Airwriting: a wearable handwriting recognition system

We present a wearable input system which enables interaction through 3D handwriting recognition. Users can write text in the air as if they were using an imaginary blackboard. The handwriting gestures are captured wirelessly by motion sensors applying accelerometers and gyroscopes which are attached to the back of the hand. We propose a two-stage approach for spotting and recognition of handwriting gestures. The spotting stage uses a support vector machine to identify those data segments which contain handwriting. The recognition stage uses hidden Markov models (HMMs) to generate a text representation from the motion sensor data. Individual characters are modeled by HMMs and concatenated to word models. Our system can continuously recognize arbitrary sentences, based on a freely definable vocabulary. A statistical language model is used to enhance recognition performance and to restrict the search space. We show that continuous gesture recognition with inertial sensors is feasible for gesture vocabularies that are several orders of magnitude larger than traditional vocabularies for known systems. In a first experiment, we evaluate the spotting algorithm on a realistic data set including everyday activities. In a second experiment, we report the results from a nine-user experiment on handwritten sentence recognition. Finally, we evaluate the end-to-end system on a small but realistic data set.     

Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Digital PCR Panel for Sensitive Hematopoietic Chimerism Quantification after Allogeneic Stem Cell Transplantation

Accurate and sensitive determination of hematopoietic chimerism is a crucial diagnostic measure after allogeneic stem cell transplantation to monitor engraftment and potentially residual disease. Short tandem repeat (STR) amplification, the current “gold standard” for chimerism assessment facilitates reliable accuracy, but is hampered by its limited sensitivity (≥1%). Digital PCR (dPCR) has been shown to combine exact quantification and high reproducibility over a very wide measurement range with excellent sensitivity (routinely ≤0.1%) and thus represents a promising alternative to STR analysis. We here aimed at developing a whole panel of digital-PCR based assays for routine diagnostic. To this end, we tested suitability of 52 deletion/insertion polymorphisms (DIPs) for duplex analysis in combination with either a reference gene or a Y-chromosome specific PCR. Twenty-nine DIPs with high power of discrimination and good performance were identified, optimized and technically validated. We tested the newly established assays on retrospective patient samples that were in parallel also measured by STR amplification and found excellent correlation. Finally, a screening plate for initial genotyping with DIP-specific duplex dPCR assays was designed for convenient assay selection. In conclusion, we have established a comprehensive dPCR system for precise and high-sensitivity measurement of hematopoietic chimerism, which should be highly useful for clinical routine diagnostics.     

Functionalizable composite nanoparticles as a dual magnetic resonance imaging/computed tomography contrast agent for medical imaging

A dual contrast agent for computed tomography (CT) and magnetic resonance imaging (MRI) was synthesized via microemulsion polymerization. This contrast agent consists of Fe₃O₄ particles (d = 7 nm) with an iodine-carrying nanopolymeric shell, with overall particle sizes ranging from 50 to 250 nm. 2-Methacryloyloxyethyl(2,3,5-triiodobenzoate) was used as the monomer. Sodium oleate was used as the surfactant and its amount was varied to control the overall particle size. The composite nanoparticles were mainly characterized via dynamic light scattering, with further analyses using transmission electron microscopy and atomic force microscopy. The particles provided a highly visible contrast in CT and MR images. A template for biomedical applications was created by adding a comonomer and the particles were further functionalized with the somatostatin analogue Tyr³-octreotate. The particles were tested for specific uptake into somatostatin receptor-positive AR42J cells. The additional uptake of the functionalized particles was investigated. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47571.     

Secreted production of a custom-designed, highly hydrophilic gelatin in Pichia pastoris

A custom-designed, highly hydrophilic gelatin was produced inPichia pastoris. Secreted production levels in single-copytransformants were in the range 3–6 g/l of clarified brothand purification to near homogeneity could be accomplished bydifferential ammonium sulfate precipitation. Despite the factthat gelatins are highly susceptible to proteolysis becauseof their unfolded structure, the recombinant protein was shownto be fully intact by SDS–PAGE, N-terminal sequencing,gel filtration chromatography and mass spectrometry. Owing toits highly hydrophilic nature, the migration of the syntheticgelatin in SDS–PAGE was severely delayed. Esterificationof the carboxylic amino acid side chains resulted in normalmigration. The high polarity of the synthetic gelatin also accountsfor its negligible surface activity in water at concentrationsup to 5% (w/v), as determined by tensiometry. Circular dichroismspectrometry showed that the non-hydroxylated gelatin did notform triple helices at 4°C. The spectrum was even more representativeof the random coil conformation than the spectrum of naturalnon-hydroxylated gelatins.     

Synthesis and characterization of cytidine derivatives that inhibit the kinase IspE of the non-mevalonate pathway for isoprenoid biosynthesis

The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are attractive targets for the development of novel drugs against malaria and tuberculosis. This pathway is used exclusively by the corresponding pathogens, but not by humans. A series of water-soluble, cytidine-based inhibitors that were originally designed for the fourth enzyme in the pathway, IspD, were shown to inhibit the subsequent enzyme, the kinase IspE (from Escherichia coli). The binding mode of the inhibitors was verified by co-crystal structure analysis, using Aquifex aeolicus IspE. The crystal structures represent the first reported example of a co-crystal structure of IspE with a synthetic ligand and confirmed that ligand binding affinity originates mainly from the interactions of the nucleobase moiety in the cytidine binding pocket of the enzyme. In contrast, the appended benzimidazole moieties of the ligands adopt various orientations in the active site and establish only poor intermolecular contacts with the protein. Defined binding sites for sulfate ions and glycerol molecules, components in the crystallization buffer, near the well-conserved ATP-binding Gly-rich loop of IspE were observed. The crystal structures of A. aeolicus IspE nicely complement the one from E. coli IspE for use in structure-based design, namely by providing invaluable structural information for the design of inhibitors targeting IspE from Mycobacterium tuberculosis and Plasmodium falciparum. Similar to the enzymes from these pathogens, A. aeolicus IspE directs the OH group of a tyrosine residue into a pocket in the active site. In the E. coli enzyme, on the other hand, this pocket is lined by phenylalanine and has a more pronounced hydrophobic character.     

Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident.

This study examined whether patients with posttraumatic stress disorder (PTSD) related to motor vehicle accidents (MVAs) would show an abnormal pattern of electroencephalographic (EEG) alpha asymmetries, which has been proposed for particular types of anxiety. Patients with PTSD (n = 22) or subsyndromal PTSD (n = 21), traumatized controls without PTSD (non-PTSD with MVA; n = 21), and healthy controls without MVA (n = 23) underwent measurement of EEG activity during baseline and exposure to a neutral, a positive, a negative, and an accident-related picture. Differences in brain asymmetry between groups were observed only during exposure to trauma-related material. PTSD and subsyndromal PTSD patients showed a pattern of enhanced right anterior and posterior activation, whereas non-PTSD with MVA participants showed the opposite pattern. Furthermore, posterior asymmetry in nontraumatized healthy controls varied with gender, with female participants showing a pattern of higher right posterior activation. The results support the hypothesis that symptomatic MVA survivors are characterized by a pattern of right hemisphere activation that is associated with anxious arousal and symptoms of PTSD during processing of trauma-specific information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Donor Agency Scramble for South Africa

The international development community invests bulk of its financial aid to South Africa in establishing procedural conditions through which development actions may be realized. Accordingly, ‘democracy assistance’ is designed to target governmental structures and civil society organizations (CSOs). International donor governments and aid agencies also assign an operational role to civil society so that it may assist in the process of change. However, an overt emphasis on the procedural aspects of democracy, governance, and development ignores the context and object of planning. Consequently, development planning in South Africa is perceived in narrow procedural terms alone, and not in terms of more holistic and equitable development responses.     

Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays

We investigated the reactions between substituted α,β‐unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS‐CoV M^pro) by etacrynic acid derivatives as well as for the excess toxicity of substituted α,β‐unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4‐addition followed by a ketonization step, and underscores the importance of a base‐catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron‐pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s‐cis conformation leads to higher reactivity than the s‐trans conformation. The computed data explain the trends in measured inhibition potencies of substituted α,β‐unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease.     

Surface crack in tension or in bending – A reassessment of the Newman and Raju formula in respect to fracture toughness measurements in brittle materials

The Newman and Raju formula for the stress intensity factor of a semi-elliptical surface crack loaded in uniaxial tension or in bending has been developed about 30 years ago using an FE-analysis for several geometric parameters and fitting an empirical equation to the data points. The Poisson's ratio analyzed was 0.3.In this paper a reassessment of the Newman and Raju formula is made, where all relevant geometric parameters of crack and specimen and the Poisson's ratio are considered. The deviations of the old formula from the new results are up to 21%, if the full range of Poisson's ratio is taken into account. Furthermore the influence of the crack-surface intersection angle is discussed.The results of this work are important for more precise fracture toughness measurements in brittle materials and give a practical guidance for appropriate specimen preparation for fracture toughness measurements, which is also considered here.