| 1. |
- Scott, James S., et al.
(författare)
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Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
- 2014
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998
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Tidskriftsartikel (refereegranskat)abstract
- Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
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| 2. |
- Bhattacharya, Kunal, et al.
(författare)
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Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
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Tidskriftsartikel (refereegranskat)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
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| 3. |
- Brown, Christopher A., et al.
(författare)
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Multiscale analyses and characterizations of surface topographies
- 2018
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Ingår i: CIRP Annals - Manufacturing Technology. - : Elsevier BV. - 1726-0604 .- 0007-8506. ; 67:2, s. 839-862
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Tidskriftsartikel (refereegranskat)abstract
- This work studies multiscale analyses and characterizations of surface topographies from the engineering and scientific literature with an emphasis on production engineering research and design. It highlights methods that provide strong correlations between topographies and performance or topographies and processes, and methods that can confidently discriminate topographies that were processed or that perform differently. These methods have commonalities in geometric characterizations at certain scales, which are observable with statistics and measurements. It also develops a semantic and theoretical framework and proposes a new system for organizing and designating multiscale analyses. Finally, future possibilities for multiscale analyses are discussed.
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| 4. |
- Hithnawi, A., et al.
(författare)
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Poster abstract : Cross-layer optimization for low-power wireless coexistence
- 2015
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Ingår i: SenSys 2015 - Proceedings of the 13th ACM Conference on Embedded Networked Sensor Systems. - New York, NY, USA : ACM Digital Library. - 9781450336314 ; , s. 443-444
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Konferensbidrag (refereegranskat)abstract
- We present a system that leverages physical layer features to combat Cross-Technology Interference (CTI) in low-power wireless networks. Our system incorporates: (i) a lightweight interference detection mechanism for low-power radios that recognizes the type of interference in the received signal, (ii) a lightweight error detection mechanism to estimate and characterize error patterns within interfered packets, and (iii) a CTI-aware protocol that dynamically adapts transmission and recovery mode to the current interference patterns. We implement a prototype of our system for the lowpower IEEE 802.15.4 in software defined radios (SDR). Our early results of the system components demonstrate that we can achieve a high accuracy in error detection and interference type identification. Moreover, we observed a significant performance improvement compared to the standard 802.15.4 systems without interference-awareness.
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| 5. |
- Lindgren, Johan, et al.
(författare)
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Fossil insect eyes shed light on trilobite optics and the arthropod pigment screen
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 573:7772, s. 122-125
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Tidskriftsartikel (refereegranskat)abstract
- Fossilized eyes permit inferences of the visual capacity of extinct arthropods1–3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes of 54-million-year-old crane-flies, which together provide a proxy for the interpretation of optical systems in some other ancient arthropods. These well-preserved visual organs comprise calcified corneal lenses that are separated by intervening spaces containing eumelanin pigment. We also show that eumelanin is present in the facet walls of living crane-flies, in which it forms the outermost ommatidial pigment shield in compound eyes incorporating a chitinous cornea. To our knowledge, this is the first record of melanic screening pigments in arthropods, and reveals a fossilization mode in insect eyes that involves a decay-resistant biochrome coupled with early diagenetic mineralization of the ommatidial lenses. The demonstrable secondary calcification of lens cuticle that was initially chitinous has implications for the proposed calcitic corneas of trilobites, which we posit are artefacts of preservation rather than a product of in vivo biomineralization4–7. Although trilobite eyes might have been partly mineralized for mechanical strength, a (more likely) organic composition would have enhanced function via gradient-index optics and increased control of lens shape.
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| 6. |
- Zimmerman, Jordan J, et al.
(författare)
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Riveting hammer vibration damages mechanosensory nerve endings
- 2020
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Ingår i: Journal of the peripheral nervous system. - : John Wiley & Sons, Ltd. - 1085-9489 .- 1529-8027. ; 25:3, s. 279-287
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Hand-arm vibration syndrome (HAVS) is an irreversible neurodegenerative, vasospastic and musculoskeletal occupational disease of workers using powered hand tools. The etiology is poorly understood. Neurological symptoms include numbness, tingling and pain. This study examines impact hammer vibration-induced injury and recoverability of hair mechanosensory innervation. Methods Rat tails were vibrated 12?min/d for 5 wk followed by 5 wk recovery with synchronous non-vibrated controls. Nerve fibers were PGP9.5 immunostained. Lanceolate complex innervation was compared quantitatively in vibrated vs sham. Vibration peak acceleration magnitudes were characterized by frequency power spectral analysis. Results Average magnitude (2515?m/s2, rms) in kHz frequencies was 109 times that (23?m/s2) in low Hz. Percentage of hairs innervated by lanceolate complexes was 69.1% in 5wk sham and 53.4% in 5wk vib generating a denervation difference of 15.7% higher in vibration. Hair innervation was 76.9% in 5wk recovery sham and 62.0% in 5wk recovery vibration producing a denervation difference 14.9% higher in recovery vibration. Lanceolate number per complex (18.4?±?0.2) after vibration remained near sham (19.3?±?0.3), but 44.9% of lanceolate complexes were abnormal in 5 wk vibrated compared to 18.8% in sham. Interpretation The largest vibration energies are peak kHz accelerations (~?100?000?m/s2) from shock waves. The existing ISO 5349-1 standard excludes kHz vibrations, seriously underestimating vibration injury risk. The present study validates the rat-tail, impact hammer vibration as a model for investigating irreversible nerve damage. Persistence of higher denervation difference after 5-week recovery suggests repeated vibration injury destroys the capability of lanceolate nerve endings to regenerate.
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