In situ X-ray diffraction measurement of shock-wave-driven twinning and lattice dynamics.

Pressure-driven shock waves in solid materials can cause extreme damage and deformation. Understanding this deformation and the associated defects that are created in the material is crucial in the study of a wide range of phenomena, including planetary formation and asteroid impact sites, the formation of interstellar dust clouds, ballistic penetrators, spacecraft shielding and ductility in high-performance ceramics. At the lattice level, the basic mechanisms of plastic deformation are twinning (whereby crystallites with a mirror-image lattice form) and slip (whereby lattice dislocations are generated and move), but determining which of these mechanisms is active during deformation is challenging. Experiments that characterized lattice defects have typically examined the microstructure of samples after deformation, and so are complicated by post-shock annealing and reverberations. In addition, measurements have been limited to relatively modest pressures (less than 100 gigapascals). In situ X-ray diffraction experiments can provide insights into the dynamic behaviour of materials, but have only recently been applied to plasticity during shock compression and have yet to provide detailed insight into competing deformation mechanisms. Here we present X-ray diffraction experiments with femtosecond resolution that capture in situ, lattice-level information on the microstructural processes that drive shock-wave-driven deformation. To demonstrate this method we shock-compress the body-centred-cubic material tantalum-an important material for high-energy-density physics owing to its high shock impedance and high X-ray opacity. Tantalum is also a material for which previous shock compression simulations and experiments have provided conflicting information about the dominant deformation mechanism. Our experiments reveal twinning and related lattice rotation occurring on the timescale of tens of picoseconds. In addition, despite the common association between twinning and strong shocks, we find a transition from twinning to dislocation-slip-dominated plasticity at high pressure (more than 150 gigapascals), a regime that recovery experiments cannot accurately access. The techniques demonstrated here will be useful for studying shock waves and other high-strain-rate phenomena, as well as a broad range of processes induced by plasticity.

Experimental Observations of Laser-Driven Tin Ejecta Microjet Interactions.

The study of high-velocity particle-laden flow interactions is of importance for the understanding of a wide range of natural phenomena, ranging from planetary formation to cloud interactions. Experimental observations of particle dynamics are sparse given the difficulty of generating high-velocity flows of many particles. Ejecta microjets are micron-scale jets formed by strong shocks interacting with imprinted surfaces to generate particle plumes traveling at several kilometers per second. As such, the interaction of two ejecta microjets provides a novel experimental methodology to study interacting particle streams. In this Letter, we report the first time sequences of x-ray radiography images of two interacting tin ejecta microjets taken on a platform designed for the OMEGA Extended Performance (OMEGA EP) laser. We observe that the microjets pass through each other unattenuated for the case of 11.7±3.2 GPa shock pressures and jet velocities of 2.2±0.5 km/s but show strong interaction dynamics for 116.0±6.1 GPa shock pressures and jet velocities of 6.5±0.5 km/s. We find that radiation-hydrodynamic simulations of the experiments are able to capture many aspects of the collisional behavior, such as the attenuation of jet velocity in the direction of propagation, but are unable to match the full spread of the strongly interacting cloud.

Measurement of Kinetic-Scale Current Filamentation Dynamics and Associated Magnetic Fields in Interpenetrating Plasmas.

We present the first local, quantitative measurements of ion current filamentation and magnetic field amplification in interpenetrating plasmas, characterizing the dynamics of the ion Weibel instability. The interaction of a pair of laser-generated, counterpropagating, collisionless, supersonic plasma flows is probed using optical Thomson scattering (TS). Analysis of the TS ion-feature revealed anticorrelated modulations in the density of the two ion streams at the spatial scale of the ion skin depth c/ω_{pi}=120 µm, and a correlated modulation in the plasma current. The inferred current profile implies a magnetic field amplitude ∼30±6 T, corresponding to ∼1% of the flow kinetic energy, indicating that magnetic trapping is the dominant saturation mechanism.

Fuel gain exceeding unity in an inertially confined fusion implosion.

Ignition is needed to make fusion energy a viable alternative energy source, but has yet to be achieved. A key step on the way to ignition is to have the energy generated through fusion reactions in an inertially confined fusion plasma exceed the amount of energy deposited into the deuterium-tritium fusion fuel and hotspot during the implosion process, resulting in a fuel gain greater than unity. Here we report the achievement of fusion fuel gains exceeding unity on the US National Ignition Facility using a 'high-foot' implosion method, which is a manipulation of the laser pulse shape in a way that reduces instability in the implosion. These experiments show an order-of-magnitude improvement in yield performance over past deuterium-tritium implosion experiments. We also see a significant contribution to the yield from α-particle self-heating and evidence for the 'bootstrapping' required to accelerate the deuterium-tritium fusion burn to eventually 'run away' and ignite.

Nonisentropic Release of a Shocked Solid.

We present molecular dynamics simulations of shock and release in micron-scale tantalum crystals that exhibit postbreakout temperatures far exceeding those expected under the standard assumption of isentropic release. We show via an energy-budget analysis that this is due to plastic-work heating from material strength that largely counters thermoelastic cooling. The simulations are corroborated by experiments where the release temperatures of laser-shocked tantalum foils are deduced from their thermal strains via in situ x-ray diffraction and are found to be close to those behind the shock.

Extreme Hardening of Pb at High Pressure and Strain Rate.

We study the high-pressure strength of Pb and Pb-4wt%Sb at the National Ignition Facility. We measure Rayleigh-Taylor growth of preformed ripples ramp compressed to ∼400 GPa peak pressure, among the highest-pressure strength measurements ever reported on any platform. We find agreement with 2D simulations using the Improved Steinberg-Guinan strength model for body-centered-cubic Pb; the Pb-4wt%Sb alloy behaves similarly within the error bars. The combination of high-rate, pressure-induced hardening and polymorphism yield an average inferred flow stress of ∼3.8 GPa at high pressure, a ∼250-fold increase, changing Pb from soft to extremely strong.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. METHODS: The serum SPD level was measured in patients with AERD (n = 336), those with aspirin-tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated. RESULTS: The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P = .002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD. CONCLUSION: The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.

Akt1-Mediated Phosphorylation of RBP-Jk Controls Notch1 Signaling.

The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI3K-Akt1 signaling pathway was shown to inhibit Notch1 signaling via phosphorylation of RBP-Jk. We observed not only reduced association between Notch1 and RBP-Jk, but also suppression of the Notch1 transcriptional activity. Our results demonstrated that Akt1 functions as a natural inhibitor of the Notch1 signaling pathway via phosphorylation of RBP-Jk.

Is calcium phosphate augmentation a viable option for osteoporotic hip fractures?

The use of calcium phosphate bone cement has been described to allow for retention of reduction. Therefore, we evaluated whether augmentation with resorbable calcium phosphate could improve fracture stability in osteoporotic hip fractures. The results showed that augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures. INTRODUCTION: The aim with this study was to measure whether augmentation with resorbable calcium phosphate cement could improve fracture stability in osteoporotic hip fractures. METHODS: We retrospectively reviewed 82 patients who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2017. In 42 of 82 patients, patients were treated with a PFN alone (group I). These patients were compared with 40 patients for whom the same device combined with calcium phosphate cement for augmentation was used (group II). Questionnaire surveys or telephone interviews were conducted and patients completed a self-report Harris hip score (HHS) and visual analog scale (VAS) scores. Radiographic outcomes including mean sliding distance of screw, femoral shortening, and varus collapse were compared. Postoperative complications were compared. RESULTS: Clinical outcomes at 6 months after surgery were equivalent in both groups. Screw sliding, femoral shortening, and varus collapse were all significantly reduced in the cemented group at the last follow-up (p < 0.001, p = 0.005, p < 0.001, respectively). A total of 9 (21%) complications occurred in group I. In contrast, 2 (5%) complications were seen in group II (p = 0.029). CONCLUSIONS: Augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures fixed with a PFN and reduced overall failure rates. We believe augmentation with resorbable calcium phosphate cement for osteoporotic hip fractures is a reasonable option in selected patients.

Highly Resolved Measurements of a Developing Strong Collisional Plasma Shock.

The structure of a strong collisional shock front forming in a plasma is directly probed for the first time in laser-driven gas-jet experiments. Thomson scattering of a 526.5 nm probe beam was used to diagnose temperature and ion velocity distribution in a strong shock (M∼11) propagating through a low-density (ρ∼0.01 mg/cc) plasma composed of hydrogen. A forward-streaming population of ions traveling in excess of the shock velocity was observed to heat and slow down on an unmoving, unshocked population of cold protons, until ultimately the populations merge and begin to thermalize. Instabilities are observed during the merging, indicating a uniquely plasma-phase process in shock front formation.

Generation of scaled protogalactic seed magnetic fields in laser-produced shock waves.

The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations. Although other mechanisms may also operate, currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10(-21) gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations, astrophysical environments can effectively be reproduced in the laboratory. Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields sufficiently to affect galaxy evolution.

Evolution of asexual and sexual reproduction in the aspergilli.

Aspergillus nidulans has long-been used as a model organism to gain insights into the genetic basis of asexual and sexual developmental processes both in other members of the genus Aspergillus, and filamentous fungi in general. Paradigms have been established concerning the regulatory mechanisms of conidial development. However, recent studies have shown considerable genome divergence in the fungal kingdom, questioning the general applicability of findings from Aspergillus, and certain longstanding evolutionary theories have been questioned. The phylogenetic distribution of key regulatory elements of asexual reproduction in A. nidulans was investigated in a broad taxonomic range of fungi. This revealed that some proteins were well conserved in the Pezizomycotina (e.g. AbaA, FlbA, FluG, NsdD, MedA, and some velvet proteins), suggesting similar developmental roles. However, other elements (e.g. BrlA) had a more restricted distribution solely in the Eurotiomycetes, and it appears that the genetic control of sporulation seems to be more complex in the aspergilli than in some other taxonomic groups of the Pezizomycotina. The evolution of the velvet protein family is discussed based on the history of expansion and contraction events in the early divergent fungi. Heterologous expression of the A. nidulans abaA gene in Monascus ruber failed to induce development of complete conidiophores as seen in the aspergilli, but did result in increased conidial production. The absence of many components of the asexual developmental pathway from members of the Saccharomycotina supports the hypothesis that differences in the complexity of their spore formation is due in part to the increased diversity of the sporulation machinery evident in the Pezizomycotina. Investigations were also made into the evolution of sex and sexuality in the aspergilli. MAT loci were identified from the heterothallic Aspergillus (Emericella) heterothallicus and Aspergillus (Neosartorya) fennelliae and the homothallic Aspergillus pseudoglaucus (=Eurotium repens). A consistent architecture of the MAT locus was seen in these and other heterothallic aspergilli whereas much variation was seen in the arrangement of MAT loci in homothallic aspergilli. This suggested that it is most likely that the common ancestor of the aspergilli exhibited a heterothallic breeding system. Finally, the supposed prevalence of asexuality in the aspergilli was examined. Investigations were made using A. clavatus as a representative 'asexual' species. It was possible to induce a sexual cycle in A. clavatus given the correct MAT1-1 and MAT1-2 partners and environmental conditions, with recombination confirmed utilising molecular markers. This indicated that sexual reproduction might be possible in many supposedly asexual aspergilli and beyond, providing general insights into the nature of asexuality in fungi.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma.

BACKGROUND: Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. OBJECTIVES: We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). METHODS: Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). RESULTS: Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = -0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin-exacerbated respiratory disease.

BACKGROUND: To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. METHODS: An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. RESULTS: A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4 /PGF2 α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4 /PGF2 α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). CONCLUSIONS AND CLINICAL RELEVANCE: Serum metabolite level of LTE4 and LTE4 /PGF2 α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

Transition from Collisional to Collisionless Regimes in Interpenetrating Plasma Flows on the National Ignition Facility.

A study of the transition from collisional to collisionless plasma flows has been carried out at the National Ignition Facility using high Mach number (M>4) counterstreaming plasmas. In these experiments, CD-CD and CD-CH planar foils separated by 6-10 mm are irradiated with laser energies of 250 kJ per foil, generating ∼1000 km/s plasma flows. Varying the foil separation distance scales the ion density and average bulk velocity and, therefore, the ion-ion Coulomb mean free path, at the interaction region at the midplane. The characteristics of the flow interaction have been inferred from the neutrons and protons generated by deuteron-deuteron interactions and by x-ray emission from the hot, interpenetrating, and interacting plasmas. A localized burst of neutrons and bright x-ray emission near the midpoint of the counterstreaming flows was observed, suggesting strong heating and the initial stages of shock formation. As the separation of the CD-CH foils increases we observe enhanced neutron production compared to particle-in-cell simulations that include Coulomb collisions, but do not include collective collisionless plasma instabilities. The observed plasma heating and enhanced neutron production is consistent with the initial stages of collisionless shock formation, mediated by the Weibel filamentation instability.

Drug-specific CD4+ T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome.

BACKGROUND: A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first-line treatment for tuberculosis. However, this regimen can occasionally result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug-induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown. OBJECTIVES: To investigate drug-specific T-cell responses in patients with antituberculosis drug (ATD)-induced cutaneous hypersensitivity and its underlying mechanism. METHODS: We enrolled eight patients with ATD-induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug-specific T-cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug-specific proliferative responses and counted the drug-specific interferon (IFN)-γ/granzyme B-producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigen-restricted T-cell responses. RESULTS: Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin-specific T cells from patients, which consisted primarily of CD4+ T cells. Drug-specific CD4+ T cells proliferated and secreted IFN-γ/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid-responsive T-cell clones did not proliferate in the presence of rifampicin and vice versa. Drug-specific T-cell responses were blocked in the presence of anti-HLA class II antibodies. CONCLUSIONS: This study identifies the presence of isoniazid/rifampicin-specific T cells in patients with ATD-induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug-specific T-cell immune responses in the pathogenesis of these reactions.

Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target.

BACKGROUND: Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the pathogenesis of severe asthma. OBJECTIVE: We compared autophagy in the sputum granulocytes, peripheral blood cells (PBCs) and peripheral blood eosinophils (PBEs) between patients with severe asthma and those with non-severe asthma and investigated the functional effects of autophagy. METHODS: We enrolled 36 patients with severe asthma, 14 with non-severe asthma and 23 normal healthy controls in this study. Sputum granulocytes, PBCs and PBEs were isolated from each subject. Autophagy was evaluated based on the expression of microtubule-associated protein light chain 3 (LC3) by Western blot, confocal microscopy, transmission electron microscopy and flow cytometry. IL-8 levels were measured by ELISA. To induce autophagy, HL-60 cells, human primary small airway epithelial cells (SAECs) and A549 cells were treated with IL-5, IL-1ß and TNF-α. To inhibit autophagy, PI3K inhibitors (LY29400 and 3-methyladenine [3-MA]) and hydroxychloroquine (HCQ) were used. Knockdown of ATG5 and Beclin-1 was performed in A549 cells, and the therapeutic effects of dexamethasone were evaluated. RESULTS: Higher autophagy levels were noted in sputum granulocytes, PBCs and PBEs from patients with severe asthma than from patients with non-severe asthma and healthy controls (P < 0.05 for all). IL-5 increased autophagy levels in both PBCs and PBEs (P < 0.05). 3-MA attenuated the increased expression of LC3-II and eosinophil cationic protein in HL-60 cells induced by IL-5 (P = 0.034 for both). Dexamethasone did not affect autophagy levels in PBEs. IL-1ß increased LC3-II expression and IL-8 production (P < 0.01) in SAECs, and this was attenuated by LY294002, 3-MA, HCQ and knockdown of ATG5 and Beclin-1 (in A549 cells) (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy-resistant severe asthma.

Building the SeqChromMM Markov property atlas of the human genome by analyzing the 200-bp units of the 15 different chromatin regions of ENCODE.

We analyzed the publicly available ChromHMM BED files of the ENCODE project and tested the Markov properties of the different chromatin states in the human genome. Nucleotide frequency profiles of regional chromatin segmentations were analyzed, and Markov chains were built to detect Markov properties in the chromatin states of different ChromHMM regions. By estimating the transition probabilities of 200-base pair nucleotide sequences of the human genome, we constructed a nucleotide-sequence-based Markovian chromatin map called SeqChromMM.

Using Markov chains of nucleotide sequences as a possible precursor to predict functional roles of human genome: a case study on inactive chromatin regions.

Recent advances in computational epigenetics have provided new opportunities to evaluate n-gram probabilistic language models. In this paper, we describe a systematic genome-wide approach for predicting functional roles in inactive chromatin regions by using a sequence-based Markovian chromatin map of the human genome. We demonstrate that Markov chains of sequences can be used as a precursor to predict functional roles in heterochromatin regions and provide an example comparing two publicly available chromatin annotations of large-scale epigenomics projects: ENCODE project consortium and Roadmap Epigenomics consortium.