Preparations for Variable-Gravity Regolith Penetration with an Ultrasonically-Active Probe

The set of experiments proposed in this paper intend to investigate the properties of ultrasonic penetration through granular materials in hypergravity. As part of ESA's 6 th 'Spin Your Thesis' campaign, the University of Glasgow will be allowed to use the Large Diameter Centrifuge at the ESTEC facilities in Noordwijk, Netherlands, to achieve these hypergravity conditions. This paper describes the progress of the design and manufacture of the experimental apparatus, analysis of structural integrity to insure the rig can be subjected to the rigors of hypergravity, and discussion of the anticipated results and implications

An experimental study of ultrasonic vibration and the penetration of granular material

This work investigates the potential use of direct ultrasonic vibration as an aid to penetration of granular material. Compared with non-ultrasonic penetration, required forces have been observed to reduce by an order of magnitude. Similarly, total consumed power can be reduced by up to 27%, depending on the substrate and ultrasonic amplitude used. Tests were also carried out in high-gravity conditions, displaying a trend that suggests these benefits could be leveraged in lower gravity regimes

Amputació de la cua en la vaca lletera

Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

Structural studies of recombinant TGIF1 and FBP28 WW domains using NMR and peptide ligation strategies

[eng] The present thesis is divided in three different but related projects. In the first project, the interaction between TGIF1 and SMAD proteins is investigated. TGIF1 is a transcriptional suppressor that prevents the gene transcription due to its interaction with DNA and protein suppressor complexes. TGIF1 has a role in different signalling pathways such as retinoid, Wnt or TGF-β. Focusing on TGF-β, this is one of the main signalling pathways that regulates a plethora of functions in metazoans, including cell differentiation, proliferation and tissue homeostasis, among many others. SMAD proteins are the centrals mediators of the pathways, carrying the signal from the TGF-β receptors at the plasma membrane to the DNA. The aim of this project was to describe, from a structurally point of view, the interaction between TGIF1 and SMAD proteins, already detected biochemically. Using NMR spectroscopy and EMSA assays we could observe the interaction between TGIF1 and the MH1 domain of SMAD2 and SMAD4. Furthermore, the addition of SMAD2/4-MH1 disrupts the TGIF1-DNA interaction. On the other hand, the binding between SMAD2-MH2 and TGIF1 (256-347) was not detected in our experimental conditions. Moreover, we found that p38α and CK1 kinases phosphorylate serines 286, 291 and 294 of TGIF1 (256-347) in vitro. While these serines are located in a region where TGIF1 interacts with many proteins - including SMAD2, HDAC, or Axin-2 - , the phosphorylation could indicate a regulation mechanism. However, the phosphorylation does not change the overall structure of the TGIF1 fragment. Finally, we have detected an interaction between TGIF1 fragments 150-248 and 256-347, suggesting the presence of open and closed conformations of full-length TGIF1. The second project is related to the ligation reaction between two peptides. Our study demonstrates that the addition of HOBt to the cysteine-free direct aminolysis ligation reaction between one thioester peptide and one N-terminal free peptide increase the conversion but not the rate of the ligation. This effect is especially increased when sterically hindered amino acid (such as valine or leucine) are present in the ligation junction. The reaction is also compatible with phosphorylated peptides but intramolecular cyclisation side-reactions appear when the peptide thioester is not protected at the N-terminus. Lastly, six selected mutants structures of FBP28-WW2 were determined de novo by NMR spectroscopy. The six mutant structures maintain the main characteristics of WW domain structure, even for the mutations introducing deletions at the N and C termini. The structures were the experimental confirmation of the effect of this set of mutations in the structure. The existence of the WW fold in all these mutations was key to provide the grounds for the simulated folding curves generated using the UNRES force field.[cat] TGF-β és una de les principals vies de senyalització que tenen les cèl·lules animals per regular gran part dels processos cel·lulars, tals com la diferenciació i proliferació cel·lular o la regeneració, entre d’altres. Les proteïnes SMAD són les principals mediadores d’aquesta via, portant la senyal des dels receptors de TGF-β situats a la membrana cel·lular fins al DNA a l’interior del nucli. En la present tesi s’ha dut a terme un estudi sobre la interacció entre el factor de supressió TGIF1 i les proteïnes SMAD2 i SMAD4. Mitjançant ressonància magnètica nuclear s’ha demostrat la interacció entre TGIF1 i el domini MH1 de SMAD2 i SMAD4. A més, aquesta unió interromp el contacte entre TGIF1 i el seu DNA canònic tal com demostren els EMSA efectuats. Altrament, s’ha determinat per primera vegada que TGIF1 és un substrat de les quinases p38α i CK1, que fosforilen les serines 286, 291 i 294, localitzades en una regió d’interacció amb diverses proteïnes, com per exemple SMAD2, HDAC o Axin-2. D’altra banda, en aquest treball s’ha estudiat la lligació nativa de dos pèptids mitjançant una reacció d’aminòlisis directa sense la presència de cisteïnes en el lloc d’unió. Específicament, s’ha demostrat que l’addició de HOBt a la mescla de reacció augmenta la conversió però no la velocitat de la lligació entre els dos pèptids. Aquest increment en la conversió és especialment rellevant quan aminoàcids estericament impedits, com valina o leucina, es troben en el lloc d’unió. Finalment, s’han determinat les estructures de 6 mutants del domini WW2 de FBP28. Tots els mutants conserven el plegament característic dels dominis WW tot i les delecions que presenten tant a C com a N-terminal. Les estructures han servit per confirmar els resultats de simulacions moleculars efectuades mitjançant el camp de força UNRES

Ultrasonically Assisted Penetration Through Granular Materials

Gaining access to the subsurface of planetary bodies is troublesome for a number of reasons, but particularly due to the low gravity encountered resulting in a lower available weight of spacecraft. A lower weight-on-bit (WOB) often results in sub-optimal drilling, and without complex anchoring or thrusting systems a planetary lander can only impart as much force as it weighs. This work investigates the use of ultrasonic vibration in assisting penetration through granular material. Compared to non-ultrasonic penetration, required forces have been observed to reduce by over a factor of 12. Similarly, total consumed power can be reduced by 28%, depending on the substrate and ultrasonic amplitude used. Tests were also carried out in high-gravity situations, displaying a trend that suggests these benefits would strengthen in lower gravity regimes

Experimental setup for the study of jet interactions

We present a new experimental setup for the study of bubble coalescence and bubble jet interactions in microgravity conditions [1].Test section consists of a cavity full of liquid containing two bubble injectors whose separation distance and relative orientation angle can be controlled. Injection of bubbles is based on the generation of a slug flow in a capillary T-junction [2]. We have studied both individual and collective behavior of bubbles. On ground results on bubble trajectories, maximum distance reached, and the delimitation between turbulence and buoyancy regions are presented. The influence on these results of the inclination angle of an injector with respect to gravity has also been considered.Peer ReviewedPostprint (published version

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

Proteomic profile; Organ dysfunction; Septic shockPerfil proteòmic; Disfunció orgànica; Xoc sèpticPerfil proteómico; Disfunción orgánica; Choque sépticoIntroduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality.To Toni del Pino, Rosa Ras and Pol Herrero from the Proteomics and Metabolomics Area of the Center for Omic Sciences (COS), a Joint between Rovira I Virgili University and Eurecat (Reus, Spain), for their contribution to the proteomics analysis. Samples and data from patients included in this study were provided by the Vall d’Hebron University Hospital Biobank (PT20/00107), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committees. The authors kindly appreciate the generous donation of samples and clinical data of the donors of the Sepsis Bank of HUVH Biobank

The Perspectives of Patients with Chronic Diseases and Their Caregivers on Self-Management Interventions : A Scoping Review of Reviews

Self-management (SM) interventions are supportive interventions systematically provided by healthcare professionals, peers, or laypersons to increase the skills and confidence of patients in their ability to manage chronic diseases. We had two objectives: (1) to summarise the preferences and experiences of patients and their caregivers (informal caregivers and healthcare professionals) with SM in four chronic diseases and (2) to identify and describe the relevant outcomes for SM interventions from these perspectives. We conducted a mixed-methods scoping review of reviews. We searched three databases until December 2020 for quantitative, qualitative, or mixed-methods reviews exploring patients' and caregivers' preferences or experiences with SM in type 2 diabetes mellitus (T2DM), obesity, chronic obstructive pulmonary disease (COPD), and heart failure (HF). Quantitative data were narratively synthesised, and qualitative data followed a three-step descriptive thematic synthesis. Identified themes were categorised into outcomes or modifiable factors of SM interventions. We included 148 reviews covering T2DM (n = 53 [35.8%]), obesity (n = 20 [13.5%]), COPD (n = 32 [21.6%]), HF (n = 38 [25.7%]), and those with more than one disease (n = 5 [3.4%]). We identified 12 main themes. Eight described the process of SM (disease progression, SM behaviours, social support, interaction with healthcare professionals, access to healthcare, costs for patients, culturally defined roles and perceptions, and health knowledge), and four described their experiences with SM interventions (the perceived benefit of the intervention, individualised care, sense of community with peers, and usability of equipment). Most themes and subthemes were categorised as outcomes of SM interventions. The process of SM shaped the perspectives of patients and their caregivers on SM interventions. Their perspectives were influenced by the perceived benefit of the intervention, the sense of community with peers, the intervention's usability, and the level of individualised care. Our findings can inform the selection of patient-important outcomes, decision-making processes, including the formulation of recommendations, and the design and implementation of SM interventions

Alterations in Metabolome and Microbiome Associated with an Early Stress Stage in Male Wistar Rats: A Multi-Omics Approach

Stress disorders have dramatically increased in recent decades becoming the most prevalent psychiatric disorder in the United States and Europe. However, the diagnosis of stress disorders is currently based on symptom checklist and psychological questionnaires, thus making the identification of candidate biomarkers necessary to gain better insights into this pathology and its related metabolic alterations. Regarding the identification of potential biomarkers, omic profiling and metabolic footprint arise as promising approaches to recognize early biochemical changes in such disease and provide opportunities for the development of integrative candidate biomarkers. Here, we studied plasma and urine metabolites together with metagenomics in a 3 days Chronic Unpredictable Mild Stress (3d CUMS) animal approach that aims to focus on the early stress period of a well-established depression model. The multi-omics integration showed a profile composed by a signature of eight plasma metabolites, six urine metabolites and five microbes. Specifically, threonic acid, malic acid, alpha-ketoglutarate, succinic acid and cholesterol were proposed as key metabolites that could serve as key potential biomarkers in plasma metabolome of early stages of stress. Such findings targeted the threonic acid metabolism and the tricarboxylic acid (TCA) cycle as important pathways in early stress. Additionally, an increase in opportunistic microbes as virus of the Herpesvirales was observed in the microbiota as an effect of the primary stress stages. Our results provide an experimental biochemical characterization of the early stage of CUMS accompanied by a subsequent omic profiling and a metabolic footprinting that provide potential candidate biomarkers

Clinical, genomic, and pharmacological study of MYCN-amplified RB1 wild-type metastatic retinoblastoma

An uncommon subgroup of unilateral retinoblastomas with highly aggressive histological features, lacking aberrations in RB1 gene with high-level amplification of MYCN (MCYNampl RB1+/+) has only been described as intra-ocular cases treated with initial enucleation. Here, we present a comprehensive clinical, genomic, and pharmacological analysis of two cases of MCYNampl RB1+/+ with orbital and cervical lymph node involvement, but no central nervous system spread, rapidly progressing to fatal disease due to chemoresistance. Both patients showed in common MYCN high amplification and chromosome 16q and 17p loss. A somatic mutation in TP53, in homozygosis by LOH, and high chromosomal instability leading to aneuploidy was identified in the primary ocular tumor and sites of dissemination of one patient. High-throughput pharmacological screening was performed in a primary cell line derived from the lymph node dissemination of one case. This cell line showed resistance to broad spectrum chemotherapy consistent with the patient’s poor response but sensitivity to the synergistic effects of panobinostat–bortezomib and carboplatin–panobinostat associations. From these cells we established a cell line derived xenograft model that closely recapitulated the tumor dissemination pattern of the patient and served to evaluate whether triple chemotherapy significantly prolonged survival of the animals. We report novel genomic alterations in two cases of metastatic MCYNampl RB1+/+ that may be associated with chemotherapy resistance and in vitro/in vivo models that serve as basis for tailoring therapy in these cases.Fil: Zugbi, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ganiewich, Daiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bhattacharyya, Arpita. Tata Memorial Hospital; IndiaFil: Aschero, María del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ottaviani, Daniela. Centre National de la Recherche Scientifique; FranciaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mena, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Suñol, Mariona. Hospital Sant Joan de Deu Barcelona; EspañaFil: Daroqui, Manuel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Baialardo, Edgardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Salas, Beatriz. Hospital Asencio Villaroel; BoliviaFil: Das, Anirban. Tata Memorial Hospital; IndiaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Francis, Jasmine H.. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Garippa, Ralph. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Abramson, David. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Radvanyi, François. Centre National de la Recherche Scientifique; FranciaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin