Highly stretchable and ultrathin nanopaper composites for epidermal strain sensors.

Multifunctional electronics are attracting great interest with the increasing demand and fast development of wearable electronic devices. Here, we describe an epidermal strain sensor based on an all-carbon conductive network made from multi-walled carbon nanotubes (MWCNTs) impregnated with poly(dimethyl siloxane) (PDMS) matrix through a vacuum filtration process. An ultrasonication treatment was performed to complete the penetration of PDMS resin in seconds. The entangled and overlapped MWCNT network largely enhances the electrical conductivity (1430 S m-1), uniformity (remaining stable on different layers), reliable sensing range (up to 80% strain), and cyclic stability of the strain sensor. The homogeneous dispersion of MWCNTs within the PDMS matrix leads to a strong interaction between the two phases and greatly improves the mechanical stability (ca. 160% strain at fracture). The flexible, reversible and ultrathin (<100 µm) film can be directly attached on human skin as epidermal strain sensors for high accuracy and real-time human motion detection.

Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) System for Outcome Prediction in Elderly Patients Undergoing Major Vascular Surgery.

OBJECTIVE: POSSUM system is widely used and validated for 30-day mortality and morbidity prediction. The aim of this study was to evaluate the performance of five POSSUM's equations (POSSUM, P-POSSUM, V-POSSUM, V-POSSUM physiology and V-POSSUM Cambridge) on predicting 30-day mortality and morbidity in elderly patients undergoing major elective vascular surgery. DESIGN: A retrospective longitudinal cohort study. SETTING: A study conducted at an University Hospital. PARTICIPANTS: 208 elderly patients (≥ 60 years) undergoing major elective vascular surgery. MEASUREMENTS: Data collected from the clinical files included patient's characteristics, diagnosis, surgery, comorbidities, parameters from POSSUM score, 30, 60 and 90-day mortality and 30-day morbidity. POSSUM system's goodness-of-fit for predicting mortality and morbidity was assessed by Hosmer-Lemeshow test (H-L T) and Standardized Mortality/Morbidity Ratio (SMR) and discriminative ability by the area under the ROC curves (ROC-AUC). Patients' average age was 70.8 years, 81% males. INTERVENTIONS: None. MAIN RESULTS: The overall 30-day mortality rate was 2.97% (n=6) and 30-day morbidity was 29.2% (n=59). POSSUM, P-POSSUM, V-POSSUM, V-POSSUM physiology and V-POSSUM Cambridge equation predicted an overall of 29.1, 4.43, 15.3, 21.9 and 13.5 deaths, respectively. POSSUM morbidity equation predicted 105.0 complications. H-LT p-values were 0.001, 0.164, 0.208, 0.011, 0.331 and <0.001, respectively. SMRs and 95% confidence interval (CI) were 0.21[0.04-0.37], 1.35[0.27-2.44], 0.39[0.08-0.71], 0.27[0.06-0.49], 0.44[0.09-0.80] and 0.56[0.42-0.71], respectively. ROC-AUC and 95% CI were 0.72[0.49-0.95], 0.72[0.49-0.95], 0.73[0.51-0.94], 0.69[0.50-0.89], 0.72[0.52-0.92] and 0.71[0.63-0.79], respectively. CONCLUSIONS: P-POSSUM had the best performance predicting 30-day mortality. All the other overestimated 30-day mortality. Prediction of morbidity was inadequate. POSSUM scoring models may not be robust tools for risk prediction in elderly patients undergoing major elective vascular surgery and need further calibration and discrimination.

Recombinant expression and purification of the RNA-binding LARP6 proteins from fish genetic model organisms.

The RNA-binding proteins that comprise the La-related protein (LARP) superfamily have been implicated in a wide range of cellular functions, from tRNA maturation to regulation of protein synthesis. To more expansively characterize the biological function of the LARP6 subfamily, we have recombinantly expressed the full-length LARP6 proteins from two teleost fish, platyfish (Xiphophorus maculatus) and zebrafish (Danio rerio). The yields of the recombinant proteins were enhanced to >2 mg/L using a tandem approach of an N-terminal His6-SUMO tag and an iterative solubility screening assay to identify structurally stabilizing buffer components. The domain topologies of the purified fish proteins were probed with limited proteolysis. The fish proteins contain an internal, protease-resistant 40 kDa domain, which is considerably more stable than the comparable domain from the human LARP6 protein. The fish proteins are therefore a lucrative model system in which to study both the evolutionary divergence of this family of La-related proteins and the structure and conformational dynamics of the domains that comprise the LARP6 protein.

Epistasis-Induced Evolutionary Plateaus in Selection Responses.

Understanding and predicting evolution is a central challenge in both population and quantitative genetics. The amount of genetic variance for quantitative traits available in a population conditions the particular way in which this population will (or will not) evolve under natural or artificial selection. Here, we explore the potential of gene-gene interactions (epistasis) to induce evolutionary plateaus at which evolutionary change virtually collapses for a number of generations, followed by the release of previously cryptic genetic variation. First, we demonstrate theoretically that a wide range of epistatic interactions has the potential to generate temporary decelerations in the course of response to selection. Second, we perform simulations to show that such microevolutionary plateaus may occur in selection responses under empirically based assumptions. Finally, we show that such events can be traced in artificial selection experiments, thus providing further empirical evidence for this phenomenon.

Dissection of cell cycle-dependent dynamics of Dnmt1 by FRAP and diffusion-coupled modeling.

DNA methyltransferase 1 (Dnmt1) reestablishes methylation of hemimethylated CpG sites generated during DNA replication in mammalian cells. Two subdomains, the proliferating cell nuclear antigen (PCNA)-binding domain (PBD) and the targeting sequence (TS) domain, target Dnmt1 to the replication sites in S phase. We aimed to dissect the details of the cell cycle-dependent coordinated activity of both domains. To that end, we combined super-resolution 3D-structured illumination microscopy and fluorescence recovery after photobleaching (FRAP) experiments of GFP-Dnmt1 wild type and mutant constructs in somatic mouse cells. To interpret the differences in FRAP kinetics, we refined existing data analysis and modeling approaches to (i) account for the heterogeneous and variable distribution of Dnmt1-binding sites in different cell cycle stages; (ii) allow diffusion-coupled dynamics; (iii) accommodate multiple binding classes. We find that transient PBD-dependent interaction directly at replication sites is the predominant specific interaction in early S phase (residence time Tres ≤ 10 s). In late S phase, this binding class is taken over by a substantially stronger (Tres ∼22 s) TS domain-dependent interaction at PCNA-enriched replication sites and at nearby pericentromeric heterochromatin subregions. We propose a two-loading-platform-model of additional PCNA-independent loading at postreplicative, heterochromatic Dnmt1 target sites to ensure faithful maintenance of densely methylated genomic regions.

The first hominin of Europe.

The earliest hominin occupation of Europe is one of the most debated topics in palaeoanthropology. However, the purportedly oldest of the Early Pleistocene sites in Eurasia lack precise age control and contain stone tools rather than human fossil remains. Here we report the discovery of a human mandible associated with an assemblage of Mode 1 lithic tools and faunal remains bearing traces of hominin processing, in stratigraphic level TE9 at the site of the Sima del Elefante, Atapuerca, Spain. Level TE9 has been dated to the Early Pleistocene (approximately 1.2-1.1 Myr), based on a combination of palaeomagnetism, cosmogenic nuclides and biostratigraphy. The Sima del Elefante site thus emerges as the oldest, most accurately dated record of human occupation in Europe, to our knowledge. The study of the human mandible suggests that the first settlement of Western Europe could be related to an early demographic expansion out of Africa. The new evidence, with previous findings in other Atapuerca sites (level TD6 from Gran Dolina), also suggests that a speciation event occurred in this extreme area of the Eurasian continent during the Early Pleistocene, initiating the hominin lineage represented by the TE9 and TD6 hominins.

A tool for diagnosis of Dicrocoelium dendriticum infection: hatching eggs and molecular identification of the miracidium.

DNA primers were designed from the 18S rRNA sequence from the relevant digenean trematode Dicrocoelium dendriticum to evaluate a polymerase chain reaction-based diagnostic method of this parasite from its eggs in faeces of naturally and experimentally infected sheep. In order to get DNA from D. dendriticum eggs, several hatching mechanisms were studied. Successful results were obtained when the eggs were frozen to -80 °C and/or in liquid nitrogen and then defrosted. This method allowed the opening of the egg operculum and the liberation of the miracidium. DNA from D. dendriticum adults and from hatching egg miracidia was obtained and an amplification single band of 1.95 kb was observed using primers designed for the total 18S rRNA sequence in both cases as well as when the template DNA was from adults of the closely related parasite Fasciola hepatica; in addition, a single and specific 0.8-kb band was obtained when primers based on an internal partial 18S rRNA sequence were used. The method showed to be useful not only in samples coming from adults, but in eggs from gall bladder and faeces as well. F. hepatica internal 18S rRNA primers were also designed and used as a negative control to prove that the eggs in faeces came from D. dendriticum and not from F. hepatica. A molecular tool able to detect a minimum of about 40 D. dendriticum eggs in one of the definitive host faeces has been developed for the first time and could provide a useful molecular tool to improve the conventional coprological diagnosis for detecting D. dendriticum eggs.

Characterization of Oaxaca raw milk cheese microbiota with particular interest in Lactobacillus strains.

The aim of this work was to identify and characterize lactobacilli strains from Mexican Oaxaca cheese. Twenty-seven lactobacilli isolated from Oaxaca cheese were identified at species level by 16S rRNA sequencing. Selected isolates were further characterized by ribotyping. Isolates were screened, among others, by acidifying capacity, antibiotic resistance, and activity against pathogens. Lactobacillus plantarum was predominant in Oaxaca cheese. The intraspecies variability of Lb. plantarum isolates was great. Multiple antibiotic resistances were observed. Eight isolates showed antimicrobial activity against the pathogenic species tested. Four Lb. plantarum strains showing low antibiotic resistance index, antimicrobial activity against enterotoxigenic Staphylococcus aureus and Listeria innocua stains, amine-negative decarboxylase activity, and resistance to NaCl and bile salt solutions, could be preselected to complete studies focused on designing a culture for use in pasteurized-milk Oaxaca cheese manufacturing.

Corrigendum: Gene-environment interaction in the era of precision medicine-filling the potholes rather than starting to build a new road.

[This corrects the article DOI: 10.3389/fgene.2020.00921.].

Experimental Development of an Injection Molding Process Window.

Injection molding is one of the most common and effective manufacturing processes used to produce plastic products and impacts industries around the world. However, injection molding is a complex process that requires careful consideration of several key control variables. These variables and how they are utilized greatly affect the resulting polymer parts of any molding operation. The bounds of the acceptable values of each Control Process Variable (CPV) must be analyzed and delimited to ensure manufacturing success and produce injected molded parts efficiently and effectively. One such method by which the key CPVs of an injection molding operation can be delimited is through the development of a process window. Once developed, operating CPVs at values inside the boundaries of the window or region will allow for the consistent production of parts that comply with the desired Performance Measures (PM), promoting a stable manufacturing process. This work proposes a novel approach to experimentally developing process windows and illustrates the methodology with a specific molding operation. A semicrystalline material was selected as it is more sensitive to process conditions than amorphous materials.

Modelling of genetic interactions improves prediction of hybrid patterns--a case study in domestic fowl.

A major challenge in complex trait genetics is to unravel how multiple loci and environmental factors together cause phenotypic diversity. Both first (F(1)) and second (F(2)) generation hybrids often display phenotypes that deviate from what is expected under intermediate inheritance. We have here studied two chicken F(2) populations generated by crossing divergent chicken lines to assess how epistatic loci, identified in earlier quantitative trait locus (QTL) studies, contribute to hybrid deviations from the mid-parent phenotype. Empirical evidence suggests that the average phenotypes of the intercross birds tend to be lower than the midpoint between the parental means in both crosses. Our results confirm that epistatic interactions, despite a relatively small contribution to the phenotypic variance, play an important role in the deviation of hybrid phenotypes from the mid-parent values (i.e. multi-locus hybrid genotypes lead to lower rather than higher body weights). To a lesser extent, dominance also appears to contribute to the mid-parent deviation, at least in one of the crosses. This observation coincides with the hypothesis that hybridization tends to break up co-adapted gene complexes, i.e. generate Bateson-Dobzhansky-Muller incompatibilities.

Technological characterization of Geotrichum candidum strains isolated from a traditional Spanish goats' milk cheese.

Forty-one strains of Geotrichum candidum isolated from Armada cheese, Sobado variety, were screened for their enzymatic activities, including proteolytic and lipolytic activities and aminopeptidase activity. The highest extracellular proteolytic activity was detected for 8 strains with values ranging between 2.086 and 4.685 mM Gly L⁻¹ of milk. Extracellular lipolytic activity was high for all but one of the G. candidum strains, with values ranging between 67 and 131 µmol oleic mL⁻¹. Cell-bound lipase activity showed values which were considerably lower than those for extracellular activity, ranging between 32.50 and 42.50 µmol oleic mL⁻¹ and falling below 20 µmol oleic mL⁻¹ in 28 strains. Aminopeptidase activity was not very high in the cell-free extract (CFE) of any of the strains, showing the highest values toward the substrate Lys-p-nitroanilide, with levels of activity ranging between 6.12 and 10.05 UE mg⁻¹ protein in 8 strains. In accordance with the results obtained, four G. candidum strains were selected as co-cultures in order to study their role in the ripening of a semi-hard goat's milk cheese.

More than 500,000 years of right-handedness in Europe.

Considerable research supports the high frequency of right-handedness in living Homo sapiens, with worldwide rates of approximately nine right- for every one left-hander. Right-handedness appears to be a uniquely human trait, as no other primate species, no matter how proficient in tool use, shows frequencies even close to the strong right bias typical of humans (Cashmore, Uomini, & Chapelain, 2008; McGrew & Marchant 1997; Steele & Uomini, 2009). Here we review our research on human fossils from Sima de los Huesos (Atapuerca, Spain) and their likely descendants, the European Neandertals. We document hand preference in fossils by scratch patterns that occur on the labial (lip) face of incisors and canines, and contend that these patterns provide a reliable means for identifying predominant hand use in these samples. Manipulatory marks on the anterior teeth show a persistent pattern of right-handed actions, implying that the modern human pattern of dominant right-handedness extends deep into the European past.

Misfit profile of dental bridges.

Clinical evidence has shown that dental bridge (DB) misfit is more frequent than individual crown restoration misfit, and that it causes restorative failures. A comparative study of misfit profiles was performed for the most common clinical situations in mouth rehabilitation procedures with fixed restorations: gold-cast DB and porcelain metal alloy DB. Evidence from this study may lead dentists to consider the advantages and weaknesses of one structure type over the other. The results obtained showed two different profiles, with the porcelain metal alloy (PMA) DB being less predictable than the gold-cast DB. The posterior abutment restoration tends to come apart distally from the tooth structure and get closer to the mesial aspect, while keeping distal-medial separation with respect to the anterior abutment. The gold-cast DBs showed a separation pattern in which the distal end comes away from the molar and the medial end from the premolar, getting clearly closer to the faces next to the pontic: its distal aspect gets closer to the premolar and mesially to the molar The study has also shown that even though the adaptive patterns are different, is less in PMA than in gold alloys, the latter being used only in a small percentage of clinical indications in oral rehabilitation, mainly due to aesthetic demands and high costs. The impact of this research in clinical dentistry is that PMA DBs have shown worst marginal adaptation areas where clinically, there is lack of vision or inaccessibility for appropriate dental preparation.

Identification of X-linked quantitative trait loci affecting cold tolerance in Drosophila melanogaster and fine mapping by selective sweep analysis.

Drosophila melanogaster is a cosmopolitan species that colonizes a great variety of environments. One trait that shows abundant evidence for naturally segregating genetic variance in different populations of D. melanogaster is cold tolerance. Previous work has found quantitative trait loci (QTL) exclusively on the second and the third chromosomes. To gain insight into the genetic architecture of cold tolerance on the X chromosome and to compare the results with our analyses of selective sweeps, a mapping population was derived from a cross between substitution lines that solely differed in the origin of their X chromosome: one originates from a European inbred line and the other one from an African inbred line. We found a total of six QTL for cold tolerance factors on the X chromosome of D. melanogaster. Although the composite interval mapping revealed slightly different QTL profiles between sexes, a coherent model suggests that most QTL overlapped between sexes, and each explained around 5-14% of the genetic variance (which may be slightly overestimated). The allelic effects were largely additive, but we also detected two significant interactions. Taken together, this provides evidence for multiple QTL that are spread along the entire X chromosome and whose effects range from low to intermediate. One detected transgressive QTL influences cold tolerance in different ways for the two sexes. While females benefit from the European allele increasing their cold tolerance, males tend to do better with the African allele. Finally, using selective sweep mapping, the candidate gene CG16700 for cold tolerance colocalizing with a QTL was identified.

Multiallelic models of genetic effects and variance decomposition in non-equilibrium populations.

Quantitative genetics stems from the theoretical models of genetic effects, which are re-parameterizations of the genotypic values into parameters of biological (genetic) relevance. Different formulations of genetic effects are adequate to address different subjects. We thus need to generalize and unify them under a common framework for enabling researchers to easily transform genetic effects between different biological meanings. The Natural and Orthogonal Interactions (NOIA) model of genetic effects has been developed to achieve this aim. Here, we further implement the statistical formulation of NOIA with multiple alleles under Hardy-Weinberg departures (HWD). We show that our developments are straightforwardly connected to the decomposition of the genetic variance and we point out several emergent properties of multiallelic quantitative genetic models, as compared to the biallelic ones. Further, NOIA entails a natural extension of one-locus developments to multiple epistatic loci under linkage equilibrium. Therefore, we present an extension of the orthogonal decomposition of the genetic variance to multiple epistatic, multiallelic loci under HWD. We illustrate this theory with a graphical interpretation and an analysis of published data on the human acid phosphatase (ACP1) polymorphism.

Confocal-rainbow volume holographic imaging system.

The performance of broadband volume holographic imaging system in terms of depth selectivity is investigated. The mechanism for depth resolution degradation is explained. In order to overcome this resolution degradation, a novel imaging device, the confocal-rainbow volume holographic imaging system, is proposed. Modeling and experimental validation of the performance of this novel imaging system indicates that depth resolution <16 µm is achievable. The lateral resolution of this device is <2.5 µm along a field of view of 300 µm×100 µm.

Analysis of diffracted image patterns from volume holographic imaging systems and applications to image processing.

Diffracted image patterns from volume holograms that are used in volume holographic imaging systems (VHISs) are investigated. It is shown that, in VHISs, prior information about the shape and spectral properties of the diffracted patterns is important not only to determine the curvature and field of view of the image, but also for image registration and noise removal. A new methodology to study numerically and analytically the dependence of VHIS diffraction patterns with the hologram construction parameters and the readout wavelength is described. Modeling and experimental results demonstrate that, in most cases, VHIS diffracted shapes can be accurately represented by hyperbolas.

Spatial-spectral volume holographic systems: resolution dependence on effective thickness.

The resolution dependence of spatial-spectral volume holographic imaging systems on angular and spectral bandwidth of nonuniform gratings is investigated. Modeling techniques include a combination of the approximate coupled-wave analysis and the transfer-matrix method for holograms recorded in absorptive media. The effective thickness of the holograms is used as an estimator of the resolution of the imaging systems. The methodology, which assists in the design and optimization of volume holographic simulation results based on our approach, are confirmed with experiments and show proof of consistency and usefulness of the proposed models.