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.

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.].

The Ability of Porcine Reproductive and Respiratory Syndrome Virus Isolates to Induce Broadly Reactive Neutralizing Antibodies Correlates With In Vivo Protection.

Porcine reproductive and respiratory syndrome (PRRS) is considered one of the most relevant diseases of swine. The condition is caused by PRRS virus (PRRSV), an extremely variable virus of the Arteriviridae family. Its heterogeneity can be responsible, at least partially, of the poor cross-protection observed between PRRSV isolates. Neutralizing antibodies (NAs), known to play a role in protection, usually poorly recognize heterologous PRRSV isolates, indicating that most NAs are strain-specific. However, some pigs develop broadly reactive NAs able to recognize a wide range of heterologous isolates. The aim of this study was to determine whether PRRSV isolates that induce broadly reactive NAs as determined in vitro are able to confer a better protection in vivo. For this purpose two in vivo experiments were performed. Initially, 40 pigs were immunized with a PRRSV-1 isolate known to induce broadly reactive NAs and 24 additional pigs were used as controls. On day 70 after immunization, the pigs were divided into eight groups composed by five immunized and three control pigs and exposed to one of the eight different heterologous PRRSV isolates used for the challenge. In the second experiment, the same experimental design was followed but the pigs were immunized with a PRRSV-1 isolate, which is known to generate mostly strain-specific NAs. Virological parameters, specifically viremia and the presence of challenge virus in tonsils, were used to determine protection. In the first experiment, sterilizing immunity was obtained in three groups, prevention of viremia was observed in two additional groups, although the challenge virus was detected occasionally in the tonsils of immunized pigs, and partial protection, understood as a reduction in the frequency of viremia compared with controls, was recorded in the remaining three groups. On the contrary, only partial protection was observed in all groups in the second experiment. The results obtained in this study confirm that PRRSV-1 isolates differ in their ability to induce cross-reactive NAs and, although other components of the immune response might have contributed to protection, pigs with cross-reactive NAs at the time of challenge exhibited better protection, indicating that broadly reactive NAs might play a role in protection against heterologous reinfections.

Gene-Environment Interaction in the Era of Precision Medicine - Filling the Potholes Rather Than Starting to Build a New Road.

Gene-environment interaction is a key part of evolutionary biology, animal, and plant breeding, and a number of health sciences, like epidemiology and precision medicine. However, bottlenecks in models of gene-environment interaction have recently been made manifest, particularly in the field of medicine and, consequently, specific improvements have been explicitly requested-namely, an implementation of gene-environment interaction satisfactorily disentangled from gene-environment correlation. The present paper meets those demands by providing mathematical developments that implement classical models of genetic effects and bring them up to date with the prospects current available data bestow. These developments are shown to overcome the limitations of previous proposals through the analysis of illustrative examples on disease susceptibility, with special attention paid to precision medicine. Indeed, a number of misconceptions about the application of models of genetic/environmental effects to precision medicine are here identified and clarified. The theory here provided is argued to strengthen, in particular, the methodology required for high-precision characterization of strain virulence in the study of the COVID-19 pandemic.

Orthogonal Decomposition of the Genetic Variance for Epistatic Traits Under Linkage Disequilibrium-Applications to the Analysis of Bateson-Dobzhansky-Müller Incompatibilities and Sign Epistasis.

The one-century-old theory of orthogonal genetic variance decomposition originated the field of quantitative genetics and has kept on being improved ever since. Recently, serious concerns about the possibility of attaining a satisfactory implementation of genetic variance decomposition with linkage disequilibrium (LD) and epistasis have been raised. In this paper we dissipate such doubts by completing the classical theory of variance decomposition into additive, dominance and epistasis components with LD. We apply that theory to the analysis of the genotype-to-phenotype maps of two cases of particular evolutionary interest-Bateson-Dobzhansky-Müller incompatibilities and sign epistasis. For the first case we show how negative LD and reduction of heterozygotes may contribute to maintain genetic variability after secondary contact. For the second case we show that LD transforms the set of frequencies leading to an evolutionary plateau into a ridge. Our theoretical developments reassuringly reflect the complexity LD conveys to genetic systems throughout novel properties-as compared with systems under linkage equilibrium. We argue that such particularities might have actually contributed to cause confusion about the feasibility of developing this methodology. In any case, the theory we provide in this paper enables new perspectives in both evolutionary and quantitative genetics studies.

Bioactive Components and Antioxidant and Antibacterial Activities of Different Varieties of Honey: A Screening Prior to Clinical Application.

This study assessed 16 different honey samples in order to select the best one for therapeutic purposes. First, a study of honey's main bioactive compounds was carried out. Then phenolic profiles were determined and specific compounds quantified using a HPLC system coupled to a mass spectrometer. Then, antioxidant activity, by three in vitro methods, and antibacterial activity against reference strains and clinical isolates were evaluated. Great variability among samples was observed regarding ascorbic acid (between 0.34 ± 0.00 and 75.8 ± 0.41 mg/100 g honey; p < 0.001), total phenolic compounds (between 23.1 ± 0.83 and 158 ± 5.37 mg/100 g honey; p < 0.001), and total flavonoid contents (between 1.65 ± 0.11 and 5.93 ± 0.21 mg/100 g honey; p < 0.001). Forty-nine different phenolic compounds were detected, but only 46 of them were quantified by HPLC. The concentration of phenolic compounds and the phenolic profiles varied widely among samples (between 1.06 ± 0.04 and 18.6 ± 0.73 mg/100 g honey; p < 0.001). Antioxidant activity also varied significantly among the samples. All honey varieties exhibited antibacterial activity against both reference and clinical strains (effective concentrations ranged between 0.05 and 0.40 g/mL depending on the honey sample and bacteria tested). Overall, samples with better combinations of bioactive properties were avocado and chestnut honeys.

[Domiciliary intervention by occupational therapy after hospital discharge in order to prevent re-admission in the elderly: Study protocol for a randomised clinical trial]. / Intervención domiciliaria por terapia ocupacional postalta para prevenir la rehospitalización de personas mayores: protocolo de estudio de un ensayo clínico aleatorizado.

BACKGROUND AND OBJECTIVE: Re-admission to hospital by the elderly is a frequent event that is associated with complications. The aim of this article is to describe a randomised clinical trial protocol which has the aim of describing and comparing the impact of a home-based intervention by Occupational Therapists (OT) in the likelihood of re-admission at 6 months. MATERIAL AND METHOD: Randomised controlled trial conducted in medical units of the "Hospital Clínico de la Universidad de Chile" and "Hospital de la Fuerza Aérea de Chile", with 217 patients aged 60 years or older admitted for acute or decompensated chronic disease, provided that they have a person of reference after hospital discharge. The control group consists of the usual care regarding post-discharge patients. This will be compared to the experimental group that includes a home visit from OT on two occasions over a six-month period, who will apply a multicomponent intervention. Informed consent will be requested with the sociodemographic and hospital admission information, functional (Barthel index; Lawton & Brody Scale) and cognitive performance (Short Portable Mental Status Questionnaire; Functional Activities Questionnaire; Confusion Assessment Method), and comorbidity (Cumulative Illness Rating Scale for Geriatrics). Both groups will receive a telephone follow-up at 4, 12 and 24 weeks after hospital discharge. RESULTS: The intervention will reduce the rate of hospital re-admissions by at least 40% at 6 months compared with usual care. CONCLUSION: It will be useful to know the components that reduce the risk of hospital re-admissions and improve hospital discharge healthcare for elderly.

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.

On the partitioning of genetic variance with epistasis.

The decomposition of genetic variance into additive, dominance, and epistatic components is a common procedure in quantitative genetics. Yet, the interpretation of this variance partition is not trivial, especially concerning nonadditive components. In this chapter, we compile various uses of variance partitioning from published analyses, new simulations, and theoretical examples. We show ways in which advanced genetic modeling facilitates the analysis of data through variance partitioning, focusing on the natural and orthogonal interactions (NOIA) model. We also discuss how epistasis and epistatic variance may influence the outcome of selection, a topic that is still a matter of debate among quantitative and evolutionary geneticists.

New luminescence ages for the Galería Complex archaeological site: resolving chronological uncertainties on the acheulean record of the Sierra de Atapuerca, northern Spain.

The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean age = 313±14 ka; n = 4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT-OSL dating are suitable for resolving Middle Pleistocene chronologies for the Sierra de Atapuerca karstic infill sequences.

Corrigendum for "Dissecting genetic effects with imprinting".

[This corrects the article DOI: 10.3389/fevo.2014.00051.][This corrects the article on p. 198 in vol. 5, PMID: 25071828.].

MAPfastR: quantitative trait loci mapping in outbred line crosses.

MAPfastR is a software package developed to analyze quantitative trait loci data from inbred and outbred line-crosses. The package includes a number of modules for fast and accurate quantitative trait loci analyses. It has been developed in the R language for fast and comprehensive analyses of large datasets. MAPfastR is freely available at: http://www.computationalgenetics.se/?page_id=7.

Identification of potential biomarkers from microarray experiments using multiple criteria optimization.

Microarray experiments are capable of determining the relative expression of tens of thousands of genes simultaneously, thus resulting in very large databases. The analysis of these databases and the extraction of biologically relevant knowledge from them are challenging tasks. The identification of potential cancer biomarker genes is one of the most important aims for microarray analysis and, as such, has been widely targeted in the literature. However, identifying a set of these genes consistently across different experiments, researches, microarray platforms, or cancer types is still an elusive endeavor. Besides the inherent difficulty of the large and nonconstant variability in these experiments and the incommensurability between different microarray technologies, there is the issue of the users having to adjust a series of parameters that significantly affect the outcome of the analyses and that do not have a biological or medical meaning. In this study, the identification of potential cancer biomarkers from microarray data is casted as a multiple criteria optimization (MCO) problem. The efficient solutions to this problem, found here through data envelopment analysis (DEA), are associated to genes that are proposed as potential cancer biomarkers. The method does not require any parameter adjustment by the user, and thus fosters repeatability. The approach also allows the analysis of different microarray experiments, microarray platforms, and cancer types simultaneously. The results include the analysis of three publicly available microarray databases related to cervix cancer. This study points to the feasibility of modeling the selection of potential cancer biomarkers from microarray data as an MCO problem and solve it using DEA. Using MCO entails a new optic to the identification of potential cancer biomarkers as it does not require the definition of a threshold value to establish significance for a particular gene and the selection of a normalization procedure to compare different experiments is no longer necessary.

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.