178 research outputs found

    An Exploratory Study into Employee Attitudes towards Digitalisation of Library Services in Higher Education (3)

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    With the advent of technologies, library services in higher education face pressure to increase their level of digitalisation in order to meet changing user demands. While many researchers aim to understand what digitalisation means to library services from the user perspective, there is little attention paid to the employees of library services. Since employees are one of the key driving forces of digitalisation, there is a need to understand their attitudes towards digitalisation. This paper aims to explore employee attitudes towards digitalisation of library services via a case study with data collected from participant observation, focus groups and interviews. The finding suggests that the employee understanding of digitalisation is rather limited, which might have a negative impact on the benefit realisation of digitalisation. Furthermore, there are polarised views on factors of utilisation of digital applications between senior management and operational staff. Such polarised views could also have an impact on the actual use of digital applications. This exploratory study provides valuable insights into digitalisation of library services from employee perspective, which could serve as the foundation for further research

    Synthetic Studies toward 2,3-di-N-Acyl-2,4,6-Trideoxy-L-Altropyranoses as Synthetic Precursors to Pseudaminic Acid

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    With the growing therapeutic inefficiency of traditional antibiotics by rapidly spreading antimicrobial resistance (AMR) through different mechanisms, and a significant slow-down in the development of novel antimicrobials, especially in the pharmaceutical industry during recent years, it is of utmost importance to maintain research to address this global challenge. The chemical synthesis of carbohydrate antigens that are unique to pathogenic bacteria can benefit the search for antibacterial therapeutics with the development of prophylactic vaccines such as polysaccharide conjugates. Bacterial nonulosonic acids (NonAs) that include pseudaminic (Pse) and legionaminic (Leg) acids are found in important structural components that contribute to certain pathogens’ virulence, like Pseudomonas aeruginosa and Campylobacter jejuni: they have been recently shown to be good candidates for use as antigen epitopes in vaccination, and their biosynthetic precursors can also be used towards the development of other types of antibacterial therapeutics. The research presented here begins with preliminary investigations into a synthesis from L-arabinose that has the potential to produce 5 different NonA structures with only a few appropriate variations in the scheme. The synthesis of two C5-(R)/(S) hexose diastereomers was achieved with different selectivity, and those can further undergo an inversion and installation of nitrogen functionalities on C-2 and C-4, before the final three-carbon extension with a phosphoenolpyruvate (PEP) equivalent to produce the target NonA. The work showed promise, justifying future development. Next, a short, mild and scalable synthetic scheme towards 2,4-di-acetamido-2,4,6-trideoxy-L-altrose (Alt-diNAc), the biosynthetic precursor to Pse, is presented: the desired product was obtained from commercially available L-fucose in 10 steps and 23% overall yield, making it the most efficient synthesis published to-date. A further optimized shorter version of synthesis is described as well through regioselective sulfonyl activation to form a key epoxide intermediate, ultimately giving Alt-diNAc in 7 steps and 27% overall yield. Based on these achievements, a new and elegant methodology for the differentiable functionalization of the N2/N4 amide groups of Alt-diNAc was developed, which relies on a regiospecific O→N migration of acyl groups during a Staudinger reduction of the O-acylated di-azido precursor. The new methodology was proved to have broad scope and provides unprecedented versatility to introduce different N-acyl functionalities to the N5 and N7 positions of Pse. Finally, preliminary work towards a potentially stereoselective three-carbon extension of hexose precursors to NonAs is described, with the synthesis of a phenol-based cleavable linker containing an α-methyl ketone that can potentially undergo aldol addition intramolecularly, and then ruthenium-catalyzed oxidation to produce the required carboxylic functionalities for Pse. A successful selective coupling of this linker to one of the two amido groups on the L-altro-configuration precursor was then achieved, paving the way to investigate the diastereoselectivity of intramolecular aldol additions with this strategy in the future. Several possible variations to the linker functional groups and length can easily be incorporated in this synthetic plan , and provide an exciting prospect for future developments

    Novel method for hit-position reconstruction using voltage signals in plastic scintillators and its application to Positron Emission Tomography

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    Currently inorganic scintillator detectors are used in all commercial Time of Flight Positron Emission Tomograph (TOF-PET) devices. The J-PET collaboration investigates a possibility of construction of a PET scanner from plastic scintillators which would allow for single bed imaging of the whole human body. This paper describes a novel method of hit-position reconstruction based on sampled signals and an example of an application of the method for a single module with a 30 cm long plastic strip, read out on both ends by Hamamatsu R4998 photomultipliers. The sampling scheme to generate a vector with samples of a PET event waveform with respect to four user-defined amplitudes is introduced. The experimental setup provides irradiation of a chosen position in the plastic scintillator strip with an annihilation gamma quanta of energy 511~keV. The statistical test for a multivariate normal (MVN) distribution of measured vectors at a given position is developed, and it is shown that signals sampled at four thresholds in a voltage domain are approximately normally distributed variables. With the presented method of a vector analysis made out of waveform samples acquired with four thresholds, we obtain a spatial resolution of about 1 cm and a timing resolution of about 80 p

    Future feed control – Tracing banned bovine material in insect meal

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    In the present study, we assessed if different legacy and novel molecular analyses approaches can detect and trace prohibited bovine material in insects reared to produce processed animal protein (PAP). Newly hatched black soldier fly (BSF) larvae were fed one of the four diets for seven days; a control feeding medium (Ctl), control feed spiked with bovine hemoglobin powder (BvHb) at 1% (wet weight, w/w) (BvHb 1%, w/w), 5% (BvHb 5%, w/w) and 10% (BvHb 10%, w/w). Another dietary group of BSF larvae, namely *BvHb 10%, was first grown on BvHb 10% (w/w), and after seven days separated from the residual material and placed in another container with control diet for seven additional days. Presence of ruminant material in insect feed and in BSF larvae was assessed in five different laboratories using (i) real time-PCR analysis, (ii) multi-target ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS), (iii) protein-centric immunoaffinity-LC-MS/MS, (iv) peptide-centric immunoaffinity-LC-MS/MS, (v) tandem mass spectral library matching (SLM), and (vi) compound specific amino acid analysis (CSIA). All methods investigated detected ruminant DNA or BvHb in specific insect feed media and in BSF larvae, respectively. However, each method assessed, displayed distinct shortcomings, which precluded detection of prohibited material versus non-prohibited ruminant material in some instances. Taken together, these findings indicate that detection of prohibited material in the insect-PAP feed chain requires a tiered combined use of complementary molecular analysis approaches. We therefore advocate the use of a combined multi-tier molecular analysis suite for the detection, differentiation and tracing of prohibited material in insect-PAP based feed chains and endorse ongoing efforts to extend the currently available battery of PAP detection approaches with MS based techniques and possibly δ13CAA fingerprinting.publishedVersio

    Future feed control – Tracing banned bovine material in insect meal

    Get PDF
    In the present study, we assessed if different legacy and novel molecular analyses approaches can detect and trace prohibited bovine material in insects reared to produce processed animal protein (PAP). Newly hatched black soldier fly (BSF) larvae were fed one of the four diets for seven days; a control feeding medium (Ctl), control feed spiked with bovine hemoglobin powder (BvHb) at 1% (wet weight, w/w) (BvHb 1%, w/w), 5% (BvHb 5%, w/w) and 10% (BvHb 10%, w/w). Another dietary group of BSF larvae, namely *BvHb 10%, was first grown on BvHb 10% (w/w), and after seven days separated from the residual material and placed in another container with control diet for seven additional days. Presence of ruminant material in insect feed and in BSF larvae was assessed in five different laboratories using (i) real time-PCR analysis, (ii) multi-target ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS), (iii) protein-centric immunoaffinity-LC-MS/MS, (iv) peptide-centric immunoaffinity-LC-MS/MS, (v) tandem mass spectral library matching (SLM), and (vi) compound specific amino acid analysis (CSIA). All methods investigated detected ruminant DNA or BvHb in specific insect feed media and in BSF larvae, respectively. However, each method assessed, displayed distinct shortcomings, which precluded detection of prohibited material versus non-prohibited ruminant material in some instances. Taken together, these findings indicate that detection of prohibited material in the insect-PAP feed chain requires a tiered combined use of complementary molecular analysis approaches. We therefore advocate the use of a combined multi-tier molecular analysis suite for the detection, differentiation and tracing of prohibited material in insect-PAP based feed chains and endorse ongoing efforts to extend the currently available battery of PAP detection approaches with MS based techniques and possibly δ13CAA fingerprinting.</p

    Automated NMR relaxation dispersion data analysis using NESSY

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    <p>Abstract</p> <p>Background</p> <p>Proteins are dynamic molecules with motions ranging from picoseconds to longer than seconds. Many protein functions, however, appear to occur on the micro to millisecond timescale and therefore there has been intense research of the importance of these motions in catalysis and molecular interactions. Nuclear Magnetic Resonance (NMR) relaxation dispersion experiments are used to measure motion of discrete nuclei within the micro to millisecond timescale. Information about conformational/chemical exchange, populations of exchanging states and chemical shift differences are extracted from these experiments. To ensure these parameters are correctly extracted, accurate and careful analysis of these experiments is necessary.</p> <p>Results</p> <p>The software introduced in this article is designed for the automatic analysis of relaxation dispersion data and the extraction of the parameters mentioned above. It is written in Python for multi platform use and highest performance. Experimental data can be fitted to different models using the Levenberg-Marquardt minimization algorithm and different statistical tests can be used to select the best model. To demonstrate the functionality of this program, synthetic data as well as NMR data were analyzed. Analysis of these data including the generation of plots and color coded structures can be performed with minimal user intervention and using standard procedures that are included in the program.</p> <p>Conclusions</p> <p>NESSY is easy to use open source software to analyze NMR relaxation data. The robustness and standard procedures are demonstrated in this article.</p

    The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners

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    The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was indentified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. Proteins 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77451/1/22738_ftp.pd

    Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1

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    The 5′-cap of spliceosomal small nuclear RNAs, some small nucleolar RNAs and of telomerase RNA was found to be hypermethylated in vivo. The Trimethylguanosine Synthase 1 (TGS1) mediates this conversion of the 7-methylguanosine-cap to the 2,2,7-trimethylguanosine (m3G)-cap during maturation of the RNPs. For mammalian UsnRNAs the generated m2,2,7G-cap is one part of a bipartite import signal mediating the transport of the UsnRNP-core complex into the nucleus. In order to understand the structural organization of human TGS1 as well as substrate binding and recognition we solved the crystal structure of the active TGS1 methyltransferase domain containing both, the minimal substrate m7GTP and the reaction product S-adenosyl-l-homocysteine (AdoHcy). The methyltransferase of human TGS1 harbors the canonical class 1 methyltransferase fold as well as an unique N-terminal, α-helical domain of 40 amino acids, which is essential for m7G-cap binding and catalysis. The crystal structure of the substrate bound methyltransferase domain as well as mutagenesis studies provide insight into the catalytic mechanism of TGS1

    A novel synthesis and detection method for cap-associated adenosine modifications in mouse mRNA

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    A method is described for the detection of certain nucleotide modifications adjacent to the 5' 7-methyl guanosine cap of mRNAs from individual genes. The method quantitatively measures the relative abundance of 2'-O-methyl and N6,2'-O-dimethyladenosine, two of the most common modifications. In order to identify and quantitatify the amounts of N6,2'-O-dimethyladenosine, a novel method for the synthesis of modified adenosine phosphoramidites was developed. This method is a one step synthesis and the product can directly be used for the production of N6,2'-O-dimethyladenosine containing RNA oligonucleotides. The nature of the cap-adjacent nucleotides were shown to be characteristic for mRNAs from individual genes transcribed in liver and testis

    A feasibility study of the time reversal violation test based on polarization of annihilation photons from the decay of ortho-Positronium with the J-PET detector

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    The Jagiellonian Positron Emission Tomograph (J-PET) is a novel de- vice being developed at Jagiellonian University in Krakow, Poland based on or- ganic scintillators. J-PET is an axially symmetric and high acceptance scanner that can be used as a multi-purpose detector system. It is well suited to pur- sue tests of discrete symmetries in decays of positronium in addition to medical imaging. J-PET enables the measurement of both momenta and the polarization vectors of annihilation photons. The latter is a unique feature of the J-PET detector which allows the study of time reversal symmetry violation operator which can be constructed solely from the annihilation photons momenta before and after the scattering in the detector
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