(−)-N,N′-Bis[(1S,2R,5S)-6,6-dimethyl-bicyclo­[3.1.1]heptan-2-ylmeth­yl]pyridine-2,6-dicarboxamide monohydrate

The title compound, C27H39N3O2·H2O, is a chiral pyridine-2,6-dicarboxamide derivative including cis-myrtanyl groups as amine substituents. The pyridine-2,6-dicarboxamide core approximates C 2 point symmetry and a solvent water mol­ecule lies on the pseudo-twofold axis. The water mol­ecule serves both as acceptor and donor for efficient hydrogen bonds involving N—H and C=O functional groups as donor and acceptor groups, respectively. As a result, each water mol­ecule in the crystal structure is tetra­hedrally bonded to three symmetry-related mol­ecules, forming a three-dimensional supra­molecular network. Such an arrangement is a common feature found in the majority of X-ray-characterized sym­metrically substituted pyridine-2,6-dicarboxamide derivatives

Effective user studies in computer graphics

User studies are a useful tool for researchers, allowing them to collect data on how users perceive, interact with and process different types of sensory information. If planned in advance, user experiments can be leveraged in every stage of a research project, from early design, prototyping and feature exploration to applied proofs of concept, passing through validation and data collection for model training. User studies can provide the researcher with different types of information depending on the chosen methodology: user performance metrics, surveys and interviews, field studies, physiological data, etc. Considering human perception and other cognitive processes is particularly important in computer graphics, where most research produces outputs whose ultimate purpose is to be seen or perceived by a human. Being able to measure in an objective and systematic way how the information we generate is integrated into the representational space humans create to situate themselves in the world means that researchers will have more information to implement optimal algorithms, tools and techniques. In this tutorial we will give an overview of good practices for user studies in computer graphics with a particular focus on virtual reality use cases. We will cover the basics on how to design, carry out and analyze good user studies, as well as different particularities to be taken into account in immersive environments.Peer ReviewedPostprint (published version

MRD detection in multiple myeloma: comparison between MSKCC 10-color single-tube and EuroFlow 8-color 2-tube methods

[EN] In patients with multiple myeloma, obtaining posttreatment minimal residual disease (MRD) negativity is associated with longer progression-free survival and overall survival. Here, we compared the diagnostic performance of a single 10-color tube with that of a EuroFlow 8-color 2-tube panel for MRD testing. Bone marrow samples from 41 multiple myeloma patients were tested in parallel using the 2 approaches. Compared with the sum of the cells from the EuroFlow two 8-color tubes, the Memorial Sloan Kettering Cancer Center (MSKCC) single 10-color tube had a slight reduction in total cell number with a mean ratio of 0.85 (range, 0.57-1.46; P < .05), likely attributable to permeabilization of the cells. Percent of plasma cells showed a high degree of concordance (r2 = 0.97) as did normal plasma cells (r2 = 0.96), consistent with no selective plasma cell loss. Importantly, concordant measurement of residual disease burden was seen with abnormal plasma cells (r2 = 0.97). The overall concordance between the 2 tests was 98%. In 1 case, there was a discrepancy near the limit of detection of both tests in favor of the slightly greater theoretical sensitivity of the EuroFlow 8-color 2-tube panel (analytical sensitivity limit of MSKCC single 10-color tube: 6 cells in 1 million with at least 3 million cell acquisitions; EuroFlow 8-color 2-tube panel: 2 cells in 1 million with the recommended 10 million cell acquisitions)

Callose depositionin plasmodesmata and viroid invasion of the shoot apical meristem

Research in Ricardo Flores laboratory is currently supported by the Spanish Ministerio de Economía y Competitividad (grant BFU2014-56812-P).Flores Pedauye, R. (2016). Callose depositionin plasmodesmata and viroid invasion of the shoot apical meristem. Frontiers in Microbiology. 7:1-3. https://doi.org/10.3389/fmicb.2016.00052S137Adkar-Purushothama, C. R., Brosseau, C., Giguère, T., Sano, T., Moffett, P., & Perreault, J.-P. (2015). Small RNA Derived from the Virulence Modulating Region of the Potato spindle tuber viroid Silences callose synthase Genes of Tomato Plants. The Plant Cell, 27(8), 2178-2194. doi:10.1105/tpc.15.00523Ding, B., Kwon, M.-O., Hammond, R., & Owens, R. (1997). Cell-to-cell movement of potato spindle tuber viroid. The Plant Journal, 12(4), 931-936. doi:10.1046/j.1365-313x.1997.12040931.xDi Serio, F., Martinez de Alba, A.-E., Navarro, B., Gisel, A., & Flores, R. (2009). RNA-Dependent RNA Polymerase 6 Delays Accumulation and Precludes Meristem Invasion of a Viroid That Replicates in the Nucleus. Journal of Virology, 84(5), 2477-2489. doi:10.1128/jvi.02336-09Flores, R., Minoia, S., Carbonell, A., Gisel, A., Delgado, S., López-Carrasco, A., … Di Serio, F. (2015). Viroids, the simplest RNA replicons: How they manipulate their hosts for being propagated and how their hosts react for containing the infection. Virus Research, 209, 136-145. doi:10.1016/j.virusres.2015.02.027Iglesias, V. A., & Meins, F. (2000). Movement of plant viruses is delayed in a beta-1,3-glucanase-deficient mutant showing a reduced plasmodesmatal size exclusion limit and enhanced callose deposition. The Plant Journal, 21(2), 157-166. doi:10.1046/j.1365-313x.2000.00658.xMatsushita, Y., Usugi, T., & Tsuda, S. (2011). Distribution of tomato chlorotic dwarf viroid in floral organs of tomato. European Journal of Plant Pathology, 130(4), 441-447. doi:10.1007/s10658-011-9766-6Qi, Y., & Ding, B. (2003). Inhibition of Cell Growth and Shoot Development by a Specific Nucleotide Sequence in a Noncoding Viroid RNA. The Plant Cell, 15(6), 1360-1374. doi:10.1105/tpc.011585Rodio, M.-E., Delgado, S., De Stradis, A., Gómez, M.-D., Flores, R., & Di Serio, F. (2007). A Viroid RNA with a Specific Structural Motif Inhibits Chloroplast Development. The Plant Cell, 19(11), 3610-3626. doi:10.1105/tpc.106.049775Xu, X. M., & Jackson, D. (2010). Lights at the end of the tunnel: new views of plasmodesmal structure and function. Current Opinion in Plant Biology, 13(6), 684-692. doi:10.1016/j.pbi.2010.09.003Zhang, Z., Lee, Y., Spetz, C., Clarke, J. L., Wang, Q., & Blystad, D.-R. (2014). Invasion of shoot apical meristems by Chrysanthemum stunt viroid differs among Argyranthemum cultivars. Frontiers in Plant Science, 6. doi:10.3389/fpls.2015.00053Zhu, Y., Green, L., Woo, Y.-M., Owens, R., & Ding, B. (2001). Cellular Basis of Potato Spindle Tuber Viroid Systemic Movement. Virology, 279(1), 69-77. doi:10.1006/viro.2000.072

Hybrid-organic-inorganic anatase as a bifunctional catalyst for enhanced production of HMF from glucose in water

Herein, we report a synthetic route for the preparation of hybrid-organic-inorganic anatase (hybrid-TiO2) via a facile hydrothermal synthesis method employing citric acid. The synthetic approach results in a high surface area nanocrystalline anatase polymorph of TiO2. The uncalcined hybrid-TiO2 is directly studied here as the catalyst for the conversion of glucose into HMF. In the presence of the hybrid-TiO2, HMF yields up to 45% at glucose conversions up to 75% were achieved in water at 130 oC in a monophasic batch reactor. As identified by Ti K-edge XANES, hybrid-TiO2 contains a large fraction of five-fold coordinatively unsaturated Ti(IV) sites, which act as the Lewis acid catalyst for the conversion of glucose into fructose. As citric acid is anchored in the structure of hybrid-TiO2, carboxylate groups seem to catalyze the sequential conversion of fructose into HMF. The fate of citric acid bounded to anatase and the Ti(IV) Lewis acid sites throughout recycling experiments is also investigated. In a broader context, the contribution outlines the importance of hydrothermal synthesis for the creation of water-resistant Lewis acid sites for the conversion of sugars. Most importantly, the utilization of the hybrid-TiO2 with no calcination step contributes to dramatically decreasing the energy consumption in the catalyst preparation

Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodeling

The renin angiotensin system (RAS) is integral to cardiovascular physiology, however, dysregulation of this system largely contributes to the pathophysiology of cardiovascular disease (CVD). It is well established that angiotensin II (Ang II), the main effector of the RAS, engages the angiotensin type 1 receptor and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodeling of the heart and vasculature, ultimately leading to the development and progression of various CVDs including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centered on the actions of angiotensin converting enzyme 2 (ACE2) and the resultant production of angiotensin-(1-7) (Ang-(1-7) from Ang II, antagonizes the actions of Ang II via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9), has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. This review will discuss the role of the counter-regulatory RAS peptides, Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodeling of the heart and vasculature

Trans-cleaving hammerhead ribozymes with tertiary stabilizing motifs: in vitro and in vivo activity against a structured viroid RNA

Trans-cleaving hammerheads with discontinuous or extended stem I and with tertiary stabilizing motifs (TSMs) have been tested previously against short RNA substrates in vitro at low Mg2+ concentration. However, the potential of these ribozymes for targeting longer and structured RNAs in vitro and in vivo has not been examined. Here, we report the in vitro cleavage of short RNAs and of a 464-nt highly structured RNA from potato spindle tuber viroid (PSTVd) by hammerheads with discontinuous and extended formats at submillimolar Mg2+. Under these conditions, hammerheads derived from eggplant latent viroid and peach latent mosaic viroid (PLMVd) with discontinuous and extended formats, respectively, where the most active. Furthermore, a PLMVd-derived hammerhead with natural TSMs showed activity in vivo against the same long substrate and interfered with systemic PSTVd infection, thus reinforcing the idea that this class of ribozymes has potential to control pathogenic RNA replicons

A comprehensive survey of the analytical, numerical and experimental methodologies for dynamics of multibody mechanical systems with clearance or imperfect joints

"Available online 19 December 2017"A comprehensive survey of the literature of the most relevant analytical, numerical, and experimental approaches for the kinematic and dynamic analyses of multibody mechanical systems with clearance joints is presented in this review. Both dry and lubricated clearance joints are addressed here, and an effort is made to include a large number of research works in this particular field, which have been published since the 1960′s. First, the most frequently utilized methods for modeling planar and spatial multibody mechanical systems with clearance joints are analyzed, and compared. Other important phenomena commonly associated with clearance joint models, such as wear, non-smooth behavior, optimization and control, chaos, and uncertainty and links’ flexibility, are then discussed. The main assumptions procedures and conclusions for the different methodologies are also examined and compared. Finally, future developments and new applications of clearance joint modeling and analysis are highlighted.This research was supported in part by the China 111 Project (B16003) and the National Natural Science Foundation of China under Grants 11290151, 11472042 and 11221202. The work was also supported by the Portuguese Foundation for Science and Technology with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941.info:eu-repo/semantics/publishedVersio

p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors

Homology between p63 and p53 has suggested that these proteins might function similarly. However, the majority of data from human tumors have not supported a similar role for p63 in tumor suppression. To investigate this issue, we studied spontaneous tumorigenesis in p63+/- mice in both WT and p53-compromised backgrounds. We found that p63+/- mice were not tumor prone and mice heterozygous for both p63 and p53 had fewer tumors than p53+/- mice. The rare tumors that developed in mice with compromised p63 were also distinct from those of p53+/- mice. Furthermore, p63+/- mice were not prone to chemically induced tumorigenesis, and p63 expression was maintained in carcinomas. These findings demonstrate that, in agreement with data from human tumors, p63 plays a markedly different biological role in cancer than p53