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As the pace of biomedical innovation rapidly evolves, there is a need to train researchers to understand regulatory science challenges associated with clinical translation. We describe a pilot course aimed at addressing this need delivered jointly through the Mayo Clinic Center for Clinical and Translational Science and the Yale-Mayo Center for Excellence in Regulatory Science and Innovation. Course design was informed by the Association for Clinical and Translational Science’s Regulatory Science Working Group’s competencies. The course used didactic, case-, and problem-based learning sessions to expose students to regulatory science concepts. Course evaluation focused on student satisfaction and learning. A total of 25 students enrolled in the first two course deliveries. Students represented several disciplines and career stages, from predoctoral to faculty. Students reported learning “an incredible amount” (7/19, 36.8%) or “a lot” (9/19, 47.4%); this was reflected in individual coursework and their course evaluations. Qualitative feedback indicated that assignments that challenged them to apply the content to their own research were appreciated. The heterogeneity of students enrolled, coupled with assessments and course evaluations, supports the statement that there is a growing need and desire for regulatory science-focused curricula. Future research will determine the long-term impact.
Turbulent flow evolution and energy cascades are significantly different in two-dimensional (2-D) and three-dimensional (3-D) flows. Studies have investigated these differences in obstacle-free turbulent flows, but solid boundaries have an important impact on the cross-over from 3-D to 2-D turbulence dynamics. In this work, we investigate the span effect on the turbulence nature of flow past a circular cylinder at
. It is found that even for highly anisotropic geometries, 3-D small-scale structures detach from the walls. Additionally, the natural large-scale rotation of the Kármán vortices rapidly two-dimensionalise those structures if the span is 50 % of the diameter or less. We show this is linked to the span being shorter than the Mode B instability wavelength. The conflicting 3-D small-scale structures and 2-D Kármán vortices result in 2-D and 3-D turbulence dynamics which can coexist at certain locations of the wake depending on the domain geometric anisotropy.
This communication assesses the use of a portable near infrared (NIR) instrument to measure quantitative (fatty acid profile) properties and qualitative (‘Premium’ and ‘Non-premium’) categories of individual Iberian pork carcasses at the slaughterhouse. Acorn-fed Iberian pigs have more unsaturated fats than pigs fed conventional compound feed. Recent advances in miniaturisation have led to a number of handheld NIR devices being developed, allowing processing decisions to be made earlier, significantly reducing time and costs. The most common methods used for assessing quality and authenticity of Iberian hams are analysis of the fatty acid composition of subcutaneous fat using gas chromatography and DNA analysis. In this study, NIR calibrations for fatty acids and classification as premium or non-premium ham, based on carcass fat measured in situ, were developed using a portable NIR spectrometer. The accuracy of the quantitative equations was evaluated through the standard error of cross validation or standard error of prediction of 0.84 for palmitic acid (C16:0), 0.94 for stearic acid (C18:0), 1.47 for oleic acid (C18:1) and 0.58 for linoleic acid (C18:2). Qualitative calibrations provided acceptable results, with up to 98% of samples (n = 234) correctly classified with probabilities ⩾0.9. Results indicated a portable NIR instrument has the potential to be used to measure quality and authenticity of Iberian pork carcasses.
Fermented feeds are being considered as practical alternatives to antimicrobial growth promoters (AGP) supplemented in nursery pig diets. This study aimed to investigate health-promoting effects of fermented barley in weaned pigs challenged with Escherichia coli K88 +. A total of 37 piglets were weaned at 21 ± 1 day of age (6.41 ± 0.47 kg of BW) and assigned to either of the following five treatment groups: (1) unchallenged control (UCC; n = 7), (2) challenged control (CC; n = 7), (3) AGP (CC + 0.1% AGP; n = 7), (4) Ferm1 (challenged and fed homofermentative Lactobacillus plantarum (Homo)-fermented barley; n = 8) and (5) Ferm2 (challenged and fed heterofermentative L. buchneri (Hetero)-fermented barley; n = 8). The control diet included unfermented barley. Barley was fermented with either Homo or Hetero for 90 days under anaerobic conditions. On day 10, all pigs except those in UCC group were orally inoculated with E. coli K88 + (6 × 109 colony forming units/ml). The pre-planned orthogonal test was performed to compare (1) UCC and CC, (2) CC and AGP, (3) CC and Ferm1 + Ferm2, as well as (4) Ferm1 and Ferm2. Challenged control pigs showed shorter (P < 0.05) villus height (VH) in the duodenum and deeper (P < 0.05) crypt depth (CD) in the jejunum than UCC pigs. The AGP group had higher (P < 0.05) VH and lower (P < 0.05) IL-6 gene expression in the jejunum compared with CC group. Compared to CC, Ferm1 and Ferm2 had decreased (P < 0.05) CD in the duodenum, IL-6 gene expression in the jejunum and rectal temperature at 24 h post-challenge. Pigs fed fermented barley diets showed greater (P < 0.05) faecal abundance of Clostridium Cluster IV and Lactobacilli than those fed UCC diet. Ferm2-fed pigs showed lower (P < 0.05) concentrations of band cells, eosinophils and lymphocytes at 6, 24 and 48 h after challenge, respectively, and lower (P < 0.05) faecal abundance of Enterobacteriaceae 24 h after challenge than the Ferm1-fed pigs. In conclusion, the substitution of unfermented barley with fermented barley in a nursery diet showed similar results as those shown by AGP supplementation in terms of enhancing the intestinal morphology and modulating faecal microbiota composition, as well as down-regulating the pro-inflammatory cytokines; therefore, fermented barley can be a possible nutritional strategy for managing nursery pigs fed diets without in-feed AGP.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
In this paper, a robust geometric navigation algorithm, designed on the special Euclidean group SE(3), of a quadrotor is proposed. The equations of motion for the quadrotor are obtained using the Newton–Euler formulation. The geometric navigation considers a guidance frame which is designed to perform autonomous flights with a convergence to the contour of the task with small normal velocity. For this purpose, a super twisting algorithm controls the nonlinear rotational and translational dynamics as a cascade structure in order to establish the fast and yet smooth tracking with the typical robustness of sliding modes. In this sense, the controller provides robustness against parameter uncertainty, disturbances, convergence to the sliding manifold in finite time, and asymptotic convergence of the trajectory tracking. The algorithm validation is presented through experimental results showing the feasibility of the proposed approach and illustrating that the tracking errors converge asymptotically to the origin.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
A completely randomized experiment was designed to evaluate the effects of α-amylase (AMY) and glucoamylase (GLU) on total losses, fermentative profile, chemical composition and amylolytic activity of rehydrated maize. Eighty-four experimental silos of rehydrated maize [0.33 litres/kg ground maize, 4-mm theoretical particle size, and 625 g/kg dry matter (DM)] were assigned to the following treatments: (1) control (CON), no enzyme addition; (2) GLU added at 300 µl/kg of ground maize (as-fed); and (3) AMY added at 300 µl/kg of ground maize. Seven silos from each treatment were opened after 7, 14, 21 and 28 days. Differences among treatments were evaluated through orthogonal contrasts (CON v. enzymes, and AMY v. GLU). Time effects were decomposed using polynomial regression. Glucoamylase silage exhibited greater total losses than AMY. Enzymes increased acetate and lactic acid concentrations and decreased ethanol concentration. Regardless of treatment, gas, effluent and total fermentative losses linearly increased, whereas DM recovery linearly decreased with higher storage length. Glucoamylase silage had lower ammonia nitrogen and higher lactic acid concentrations than AMY. Enzyme treatments decreased silage neutral detergent fibre content and increased in vitro DM degradation. Glucoamylase silage exhibited a more moderate starch content and greater in vitro DM degradation than AMY. Storage time linearly decreased DM, starch and fibre content of rehydrated maize. In vitro degradation of DM linearly increased as the storage length increased. This study showed evidence that enzymes with amylolytic activity, particularly GLU, improve the fermentative profile and DM degradation of rehydrated maize silage.
In this study, we examine how the Guri catfish Genidens genidens uses estuarine and freshwater habitats along the largest South American coastal lagoon, through the chemical analysis of otoliths and microscopic analysis of gonads. Chemical composition (Sr:Ca) of otolith edges allowed distinguishing between individuals who used the estuarine or freshwater compartments of the lagoon. The analysis of core-to-edge chemical profiles of each individual otolith revealed that the population may present two different patterns of habitat use along the lagoon. The ‘type 1’ pattern (89.5%) includes fish who appear to have been born in estuarine waters, whereas ‘type 2’ (9.5%) includes those fish born in fresh water. Nevertheless, juveniles from both patterns appear to migrate to estuarine waters. The gonad analysis shows G. genidens may reproduce in fresh water, as nearly 57% of all sampled fish were found to spawn in the freshwater portion of the lagoon. Also, the otolith core of many adult fish presented freshwater signatures, thus suggesting consistent fresh water use during early life. Our findings based on otolith and gonadal analyses challenge the previous classification of G. genidens as an estuarine resident. Rather, our results allow the suggestion that this species should be placed in the ‘estuarine and fresh water’ guild, which includes both fish completing their life cycles within the estuary and fish who consistently use freshwater habitats.
Breeding for resilience requires a better understanding of intra-flock variability and the related mechanisms responsible for robustness traits. Among such traits, the animals’ ability to cope with feed fluctuations by mobilizing or restoring body reserves (BR) is a key mechanism in ruminants. The objective of this work was to characterize individual variability in BR dynamics in productive Romane ewes reared in extensive conditions. The BR dynamics profiles were characterized by combining individual longitudinal measurements of BW and body condition scores (BCS) over several production cycles. Historical data, including up to 2628 records per trait distributed in 1146 ewes, underwent cluster analysis. Two to four trajectories were observed for BW depending on the cycle, while three trajectories were found for BCS, whatever the cycle. Most trajectories suggested that BR dynamics were similar but the level of BR may differ between ewes. Nevertheless, some trajectories suggested that both BR dynamics and levels were different for a proportion of ewes. Clustering on BW and BCS profiles adjusted for individual level trends, resulted in differences only in the level of BW or BCS, rather than differences in trajectories. Thus, the overall shape of trajectories was not changed considering or not the individual level trend across cycles. In addition to individual variability, the ewe’s age at first lambing and litter size contributed to the distribution of the ewes between the trajectories. Regarding the entire productive life, three trajectories were observed for BW and BCS changes over three productive cycles. Increase in BW at each cycle suggested that ewes kept growing up until 3 to 4 years old in our conditions. Similar alternation of BCS gains and losses across cycles suggested BR dynamics might be repeatable. Many individual trajectories remained the same throughout a ewe’s life, whatever the age at first lambing, parity or litter size. Our results demonstrate the relevance of using BW and BCS changes for characterizing the diversity of BR mobilization–accretion profiles in sheep in a long timespan perspective.
Since ancient times, lubricants have been used to reduce friction and wear problems of mechanical systems. However, nowadays, there is a constant effort to improve their performance through additives so that they can accomplish properly in this modern world. In that sense, in this study, it was proposed the use of Poly(ε-Caprolactone) (PCL) as a biodegradable additive in Castor oil. The effect that this additive has on the tribological properties of AISI 4140 steel/Al2O3 tribosystem was analyzed. For this purpose, PCL was dissolved in Castor oil at 65 °C for 15 minutes. Later, once the lubricant formulations got into room temperature, friction tests were conducted with a ball-on-disk configuration. Several experiments were systematically carried out in order to study the factors that could influence the performance of the tribological system, for instance: additive concentration, velocity, temperature, and wear track radius. The kinetic friction coefficient was used to analyze the results as an output variable. The parameters in which the best friction behavior was observed were employed again to compare the efficiency of the polymeric additive by profoundly analyzing and comparing the wear response of the system. The PCL additive showed great results by decreasing friction up to 30% compared to the neat Castor oil. Nevertheless, as the opposite effect, this additive increased the steel wear to almost half an order of magnitude. Given the above, this investigation showed that, with further studies, Poly(ε-Caprolactone) could be used as an additive in vegetable oil-based lubricants for the improvement of friction performance.
The Centro de Laseres Pulsados in Salamanca, Spain has recently started operation phase and the first user access period on the 6 J 30 fs 200 TW system (VEGA 2) already started at the beginning of 2018. In this paper we report on two commissioning experiments recently performed on the VEGA 2 system in preparation for the user campaign. VEGA 2 system has been tested in different configurations depending on the focusing optics and targets used. One configuration (long focal length
cm) is for underdense laser–matter interaction where VEGA 2 is focused onto a low density gas-jet generating electron beams (via laser wake field acceleration mechanism) with maximum energy up to 500 MeV and an X-ray betatron source with a 10 keV critical energy. A second configuration (short focal length
cm) is for overdense laser–matter interaction where VEGA 2 is focused onto a
thick Al target generating a proton beam with a maximum energy of 10 MeV and temperature of 2.5 MeV. In this paper we present preliminary experimental results.
The aim of this investigation was to study castor, canola, and sesame vegetable oils in order to evaluate their potential use as lubricants in steel mechanical components. For this purpose, densities of each oil were evaluated using the pycnometer method, as well as their dynamic viscosities through a Brookfield DV-II rotational viscometer. Both properties were evaluated at temperatures of 25, 40 and 100 °C. Additionally, viscosity indexes were determined according to ASTM D 2270. These rheological properties were used to estimate the lubrication regime considering parameters of real contact conditions in mechanical components. Friction and wear analyses were carried out to investigate the behaviour of the vegetable oil as lubricants. Such tests were carried out at room temperature on a CSM tribometer with pin-on-disk configuration by using castor, canola and sesame oils as lubricants. AISI 4140 hardened steel against AISI 100Cr6 steel pin was used as a mechanical component. From the rheological study, it was observed that canola and sesame oils behave as dilatant fluids at the evaluated temperatures, while castor oil behaves like a Newtonian fluid at 25 and 40 °C. Castor oil showed the highest density value among oils studied, but it also exhibited the lowest value of viscosity index (271). Contrarily, sesame oil was the least dense, but it exhibited the highest viscosity index (545). On the other hand, the lubrication regime study showed that by using castor oil as a lubricant in the mechanical component (4140/100Cr6), the system worked in a mixed lubrication regime while by using canola and sesame oils the system operated in boundary lubrication conditions. Finally, the kinetic friction coefficients were different for each lubricant obtaining the lowest value with castor oil while the highest value of friction coefficient was exhibited by the sesame oil lubricant.
In this work, the anodization of grade 2 titanium was performed using a HCl-based electrolyte in order to obtain Titania nanostructures. Different glycerol concentrations were added to the HCl electrolyte to study the effect it has on the shape and density of the nanostructures, additionally, anodization time and voltage was also varied. The anodized samples were observed by SEM microscopy and studied by Raman spectroscopy and X-ray diffraction. Raman spectroscopy and XRD showed the formation of the anatase phase of the TiO2. By SEM it was possible to observe several changes in the shape of the structures, by adding glycerol ball-like structures were visible, anodization time did not change the shape of the nanostructures. However, the voltage variation showed a clear control on the shape of the structures, forming nanotubes at higher voltages. It was concluded that a better control of the shape and density of the nanostructures is achieved by adding glycerol, however, in order to overcome the resistance that the electrolyte brings, higher voltages are required.