A microstructured fiber with defined borosilicate regions to produce a radial micronozzle array for nanoelectrospray ionization

This work highlights the possibility of using microstructured fibres with predefined doped regions to produce functional microstructures at a fibre facet with differential chemical etching. A specially designed silica microstructured fibre (MSF) that possesses specific boron-doped silica regions was fabricated for the purpose of generating a radial micronozzle array. The MSF was drawn from a preform comprising pure silica capillaries surrounded by boron-doped silica rods. Different etching rates of the boron-doped and silica regions at the fiber facet produces raised nozzles where the silica capillaries were placed. Fabrication parameters were explored in relation to the fidelity and protrusion length of the nozzle. Using etching alone, the nozzle protrusion length was limited, and the inner diameter of the channels in the array is expanded. However with the addition of a protective water counter flow, nozzle protrusion is increased to 60 μm with a limited increase in hole diameter. The radial micronozzle array generated nine individual electrosprays which were characterized using spray current measurements and related to theoretical prediction. Signal enhancement for the higher charge state ions for two peptides showed a substantial signal enhancement compared to conventional emitter technology.Y. Fu, S. Morency, K. Bachus, D. Simon, T. Hutama, G. T. T. Gibson, Y. Messaddeq and R. D. Oleschu

Total Syntheses of Amphidinolides B1, B4, G1, H1 and Structure Revision of Amphidinolide H2

Nature is a pretty unselective “chemist” when it comes to making the highly cytotoxic amphidinolide macrolides of the B/G/H series. To date, 16 different such compounds have been isolated, all of which could now be approached by a highly convergent and largely catalysis-based route (see figure). This notion is exemplified by the total synthesis of five prototype members of this family. Dinoflagellates of the genus Amphidinium produce a “library” of closely related secondary metabolites of mixed polyketide origin, which are extremely scarce but highly promising owing to the exceptional cytotoxicity against various cancer cell lines. Because of the dense array of sensitive functionalities on their largely conserved macrocyclic frame, however, these amphidinolides of the B, D, G and H types elapsed many previous attempts at their synthesis. Described herein is a robust, convergent and hence general blueprint which allowed not only to conquest five prototype members of these series, but also holds the promise of making “non-natural” analogues available by diverted total synthesis. This notion transpires for a synthesis-driven structure revision of amphidinolide H2. The successful route hinges upon a highly productive Stille–Migita cross-coupling reaction at the congested and chemically labile 1,3-diene site present in all such targets, which required the development of a modified chloride- and fluoride-free protocol. The macrocyclic ring could be formed with high efficiency and selectivity by ring-closing metathesis (RCM) engaging a vinyl epoxide unit as one of the reaction partners. Because of the sensitivity of the targets to oxidizing and reducing conditions as well as to pH changes, the proper adjustment of the protecting group pattern for the peripheral -OH functions also constitutes a critical aspect, which has to converge to silyl groups only once the diene is in place. Tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) turned out to be a sufficiently mild fluoride source to allow for the final deprotection without damaging the precious macrolides

Detection of delirium by nurses among long-term care residents with dementia

<p>Abstract</p> <p>Background</p> <p>Delirium is a prevalent problem in long-term care (LTC) facilities where advanced age and cognitive impairment represent two important risk factors for this condition. Delirium is associated with numerous negative outcomes including increased morbidity and mortality. Despite its clinical importance, delirium often goes unrecognized by nurses. Although rates of nurse-detected delirium have been studied among hospitalized older patients, this issue has been largely neglected among demented older residents in LTC settings. The goals of this study were to determine detection rates of delirium and delirium symptoms by nurses among elderly residents with dementia and to identify factors associated with undetected cases of delirium.</p> <p>Methods</p> <p>In this prospective study (N = 156), nurse ratings of delirium were compared to researcher ratings of delirium. This procedure was repeated for 6 delirium symptoms. Sensitivity, specificity, positive and negative predictive values were computed. Logistic regressions were conducted to identify factors associated with delirium that is undetected by nurses.</p> <p>Results</p> <p>Despite a high prevalence of delirium in this cohort (71.5%), nurses were able to detect the delirium in only a minority of cases (13%). Of the 134 residents not identified by nurses as having delirium, only 29.9% of them were correctly classified. Detection rates for the 6 delirium symptoms varied between 39.1% and 58.1%, indicating an overall under-recognition of symptoms of delirium. Only the age of the residents (≥ 85 yrs) was associated with undetected delirium (OR: 4.1; 90% CI: [1.5–11.0]).</p> <p>Conclusion</p> <p>Detection of delirium is a major issue for nurses that clearly needs to be addressed. Strategies to improve recognition of delirium could result in a reduction of adverse outcomes for this very vulnerable population.</p

When to elicit feedback in dialogue: Towards a model based on the information needs of speakers

Buschmeier H, Kopp S. When to elicit feedback in dialogue: Towards a model based on the information needs of speakers. In: Proceedings of the 14th International Conference on Intelligent Virtual Agents. Boston, MA, USA; 2014: 71-80.Communicative feedback in dialogue is an important mechanism that helps interlocutors coordinate their interaction. Listeners pro-actively provide feedback when they think that it is important for the speaker to know their mental state, and speakers pro-actively seek listener feedback when they need information on whether a listener perceived, understood or accepted their message. This paper presents first steps towards a model for enabling attentive speaker agents to determine when to elicit feedback based on continuous assessment of their information needs about a user's listening state

Are transit trips symmetrical in time and space? Evidence from the Twin Cities

This study exploits electronic fare collection data to examine the symmetry of boardings and alightings along a transit route. The symmetry of boardings and alightings is arguably the most important concept in the estimation of travel distances such as average trip lengths and passenger miles from data from entry-only fare collection systems. The paper shows the ways such data can be used to examine the symmetry of boardings and alightings through travel patterns in spatial and temporal dimensions. A novel method for aggregating stops, especially for the nearest stops in the opposite direction, is used to compare boardings in one direction with alightings in the opposite direction. Spatially, the method allows examination of the characteristics of boardings and alightings in a spatial dimension. Temporally, the method examines whether a specific and symmetric passenger flow is observed between specific periods (e.g., between morning and afternoon peaks). A case study of the Minneapolis-Saint Paul, Minnesota, region is performed by using automatically collected data from Metro Transit. Automatic fare collection data reveal considerable variation in passenger flow between specific periods. The use of automated passenger-counting data shows this variation to be statistically significant when both temporal and spatial symmetry are examined on an individual day

Potential Role for Peptidylarginine Deiminase 2 (PAD2) in Citrullination of Canine Mammary Epithelial Cell Histones

Peptidylarginine Deiminases (PADs) convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25) shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus

"Those are your words, not mine!" Defence strategies for denying speaker commitment

Language Use in Past and Presen

Coilin Phosphomutants Disrupt Cajal Body Formation, Reduce Cell Proliferation and Produce a Distinct Coilin Degradation Product

Coilin is a nuclear phosphoprotein that accumulates in Cajal bodies (CBs). CBs participate in ribonucleoprotein and telomerase biogenesis, and are often found in cells with high transcriptional demands such as neuronal and cancer cells, but can also be observed less frequently in other cell types such as fibroblasts. Many proteins enriched within the CB are phosphorylated, but it is not clear what role this modification has on the activity of these proteins in the CB. Coilin is considered to be the CB marker protein and is essential for proper CB formation and composition in mammalian cells. In order to characterize the role of coilin phosphorylation on CB formation, we evaluated various coilin phosphomutants using transient expression. Additionally, we generated inducible coilin phosphomutant cell lines that, when used in combination with endogenous coilin knockdown, allow for the expression of the phosphomutants at physiological levels. Transient expression of all coilin phosphomutants except the phosphonull mutant (OFF) significantly reduces proliferation. Interestingly, a stable cell line induced to express the coilin S489D phosphomutant displays nucleolar accumulation of the mutant and generates a N-terminal degradation product; neither of which is observed upon transient expression. A N-terminal degradation product and nucleolar localization are also observed in a stable cell line induced to express a coilin phosphonull mutant (OFF). The nucleolar localization of the S489D and OFF coilin mutants observed in the stable cell lines is decreased when endogenous coilin is reduced. Furthermore, all the phosphomutant cells lines show a significant reduction in CB formation when compared to wild-type after endogenous coilin knockdown. Cell proliferation studies on these lines reveal that only wild-type coilin and the OFF mutant are sufficient to rescue the reduction in proliferation associated with endogenous coilin depletion. These results emphasize the role of coilin phosphorylation in the formation and activity of CBs

Involvement of Pinus taeda MYB1 and MYB8 in phenylpropanoid metabolism and secondary cell wall biogenesis: a comparative in planta analysis

The involvement of two R2R3-MYB genes from Pinus taeda L., PtMYB1 and PtMYB8, in phenylpropanoid metabolism and secondary cell wall biogenesis was investigated in planta. These pine MYBs were constitutively overexpressed (OE) in Picea glauca (Moench) Voss, used as a heterologous conifer expression system. Morphological, histological, chemical (lignin and soluble phenols), and transcriptional analyses, i.e. microarray and reverse transcription quantitative PCR (RT-qPCR) were used for extensive phenotyping of MYB-overexpressing spruce plantlets. Upon germination of somatic embryos, root growth was reduced in both transgenics. Enhanced lignin deposition was also a common feature but ectopic secondary cell wall deposition was more strongly associated with PtMYB8-OE. Microarray and RT-qPCR data showed that overexpression of each MYB led to an overlapping up-regulation of many genes encoding phenylpropanoid enzymes involved in lignin monomer synthesis, while misregulation of several cell wall-related genes and other MYB transcription factors was specifically associated with PtMYB8-OE. Together, the results suggest that MYB1 and MYB8 may be part of a conserved transcriptional network involved in secondary cell wall deposition in conifers