics and physiology, we have used a combination of standard and atypical approaches to achieve a quality of the genome sequence and annotation, above current standards for automated pathways. Assembly of Illumina reads to a PacBio genome sequence created a retrospectively hybrid assembly, identifying and fixing 415 sequencing errors which would otherwise affect almost 5% of annotated coding regions. Our annotation pipeline combined automation based on related well-annotated genomes and stringent, partially manual, tests for functional features. The strain was close to P. synxantha and P. libaniensis and was found to be highly similar to a strain being developed as a weed-pest control agent in Canada. Since mupirocin is a secondary metabolite whose production is switched on late in exponential phase, we carried out RNAseq analysis over an 18 h growth period and have developed a method to normalise RNAseq samples as a group, rather than pair-wise. To review such data we have developed an easily interpreted way to present the expression profiles across a region, or the whole genome at a glance. At the 2-hour granularity of our time-course, the mupirocin cluster increases in expression as an essentially uniform bloc, although the mupirocin resistance gene stands out as being expressed at all the time points.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder, affecting both the corneal endothelium and Descemet's membrane. In the Czech Republic, PPCD is one of the most ...prevalent corneal dystrophies. The purpose of this study was to determine the chromosomal locus of PPCD in two large Czech families, by using linkage analysis.
Linkage analysis was performed on 52 members of two Czech families with PPCD and polymorphic microsatellite markers and lod scores were calculated. The candidate gene VSX1 was also screened for mutations.
Significant lod scores were obtained with microsatellite markers on chromosome 20. Linkage analysis delineated the Czech PPCD locus to a 2.7-cM locus on chromosome 20, region p11.2, between flanking markers D20S48 and D20S139, which excluded VSX1 as the disease-causing gene in both families. In addition, the exclusion of VSX1 was confirmed by sequence analysis.
This study reports the localization of PPCD in patients of Czech origin to chromosome 20 at p11.2. Linkage data and sequence analysis exclude VSX1 as causative of PPCD in two Czech families. This refined locus for PPCD overlaps the congenital hereditary endothelial dystrophy (CHED1) disease interval, and it is possible that these corneal dystrophies are allelic.
The swift ultra-violet/optical telescope ROMING, Peter W. A; KENNEDY, Thomas E; HUNSBERGER, S. D ...
Space science reviews,
10/2005, Letnik:
120, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
The Ultra-Violet/Optical Telescope (UVOT) is one of three instruments flying aboard the Swift Gamma-ray Observatory. It is designed to capture the early (1 min) UV and optical photons from the ...afterglow of gamma-ray bursts in the 170-600 nm band as well as long term observations of these afterglows. This is accomplished through the use of UV and optical broadband filters and grisms. The UVOT has a modified Ritchey-Chrétien design with micro-channel plate intensified charged-coupled device detectors that record the arrival time of individual photons and provide sub-arcsecond positioning of sources. We discuss some of the science to be pursued by the UVOT and the overall design of the instrument.PUBLICATION ABSTRACT
Over the last 10 years, 40% of approved oral drugs exhibited a significant effect of food on their pharmacokinetics (PK) and currently the only method to characterize the effect of food on drug ...absorption, which is recognized by the authorities, is to conduct a clinical evaluation. Within the pharmaceutical industry, there is a significant effort to predict the mechanism and clinical relevance of a food effect. Physiologically based pharmacokinetic (PBPK) models combining both drug-specific and physiology-specific data have been used to predict the effect of food on absorption and to reveal the underlying mechanisms. This manuscript provides detailed descriptions of how a middle-out modeling approach, combining bottom-up
in vitro
-based predictions with limited top-down fitting of key model parameters for clinical data, can be successfully used to predict the magnitude and direction of food effect when it is predicted poorly by a bottom-up approach. For nefazodone, a mechanistic clearance for the gut and liver was added, for furosemide, an absorption window was introduced, and for aprepitant, the biorelevant solubility was refined using multiple solubility measurements. In all cases, these adjustments were supported by literature data and showcased a rational approach to assess the factors limiting absorption and exposure.
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