An inhomogeneous toy-model of the quantum gravity with explicitly evolvable observables

An inhomogeneous (1+1)-dimensional model of the quantum gravity is considered. It is found, that this model corresponds to a string propagating against some curved background space. The quantization scheme including the Wheeler-DeWitt equation and the "particle on a sphere" type of the gauge condition is suggested. In the quantization scheme considered, the "problem of time" is solved by building of the quasi-Heisenberg operators acting in a space of solutions of the Wheeler-DeWitt equation and the normalization of the wave function corresponds to the Klein-Gordon type. To analyze the physical consequences of the scheme, a (1+1)-dimensional background space is considered for which a classical solution is found and quantized. The obtained estimations show the way to solution of the cosmological constant problem, which consists in compensation of the zero-point oscillations of the matter fields by the quantum oscillations of the scale factor. Along with such a compensation, a slow global evolution of a background corresponding to an universe expansion exists.Comment: 18 page

Malaria in rural Mozambique. Part I: Children attending the outpatient clinic

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers

B7-H3 (CD276) has emerged as a target for cancer immunotherapy by virtue of consistent expression in many malignancies, relative absence from healthy tissues, and an emerging role as a driver of tumor immune inhibition. Recent studies have reported B7-H3 to be a suitable target for chimeric antigen receptor-modified T cell (CAR-T) therapy using CARs constructed from established anti-B7-H3 antibodies converted into single-chain Fv format (scFv). We constructed and screened binders in an scFv library to generate a new anti-B7-H3 CAR-T with favorable properties. This allowed access to numerous specificities ready formatted for CAR evaluation. Selected anti-human B7-H3 scFvs were readily cloned into CAR-T and evaluated for anti-tumor reactivity in cytotoxicity, cytokine, and proliferation assays. Two binders with divergent complementarity determining regions were found to show optimal antigen-specific cytotoxicity and cytokine secretion. One binder in second-generation CD28-CD3ζ CAR format induced sustained in vitro proliferation on repeat antigen challenge. The lead candidate CAR-T also demonstrated in vivo activity in a resistant neuroblastoma model. An empirical approach to B7-H3 CAR-T discovery through screening of novel scFv sequences in CAR-T format has led to the identification of a new construct with sustained proliferative capacity warranting further evaluation

Predicting mental imagery based BCI performance from personality, cognitive profile and neurophysiological patterns

Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy— EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants’ BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants’ performance with a mean error of less than 3 points. This study determined how users’ profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user

Implant removal associated complications in children with limb fractures due to trauma

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Unusually thick dinosaur eggshell fragments from the Spanish Late Cretaceous

[EN] Fieldwork carried out recently in the southeastern branch of the Iberian Range (Valencia Province, Spain) has led to the collection of a large volume of dinosaur eggshell fragments of unusual thickness. These specimens, up to 4.9 mm thick, were recovered from palustrine grey marls of the upper Campanian-lower Maastrichtian Sierra Perenchiza Formation, which comprises a wetland paleoenvironment deposit. These eggshell fragments have a characteristic compactituberculate ornamentation, dinosauroid-spherulitic organisation, and exhibit a complex canaliculate respiratory system. The external tuberculate surface of the shell as well as the internal microstructure enable referral to Megaloolithus aff. siruguei, the most common megaloolithid oospecies known from the Iberian Peninsula and southern France. The biostratigraphic range of M. siruguei matches the temporal distribution of titanosaurid dinosaurs across the Iberian Range, tentatively considered to be potential producers.This work was supported by the Ministerio de Economia y Competitividad of Spain [Secretaria de Estado de Investigacion, Desarrollo e Innovacion, projects CGL2013-47521-P and CGL2014-53548-P]Company Rodríguez, J. (2017). Unusually thick dinosaur eggshell fragments from the Spanish Late Cretaceous. Historical Biology (Online). 31(2):203-210. https://doi.org/10.1080/08912963.2017.1357717S203210312Allain, R., & Suberbiola, X. P. (2003). Dinosaurs of France. Comptes Rendus Palevol, 2(1), 27-44. doi:10.1016/s1631-0683(03)00002-2Bravo, A. M., & Gaete, R. (2014). Titanosaur eggshells from the Tremp Formation (Upper Cretaceous, Southern Pyrenees, Spain). Historical Biology, 27(8), 1079-1089. doi:10.1080/08912963.2014.934231Canudo, J. I., Oms, O., Vila, B., Galobart, À., Fondevilla, V., Puértolas-Pascual, E., … Blanco, A. (2016). The upper Maastrichtian dinosaur fossil record from the southern Pyrenees and its contribution to the topic of the Cretaceous–Palaeogene mass extinction event. Cretaceous Research, 57, 540-551. doi:10.1016/j.cretres.2015.06.013Cruzado-Caballero, P., Ruiz-Omeñaca, J. I., Gaete, R., Riera, V., Oms, O., & Canudo, J. I. (2013). A new hadrosaurid dentary from the latest Maastrichtian of the Pyrenees (north Spain) and the high diversity of the duck-billed dinosaurs of the Ibero-Armorican Realm at the very end of the Cretaceous. Historical Biology, 26(5), 619-630. doi:10.1080/08912963.2013.822867Chiappe, L. M., Coria, R. A., Dingus, L., Jackson, F., Chinsamy, A., & Fox, M. (1998). Sauropod dinosaur embryos from the Late Cretaceous of Patagonia. Nature, 396(6708), 258-261. doi:10.1038/24370Company J. 2004. Vertebrados continentales del Cretácico superior (Campaniense-Maastrichtiense) de Valencia [PhD dissertation]. Valencia: Universidad de Valencia.Company, J., & Szentesi, Z. (2012). Amphibians from the Late Cretaceous Sierra Perenchiza Formation of the Chera Basin, Valencia Province, Spain. Cretaceous Research, 37, 240-245. doi:10.1016/j.cretres.2012.04.003Csiki-Sava, Z., Buffetaut, E., Ősi, A., Pereda-Suberbiola, X., & Brusatte, S. L. (2015). Island life in the Cretaceous - faunal composition, biogeography, evolution, and extinction of land-living vertebrates on the Late Cretaceous European archipelago. ZooKeys, 469, 1-161. doi:10.3897/zookeys.469.8439Erben, H. K., Hoefs, J., & Wedepohl, K. H. (1979). Paleobiological and isotopic studies of eggshells from a declining dinosaur species. Paleobiology, 5(4), 380-414. doi:10.1017/s0094837300016900García, R. A. (2007). An «egg-tooth»–like structure in titanosaurian sauropod embryos. Journal of Vertebrate Paleontology, 27(1), 247-252. doi:10.1671/0272-4634(2007)27[247:aesits]2.0.co;2Garcia, G., & Vianey-Liaud, M. (2001). Dinosaur eggshells as biochronological markers in Upper Cretaceous continental deposits. Palaeogeography, Palaeoclimatology, Palaeoecology, 169(1-2), 153-164. doi:10.1016/s0031-0182(01)00215-2Grellet-Tinner, G., Chiappe, L. M., & Coria, R. (2004). Eggs of titanosaurid sauropods from the Upper Cretaceous of Auca Mahuevo (Argentina). Canadian Journal of Earth Sciences, 41(8), 949-960. doi:10.1139/e04-049Grigorescu, D., Garcia, G., Csiki, Z., Codrea, V., & Bojar, A.-V. (2010). Uppermost Cretaceous megaloolithid eggs from the Haţeg Basin, Romania, associated with hadrosaur hatchlings: Search for explanation. Palaeogeography, Palaeoclimatology, Palaeoecology, 293(3-4), 360-374. doi:10.1016/j.palaeo.2010.03.031Izquierdo LA, Montero D, Pérez G, Urién V, Meijide M. 2001. Macroestructura de huevos de dinosaurios en el Cretácico superior de “La Rosaca” (Burgos, España). Actas de las I Jornadas Internacionales Sobre Paleontología de Dinosaurios y su Entorno. Ed. Colectivo Arqueológico y Paleontológico de Salas. Salas de los Infantes. p. 389–395.Jackson FD. 2007. Titanosaur reproductive biology: comparison of the Auca Mahuevo Titanosaur nesting locality (Argentina), to the Pinyes Megaloolithus nesting locality (Spain) [PhD dissertation]. Bozeman (MT): Montana State University.Jackson, F. D., Garrido, A., Schmitt, J. G., Chiappe, L. M., Dingus, L., & Loope, D. B. (2004). Abnormal, multilayered titanosaur (Dinosauria: Sauropoda) eggs from in situ clutches at the Auca Mahuevo locality, Neuquen Province, Argentina. Journal of Vertebrate Paleontology, 24(4), 913-922. doi:10.1671/0272-4634(2004)024[0913:amtdse]2.0.co;2Jackson, F. D., Varricchio, D. J., Jackson, R. A., Vila, B., & Chiappe, L. M. (2008). Comparison of water vapor conductance in a titanosaur egg from the Upper Cretaceous of Argentina and a Megaloolithus siruguei egg from Spain. Paleobiology, 34(2), 229-246. doi:10.1666/0094-8373(2008)034[0229:cowvci]2.0.co;2López-Martı́nez, N., Moratalla, J. J., & Sanz, J. L. (2000). Dinosaurs nesting on tidal flats. Palaeogeography, Palaeoclimatology, Palaeoecology, 160(1-2), 153-163. doi:10.1016/s0031-0182(00)00063-8Mohabey, D. M. (1998). Systematics of Indian Upper Cretaceous dinosaur and chelonian eggshells. Journal of Vertebrate Paleontology, 18(2), 348-362. doi:10.1080/02724634.1998.10011063Moratalla JJ. 1993. Restos indirectos de dinosaurios del registro español: paleoicnología de la Cuenca de (Jurásico superior-Cretácico inferior) y paleoología del Cretácico superior [PhD dissertation]. Madrid: Universidad Autónoma de Madrid.Moreno-Azanza, M., Bauluz, B., Canudo, J. I., Gasca, J. M., & Torcida Fernández-Baldor, F. (2016). Combined Use of Electron and Light Microscopy Techniques Reveals False Secondary Shell Units in Megaloolithidae Eggshells. PLOS ONE, 11(5), e0153026. doi:10.1371/journal.pone.0153026Moreno-Azanza, M., Bauluz, B., Canudo, J. I., Puértolas-Pascual, E., & Sellés, A. G. (2013). A re-evaluation of aff. Megaloolithidae eggshell fragments from the uppermost Cretaceous of the Pyrenees and implications for crocodylomorph eggshell structure. Historical Biology, 26(2), 195-205. doi:10.1080/08912963.2013.786067Oms, O., Dinarès-Turell, J., Vicens, E., Estrada, R., Vila, B., Galobart, À., & Bravo, A. M. (2007). Integrated stratigraphy from the Vallcebre Basin (southeastern Pyrenees, Spain): New insights on the continental Cretaceous−Tertiary transition in southwest Europe. Palaeogeography, Palaeoclimatology, Palaeoecology, 255(1-2), 35-47. doi:10.1016/j.palaeo.2007.02.039Ortega, F., Bardet, N., Barroso-Barcenilla, F., Callapez, P. M., Cambra-Moo, O., Daviero- Gómez, V., … Sanz, J. L. (2015). The biota of the Upper Cretaceous site of «Lo Hueco» (Cuenca, Spain). Journal of Iberian Geology, 41(1). doi:10.5209/rev_jige.2015.v41.n1.48657Rasskin-Gutman, D., Elez, J., Esteve-Altava, B., & López-Martínez, N. (2020). Reconstruction of the internal structure of the pore system of a complex dinosaur eggshell (Megaloolithus siruguei). Spanish Journal of Palaeontology, 28(1), 61. doi:10.7203/sjp.28.1.17831Riera, V., Oms, O., Gaete, R., & Galobart, À. (2009). The end-Cretaceous dinosaur succession in Europe: The Tremp Basin record (Spain). Palaeogeography, Palaeoclimatology, Palaeoecology, 283(3-4), 160-171. doi:10.1016/j.palaeo.2009.09.018Sellés, A. G., Bravo, A. M., Delclòs, X., Colombo, F., Martí, X., Ortega-Blanco, J., … Galobart, À. (2013). Dinosaur eggs in the Upper Cretaceous of the Coll de Nargó area, Lleida Province, south-central Pyrenees, Spain: Oodiversity, biostratigraphy and their implications. Cretaceous Research, 40, 10-20. doi:10.1016/j.cretres.2012.05.004Tanaka, K., & Zelenitsky, D. K. (2014). Comparisons between experimental and morphometric water vapor conductance in the eggs of extant birds and crocodiles: implications for predicting nest type in dinosaurs. Canadian Journal of Zoology, 92(12), 1049-1058. doi:10.1139/cjz-2014-0078Vianey-Liaud, M., Khosla, A., & Garcia, G. (2003). Relationships between European and Indian dinosaur eggs and eggshells of the oofamily Megaloolithidae. Journal of Vertebrate Paleontology, 23(3), 575-585. doi:10.1671/0272-4634(2003)023[0575:rbeaid]2.0.co;2Vianey-Liaud, M., & Lopez-Martinez, N. (1997). Late Cretaceous dinosaur eggshells from the Tremp Basin, southern Pyrenees, Lleida, Spain. Journal of Paleontology, 71(6), 1157-1171. doi:10.1017/s002233600003609xVila, B., Galobart, À., Canudo, J. I., Le Loeuff, J., Dinarès-Turell, J., Riera, V., … Gaete, R. (2012). The diversity of sauropod dinosaurs and their first taxonomic succession from the latest Cretaceous of southwestern Europe: Clues to demise and extinction. Palaeogeography, Palaeoclimatology, Palaeoecology, 350-352, 19-38. doi:10.1016/j.palaeo.2012.06.008(2010). Lethaia, 43(2). doi:10.1111/let.2010.43.issue-2Vila, B., Jackson, F. D., Fortuny, J., Sellés, A. G., & Galobart, À. (2010). 3-D Modelling of Megaloolithid Clutches: Insights about Nest Construction and Dinosaur Behaviour. PLoS ONE, 5(5), e10362. doi:10.1371/journal.pone.0010362Vila, B., Riera, V., Bravo, A. M., Oms, O., Vicens, E., Estrada, R., & Galobart, À. (2011). The chronology of dinosaur oospecies in south-western Europe: Refinements from the Maastrichtian succession of the eastern Pyrenees. Cretaceous Research, 32(3), 378-386. doi:10.1016/j.cretres.2011.01.009Vila, B., Sellés, A. G., & Brusatte, S. L. (2016). Diversity and faunal changes in the latest Cretaceous dinosaur communities of southwestern Europe. Cretaceous Research, 57, 552-564. doi:10.1016/j.cretres.2015.07.003Vissers, R. L. M., & Meijer, P. T. (2012). Iberian plate kinematics and Alpine collision in the Pyrenees. Earth-Science Reviews, 114(1-2), 61-83. doi:10.1016/j.earscirev.2012.05.001Wright, V. P., & Platt, N. H. (1995). Seasonal wetland carbonate sequences and dynamic catenas: a re-appraisal of palustrine limestones. Sedimentary Geology, 99(2), 65-71. doi:10.1016/0037-0738(95)00080-

Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor β

Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ−/− mice to study whether ERβ is involved in the rapid regulation of KATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased KATP channel activity, increased glucose-induced [Ca2+]i signals and insulin release in β-cells from WT mice but not in cells from ERβ−/− mice. The rapid reduction in the KATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans

Ancestral Origin of the ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10 (SCA10)

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil