Towards comprehensive characterisation and modelling of the forming and wrinkling mechanics of engineering fabrics

Through a combination of direct measurement and inverse modelling, a route to characterising the main mechanical forming properties of engineering fabric is demonstrated. The process involves just two experimental tests, a cantilever bending test and a modified version of the uniaxial bias extension test. The mechanical forming properties of a twill weave carbon fabric have been determined, including estimates of the in-plane bending stiffness and the torsional stiffness of a sheared fabric. As a result of measuring and incorporating all the main mechanical properties of the fabric in forming simulations (tensile, shear, out-of-plane bending, in-plane bending & torsion), the specimen size-dependent shear kinematics and wrinkling response measured in experiments, is faithfully reproduced in simulations of the uniaxial bias extension (UBE) test

Probabilistic delineation of soil layers using Soil Behavior Type Index

CPTu-based soil profiling has become a key component in the geotechnical design process. However, this is an interpretative process, affected by the inherent variability of soil properties, measurement noise and subjective heuristics. These are difficult to communicate to other interpreters or, even for the same interpreter, to transfer across profiles. A semi-automated tool for CPTu data interpretation is presented as an aid in this interpretation process. A probabilistic-based algorithm is employed to elicit the implicit heuristics in CPTu-based soil profiling and facilitate transference. Univariate normal distributions fit Soil Behavior Type Index data. Soil class boundaries, taken from a conventionally accepted chart, are sequentially activated with user-specified refinement. Thin layers under cone resolution are merged using well-established criteria. An application to CPTu records on finely interlayered deltaic deposits is illustrated, in which output delineations resulting from different analyst choices are compared among themselves and with one based on core description.Peer ReviewedPostprint (published version

Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality

Replicative stress during embryonic development influences ageing and predisposition to disease in adults. A protective mechanism against replicative stress is provided by the licensing of thousands of origins in G1 that are not necessarily activated in the subsequent S-phase. These `dormant' origins provide a backup in the presence of stalled forks and may confer flexibility to the replication program in specific cell types during differentiation, a role that has remained unexplored. Here we show, using a mouse strain with hypomorphic expression of the origin licensing factor mini-chromosome maintenance (MCM)3 that limiting origin licensing in vivo affects the functionality of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. Mcm3-deficient erythroblasts display aberrant DNA replication patterns and fail to complete maturation, causing lethal anemia. Our results indicate that hematopoietic progenitors are particularly sensitive to replication stress, and full origin licensing ensures their correct differentiation and functionality.We thank members of our laboratories for helpful discussions, Marcos Malumbres (CNIO) for advice on the design of the Mcm3-Lox allele, Isabel Blanco for her administrative help with mouse work and Soraya Ruiz for excellent handling of the mouse colony in J.M.'s group. Research was supported by the Spanish Ministry of Economy and Competitiveness (grants BFU2013-49153-P and Consolider-Ingenio CSD2007-00015 to J.M., SAF2011-23753 to O.F.-C., BFU2012-35892 to J.I.) and RO1 HL092471 to E.P., S.A. was the recipient of an EMBO short-term fellowship to visit E.P.'s laboratory at UCSF. We are grateful to Manuel Serrano (CNIO), Almudena Ramiro (CNIC) and Arkaitz Ibarra (The Salk Institute, USA) for useful comments on the manuscript.S

Plan de negocios para determinar la viabilidad y el dise?o de una soluci?n tecnol?gica que integre servicios diferenciados de valor en relaci?n a la experiencia del consumo de bebidas alcoh?licas

La tesis desarrolla un plan de negocios para determinar la viabilidad y el dise?o de una soluci?n tecnol?gica que integre servicios diferenciados de valor en relaci?n a la experiencia del consumo de bebidas alcoh?licas. La propuesta se encuentra dirigida a personas entre 18 y 40 a?os que tengan cierta afinidad por el consumo de bebidas alcoh?licas, interesados en difundir y vivir la experiencia mixol?gica. El documento consta de doce cap?tulos: El primer cap?tulo desarrolla el planteamiento del problema, los objetivos generales y espec?ficos, la justificaci?n, alcance y contribuci?n de la propuesta. El cap?tulo II, detalla la metodolog?a de Lean Startup; una metodolog?a que busca crear un modelo de negocio rentable antes de crear una empresa. Para la validaci?n de la idea de negocio (detallada en el cap?tulo III del documento), se desarroll? el producto m?nimo viable, el cual se mostr? durante las entrevistas en profundidad realizadas a los diferentes actores del negocio. Una vez validado y habiendo recogido informaci?n se desarrollaron los diferentes planes que componen nuestra propuesta, cada uno de ellos desarrollados en los cap?tulos V al XI. Finalmente el cap?tulo XII de la tesis, hace referencia a las recomendaciones y conclusiones producto del an?lisis y la investigaci?n realizada

Essential oils from native plants for the control of phytopathogenic fungi that affect fruits

El empleo constante y excesivo de fungicidas sintéticos en la industria fruti-hortícola ha provocado profundas alteraciones en el medio ambiente y en la salud humana. En este contexto, explorar fuentes naturales antifúngicas resulta de importancia económica y medioambiental. Se propuso estudiar la actividad de cinco aceites volátiles obtenidos de las especies vegetales nativas Dysphania ambrosioides, Baccharis frenguellii, Baccharis salicifolia, Lippia alba y Lippia turbinata contra hongos fitopatógenos de los géneros Botrytis, Colletotrichum, Rhizopus, Fusarium y Monilinia, aislados de frutillas y duraznos con sintomatología. La evaluación se realizó mediante el método de difusión en agar adaptado para muestras volátiles y se determinaron los porcentajes de inhibición fúngica para cada muestra en estudio utilizando el software ImageJ®. Se analizó el perfil químico de cada aceite por CG-EM y se determinaron los compuestos mayoritarios. Los resultados indicaron un alto potencial antifúngico de todas las muestras evaluadas, particularmente el producto obtenido de L. alba.The constant and excessive use of synthetic fungicides in fruit and vegetable industry has caused dangerous environmentally changes and deeply affected human health. In this context, exploring natural antifungal sources represents an economic and environmental importance. It was proposed to study the activity of fi ve volatile oils obtained from the native plant species Dysphania ambrosioides, Baccharis frenguellii, Baccharis salicifolia, Lippia alba and Lippia turbinata against phytopathogenic fungi belonging to the genus Botrytis, Colletotrichum, Rhizopus, Fusarium and Monilinia isolated from infected strawberries and peaches. The assays were carried out using the agar diffusion method adapted for volatile samples and the percentages of fungal inhibition were determined for each sample using ImageJ® software. The chemical profi le of each essential oil was analyzed by GC-MS and the majority compounds were determined. Results showed a high antifungal potential for all the samples evaluated, particularly the product obtained from L. alba.Fil: Stegmayer, María Inés. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Ciencias Agrarias; ArgentinaFil: Fernandez, Laura Noemí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Cs.agrarias. Cátedra de Fitopatologia; ArgentinaFil: Alvarez, Norma Hortensia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Ciencias Agrarias. Departamento de Producción Vegetal. Cátedra de Cultivos Intensivos; ArgentinaFil: Olivella, Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Ciencias Agrarias; ArgentinaFil: Gutiérrez, Hugo Francisco. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: Favaro, María Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Cs.agrarias. Cátedra de Fitopatologia; ArgentinaFil: Derita, Marcos Gabriel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Ciencias Agropecuarias del Litoral. - Universidad Nacional del Litoral. Instituto de Ciencias Agropecuarias del Litoral.; Argentina. Universidad Nacional del Litoral. Facultad de Ciencias Agrarias; Argentin

Two interlinked bistable switches govern mitotic control in mammalian cells

Distinct protein phosphorylation levels in interphase and M phase require tight regulation of Cdk1 activity [1, 2]. A bistable switch, based on positive feedback in the Cdk1 activation loop, has been proposed to generate different thresholds for transitions between these cell-cycle states [3, 4, 5]. Recently, the activity of the major Cdk1-counteracting phosphatase, PP2A:B55, has also been found to be bistable due to Greatwall kinase-dependent regulation [6]. However, the interplay of the regulation of Cdk1 and PP2A:B55 in vivo remains unexplored. Here, we combine quantitative cell biology assays with mathematical modeling to explore the interplay of mitotic kinase activation and phosphatase inactivation in human cells. By measuring mitotic entry and exit thresholds using ATP-analog-sensitive Cdk1 mutants, we find evidence that the mitotic switch displays hysteresis and bistability, responding differentially to Cdk1 inhibition in the mitotic and interphase states. Cdk1 activation by Wee1/Cdc25 feedback loops and PP2A:B55 inactivation by Greatwall independently contributes to this hysteretic switch system. However, elimination of both Cdk1 and PP2A:B55 inactivation fully abrogates bistability, suggesting that hysteresis is an emergent property of mutual inhibition between the Cdk1 and PP2A:B55 feedback loops. Our model of the two interlinked feedback systems predicts an intermediate but hidden steady state between interphase and M phase. This could be verified experimentally by Cdk1 inhibition during mitotic entry, supporting the predictive value of our model. Furthermore, we demonstrate that dual inhibition of Wee1 and Gwl kinases causes loss of cell-cycle memory and synthetic lethality, which could be further exploited therapeutically

Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeleton dynamics in platelets

MASTL, a Ser/Thr kinase that inhibits PP2A-B55 complexes during mitosis, is mutated in autosomal dominant thrombocytopenia. However, the connections between the cell cycle machinery and this human disease remain unexplored. We report here that, whereas Mastl ablation in megakaryocytes prevented proper maturation of these cells, mice carrying the thrombocytopenia-associated mutation developed thrombocytopenia as a consequence of aberrant activation and survival of platelets. Activation of mutant platelets was characterized by hyper-stabilized pseudopods mimicking the effect of PP2A inhibition and actin polymerization defects. These aberrations were accompanied by abnormal hyper-phosphorylation of multiple components of the actin cytoskeleton and were rescued both in vitro and in vivo by inhibiting upstream kinases such as PKA, PKC, or AMPK. These data reveal an unexpected role of Mastl in actin cytoskeleton dynamics in postmitotic cells, and suggest that the thrombocytopenia-associated mutation in MASTL is a pathogenic dominant mutation that mimics decreased PP2A activity resulting in altered phosphorylation of cytoskeletal regulatory pathways.We thank Peter Storz (Mayo Clinic; Jacksonville, FL) for sharin g reagents and Sheila Rueda for her support with the management of the mouse colony. B.H. and R.S.-M. were supported by the Juan de la Cierva Programme from the Spanish M inistry of Economy and Competitiveness (MINECO). M.T. was supported by Foundation La Caixa. A.E.B. was supported by the Programa de Empleo Juvenil, Comunidad de M adrid. M.A.-F. received a young investigator g rant from MINECO (SAF2014-60442- JIN; co-financed by FEDER funds). P.G.dF. was supported by Fundació la Marató de TV3 (project 080121 and project 20153031). J.M. was supported by the Ramon y Cajal programme (MINECO; RYC-2012-10651). M.M. lab. is supported by grants from the MINE CO (SAF2015- 69920-R), Programa iLUNG from the Comunidad de Madrid (B2017/BM D-3884), and Worldwide Cancer Research (15-0278). CNIO is a Severo Ochoa Cen ter of Excellence (MINECO awards SEV-2015-0510)S

Transforming an esterase into an enantioselective catecholase through bioconjugation of a versatile metal-chelating inhibitor

4 pags., 3 figs.Metal complexes introduced into protein scaffolds can generate versatile biomimetic catalysts endowed with a variety of catalytic properties. Here, we synthesized and covalently bound a bipyridinyl derivative to the active centre of an esterase to generate a biomimetic catalyst that shows catecholase activity and enantioselective catalytic oxidation of (+)-catechin.We acknowledge the financial support of the European Union’s Horizon 2020 (GA 101000327), and the Ministerio de Ciencia e Innovacio´n and Agencia Estatal de Investigacio´n (AEI) (DOI 10.13039/501100011033), and the ‘‘NextGenerationEU/PRTR’’ (PID2020-112758RB-I00, PDC2021-121534-I00, TED2021-130544B-I00, PID2019-105838RB-C31, PID2019-105838RB-C33).Peer reviewe

Influence of the Temperature and the Genotype of the HSP90AA1 Gene over Sperm Chromatin Stability in Manchega Rams

The present study addresses the effect of heat stress on males' reproduction ability. For that, we have evaluated the sperm DNA fragmentation (DFI) by SCSA of ejaculates incubated at 37°C during 0, 24 and 48 hours after its collection, as a way to mimic the temperature circumstances to which spermatozoa will be subject to in the ewe uterus. The effects of temperature and temperature-humidity index (THI) from day 60 prior collection to the date of semen collection on DFI were examined. To better understand the causes determining the sensitivity of spermatozoa to heat, this study was conducted in 60 males with alternative genotypes for the SNP G/C−660 of the HSP90AA1 promoter, which encode for the Hsp90α protein. The Hsp90α protein predominates in the brain and testis, and its role in spermatogenesis has been described in several species. Ridge regression analyses showed that days 29 to 35 and 7 to 14 before sperm collection (bsc) were the most critical regarding the effect of heat stress over DFI values. Mixed model analyses revealed that DFI increases over a threshold of 30°C for maximum temperature and 22 for THI at days 29 to 35 and 7 to 14 bsc only in animals carrying the GG−660 genotype. The period 29–35 bsc coincide with the meiosis I process for which the effect of the Hsp90α has been described in mice. The period 7–14 bsc may correspond with later stages of the meiosis II and early stages of epididymal maturation in which the replacement of histones by protamines occurs. Because of GG−660 genotype has been associated to lower levels of HSP90AA1 expression, suboptimal amounts of HSP90AA1 mRNA in GG−660 animals under heat stress conditions make spermatozoa DNA more susceptible to be fragmented. Thus, selecting against the GG−660 genotype could decrease the DNA fragmentation and spermatozoa thermal susceptibility in the heat season, and its putative subsequent fertility gainsPublishe