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We can now sequence and identify genome wide epigenetic patterns and perform a variety of “genomic experiments” within relatively short periods of time—ranging from days to weeks. Yet, despite these technological advances, we have a poor understanding of the inter-relationships between epigenetics, genome structure-function, and nutrition. Perhaps this limitation lies, in part, in our propensity to study epigenetics in terms of the linear arrangement of elements and genes. Here we propose that a more complete understanding of how nutrition impacts on epigenetics and cellular development resides within the inter-relationships between DNA and histone modification patterns and genome function, in the context of spatial organization of chromatin and the epigenome.

Background: With the developments of DNA sequencing technology, large amounts of sequencing data have been produced that provides unprecedented opportunities for advanced association studies between somatic mutations and cancer types/subtypes which further contributes to more accurate somatic mutation based cancer typing (SMCT). In existing SMCT methods however, the absence of high-level feature extraction is a major obstacle in improving the classification performance. Results: We propose DeepCNA, an advanced convolutional neural network (CNN) based classifier, which utilizes copy number aberrations (CNAs) and HiC data, to address this issue. DeepCNA first pre-process the CNA data by clipping, zero padding and reshaping. Then, the processed data is fed into a CNN classifier, which extracts high-level features for accurate classification. Experimental results on the COSMIC CNA dataset indicate that 2D CNN with both cell lines of HiC data lead to the best performance. We further compare DeepCNA with three widely adopted classifiers, and demonstrate that DeepCNA has at least 78% improvement of performance. Conclusions: This paper demonstrates the advantages and potential of the proposed DeepCNA model for processing of somatic point mutation based gene data, and proposes that its usage may be extended to other complex genotype-phenotype association studies. [ABSTRACT FROM AUTHOR]

The effect of hydrogen on the fracture toughness properties of an API X65 pipeline steel is studied under simulated H 2 S in-service conditions. The fracture toughness properties are measured in LT and SL directions (perpendicular and parallel to the pipeline wall thickness, respectively), following ASTM E1820. Due to size restrictions of standard single edge notch bending (SEB) specimens at the direction parallel to the thickness of the pipeline wall, an experimental protocol (see the patent) was developed to carry out the fracture toughness tests, while complying with ASTM standard 1820. This approach is especially useful in situations where hydrogen induced cracking (HIC) and in a broader sense, stepwise cracking takes place, since these cracks initiate and grow primarily in planes parallel to the pipeline rolling plane. Such values of fracture toughness are often different from those commonly measured in planes perpendicular to the rolling plane. Hydrogen might not have the same effect on fracture toughness properties as measured in different directions, due to microstructural features which are inherent from steel manufacturing process. The steady state H 2 S in-service conditions are simulated by electrolytically charging the specimen, for 48 h and then testing ( ex-situ ) the specimen for evaluating the fracture toughness properties. The steady state H 2 S environment charging was obtained by measuring the hydrogen concentration in the bulk of the specimen through thermal desorption spectroscopy (TDS) at three levels of hydrogen concentration. It was observed that the K Q was moderately decreased with increasing hydrogen concentration in the bulk of the steel, while CTOD 0 showed a significant reduction with increasing hydrogen concentration. [ABSTRACT FROM AUTHOR]

• Histone gene clusters are organized in phase-separated Histone Locus Bodies (HLBs). • Higher-order chromatin at HLBs shows variable 3D organization during G1 phase. • Invariable genomic contacts are required for the basic spatial organization at HLBs. • A novel distal enhancer outside the histone gene cluster supports HLB organization. Human Histone Locus Bodies (HLBs) are nuclear subdomains comprised of clustered histone genes that are coordinately regulated throughout the cell cycle. We addressed temporal-spatial higher-order genome organization for time-dependent chromatin remodeling at HLBs that supports control of cell proliferation. Proximity distances of specific genomic contacts within histone gene clusters exhibit subtle changes during the G1 phase in MCF10 breast cancer progression model cell lines. This approach directly demonstrates that the two principal histone gene regulatory proteins, HINFP (H4 gene regulator) and NPAT, localize at chromatin loop anchor-points, denoted by CTCF binding, supporting the stringent requirement for histone biosynthesis to package newly replicated DNA as chromatin. We identified a novel enhancer region located ∼ 2 MB distal to histone gene sub-clusters on chromosome 6 that consistently makes genomic contacts with HLB chromatin and is bound by NPAT. During G1 progression the first DNA loops form between one of three histone gene sub-clusters bound by HINFP and the distal enhancer region. Our findings are consistent with a model that the HINFP/NPAT complex controls the formation and dynamic remodeling of higher-order genomic organization of histone gene clusters at HLBs in early to late G1 phase to support transcription of histone mRNAs in S phase. [ABSTRACT FROM AUTHOR]

To achieve lightweight design while retaining its crash performance, an aluminum alloy component filled with foam has been adopted as an alternative lightweight material. In the paper, the effect of different types of filling on the automotive side member is studied. Impact performance is compared in terms of the automobile energy absorbing capability and also its occupant safety, measured in terms of head injury criteria (Manning) and chest severity index (CSI). It is shown that the partially filled side member with values of 513.6 (HIC15), 677.3 (HIC36), 807.2 (CSI) and a weight of 5.45kg is found to yield lower potential of injury, and higher specific energy absorption (SEA) compared to an empty side member. It can be concluded that, even though the fully filled side member shows remarkable performance in terms of HIC, it increases the chances of injury to the chest. Future study can include different types of foam for performance improvement.

Proper helmet fit is important for optimizing head protection during an impact, yet many motorcyclists wear helmets that do not properly fit their heads. The goals of this study are i) to quantify how a mismatch in headform size and motorcycle helmet size affects headform peak acceleration and head injury criteria (HIC), and ii) to determine if peak acceleration, HIC, and impact speed can be estimated from the foam liner’s maximum residual crush depth or residual crush volume. Shorty-style helmets (4 sizes of a single model) were tested on instrumented headforms (4 sizes) during linear impacts between 2.0 and 10.5 m/s to the forehead region. Helmets were CT scanned to quantify residual crush depth and volume. Separate linear regression models were used to quantify how the response variables (peak acceleration (g), HIC, and impact speed (m/s)) were related to the predictor variables (maximum crush depth (mm), crush volume (cm 3 ), and the difference in circumference between the helmet and headform (cm)). Overall, we found that increasingly oversized helmets reduced peak headform acceleration and HIC for a given impact speed for maximum residual crush depths less than 7.9 mm and residual crush volume less than 40 cm 3 . Below these levels of residual crush, we found that peak headform acceleration, HIC, and impact speed can be estimated from a helmet’s residual crush. Above these crush thresholds, large variations in headform kinematics are present, possibly related to densification of the foam liner during the impact. [ABSTRACT FROM AUTHOR]

Metastatic disease is the leading cause of death due to prostate cancer (PCa). Although the hypermethylated in cancer 1 (HIC1) gene has been observed to be epigenetically modified in PCa, its intrinsic role and mechanism in PCa metastasis still remain uncertain. Here, we show that hypermethylation of the HIC1 promoter markedly reduces its suppressive function in metastatic PCa tissues as compared with primary and adjacent normal prostate tissues, and is associated with poor patient survival. PCas in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout showed stronger metastatic behaviour than those in heterozygous mice, as a result of epithelial-mesenchymal transition (EMT). Moreover, impairment of HIC1 expression in PCa cells induced their migration and metastasis through EMT, by enhancing expression of Slug and CXCR4, both of which are critical to PCa metastasis; the CXCL12-CXCR4 axis promotes EMT by activating the extracellular signal-regulated kinase (ERK) 1/2 pathway. Taken together, our results suggest that evaluation of HIC1-CXCR4-Slug signalling may provide a potential predictor for PCa aggressiveness. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lumped Mass-Spring (LMS) model is simple but very effective for the design study of vehicle crashworthiness and occupant safety. To construct the LMS model, the SISAME software and the NHTSA test data were used. Using the SISAME, the weights of mass elements and the load-paths of spring elements were optimally and directly extracted from the test data. Among the various types of spring, the segmented inelastic type of spring was effective for the vehicle crash analysis. In this study, to obtain the occupant injuries such as HIC15 and 3 ms Chest g's, the LMS model containing the occupant model consisted of the head, chest and pelvis was developed and validated. The modeling for the chest deflection and neck injuries was not considered in this study because of the modeling difficulties and the limitation of the SISAME software. The simulation results of occupants showed good agreements with the test results. The modeling idea for the occupant was simple but very effective. [ABSTRACT FROM AUTHOR]

Adsorption behavior of unstable proteins, i.e., bovine serum albumin and α-lactalbumin, has been studied on a hydrophobic interaction chromatography medium under mass overloading conditions at different kosmotropic salt concentrations in the mobile phase. A mechanistic model has been formulated and used to describe kinetics and thermodynamics of protein interactions with the adsorbent surface. The model assumed two-site binding adsorption and reversible protein unfolding, which allowed predicting the inhibition of protein unfolding at high column loadings. A simplified procedure for the determination of model parameters has been developed, which was based on the inverse method. The model was successfully used to reproduce the pattern of chromatographic elution as well as the course of breakthrough curves. The model formulation was supported by Nano Differential Scanning Fluorimetry measurements, which were exploited to determine the protein stability in the liquid and adsorbed phases at different column loadings and salt concentrations. [ABSTRACT FROM AUTHOR]

Eukaryotic chromosomes exhibit a hierarchical organization that spans a spectrum of length scales, ranging from sub-regions known as loops, which typically comprise hundreds of base pairs, to much larger chromosome territories that can encompass a few mega base pairs. Chromosome conformation capture experiments that involve high-throughput sequencing methods combined with microscopy techniques have enabled a new understanding of inter- and intra-chromosomal interactions with unprecedented details. This information also provides mechanistic insights on the relationship between genome architecture and gene expression. In this article, we review the recent findings on three-dimensional interactions among chromosomes at the compartment, topologically associating domain, and loop levels and the impact of these interactions on the transcription process. We also discuss current understanding of various biophysical processes involved in multi-layer structural organization of chromosomes. Then, we discuss the relationships between gene expression and genome structure from perturbative genome-wide association studies. Furthermore, for a better understanding of how chromosome architecture and function are linked, we emphasize the role of epigenetic modifications in the regulation of gene expression. Such an understanding of the relationship between genome architecture and gene expression can provide a new perspective on the range of potential future discoveries and therapeutic research., (© 2023 IOP Publishing Ltd.)

Low alloy quenched and tempered steels are widely used as screws and studs. In this work screws of AISI 4140 steel were used to bolt the Christma's tree to his cap in offshore oil and gas production. In the moment of the cap re-motion to perform a routine maintenance five 1″ screws failed. The screws worked under cathodic protection, which means that they must have undergone hydrogen pick-up. The investigation showed that the screws had been correctly heat treated by quenching and high temperature tempering, but the sulfur content and the level of inclusions were too high. As a consequence, the screws were highly susceptible to hydrogen induced cracking (HIC). On the other hand, the analysis of the fracture surface revealed that the main cracking mechanism was fatigue. The main recommendation resulted from this work is that the specification for new screws for this kind of service must be more restrictive to sulfur and inclusions contents. [ABSTRACT FROM AUTHOR]

Background Chromosome conformation capture, coupled with high throughput DNA sequencing in protocols like Hi-C and 3C-seq, has been proposed as a viable means of generating data to resolve the genomes of microorganisms living in naturally occuring environments. Metagenomic Hi-C and 3C-seq datasets have begun to emerge, but the feasibility of resolving genomes when closely related organisms (strain-level diversity) are present in the sample has not yet been systematically characterised. Methods We developed a computational simulation pipeline for metagenomic 3C and Hi-C sequencing to evaluate the accuracy of genomic reconstructions at, above, and below an operationally defined species boundary. We simulated datasets and measured accuracy over a wide range of parameters. Five clustering algorithms were evaluated (2 hard, 3 soft) using an adaptation of the extended B-cubed validation measure. Results When all genomes in a sample are below 95% sequence identity, all of the tested clustering algorithms performed well. When sequence data contains genomes above 95% identity (our operational definition of strain-level diversity), a naive soft-clustering extension of the Louvain method achieves the highest performance. Discussion Previously, only hard-clustering algorithms have been applied to metagenomic 3C and Hi-C data, yet none of these perform well when strain-level diversity exists in a metagenomic sample. Our simple extension of the Louvain method performed the best in these scenarios, however, accuracy remained well below the levels observed for samples without strain-level diversity. Strain resolution is also highly dependent on the amount of available 3C sequence data, suggesting that depth of sequencing must be carefully considered during experimental design. Finally, there appears to be great scope to improve the accuracy of strain resolution through further algorithm development.

There are many ways of car collisions which depend on car motion modes before and after crashes, speed, kinds of baskets, their heights, weights and rigidity. The machinery of the occupant’s movement at the moment of the crash is even more diffi cult. In order to find out precisely the chance of body injury, it is important to measure not only parameters that were mentioned above but also occupant’s height, weight, age, position of sitting, condition of body, whether there was any protection system used. The largest number of car crashes happen at the moment of frontal crash. This article’s aim is to analyse the types of frontal crashes and their repartition, to diagnose what part in occupant’s safety the protection system’s use takes, and also to analyse head injury coefficient dependence on car speed and show critical injuries and fatality limits in cases when driver is driving with no seat-belts in and while the car is without airbag. The research is done at the moment of ideal frontal crash by simulating distance from the occupant body to the wheel in diff erent types of baskets.

Understanding the folding of the human genome is a key challenge of modern structural biology. The emergence of chromatin conformation capture assays ({it e.g.} Hi-C) has revolutionized chromosome biology and provided new insights into the three dimensional structure of the genome. The experimental data are highly complex and need to be analyzed with quantitative tools. It has been argued that the data obtained from Hi-C assays are consistent with a fractal organization of the genome. A key characteristic textcolor{red}{of the fractal globule} is the lack of topological complexity (knotting or inter-linking). However, the absence of topological complexity contradicts results from polymer physics showing that the entanglement of long linear polymers in a confined volume increases rapidly with the length and with decreasing volume. textcolor{red}{{it In vivo} and {it in vitro} assays support this claim in some biological systems. We simulate knotted lattice polygons confined inside a sphere and demonstrate that their contact frequencies agree with the human Hi-C data.} We conclude that the topological complexity of the human genome cannot be inferred from current Hi-C data.

Background and objective Abrupt accelerations or decelerations can cause large strain in brain tissues and, consequently, different forms of Traumatic Brain Injury (TBI). In order to predict the effect of the accelerations on the soft tissues of the brain, many different injury metrics have been proposed (typically, an injury metric is a real valued functional of the accelerations). The objective of this article is to make a formal and empirical comparison, in order to identify general criteria for reasonable injury metrics, and propose a general guideline to avoid ill-proposed injury metrics. Methods A medium-sized sample of vehicle–pedestrian collisions, from Post Mortem Human Subject (PMHS) tests, is analyzed. A statistical study has been conducted in order to determine the discriminant power of the usual metrics. We use Principal Component Analysis to reduce dimensionality and to check consistency among the different metrics. In addition, this article compares the mathematical properties of some of these functionals, trying to identify the desirable properties that any of those functionals needs to fulfill in order to be useful for optimization. Results We have found a pair-wise consistency of all the currently used metrics (any two injury metrics are always positively related). In addition, we observed that two independent principal factors explain about 72.5% of the observed variance among all collision tests. This is remarkable because it indicates that despite high number of different injury metrics, a reduced number of variables can explain the results of all these metrics. With regard to the formal properties, we found that essentially all injury mechanisms can be accounted by means of scalable, differentiable and convex functionals (we propose to call minimization suitable injury metric any metric having these three formal properties). In addition three useful functionals, usable as injury metrics, are identified on the basis of the empirical comparisons. Conclusions The commonly used metrics are highly consistent, but also highly redundant. Formal minimal conditions of a reasonable injury metric has been identified. Future proposals of injury metrics can benefit from the results of this study. [ABSTRACT FROM AUTHOR]

Various liquid chromatographic techniques are considered standard analytical methods in proteins characterization. These methods provide essential information for drug approval, for biological and life sciences. On the other hand, there are some issues and challenges which have to be taken into account when analyzing these biopharmaceuticals. The aim of this review to summarize the most recent knowledge relating to the following topics: i) sample stability and complexity ii) adsorption problems: instrument inertness iii) adsorption problems: recovery from the stationary phase and iv) challenges in method development. This information is supposed to help practicing chromatographers in the emerging field of therapeutic protein chromatography. [ABSTRACT FROM AUTHOR]

Chromosome Conformation Capture techniques regularly detect physical interactions between mitochondrial and nuclear DNA ( i.e. mito-nDNA interactions) in mammalian cells. We have evaluated mito-nDNA interactions captured by HiC and Circular Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions are statistically significant and shared between biological and technical replicates. The most frequent interactions occur with repetitive DNA sequences, including centromeres in human cell lines and the 18S rDNA in mouse cortical astrocytes. Our results demonstrate a degree of selective regulation in the identity of the interacting mitochondrial partners confirming that mito-nDNA interactions in mammalian cells are not random. [ABSTRACT FROM AUTHOR]

To overcome limitations of periodic separations of proteins in batch chromatographic columns Carousel Multi-Column Setup (CMS) has been recently suggested and theoretically analyzed in a previous study (R. Bochenek, W. Marek, W. Piątkowski, D. Antos, J. Chromatogr. A, 1301 (2013) 60–72). In this system, feed and mobile phase streams are subsequently delivered through parallel columns to mimic their countercurrent movement with respect to the fluid flow. All fluxes in the system are synchronized to ensure continuous feed delivery, which however causes reduction in the size of the operating window compared to batchwise-operating systems. In this study to improve the performance of CMS, additional process variables have been considered, such as the flow rate gradient and feed concentration. Though altering both variables allowed improving the separation selectivity and extending the operating window, the feed concentration appeared to be the most influential parameter affecting the process performance. Moreover, a procedure for practical realization of protein separations in CMS has been developed, including hints about the process design, configuration of columns and detectors, and use of pumps. As the case study, the separation of a ternary mixture of proteins, i.e. , cytochrome C, lysozyme and immunoglobulin G, on hydrophobic interaction columns was used. A target product was a protein with intermediate adsorption strength that was isolated out of a more and less strongly adsorbed compound. [ABSTRACT FROM AUTHOR]

Background: Proximity ligation-mediated methods are essential to study the impact of three-dimensional chromatin organization on gene programming. Albeit significant progress has been made in the development of computational tools that assess long-range chromatin interactions, next to nothing is known about the quality of the generated datasets. Method: We have developed LOGIQA (www.ngs-qc.org/logiqa), a database hosting quality scores for long-range genome interaction assays, accessible through a user-friendly web-based environment. Results: Currently, LOGIQA harbors QC scores for >900 datasets, which provides a global view of their relative quality and reveals the impact of genome size, coverage and other technical aspects. LOGIQA provides a user-friendly dataset query panel and a genome viewer to assess local genome-interaction maps at different resolution and quality-assessment conditions. Conclusions: LOGIQA is the first database hosting quality scores dedicated to long-range chromatin interaction assays, which in addition provides a platform for visualizing genome interactions made available by the scientific community. [ABSTRACT FROM AUTHOR]

Protein hydrophobicity can be modified after a PEGylation process. However, hydrophobic interaction chromatography (HIC) has been used to separate PEGylation reaction products less frequently than other techniques. In this context, chromatographic monoliths represent a good alternative to continue exploring the separation of PEGylated proteins with HIC. In this work, the separation of PEGylated proteins using C4 A monolith as well as Toyopearl Butyl 650C and Butyl Sepharose was analyzed. Three proteins were used as models: RNase A, β-lactoglobulin, and lysozyme. All proteins were PEGylated in the N-terminal amino groups with 20 kDa methoxy poly(ethylene glycol) propionaldehyde. The concentration of ammonium sulfate (1 M) used was the same for all stationary phases. The results obtained demonstrated that the C4 A monolith could better resolve all protein PEGylation reaction mixtures, since the peaks of mono- and di-PEGylated proteins can be clearly distinguished in the chromatographic profiles. On the contrary, while using Butyl Sepharose media only the PEGylation reaction mixtures of RNase A could be partially separated at 35 and 45 CVs. PEGylated proteins of β-lactoglobulin and lysozyme could not be resolved when Toyopearl Butyl 650C and Butyl Sepharose were used. It is then clear that monoliths are an excellent choice to explore the purification process of PEGylated proteins exploiting the advantages of HIC. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:702-707, 2016 [ABSTRACT FROM AUTHOR]

The increased number of pedestrian injuries and fatal deaths are resulting from road accidents due to the increased urban population and number of private vehicles. In order to address this issue along with other safety measurements, design, and material of engine hood has been a key point for an automotive industry. The most common materials for the manufacturing of engine hood were steel, aluminum and recently, composite materials have been used due to its added advantage for pedestrian safety. In this study, the finite element models of the pedestrian head impact on automotive hood, adult headform, composite laminate plate and sandwich composite plate were created by ABAQUS/Explicit. Simulation results are validated by Euro-NCAP pedestrian head to hood impact tests. The results show that the FEM modeling of the composite laminate plate, sandwich composite plate and engine hood can effectively predict the pedestrian head injury and deformation pattern of the models. This method can be an applicable tool for the vehicle, pedestrian safety evaluation and related development. [ABSTRACT FROM AUTHOR]

In this study, the effect of engine hood material type (aluminum, steel, carbon fiber epoxy CF/EP and glass fiber epoxy GF/EP composites) has been investigated on the pedestrian head injury in a collision (HIC). Child and adult Finite Element head models have been implemented for the simulations. In the models made of composite materials, effect of different stacking sequences has been investigated and four different 8-layered non-crimped fiber (NCF) composites with the stacking sequences of [0] 8 , [90] 8 , [0/90/0/90] s and [−45/0/45/90] s have considered. It was seen that using CF/EP composite instead of steel decreases the HIC value and hood weight by 42.6% and 46.8%, respectively. Moreover, [0] 8 and [90] 8 stacking sequences have the minimum and maximum HIC values among all the stacking sequences, respectively. Moreover, using composites made of glass fibers leads to higher HIC values with respect to those made of carbon fibers. In this study, the effect of location of head impact and hood thickness on HIC value for different hood material has also been investigated. For most of the locations, using composite materials led to lower HIC values. Increasing the skin thickness increases the HIC value for all the materials and its effect is more on steel, carbon-epoxy, glass-epoxy, and aluminum materials respectively. Increase in the hood thickness has higher effects on medial locations compared to lateral locations. [ABSTRACT FROM AUTHOR]

• A method based on high biofidelity head finite element model is developed to understand the head impact responses under different translational acceleration loads. • Influences of acceleration loading configurations (i.e., loading curve shape, impact duration and peak magnitude) on head responses (i.e., ICP, σ v and ε p) were determined for six representative acceleration loading curves. • The head injury under translational acceleration load is controlled mainly by ICP-induced and ε p -induced head injury mechanisms whereas σ v –induced head injury is unlikely for translational acceleration loads. • The most frequently-used kinematics-based head injury criterion (i.e., HIC) cannot assess head injury accurately, and biomechanics-based injury indices need to be considered to improve the impact head injury prediction. It is important to understand the relationship between impact accelerations and head responses to improve the protection of head against impact loads. This study aims to parametrically investigate the effects of different frontal translational acceleration loading configurations on head responses using a finite element head model. A series of translational accelerations defined by loading curve shape, impact duration and peak magnitude is applied to a head model to simulate different head impact accidents. The effects of loading configurations on the brain tissue-level responses, including intracranial pressure (ICP), von Mises stress (σ v) and maximum principal strain (ε p), were studied, and the correlations between head injury criterion (HIC) and tissue-level predictors were analysed. It is found that the head responses increase with the increase of peak magnitudes and the acceleration loading curve shape has significant influences on head responses. The largest head responses were observed for the equivalent square shape (ESS) acceleration case. Both the σ v and ε p responses increase with the increase of impact durations; however, the impact durations do not affect the ICP responses. Based on the thresholds for tissue-level injury predictors, it is found that both ICP-induced and ε p -induced head injuries may occur whereas the σ v -induced head injury is less likely to occur under translational acceleration loading conditions. For translational acceleration loading, good correlation can be found between HIC and the ε p responses; however, the HIC show a significant difference with the ICP responses for the head injury prediction. To improve the accuracy of head injury prediction with considering different injury mechanisms, ICP responses should be considered when HIC and ε p responses are applied in head injury analyses. [Display omitted] [ABSTRACT FROM AUTHOR]

We present a method to assist in interpretation of the functional impact of intergenic disease-associated SNPs that is not limited to search strategies proximal to the SNP. The method builds on two sources of external knowledge: the growing understanding of three-dimensional spatial relationships in the genome, and the substantial repository of information about relationships among genetic variants, genes, and diseases captured in the published biomedical literature. We integrate chromatin conformation capture data (HiC) with literature support to rank putative target genes of intergenic disease-associated SNPs. We demonstrate that this hybrid method outperforms a genomic distance baseline on a small test set of expression quantitative trait loci, as well as either method individually. In addition, we show the potential for this method to uncover relationships between intergenic SNPs and target genes across chromosomes. With more extensive chromatin conformation capture data becoming readily available, this method provides a way forward towards functional interpretation of SNPs in the context of the three dimensional structure of the genome in the nucleus.

The hyperactive Tn5 transposase in the ATAC-seq method has been widely used to determine the open DNA regions and understand the overall epigenomic regulation in the chromatins of eukaryotic cells. Here, we describe POP-seq (Prokaryotic chromatin Openness Profiling sequencing), an adaptation of the ATAC-seq method, to interrogate changes in the openness of prokaryotic nucleoids., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Populations are ageing at varying rates of development. Countries with developed economies have experienced such changes to their population structures. Examinations have been conducted with regard to how respective societies can accommodate the said changes in their health and social systems, but this research mostly focuses on more developed regions rather than lowerincome countries. This paper discussed the experience of ageing populations in developing economies, which comprise the majority of the global older population. They display a vastly different experience from high-income countries, especially when viewed within the level of world regions. The cases presented here were from Southeast Asian countries in order to have a wide range of examples in terms of differences in country-income categories. In lower and middle-income countries, there are older adults who: continue working as their primary income source, are nonmembers of pension systems, and provide intergenerational support rather than only receiving it. The COVID-19 pandemic situation was also included here, as policies were reformed to address current needs that highlighted the challenging situation of older adults. The populations of countries that have yet to age substantially, especially those in the least-developed regions, can utilise this paper's recommendations in order to prepare for changes in the age structures of their societies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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The hydrogen-induced cracking (HIC) and blistering behaviour of A537 steel was investigated by electrochemical hydrogen permeation measurements, electrochemical hydrogen-charging tests, and surface characterisation techniques. The results indicate that at ambient temperatures the diffusivity of hydrogen in A537 steel varies along three perpendicular directions. The diffusivity of hydrogen along the through-surface ( S ) direction was observed to be lower than that along each of the other two directions. The hydrogen concentration of A537 steel increased with increasing charging current density, which promoted the HIC susceptibility of the A537 steel. HIC initiated primarily at the interface of ferritic/pearlitic bands and nucleated at non-metallic inclusions in the A537 steel. [ABSTRACT FROM AUTHOR]

Existing helmet sensor technologies are cost prohibitive or limited in capability to comprehensively assess sports-related head injury. Therefore, development of an accurate, fully compatible low-cost pressure-sensitive sensor is warranted. The aim was to develop a piezo-resistive sensor platform for direct measurement of HIC. Using a programmable microcontroller and 30x35 mm sensor, fifty drop tests with a 5 kg mass were conducted using a Kistler force plate with maximum vertical force of 5000 N. The Power function correlation between force-plate-derived peak force and sensor-derived peak resistance was high (r 2 = 0.974) and used to calculate sensor-derived force-time data. Analysis of force-time curves yielded comparable peak forces (R = 0.982) and time to peak forces (R = 0.938), yet sensor-derived impact durations were elevated (R = 0.498). High linear correlation was found between force-plate- and sensor-derived HIC (r 2 = 0.974). The force plate-derived HIC can be directly estimated with sufficient accuracy from sensor-derived force (r 2 = 0.980) and a residual standard deviation of 11% at HIC >100. Overall, results substantiated the piezo-resistive sensor platform for direct HIC measurement and development of a full-scale helmet system. [ABSTRACT FROM AUTHOR]