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Supplementary Data from A Proof-of-Principle Clinical Trial of Bexarotene in Patients with Non–Small Cell Lung Cancer

Purpose: Bexarotene is a rexinoid (selective retinoid X receptor agonist) that affects proliferation, differentiation, and apoptosis in preclinical studies. The relationship between bexarotene levels and biomarker changes in tumor tissues has not been previously studied.Experimental Design: BEAS-2B human bronchial epithelial (HBE) cells, retinoid-resistant BEAS-2B-R1 cells, A427, H226, and H358 lung cancer cells were treated with bexarotene. Proliferation and biomarker expression were assessed. In a proof-of-principle clinical trial, bexarotene tumor tissue levels and intratumoral pharmacodynamic effects were assessed in patients with stages I to II non–small cell lung cancer. Bexarotene (300 mg/m2/day) was administered p.o. for 7 to 9 days before resection.Results: Bexarotene-induced dosage-dependent repression of growth, cyclin D1, cyclin D3, total epidermal growth factor receptor (EGFR), and phospho-EGFR expression in BEAS-2B, BEAS-2B-R1, A427, and H358, but not H226 cells. Twelve patients were enrolled, and 10 were evaluable. Bexarotene treatment was well tolerated. There was nonlinear correlation between plasma and tumor bexarotene concentrations (r2 = 0.77). Biomarker changes in tumors were observed: repression of cyclin D1, total EGFR and proliferation in one case; repression of cyclin D3, total and phospho-EGFR in another. The cases with multiple biomarker changes had high tumor bexarotene (107-159 ng/g). A single biomarker change was detected in one case with low tumor bexarotene.Conclusion: Bexarotene represses proliferation and biomarker expression in responsive, but not resistant HBE and lung cancer cells. Similar biomarker changes occur in lung tumors when therapeutic intratumoral bexarotene levels are achieved. This proof-of-principle trial approach is useful to uncover pharmacodynamic mechanisms in vivo and relate these to intratumoral pharmacokinetic effects.

The design of hybrid nucleic acid nanomaterials capitalizes on the partitioning of architectural and functional roles between structurally diverse RNA modules and chemically robust DNA components. Selecting optimal combinations of RNA and DNA building blocks is the key to preparing stable polygonal RNA-DNA hybrid nanoshapes. Here, we outline a simple screening strategy by gel electrophoresis under native folding conditions to identify combinations of RNA and DNA modules that self-assemble to robust polygonal hybrid nanoshapes. As a proof of concept, we outline the preparation of RNA-DNA hybrid nanoshapes containing a set of different RNA architectural joints, including internal loop motifs and three-way junction (3WJ) folds. For each hybrid nanoshape, we demonstrate the selection process used to identify optimal DNA modules from a library of DNA connectors. The simple screening strategy outlined here provides a general robust method to identify and prepare RNA-DNA hybrid nanoshapes from diverse libraries of discrete nucleic acid building blocks.

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA–DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein–RNA–DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.

INTRODUCTION: ST segment elevation myocardial infarction is a common reason for out-of-hospital cardiac arrest in adult patients. The surveillance of the ST segment in the electrocardiogram is limited to visual presentation. However, the ST segment can change during the course of treatment. If ST elevation is present immediate coronary revascularization is needed, therefore detecting ST elevation changes the treatment fundamentally. Sonification of the ST segment is a new method which enables the emergency team to detect intermediate changes of the ST segment.; MATERIAL AND METHODS: We have chosen two sonification designs which were introduced to two groups, medical students and computer science students. Twenty-one participants took part in the study. The sonification was designed for evaluation of the ST segment. The user was supposed to become empowered to distinguish between no, medium-low, medium-high or extreme ST elevation by listening to the sonification. The two groups were asked to evaluate the sounds for possible ST elevation as well as for aesthetics and usability. In a second study twenty-five medical students were taking part in a medical scenario in which sonification was played during a simulated case. The patient was suffering from a myocardial infarction, ST elevation was transient and sonification sounds were changing appropriately. The students were supposed to detect these changes and act accordingly by modifying the treatment.; RESULTS: Both groups were able to classify ST segment elevation by listening to the sonification samples. The higher the ST segment, the better was the detection rate overall. In all of the three categories (pleasantness, informativeness and long-term listening) the Water Ambience sonification was rated higher compared to the Polarity sonification. Moreover, in the two groups that took part in the study, we found a significant difference when comparing classification performance using both sonification designs. For the group of medical students as t(20) = 4.31, p = 3.44 * 10-4, p < 0.01 and for the computer science students as t(19) = 3.40, p = 9.39 * 10-6, p < 0.01. In the simulated medical scenario participants indicated that 96% detected the ST elevation. 60% stated that sonification played a role whereas for 32% it did not play a role for the detection of ST elevation.; CONCLUSIONS: Sonification has the potential to play an important role as a new supporting tool for the surveillance of the ST segment during the care of patients with suspicion of myocardial infarction. It can be helpful to differentiate between ST segment elevation myocardial infarction and non-ST segment myocardial infarction especially if ST elevation is transient. Furthermore, sonification is viewed as pleasant to listen to and might not contribute to alarm fatigue. Copyright © 2022 Elsevier Inc. All rights reserved.

Elaphoglossum multisquamosum Bonap. in Notes Pt��ridol. 1: 67. 1915 (Fig. 2). ��� Elaphoglossum poolii var. multisquamosum (Bonap.) Tardieu in Humbert, Fl. Madagascar 5(2): 54. 1960. Lectotypus (hic designatus): MADAGASCAR. Reg. Analamanga [Prov. Antananarivo]: �� Halfy ��, Ilafy, [18��51"S 47 ��33,5"E], I.1906, D���Alleizette 42 (P [P00466228]!). Syntypus: MADAGASCAR. Reg. Analamanga [Prov. Antananarivo]: Ambohimanga, [18��45'S 47 ��33'E], 12.VI.1905, D���Alleizette 167 (P [P00466229, P00466230]!). Rhizomes courtement rampant parfois ascendant, 3,5��� 6,5 mm de diam��tre, ramifi��s, plus ou moins glutineux, dens��ment couverts d�����cailles au moins �� l���apex (Fig. 2I, L); ��cailles du rhizome peu �� enti��rement appliqu��es (et alors non distinctes les unes des autres), ov��es �� lanc��ol��es, 2,5��� 6(���10) �� 1���2 mm, la plupart brun clair mat, scarieuses, bases cord��es, apex cun��iformes �� att��nu��s, marges subenti��res avec des glandes sessiles et des cils courts (Frondes st��riles dress��es �� ��tal��es (Fig. 2D, E), ins��r��es sur au moins deux rangs peu distincts, distantes de moins de 5 mm, longues de 8��� 47 cm. P��tioles longs de 2���16 cm, repr��sentant g��n��ralement moins de la moiti�� de la longueur de la fronde, 0,5���1,5 mm de diam��tre, dens��ment couverts d�����cailles; ��cailles du p��tiole dress��es en toutes directions, lanc��ol��es, 2���6 �� 1���1,5 mm, roux clair mat, translucides, scarieuses, bases pseudo-pelt��es, apex cun��iformes �� acumin��s, marges sub-enti��res �� cili��es avec plus de 10 cils de chaque c��t��, courts (Limbe st��rile ��troitement elliptique ou oblanc��ol��, rarement lin��aire, 6���32 �� 1,3���4 cm, base cun��iforme �� att��nu��e, apex arrondi ou aigu, texture chartac��e �� coriace, les deux faces et les marges dens��ment ��cailleuses jusqu����� masquer parfois la face inf��rieure du limbe, face sup��rieure glabrescente (Fig. 2G���H); ��cailles du limbe imbriqu��es, ov��es �� lanc��ol��es, 1,5���3 �� 0,5���1 mm, rousses, souvent blanches sur la face sup��rieure du limbe, translucides, scarieuses, base cord��e �� h��miinfundibuliforme, apex obtus, arrondi ou cun��iforme, marges cili��es avec 10���15 cils aciculaires de chaque c��t��, souvent aussi longs que la largeur du corps de l�����caille (Fig. 2A); nervure m��diane pro��minente et arrondie sur la face inf��rieure, aplatie sur la face sup��rieure; nervures lat��rales parfois l��g��rement pro��minentes sur la face inf��rieure, simples ou 1���2-bifurqu��es, libres jusqu����� leur apex. Frondes fertiles plus longues que les st��riles, atteignant 60 cm, plus ��troites Distribution et ��cologie. ��� Elaphoglossum multisquamosum est pr��sent �� Madagascar au centre et au sud (et une r��colte �� Mahajanga), dans les domaines phytog��ographiques du Centre et de l���Ouest (HUMBERT, 1955), �� 100���2650 m d���altitude. Elle pousse dans la for��t sempervirente r��siduelle, le long des cours d���eau et dans les ravins o�� elle est peu fr��quente. C���est une plante ��pilithe ou terrestre, rarement ��piphyte. A la R��union, une seule station est connue, dans le cirque de Cilaos, �� plus de 1950 m, au niveau de la Plaine aux Fraises sous le rempart des trois Salazes. La plante s���y d��veloppe sur une falaise rocheuse avec d���autres herbac��es communes des prairies d���altitude, dans une zone de transition entre ��for��t de bois de couleurs d���altitude�� (Dombeya spp.) et v��g��tation ��rico��de (Erica spp.). Selon la typologie des habitats ��Corine Biotope�� (STRASBERG et al., 2010), le code habitat [49.214] de la station est qualifi�� de for��t semi-s��che de transition vers l�����tage m��sotherme des cirques et grandes vall��es sous le vent, ��tage �� Dombeya spp. A La R��union, l���esp��ce pourrait ��tre menac��e par la pr��sence de l���exotique envahissante Erigeron karvinskianus DC. (C. Lavergne, comm. pers.). Notes. ��� Les trois sp��cimens types (deux r��coltes) repr��sentent tous la m��me esp��ce, Elaphoglossum multisquamosum, et deux portent la mention ��Original�� de la main de Bonaparte, auteur de l���esp��ce. Nous avons choisi comme lectotype le sp��cimen [P00466228] avec deux plantes fertiles. Elaphoglossum multisquamosum est polymorphe �� Madagascar, avec deux morphologies extr��mes, la premi��re �� rhizome tr��s glutineux couvert d�����cailles appliqu��es et la seconde �� rhizome peu glutineux couvert d�����cailles plut��t dress��es dont certaines pr��sentent une marge marron brillant; cependant, les interm��diaires entre ces morphologies existent. La forme de l���apex du limbe et la taille des ��cailles du limbe sont aussi variables. Sp��cimens observ��s. ��� MADAGASCAR. Reg. Alaotra-Mangoro [Prov. Toamasina]: Analanomby, for��t du N du pays Sihanaka, 2.IX.1937, Jard. Bot. 3016 (P). Reg. Amoron���i Mania Prov. Fianarantsoa]: au N d���Ambatoandrano, 7.II.2001, Andriamihajarivo 45 (P); env. d���Ambatofinandrahana, 21.II.1938, Decary 13200 (P); montagnes �� l���W d���Itremo (W Betsileo), 17.I���22.IV.1955, Humbert 28227 p.p. (P [P 00915740, P 01556626]); juste �� l���E du col d���Itremo, 26.XI.1993, Labat 2439 (P); Fiadanana, Ilaka, Ambositra, 20.III.1960, Peltier 2145 (P); Fianarantsoa, Mania, IV.1919, Perrier de la B��thie 12575 (P). Analamanga [Prov. Antananarivo]: Mandraka, III.1961, Bosser 15215 p.p. (P [P00611253]); Ambohidempona, 26.VII.1911, Colin s.n. (P); Vodivato, montagne, 5.XI.1946, Cours 3060 (P); Mandraka, VIII.1906, D���Alleizette 213 (P); Antananarivo, IX.1921, Decary s.n. (P00611275); Ambohimanga, 27.III.1921, Decary 489 (P); Tananarive (foss��s du Fort Voyron), 11.III.1928, Decary 6168 (P); Andramasina, 30 km SSE Tananarive, 17.II.1960, Leandri 3088 (P); Ambohimanga, �� 20 km de Tananarive, 1919, Raharijaona 9 (P); RS d���Ambohitantely, 8.XII.1997, Rakotondrainibe 4445 (P); for��t de la Mandraka, 17.VIII.1906, Rotereau s.n. (P [2 planches]); Tananarive, 1.IV���30.IV.1915, Waterlot s.n. (P [6 planches]). Reg. Androy [Prov. Toliara]: Ambohibe, s.d., Decary 4217 (P). Reg. Anosy [Prov. Toliara]: Mt. Itrafanaomby (Ankazondrano) et ses contreforts SW (Haut Mandrare), XII.1933, Humbert 13521 (P); massif de l���Andohahela (SE), I.1934, Humbert 13589 (P); R.N.I. d���Andohahela, versant E et sommet du Trafon���omby, 23.XI.1995, Rakotondrainibe 3186 (P [P00067309]); ibid. loco, versant du Trafon���omby, 28.XI.1995, Rakotondrainibe 3216 (P). Reg. Boeny [Prov. Mahajanga]: Mt Namiaka (Boeny E), VIII.1905, Perrier de la B��thie 7454 (P). Reg. Bongolova [Prov. Antananarivo]: for��t de Bongolava (100 km W Tsironomandidy vers Morafenobe), 17.VII.1974, Cremers 3251 (P); Mt Tsitondriana, 15.IV.1941, Jard. Bot. 4757 (P). Reg. Ihorombe [Prov. Fianarantsoa]: Andringitra, distr. Ambalavao autour du lieu-dit Anosibe, 9.V.1957, Cours 5172 (P); Andringitra, distr. Ambalavao au pied du Tsoraha, 10.V.1957, Cours 5179 (P); Pic d���Ivohibe, 23.IX.1926, Decary 5288 (P); Andringitra AP, II.1995, Goodman s.n. (P); Pic Boby, s.d., Homolle 1185 (P); Pic d���Ivohibe (Bara), 5.XI.1924, Humbert 3276 (P); ibid. loco, vall��e de la Riambava et de l���Antsifotra, 27.XII.1924, Humbert 3776 (P); massif du Kalambatitra (centre-sud), Mt. Analatsitendrika, XII.1933, Humbert 11931 (P); Pic d���Ivohibe, haute vall��e de l���Andranomainty, 23.IV.2005, Janssen 2810 p.p. (P [P00590873]); Ambalavao, Anara, R��serve d���Anja, 22.III.2006, Labat 3662 p.p. (P [P00533707]); massif d���Andringitra, IX.1911, Perrier de la B��thie 7563 (P); ibid. loco, III.1921, Perrier de la B��thie 13697 (P); RS d���Ivohibe, �� 6,5 km �� l���ESE du village d���Ivohibe, pr��s de la source de la riv. Andranomainty, 25.X.1997, Rakotondrainibe 4241 (P); ibid. loco, 25.X.1997, Rakotondrainibe 4243 (P); PN de l���Andringitra, for��t de Riambavy, 17.XI.2004, Rouhan 439 (P), Rouhan 443 (P); ibid. loco, for��t de Ramiova, 17.XI.2004, Rouhan 449 (P), Rouhan 450 (P); ibid. loco, for��t de Anjavidilava, 19.XI.2004, Rouhan 471 (P), Rouhan 472 (P), Rouhan 473 (P), Rouhan 474 (P); RS du Pic d���Ivohibe, versant S au S du sommet, for��t dite du ��plateau du Pic��, 16.XI.2011, Rouhan 1397 (P). Reg. Itasy [Prov. Antananarivo]: Ankaratra, Antsahapandrano, 10.II.1942, Decary 17638 (P); Massif de l���Ankaratra, XII.1913, Perrier de la B��thie 7613 (P); Ankaratra, IV.1980, Proisy 225 (P); for��t de Manjakatompo, versant E de l���Ankaratra, VII.1953, Service Forestier 58 (P). Reg. Vakinankaratra [Prov. Antananarivo]: summit Ibity, 5.II.2003, Birkinshaw 1193 (P); Manjakatompo, versant SE, 10.XI.1983, Rakotondrainibe 766 (P); sur la cr��te du Mt Ibity, 21.XI.1912, Viguier 1453 (P); massif du Vakinankaratra, 25.XI.1912, Viguier 1615bis (P); ibid. loco, coteaux bois��s pr��s de Tsinjoarivo, 30.XI.1912, Viguier 1884 (P). Reg. Vatovavy-Fitovinany [Prov. Fianarantsoa]: Ambohimanga Sud, V.1980, Proisy 249 (P). Sine loco: 19.IX.1917, D���Alleizette 212m p.p. (P [P00611279]); s.d., Homolle 1243 (P). LA R��UNION: Cirque de Cilaos, plaine aux Fraises sous l���arr��te des Salazes, 29.V.2010, Robert 1335 (P, herbier priv�� Y. Robert)., Published as part of Robert, Yannis, Thomas, Hermann, Tamon, Jean Maurice & Rouhan, Germinal, 2021, D��couverte �� La R��union de Elaphoglossum multisquamosum (Dryopteridaceae), connue jusqu'alors comme end��mique de Madagascar, pp. 99-104 in Candollea 76 (1) on pages 102-103, DOI: 10.15553/c2021v761a10, http://zenodo.org/record/5683845, {"references":["HUMBERT, H. (1955). Les territoires phytogeographiques de Madagascar. Annee Biol. 31: 439 - 448.","STRASBERG, D., J. DUPONT & J. - C. RAMEAU (2010). Typologie des milieux naturels et des habitats de La Reunion, 2000. DIREN Reunion / Universite de la Reunion. [Revision de fevrier 2010 par F. Picot & M. Saliman]."]}

International audience; A species of the fern genus Elaphoglossum Schott ex J. Sm. (Dryopteridaceae) has been discovered in La Réunion. It is ascribed to Elaphoglossum multisquamosum Bonap., described and known so far as endemic to Madagascar. Taking advantage of this new record, Elaphoglossum multisquamosum is reinstated as a species distinct from the Malagasy endemic Elaphoglossum poolii (Baker) Christ. Morphologically close to Elaphoglossum poolii that is often observed in sympatry in Madagascar, Elaphoglossum multisquamosum has often been treated as a variety of Elaphoglossum poolii or even placed in synonymy of the latter species. We provide a novel, fully detailed description of Elaphoglossum multisquamosum, all critical characters supporting it as distinct from Elaphoglossum poolii, and a comparative map of distribution for the two species in Madagascar and La Réunion. Finally, the name Elaphoglossum multisquamosum is lectotypified.; Une espèce de fougère du genre Elaphoglossum Schott ex J. Sm. (Dryopteridaceae) a été découverte à La Réunion et identifiéecomme Elaphoglossum multisquamosum Bonap., décrite et connue jusqu’alors comme endémique de Madagascar.A l’occasion de cette découverte, Elaphoglossum multisquamosum est confirmée comme une espèce distincte de l’endémiquemalgache Elaphoglossum poolii (Baker) Christ. Morphologiquement proche de Elaphoglossum poolii qui se trouvesouvent en sympatrie à Madagascar, Elaphoglossum multisquamosum a ainsi souvent été considérée au rang variétal deElaphoglossum poolii ou même placée en synonymie de cette dernière. Nous fournissons une nouvelle description morphologiquedétaillée de Elaphoglossum multisquamosum, tous les caractères nécessaires la soutenant comme distincte deElaphoglossum poolii, ainsi qu’une carte de répartition comparative pour les deux espèces à Madagascar et à La Réunion.Enfin, le nom Elaphoglossum multisquamosum est lectotypifié.

Mass-selective threshold photoelectron spectroscopy in the gas phase was employed to characterize the dialkynyl triplet carbenes pentadiynylidene (HC5H), methylpentadiynylidene (MeC5H), and dimethylpentadiynylidene (MeC5Me). Diazo compounds were employed as precursors to generate the carbenes by flash pyrolysis. The R1-C5-R2 carbon chains were photoionized by vacuum ultraviolet (VUV) synchrotron radiation in photoelectron photoion coincidence (PEPICO) experiments. High-level ab initio computations were carried out to support the interpretation of the experiments. For the unsubstituted pentadiynylidene (R1 = R2 = H) the recorded spectrum yields an adiabatic ionization energy (IEad) of 8.36 ± 0.03 eV. In addition, a second carbene isomer, 3-(didehydrovinylidene)cyclopropene, with a singlet electronic ground state, was identified in the spectrum based on the IEad of 8.60 ± 0.03 eV and Franck-Condon simulations. We found that multireference computations are required to reliably calculate the IEad for this molecule. CASPT2 computations predicted an IEad = 8.55 eV, while coupled-cluster computations significantly overestimate the IE. The cyclic isomer is most likely formed from another isomer of the precursor present in the sample. Stepwise methyl-substitution of the carbene leads to a reduction of the IE to 7.77 ± 0.04 eV for methylpentadiynylidene and 7.27 ± 0.06 eV for dimethylpentadiynylidene. The photoionization and dissociative photoionization of the precursors is investigated as well.

Vector-borne diseases cause more than 1 million deaths annually. The research into new medicines is urgent, especially as there is currently no specific treatment. In this study, the authors have selected 64 endemic plants from the Mascarene Islands based on their endemism, their medicinal use and their registration in the French Pharmacopeia to evaluate the antiplasmodial, anti-chikungunya and antioxidant activities. The list of these 64 plants including their local name, population, data of collection and voucher number are available in the Supporting Information. Forty active extracts were identified from the 38 species: 22 responded positively to the antiplasmodial activity, 8 to the anti-chikungunya activity and 8 to the antioxidant activity. Six plants demonstrated high antiplasmodial activity (concentration inhibiting 50% of parasitic growth (IC50) 2000 µM of Trolox equivalent per mg/mL of extract: Bertiera borbonica, Erythroxylon laurifolium, Erythroxylon sideroxyloides, I. ammoxylum, P. borbonica, Scolopia heterophylla, Sophora denudata, and Terminalia bentzoe. Some data obtained tend to corroborate the reported traditional use of the plant, such as Z. heterophyllum (antiplasmodial), A. theiformis (anti-chikungunya), and E. laurifolium (antioxidant). ispartof: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS vol:52 issue:5 pages:622-628 ispartof: location:Netherlands status: published

International audience; Dodonea viscosa(L.) Jacq from Reunion Island (Indian Ocean) was investigated for itsleaf essential oil composition. The plant was extracted by hydrodistillation and its essential oilanalysed by gas chromatography coupled to mass spectrometry. This study revealed that oxygenatednor-diterpenes and diterpenes were one of the major chemical classes (>50%) mainly consisting ofthree modified cyclopropylclerodanes containing a bicyclo[5.4.0]undecane ring system: one newfuranoid norditerpene, dodovisate C, and two furanoid diterpenes, the known methyl dodovisate Aand the new methyl iso-dodovisate A. These three compounds were isolated by liquid chromatographyand their structures established on the basis of spectroscopic studies. The absolute configurationof dodovisate C was elucidated through a joint experimental and theoretical (B3LYP/6-311+G(d,p))electronic circular dichroism study. The relative configurations of methyl dodovisate A and methyliso-dodovisate A were determined using linear regressions of theoretical chemical shifts versusexperimental values with the (B3LYP/6-311+G(d,p)) method.

Background: International guidelines recommend psychosocial care for children and adolescents with type 1 diabetes. Objective: To assess psychological care in children and adolescents with type 1 diabetes in a real-world setting and to evaluate associations with metabolic outcome. Methods: Delivery of psychological care, HbA1c, and rates of severe hypoglycemia and diabetic ketoacidosis (DKA) in children and adolescents with type 1 diabetes from 199 diabetes care centers participating in the German diabetes survey (DPV) were analyzed. Results: Overall, 12 326 out of 31 861 children with type 1 diabetes were supported by short-term or continued psychological care (CPC). Children with psychological care had higher HbA1c (8.0% vs 7.7%, P

This paper presents the design and evaluation of four sonification methods to support monitoring and diagnosis in Electrocardiography (ECG). In particular we focus on an ECG abnormality called ST-elevation which is an important indicator of a myocardial infarction. Since myocardial infarction represents a life-threatening condition it is of essential value to detect an ST-elevation as early as possible. As part of the evaluated sound designs, we propose two novel sonifications: (i) Polarity sonification, a continuous parameter-mapping sonification using a formant synthesizer and (ii) Stethoscope sonification, a combination of the ECG signal and a stethoscope recording. The other two designs, (iii) the water ambience sonification and the (iv) morph sonification, were presented in our previous work about ECG sonification (Aldana Blanco AL, Steffen G, Thomas H (2016) In: Proceedings of Interactive Sonification Workshop (ISon). Bielefeld, Germany). The study evaluates three components across the proposed sonifications (1) detection performance, meaning if participants are able to detect a transition from healthy to unhealthy states, (2) classification accuracy, that evaluates if participants can accurately classify the severity of the pathology, and (3) aesthetics and usability (pleasantness, informativeness and long-term listening). The study results show that the polarity design had the highest accuracy rates in the detection task whereas the stethoscope sonification obtained the better score in the classification assignment. Concerning aesthetics, the water ambience sonification was regarded as the most pleasant. Furthermore, we found a significant difference between sound/music experts and non-experts in terms of the error rates obtained in the detection task using the morph sonification and also in the classification task using the stethoscope sonification. Overall, the group of experts obtained lower error rates than the group of non-experts, which means that further training could improve accuracy rates and, particularly for designs that rely mainly on pitch variations, additional training is needed in the non-experts group.

The use of Personal Voice Assistants (PVAs)1 such as Alexa and the Google Assistant is rising steadily, but there is a lack of research investigating common issues and requests of PVAs in the context of smart home control. We address this research question with an online survey (n = 65), using a qualitative evaluation of users’ problems and improvement requests. Our analysis leads to a partly hierarchic clustering of issues & recommendations for interaction capabilities of PVAs into seven basic categories, allowing us in turn to derive implications and to condense them into design guidelines for future Human-Agent Interaction (HAI) with PVAs. Specifically, we formulate and elaborate the concepts Authentication & Authorization, Activity-Based Interaction, Situated Dialogue, and Explainability & Transparency as key topics for making progress towards smooth interaction with smart homes.

Comprehensive understanding of the structure–function relationship of RNA both in real time and at atomic level will have a profound impact in advancing our understanding of RNA functions in biology. Here, we describe the first example of a multifunctional nucleoside probe, containing a conformation‐sensitive fluorophore and an anomalous X‐ray diffraction label (5‐selenophene uracil), which enables the correlation of RNA conformation and recognition under equilibrium and in 3D. The probe incorporated into the bacterial ribosomal RNA decoding site, fluorescently reports antibiotic binding and provides diffraction information in determining the structure without distorting native RNA fold. Further, by comparing solution binding data and crystal structure, we gained insight on how the probe senses ligand‐induced conformational change in RNA. Taken together, our nucleoside probe represents a new class of biophysical tool that would complement available tools for functional RNA investigations.

CardioScope is a sonification/auditory augmentation tool intendedto support cardiac diagnosis and monitoring. It allows usersto record and visualize synchronized Electrocardiogram (ECG)and Phonocardiogram (PCG) signals, to sonify the electrical activityof the heart or to augment the sound produced by its mechanicalbehaviour. As first step towards a realtime-interactive auditoryaugmentation, we here propose an auditory augmentation methodusing amplitude modulation that allows users to accentuate specificsegments of the heart sound in order to make pathologicalsignals from the heart sound more salient. We present a set ofsound examples illustrating the proposed method, and discuss resultsof a preliminary qualitative test with two physicians who aredoing their residency in cardiology.

The largest area of intact vegetation in the Mascarene Archipelago is found on La Reunion Island. In 2007, a national park has been established where most protected habitats and rare species are targeted by some conservation actions. Invasions by exotic plants are the main threat to the biodiversity within this park and several management programs aim at controlling the main invasive alien plant species. For decades, inventories of alien species have been carrying out at La Reunion, constituting a large amount of data but these data never been synthetized, assembled and exploited to assess the level of invasion. Here, data from different organizations were combined to quantify the overall level of invasion by exotic plants island-wide. These data were extrapolated to grid cells of 250 x 250 m and categorized into four invasion categories ranging from intact to heavily invaded areas. Here, we present the spatial pattern of invasion on La Reunion Island. Only 12% of the island remain intact while 60%is moderately to heavily invaded. Inside the national park, more than 55% is lightly invaded or intact. We then discuss the invasion rate according to several factors: altitude, habitats, geomorphology, land cover and the presence of pathways or streams.

Biological invasions threaten biodiversity worldwide, especially on tropical islands such as Reunion Island. Here we present the results of a collaborative effort to map biodiversity priorities and to prioritise alien plant clearing. We first combined all existing data on habitats, threatened and endemic species and the distribution of alien plant species. Using expert-knowledge where necessary, we provide the first map of invasion level for the whole island. We developed a decision-making process using Zonation, a conservation-planning tool, to identify biodiversity conservation priorities. Conservation priority areas were selected to maximise biodiversity levels in areas lightly invaded. We then included criteria to identify priority areas for alien plant clearing based on clearing costs, accessibility and history of previous clearing programmes. Almost 40% of the remaining natural habitats on Reunion Island are moderately to heavily invaded. We identify 58,500 ha as conservation priority areas of which 30%are considered to be not invaded at all. We discuss how this will impact future alien plant clearing programmes and propose the basis for an integrated clearing and restoration plan for Reunion Island.

Every day, we rely on the information that is encoded in the auditory feedback of our physical interactions. With the goal to perceptually enhance those sound characteristics that are relevant to us -- especially within professional practices such as percussion and auscultation, we introduce the method of real-time Auditory Contrast Enhancement (ACE). The method is derived from algorithms for speech enhancement as well from the remarkable sound processing mechanisms of our ears. ACE is achieved by individual sharpening of spectral as well as temporal structures contained in a sound. It is designed for real-time application with low latency. The discussed examples illustrate that the proposed algorithms are able to significantly enhance spectral and temporal contrast. ### Sound examples and interaction examples #### **ACE of Impact Sounds** ##### **S1.0-xxx.wav** see article for further details.

Smart products not only provide novel functionalities, but also may establish new business models, markets, or distribution channels, strengthen relationships with consumers, and/or add smart remote services. While many technical obstacles of such products have already been overcome, the broad market dissemination of smart products still poses some vital managerial challenges for decision makers. In this paper, we outline the technical potential and future trends of smart consumer products, discuss economic challenges in four scopes, namely, preference-based new product development, market analysis, supply chain design, and industry development, and, in particular, we highlight research perspectives for management science in this promising field.

Self-induced aquatic propulsion is an effect of interaction of the limbs and water mass (LWI) which change the energy-density per volume and the momentum of water mass, simultaneously. The change of volumetric energy-density of water can be measured via pressure tap probes detecting static pressure of unsteady flow via pressure sensors. The data of elite breaststroke swimmers wearing gloves with pressure taps on both sides of the hands were presented as pressure difference per hand (p-diff) in real-time in a split screen video together with the hand action. The purpose of this preliminary study was to check a) the stability of the setup including the data collection under pool condition with various swimmers and b) to answer coaches’ questions concerning the relation of peak pdiff-data and hand action. Among others it is shown that p-diff(max) coincides with a) deepest hand penetration at the end of the inward sweep of the hands and b) max body acceleration during hand action, shortly before max body velocity occurs.

The function of RNA switches involved in the regulation of transcription and translation relies on their ability to adopt different, structurally well-defined states. A new class of ligand-responsive RNA switches, which we recently discovered in positive strand RNA viruses, are distinct from conventional riboswitches. The viral switches undergo large conformational changes in response to ligand binding while retaining the same secondary structure in their free and ligand-bound forms. Here, we describe FRET experiments to study folding and ligand binding of the viral RNA switches. In addition to reviewing previous approaches involving RNA model constructs which were directly conjugated with fluorescent dyes, we outline the design and application of new modular constructs for FRET experiments, in which dye labeling is achieved by hybridization of a core RNA switch module with universal DNA fluorescent probes. As an example, folding and ligand binding of the RNA switch from the internal ribosome entry site of hepatitis C virus is studied comparatively with conventional and modular FRET constructs.