Endometriosis detection and localization in laparoscopic gynecology

Multimedia Tools and Applications - Endometriosis is a common gynecologic condition typically treated via laparoscopic surgery. Its visual versatility makes it hard to identify for non-specialized...     

Exploring design trade-offs for achieving social inclusion in multi-tiered design problems

ABSTRACT

The digital age of the future is ‘not out there to be discovered’, but it needs to be ‘designed’. The design challenge has to address questions about how we want to live, work, and learn (as individuals and as communities) and what we value and appreciate, e.g.: reflecting on quality of life and creating inclusive societies. An overriding design trade-off for the digital age is whether new developments will increase the digital divide or will create more inclusive societies. Sustaining inclusive societies means allowing people of all ages and all abilities to exploit information technologies for personally meaningful activities. Meta-design fosters the design of socio-technical environments that end-user developers can modify and evolve at use time to improve their quality of life and favour their inclusion in the society. This paper describes three case studies in the domain of assistive technologies in which end users themselves cannot act as end-user developers, but someone else (e.g.: a caregiver or a clinician) must accept this role requiring multi-tiered architectures. The design trade-offs and requirements for meta-design identified in the context of the case studies and other researchers’ projects are described to inform the development of future socio-technical environments focused on social inclusion.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

N-Substituted Nipecotic Acids as (S)-SNAP-5114 Analogues with Modified Lipophilic Domains

Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC₅₀ value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity.     

Comparative techno-economic assessment of a large-scale hydrogen transport via liquid transport media

A large-scale point to point hydrogen transport is one strategy for a prospective energy import scenario for certain countries. The case for a hydrogen transport from Australia to Japan has been addressed in several studies. However, most studies lack transparency and detailed insights into the made assumptions thus a fair evaluation of different transport pathways is challenging. To address this issue, we developed a model where a large-scale point to point hydrogen transport of liquid hydrogen is compared with the transport via liquid organic hydrogen carrier (LOHC), namely via methyl cyclohexane and hydrogenated dibenzyl toluene. We analyzed, where energy is required along the different pathways, where hydrogen losses do occur and how the costs are put together. Furthermore, the influence of hydrogen feed costs is also considered. For hydrogen production costs of 5 €₂₀₁₈/kg_H2 the total delivery costs are in the range of 6.40– 8.10 €₂₀₁₈/kg_H2.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.