Elemental composition and chemical structure of 16 kerogen samples concentrated from marine source rocks with maturity levels ranging from 0.65 %Ro to 3.3 %Ro were determined. Pyrolysis experiments ...of seven samples selected from the 16 kerogen samples were conducted in a gold tube system to clarify the process and determine the upper thermal maturity limit for primary gas generation from marine organic matter (OM). The variation of the H/C atomic ratio of the marine OM appears to evolve through three phases with increasing maturity, including a drastic decreasing phase before 1.3 %Ro, a moderate decreasing phase from 1.3 to 2.0 %Ro and a gradual decreasing phase above 2.0 %Ro. The evolution of the chemical structure measured by FTIR indicates that most oxygen containing functional groups in marine OM appear to be released prior to 0.8 %Ro. Aliphatic groups were still detected in the sample with a maturity of 3.0%Ro, but disappeared in the sample with a maturity of 3.3 %Ro. The variation of aliphatic groups VS aromatic rings (I1) displays a similar three stage pattern as the variation of H/C atomic ratio with increasing maturity. A step-by-step heating method in kerogen pyrolysis experiments was adopted to preclude secondary gas generation. The pyrolysis experimental results for samples with different maturities proved that generally the maximum yield of primary gas generated by the marine OM was not more than 140 ml per gram of total organic carbon (TOC). Only 1.16 ml/g TOC of hydrocarbon gas was generated by the sample with the maturity of 3.3 %Ro. Thus, it can be rationally inferred that the upper thermal maturity limit for gas generation from the marine OM may be around 3.5 %Ro. Nevertheless, the main maturity range for the primary gas generation is suggested to be below 2.0 %Ro. The yield of primary gas generated at the maturity range above 2.0%Ro takes up 10% of maximum yield of the primary gas generated by the marine OM.
•H/C atomic ratio variation of marine OM during maturation presents three phrases.•Methyl group in the marine OM is able to be detected at 3.0 %Ro.•The primary gas generation from marine OM mainly occurs below 2.0 %Ro.•The upper thermal maturity limit of primary gas generated from marine OM is about 3.5 %Ro.
Objective
Motile cilia impairment is a common condition in patients with chronically inflamed airways, such as is seen in nasal polyps (NPs). The mechanism underlying this pathogenic condition is ...complex and not fully understood.
Methods
We investigated the presence and localization of dynein axonemal heavy chain 5 (DNAH5) in motile cilia using immunofluorescence staining in paraffin‐embedded nasal biopsies from NPs (n = 120) and inferior turbinate mucosa (n = 35) of healthy controls. We also performed single‐cell staining on cytospin samples (NP = 5, control = 5). Three patterns of DNAH5 localization are defined, including pattern A (presence throughout the axoneme), pattern B (undetectable in the distal part of the axoneme), and pattern C (completely missing throughout the entire axoneme). We developed a semiquantitative scoring system for which 0 = (pattern A > 70%); 1 = (patterns A + B > 70%); and 2 = (pattern C ≥ 30%) in each high‐power field (5 fields per sample).
Results
Based on our DNAH5 scoring system, the median (1st and 3rd quartile) score was 0.3 (0.2 and 0.4) for samples from controls, and 1.1 (0.6 and 1.6) for samples from NPs in paraffin specimens (P < 0.001). The DNAH5 score had a significant positive relationship with the Lund‐Mackay computed tomography score (r = 0.329, P = 0.005) and was higher in patients with eosinophilic NPs (P = 0.006). For cytospin samples, the mean percentage of patterns A, B, and C were 74%, 14%, and 12% in controls, and 48%, 20%, and 32% in NPs, respectively.
Conclusion
Our results suggest that the absence or mislocalization of DNAH5 from motile cilia is a common and potentially important pathological phenomenon in chronically inflamed airway epithelium.
Level of Evidence
NA. Laryngoscope, 128:E97–E104, 2018
The characterization of the full-sized pore structure is important for the evaluation and prediction of the reservoir of shale gas with strong heterogeneity. It is of great scientific significance to ...explore the pore structure characteristics of overmature coal-bearing shale. Core descriptions, X-ray diffraction (XRD), vitrinite reflectance (
R
o), field emission scanning electron microscopy (FE-SEM), high-pressure mercury intrusion porosimetry (MIP), and low-pressure N
2
/CO
2
gas adsorption (N
2
-/CO
2
-GA) experiments were performed on overmature coal-bearing shale samples from the Wuxiang block, south-central Qinshui Basin, China. The results show that the total organic carbon (TOC) ranged from 0.29 to 8.36%, with an average of 3.84%, and the organic matter (OM) is dominated by type III kerogen. The minerals in the shale primarily consist of clay (43–85.5%, averaging 52.1%) and quartz (12.6–61.2%, averaging 43.5%). The major clay minerals are illite-smectite (I/S) and illite, ranging from 22.5 to 55.6% (mean 41.4%) and 8.7–52.7% (mean 32%), respectively. FE-SEM images reveal that intraparticle pores (IntraP pores) and interparticle pores (InterP pores) are widely developed in clay minerals, and organic pores are occasionally present. Mesopores make the greatest contribution to the total pore volume (PV), and micropores are the major contributors to the specific surface area (SSA). Clays are the main controllers of micropore development. Mesopores developed in the clay mineral layers are promoted by I/S but inhibited by illite. Macropores and microfractures are mainly developed in clays and quartz and do not correlate significantly with the TOC, or mineral composition, due to the influence of compaction and cementation. The TOC and minerals affect pore structure characteristics mainly by influencing micropores.
Aortic dissection (AD) is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases (MMPs)/tissue inhibitors of MMPs (TIMPs) system in the ...extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens (45 genes), MMPs/TIMPs (27 genes) in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated
Col5a2
knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% (64/72) genes in collagens-MMPs/TIMPs system and accounted for 31.05% (218/702) sporadic AD patients. In them, 84.86% patients (185/218) carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probably pathogenic loss-of-function (LOF) variants (20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon) in 11.06% (50/452) AD patients, which were absent in 163 controls (
P
=2.5×10
−5
). Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The
Col5a2
−/−
rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.
Immune checkpoint inhibitors (ICIs) have emerged as a powerful and efficacious therapeutic approach for many cancer patients. Sintilimab is a fully human IgG4 monoclonal antibody that binds with ...programmed cell death receptor-1 (PD-1) to block its interaction with ligands, thereby enhancing the antitumor effects of T cells. However, ICIs may induce immune-related adverse events (irAEs) in various systems and organs, with fulminant myocarditis being the most severe one. We report the case of a 45-year-old female with gastric cancer who developed chest pain two weeks after chemotherapy with sintilimab; she was diagnosed with immune-associated fulminant myocarditis and experienced an Adams-Stokes syndrome attack in the hospital. Eventually, she was discharged after being treated with methylprednisolone, immunoglobulin, and an IABP.
In this study, elemental compositions and chemical structure by solid-state 13C Nuclear Magnetic Resonance (13C NMR) of 19 coal samples with vitrinite reflectance (Ro) ranging from 0.35%Ro to 5.32%Ro ...were analyzed and measured. Pyrolysis experiments of six samples selected from the 19 coal samples were conducted to unravel the process and determine the upper thermal maturity limit for gas generation from humic coal. The variations of H/C atomic ratio of coal with increasing maturity appear to evolve through three stages which include a drastic decreasing phase before 2.0%Ro, a moderate decreasing phase from 2.0 to 6.0%Ro and a gradual decreasing phase above 6.0%Ro. The measurement results concerning the chemical structure of coal samples with increasing maturity indicate that most of the oxygen containing functional groups released was below 0.8%Ro. Aliphatic groups (especially methyl) were detected in samples with a maximum maturity of 4.46%Ro. The pyrolysis experiments for coal with different maturities using a gold tube system indicate that the main maturity intervals for CO2 and hydrocarbon gas generation from coal are below 0.8%Ro and 2.0%Ro, respectively. The pyrolysis experiment proved that only 4.37ml/g TOC of hydrocarbon gas could be generated from the sample with a maturity of 5.32%Ro. Hence, the upper thermal maturity limit for gas generation from coal was determined to be about 5.0%Ro according to the variations of elemental composition, the chemical structure evolution and pyrolysis experiments for coal with different maturities.
•H/C atomic ratio of coal with increasing maturity presents episodic variation.•Methyl could still be detected in the coal sample with a maturity of 4.46%Ro.•4.37ml/g TOC gas is generated by the coal sample with a maturity of 5.32%Ro.•The upper thermal maturity limit of gas generation from coal is about 5.0%Ro.
Pore structure in shale is an important factor influencing the storage capacity of a shale gas reservoir and the effect of shale gas development. Taking the core and outcrop shale samples from the ...Lower Cambrian Niutitang Formation and Lower Silurian Longmaxi Formation as the object of the research, combined with the scanning electron microscope, high pressure mercury injection, CO2 and N2 gas adsorption experiments, we investigated the porosity, pore types, pore structure, and pore size distribution of the Lower Paleozoic shale gas reservoirs in northern Guizhou, South China. The results indicated that there are developed various genetic types of micro-nano pores in the Lower Paleozoic marine shale in northern Guizhou, which provide the main reservoir spaces for shale gas. The porosity of the Lower Paleozoic shale in northern Guizhou is 1.30%–13.37% in range, and the average is 4.56%. The inter-granular pore, organic matter pore and intra-granular pore are most common. Micropore (<2 nm) and mesopore (2–50 nm) are the main reservoir storage space for shale gas. The specific surface area of micropore plus mesopore in the Lower Paleozoic shale accounts for 94.3% of the total specific surface area, and their pore volume accounts for 59.1% of the total pore volume in northern Guizhou. The pore size of the Lower Paleozoic shale is mainly distributed in 0.4–0.7 nm, 3–10 nm and 0.05–200 μm. The pore structure is the parallel-plate pore with slit shape, two-ends-opened tube pore and ink-bottle shape pore. There are significant differences in the porosity and pore size between the Longmaxi Formation shale and the Niutitang Formation shale. The average porosity and average pore size of the Longmaxi Formation shale is 6.4% and 4.71 nm, while the Niutitang Formation shale is 5.3% and 4.23 nm, respectively. The pore structure of the Lower Paleozoic shale gas reservoir is mainly influenced by organic matter abundance, thermal maturity, mineral composition of shale. The porosity and micropore volume of shale show an increasing trend, with the increase of total organic carbon content and quartz content. The porosity and pore volume of shale have a decreasing trend, with the increase of thermal maturity level and clay mineral content.
Joint state and parameter estimation (JSPE) has a surge of interest due to its dual purposes in many fields, such as sensor registration and signal processing. In this letter, a recursive joint ...Cramér-Rao lower bound (JCRLB) is developed for JSPE of nonlinear parametric systems with cross-correlated process and measurement noises at the same time. The JCRLBs for two special cases of such systems with additive Gaussian noises are also studied. Illustrative examples show the effectiveness of the JCRLB for the performance evaluation of JSPE of nonlinear parametric systems with cross-correlated noises at the same time.
Mutations in the
gene are the most common causes of dilated cardiomyopathy (DCM). The clinical significance of
gene variants remains inadequately understood.
Whole-exome sequencing and phenotypic ...characterisation were performed, and patients were followed up for a median of 44 months.
We analyzed the association of the
variants with the clinical outcomes in a prospective study of 1,041 patients with sporadic DCM.
truncating variants (tTTN) were detected in 120 (11.5%) patients as compared with 2.4/10,000 East Asian populations in the Genome Aggregation Database (GnomAD;
< 0.0001). Pathogenic
missense variants were also enriched in DCM as compared with the GnomAD populations (27.6 vs. 5.9%,
< 0.0001). DCM patients with tTTN had a lower left ventricular ejection fraction (28.89 ± 8.72 vs. 31.81 ± 9.97,
= 0.002) and a lower frequency of the left bundle branch block (3.3 vs. 11.3%,
= 0.011) than those without or with mutations in other known causal genes (OCG). However, tTTN were not associated with the composite primary endpoint of cardiac death and heart transplantation during the follow-up period adjusted hazard ratio (HR): 0.912; 95% confidence interval: 0.464-1.793;
= 0.790. There was also no sex-dependent effect. Concomitant tTTN and pathogenic variants in OCG were present in only eight DCM patients and did not affect the outcome.
The phenotype of DCM caused by tTTN, major causes of sporadic DCM, is not distinctly different from those caused by other causal genes for DCM.