An intervention method for occupational safety in farming -- evaluation of the effect and process

In order to increase safety in Swedish farming an intervention methodology to influence attitudes and behaviour was tested. Eighty eight farmers and farm workers in nine groups gathered on seven occasions during 1 year. The basic concept was to create socially supportive networks and encourage discussions and reflection, focusing on risk manageability. Six of the groups made structured incident/accident analyses. Three of the latter groups also received information on risks and accident consequences. Effects were evaluated in a pre-post questionnaire using six-graded scales. A significant increase in safety activity and significant reduction in stress and risk acceptance was observed in the total sample. Risk perception and perceived risk manageability did not change. Analysing incidents/accidents, but not receiving information, showed a more positive outcome. Qualitative data indicated good feasibility and that the long duration of the intervention was perceived as necessary. The socially supportive network was reported as beneficial for the change process.     

A generic interface for parallel access to large data sets from HPF applications

A critical performance issue for a number of scientific and engineering applications is the efficient transfer of data to secondary storage. Languages such as High Performance Fortran (HPF) have been introduced to allow programming distributed-memory systems at a relatively high level of abstraction. However, the present version of HPF does not provide appropriate constructs for controlling the parallel I/O capabilities of these systems. In this paper, constructs to specify parallel I/O operations on multidimensional arrays in the context of HPF are proposed. The paper also presents implementation concepts that are based on the HPF compiler VFC and the parallel I/O run-time system Panda. Experimental performance results are discussed in the context of financial management and traffic simulation applications.     

Speech-as-data technologies for personal information devices

 For small, portable devices, speech input has the advantages of low-cost and small hardware, can be used on the move or whilst the eyes & hands are busy, and is natural and quick. Rather than rely on imperfect speech recognition we propose that information entered as speech is kept as speech and suitable tools are provided to allow quick and easy access to the speech-as-data records. This paper summarises our work on the technologies needed for these tools – for organising, browsing, searching and compressing the stored speech. These technologies go a long way towards giving stored speech the characteristics of text without the associated input problems. Received: 5 March 2002 / Accepted: 1 September 2002 Nick Haddock Consultant Acknowledgements The authors would like to thank the whole HP Labs Gryphon team for their valuable contributions to this work - Mike Collins for the hierarchical chunking algorithm, Erik Geelhoed and David Frohlich for the users perspective, Richard Hull for starting off the compression work, Steve Loughran for productisation, and Dave Reynolds for his consistent advice and support. We would also like to thank our partners at Cambridge University, Steve Young and Tony Robinson, whose expertise and technology formed the foundation for this work, as well as the efforts of Kate Knill on wordspotting, Carl Seymour on compression, James Christie on recognition, and Robin Valenza whose brief excursion into the world of speech technology helped develop a simple and effective summarisation technique. Finally we would like to thank the reviewers for their many helpful comments.     

Electron energy loss spectroscopy for analysis of inhaled ultrafine particles in rat lungs

Epidemiologic studies have associated cardiovascular morbidity and mortality with ambient particulate air pollution. Particles smaller than 100 nm in diameter (ultrafine particles) are present in the urban atmosphere in very high numbers yet at very low mass concentration. Organs beyond the lungs are considered as targets for inhaled ultrafine particles, whereby the route of particle translocation deeper into the lungs is unclear. Five rats were exposed to aerosols of ultrafine titanium dioxide particles of a count median diameter of 22 nm (geometric standard deviation, GSD 1.7) for 1 hour. The lungs were fixed by intravascular perfusion of fixatives immediately thereafter. TiO(2) particles in probes of the aerosol as well as in systematic tissue samples were analyzed with a LEO 912 transmission electron microscope equipped with an energy filter for elemental microanalysis. The characteristic energy loss spectra were obtained by fast spectrum acquisition. Aerosol particles as well as those in the lung tissue were unambiguously identified by electron energy loss spectroscopy. Particles were mainly found as small clusters with a rounded shape. Seven percent of the particles in the lung tissue had a needle-like shape. The size distribution of the cluster profiles in the tissue had a count median diameter of 29 nm (GSD 1.7), which indicates no severe clustering or reshaping of the originally inhaled particles. Electron energy loss spectroscopy and related analytical methods were found to be suitable to identify and localize ultrafine titanium dioxide particles within chemically fixed and resin-embedded lung tissue.     

Towards 3D Bioprinted Spinal Cord Organoids

Three-dimensional (3D) cultures, so-called organoids, have emerged as an attractive tool for disease modeling and therapeutic innovations. Here, we aim to determine if boundary cap neural crest stem cells (BC) can survive and differentiate in gelatin-based 3D bioprinted bioink scaffolds in order to establish an enabling technology for the fabrication of spinal cord organoids on a chip. BC previously demonstrated the ability to support survival and differentiation of co-implanted or co-cultured cells and supported motor neuron survival in excitotoxically challenged spinal cord slice cultures. We tested different combinations of bioink and cross-linked material, analyzed the survival of BC on the surface and inside the scaffolds, and then tested if human iPSC-derived neural cells (motor neuron precursors and astrocytes) can be printed with the same protocol, which was developed for BC. We showed that this protocol is applicable for human cells. Neural differentiation was more prominent in the peripheral compared to central parts of the printed construct, presumably because of easier access to differentiation-promoting factors in the medium. These findings show that the gelatin-based and enzymatically cross-linked hydrogel is a suitable bioink for building a multicellular, bioprinted spinal cord organoid, but that further measures are still required to achieve uniform neural differentiation.     

Unraveling Membrane Perturbations Caused by the Bacterial Riboregulator Hfq

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.     

Differentially private histogram publication

Differential privacy (DP) is a promising scheme for releasing the results of statistical queries on sensitive data, with strong privacy guarantees against adversaries with arbitrary background knowledge. Existing studies on differential privacy mostly focus on simple aggregations such as counts. This paper investigates the publication of DP-compliant histograms, which is an important analytical tool for showing the distribution of a random variable, e.g., hospital bill size for certain patients. Compared to simple aggregations whose results are purely numerical, a histogram query is inherently more complex, since it must also determine its structure, i.e., the ranges of the bins. As we demonstrate in the paper, a DP-compliant histogram with finer bins may actually lead to significantly lower accuracy than a coarser one, since the former requires stronger perturbations in order to satisfy DP. Moreover, the histogram structure itself may reveal sensitive information, which further complicates the problem. Motivated by this, we propose two novel mechanisms, namely NoiseFirst and StructureFirst, for computing DP-compliant histograms. Their main difference lies in the relative order of the noise injection and the histogram structure computation steps. NoiseFirst has the additional benefit that it can improve the accuracy of an already published DP-compliant histogram computed using a naive method. For each of proposed mechanisms, we design algorithms for computing the optimal histogram structure with two different objectives: minimizing the mean square error and the mean absolute error, respectively. Going one step further, we extend both mechanisms to answer arbitrary range queries. Extensive experiments, using several real datasets, confirm that our two proposals output highly accurate query answers and consistently outperform existing competitors.     

HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.     

Physical Characterization of Anhydrous and Hydrous Forms of the Hydrochloride Salt of BVT.5182 A Novel 5-HT6 Receptor Antagonist

ABSTRACT

The physicochemical properties of 1-benzenesulfonyl-4-(piperazin-1-yl)-indole hydrochloride, a novel 5-HT₆ receptor antagonist for the treatment of obesity were characterized. Two solid state forms were identified at ambient conditions (23°C): an anhydrate form (1) and a hydrate form (2), with 1.5 moles of H₂O. The latter easily dehydrates and rehydrates without affecting the crystal morphology. Investigations of the propensity for interconversion between the two forms reveal that a) conversion of 2→1 takes place above 145°C and that b) conversion of 1→2 only occurs after crystallization from supersaturated aqueous solutions at a water activity ≥0.94 or in the presence of comparable amounts of crystals of 2 in water at ambient conditions. However, in an equimolar suspension of 1 and 2 at 37°C no phase transformation was observed. Thus, the difference in chemical potential between the two forms is small. Form 1 was shown to have overall favorable solid state properties and, hence, considered the preferred form for continued pharmaceutical development. The characterization was performed by means of light microscopy, scanning electron microscopy, powder X-ray diffraction, FTIR/NIR-spectroscopy, differential scanning calorimetry, hot stage microscopy, thermogravimetry, dynamic vapor sorption, Karl Fischer water content determination, phase stability studies of suspensions, solubility, and intrinsic dissolution rate measurements.     

Requirements for a virtual environment to support the social participation education of low-literates

People of low literacy experience difficulties while participating in society. Learning support software could help alleviate these difficulties. However, there is currently no overview of theoretically and empirically sound requirements for this kind of support. This paper uses the situated cognitive engineering method to create a requirements baseline for a virtual environment to support the societal participation education of low-literates (VESSEL), based on an analysis of the domain, human factors, and current applications. Four major outcomes are presented. First, a comprehensive overview is collected of the operational demands and human factors knowledge relevant to societal participation learning for low-literate citizens. Second, this overview is translated into a list of eight functional requirements: focused on low-literate learners, set in the context of societal participation, and supported by claims of cognitive, affective, and social benefits to learning. Third, a sample of Dutch societal participation learning support programs is assessed using these requirements, to highlight both current technology best practices and discrepancies between theory and practice. Fourth, virtual learning environment technology is suggested as an ‘enabling’ technology; an overview is shown of how virtual environments, actors, and objects can beneficially enable meeting the requirements baseline. Finally, directions for future study are discussed.