Assessing Optimal Digital Elevation Model Selection for Active River Area Delineation Across Broad Regions

Water Resources Management - The Active River Area (ARA) is a spatial approach for identifying the extent of functional riparian area. Given known limitations in terms of input elevation data...     

Subwords-Only Alternatives to fastText for Morphologically Rich Languages

Programming and Computer Software - In this work, we present purely subword-based alternatives to fastText word embedding algorithm The alternatives are modifications of the original fastText...     

Observing Inequality: Can Ergonomic Observations Help Interventions Transform the Role of Gender in Work Activity?

Computer Supported Cooperative Work (CSCW) - Work activity ergonomics (sometimes called francophone ergonomics) draws heavily on observation in order to support transformation of work to arrive at...     

Experimental results of a high Q quasioptical reflection cavity

A quasi-optical reflection cavity intended to be used as the resonant load of a submillimeter wavelength oscillator has been designed, constructed, and tested. The resonator consists of three elements in cascade: a high Q, high finesse folded Fabry-Perot resonator, a lower Q, low finesse Fabry-Perot resonator, and a Littrow mounted diffraction grating. The resonator exhibits a Q of 6600 and 2.5 dB of loss at 63 GHz. The design can be scaled to 1 THz, where waveguide structures become impractical, to serve as the resonator for high frequency quantum well resonant tunneling device oscillators.     

Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

Rheological analysis of vapor‐grown carbon nanofiber‐reinforced polyethylene composites

The melt rheological analysis of high‐density polyethylene reinforced with vapor‐grown carbon nanofibers (VGCNFs) was performed on an oscillatory rheometer. The influence of frequency, temperature, and nanofiber concentration (up to 30 wt %) on the rheological properties of composites was investigated. Specifically, the viscosity increase is accompanied by an increase in the elastic melt properties, represented by the storage modulus G′, which is much higher than the increase in the loss modulus G″. The composites and pure PE exhibit a typical shear thinning behavior as complex viscosity decreases rapidly with the increase of shearing frequency. The shear thinning behavior is much more pronounced for the composites with high fiber concentration. The rheological threshold value for this system was found to be around 10 wt % of VGCNF. The damping factor was reduced significantly by the inclusion of nanofibers into the matrix. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 155–162, 2004     

3-D molecular assembly of function in titania-based composite material systems

Various examples of composite titania-based nanostructured materials exhibiting cooperative functionalities between different active components are presented. The fabrication of these integrated composite materials is based on one-pot supramolecular templating techniques combined with acidic sol-gel chemistry. The defined 3-D nanoscale organization and integration of various functional components results in advanced optoelectronic and photonic applications such as visible light sensitization of mesoporous titania photocatalysts with cadmium sulfide nanocrystals acting as sensitizing integral part of the mesopore wall structure, narrow bandwidth emission from rare earth ion activated nanocrystalline mesoporous titania films, and mirrorless lasing in dye-doped hybrid organic/inorganic mesostructured titania waveguides.     

Iridoid glycoside metabolism and sequestration byPoladryas minuta (Lepidoptera: Nymphalidae) feeding onPenstemon virgatus (Scrophulariaceae)

A bivoltine checkerspot butterfly,Poladryas minuta, is aPenstemon specialist, not known to utilize any other plant genus for oviposition and larval feeding. At several intermontane plains sites of central Colorado, the butterfly utilizesPenstemon virgatus as its sole host plant. Analysis of the host plant showed it to contain three cinnamyl-type catalpol esters (scutellarioside-II, globularin, globularicisin) and catalpol. The host plant contained an average of 10% dry weight iridoids, but some variation among individual plants and leaves within plants was noted. Field-collected butterflies contained 2.1–8.7% dry weight catalpol, but no other iridoids. Adults from larvae fedP. virgatus in the lab contained 4.2–9.0% dry weight catalpol and excreted large amounts of catalpol in the meconium. No catalpol was found in the larval frass. Larvae did not consume three alternate iridoid-containing host-plant species, and most eventually died rather than feed on the alternate plants. Larvae did consume small amounts of artificial diets containing the alternate species andP. virgatus, but most went into diapause and some died. Survival was good on artificial diet containing 10% dry weight of the iridoid esters fromP. virgatus. Only catalpol was found in pupae and adults, but it was absent from the larval frass. The cinnamic-type acids expected from larval hydrolysis of the esters were not found in larval frass, pupae, or adults. These results are contrasted with those found for another checkerspot,Euphydryas anicia, which consumes a different host-plant species but was present at one of the same sites withPoladryas minuta.Paper 15 in the series Chemistry of the Scrophulariaceae. Paper 14 Boros, C.M., Stermitz, F.R., and Harris, G.H. 1990.J. Nat. Prod. 5372–80.