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Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.
Low molecular weight glutenin subunits (LWM-GSs) play a crucial role in determining wheat flour processing quality. In this work, 35 novel LMW-GS genes (32 active and three pseudogenes) from three Aegilops umbellulata (2n = 2x = 14, UU) accessions were amplified by allelic-specific PCR. We found that all LMW-GS genes had the same primary structure shared by other known LMW-GSs. Thirty-two active genes encode 31 typical LMW-m-type subunits. The MZ424050 possessed nine cysteine residues with an extra cysteine residue located in the last amino acid residue of the conserved C-terminal III, which could benefit the formation of larger glutenin polymers, and therefore may have positive effects on dough properties. We have found extensive variations which were mainly resulted from single-nucleotide polymorphisms (SNPs) and insertions and deletions (InDels) among the LMW-GS genes in Ae. umbellulata. Our results demonstrated that Ae. umbellulata is an important source of LMW-GS variants and the potential value of the novel LMW-GS alleles for wheat quality improvement.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
Triticum monococcum ssp. monococcum has useful traits for bread wheat improvement. The synthesis of Triticum turgidum–T. monococcum amphiploids is an essential step for transferring genes from T. monococcum into bread wheat. In this study, 264 wide hybridization combinations were done by crossing 60 T. turgidum lines belonging to five subspecies with 83 T. monococcum accessions. Without embryo rescue and hormone treatment, from the 10,810 florets pollinated, 1983 seeds were obtained, with a mean crossability of 18.34% (range 0–89.29%). Many hybrid seeds (90.73%, 923/1017) could germinate and produce plants. A total of 56 new amphiploids (AABBAmAm) were produced by colchicine treatment of T. turgidum × T. monococcum F1 hybrids. The chromosome constitution of amphiploids was characterized by fluorescence in situ hybridization using oligonucleotides probes with different chromosome and sub-chromosome specificities. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis indicated that the Glu-A1m-b, Glu-A1m-c, Glu-A1m-d and Glu-A1m-h proteins of T. monococcum were expressed in some amphiploids. Despite resistance reduction in several cases, 45 out of 56 amphiploids exhibited resistance to the current predominant Chinese stripe rust races at both the seedling and adult plant stage. These novel amphiploids provide new germplasm for the potential improvement of bread wheat quality and stripe rust resistance.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
This paper provides a brief outline of the current, detailed inter-disciplinary work on the Xiaoyangquiao section, trying to expose all the aspects for reference tied to the Global Single Stratigraphic Point (GSSP) Concept for defining the Cambrian–Ordovician Boundary. The 45 m critical interval of this section outcrops very well along the steep bank of a stream and is free from folding, faulting, intrusions, and has not been affected by weathering. Colour alternation of conodonts and acritarchs, and crystallinity indices of illite all indicate a maximum thermal grade of 100 °C. The lithofacies, being of great lateral persistence for a hundred kilometres, consists mainly of a rhythmical sequence of lime mudstone and shales deposited in a moderately deep outer shelf environment of quiet water, well below the normal storm wave base. Chemical investigation of the rocks demonstrates strong positive correlation between A12O3 content and those of K2O, MgO, Fe2O3, TiO2, Be, Cr, Co, Ni, Zn and Ba, indicating these components are tied to the clay fractions. A stable depositional environment is demonstrated by the uniform chemistries through the boundary interval. Close to the boundary itself P2O5 contents are low, indicating continuous sedimentation at fairly substantial rates.
The major biological events, the biostratigraphic framework, and the stratigraphic range of conodont, graptolite, trilobite, and acritarch taxa are illustrated briefly with diagrams. Following the majority views of the Calgary Plenary Session, the boundary level is to be chosen at a point marked by the First Appearance Datum (FAD) of the selected conodont taxon or taxa in the vicinity of the level close to, but below, the first influx of nematophorous graptolites. The following four points marked by the incoming of conodont taxon or taxa are recommended for consideration of the ‘Golden Spike'‘: (1) FAD of Cordylodus intermedius at 5.28 m below the first influx of nematophorous graptolites; (2) FAD of Hirsutodontus simpler–Cordylodus drucei–Albiconus postcostatus at 5.23 m; (3) FAD of Semiacontiodus lavadamensis–Utahconus utahensis–Monocostodus sevierensis at 3.85 m; (4) FAD of Cordylodus lindstromi at 2.23 m. For the following reasons the FAD of H. simplex–C. drucei–A. postcostatus is favoured: (1) the taxa are all distinct and widely dispersed; (2) intensive evolutionary change took place in conodonts, graptolites, trilobites and acritarchs prior to or after this point; all the fossil groups occur together, providing correlation with many regions throughout the world; (3) the point is in a position between the previously widely accepted boundary levels based on graptolites and trilobites; (4) the proposed point lies within a thin, laterally persistent, rhythmical sequence. The FAD of Cordylodus lindstromi is also a favourable point, sharing many advantages mentioned above. But this point is less satisfactory in being defined by the FAD of a single taxon C. lindstromi which also has an extremely small population size.
An isochron age of 500.7 ± 7.4 Ma is determined from clay fractions of mudstones 8.5 m below the proposed point by means of the Rubidium–Strontium method.
The ɛND signature determined from conodonts, trilobites hyolithids and acrotretid brachiopods has a mean value of −6.7, comparable with that of the coeval oceanic water mass occupying southeastern North America and Europe, and indicating that northeastern China bordered the same ocean. The mean Tdm model age determined was 1.26 Ga at the time of sedimentation, compatible with the mean Tdm model age of approximately 1.1 Ga for the Pacific Ocean today. The relatively low value of the Tdm model age indicates a substantial input from young orogenic volcanic island arcs and terranes.
Ferroelectric random access memory (FeRAM) is believed to be the most promising candidate for the next generation non-volatile memory due to its fast access time and low power consumption. Fabrication technologies of FeRAM can be divided into two parts: CMOS technologies for circuits which are standard and can be shared with traditional IC process line, and process relating to ferroelectric which is separated with CMOS process and defined as backend module. This paper described technologies for integrating ferroelectric capacitors into standard CMOS, mainly about modeling of ferroelectric capacitors and backend fabrication technologies. Hysteresis loop of the ferroelectric capacitor is the basis for FeRAM to store data. Models to describe this characteristic are the key for the design of FeRAM. A transient behavioral ferroelectric capacitor model based on C-V relation for circuit simulation is developed. The arc tangent function is used to describe the hysteresis loop. “Negative capacitance” phenomenon at reversing points of applied voltage is analyzed and introduced to the model to describe transient behaviors of the capacitor. Compact equivalent circuits are introduced to integrate this model into HSPICE for circuit simulation. Ferroelectric materials fabrication, electrodes integration and etching are the main technologies of FeRAM fabrication process. An metal organic chemical vapor deposition (MOCVD) process is developed to fabricate high quality Pb(Zr1-xTix)O3 (PZT) films. Pt is known to cause the fatigue problems when used as electrodes with PZT. Ir is used as electrodes to improve the fatigue property of PZT based capacitors, and mechanism of the fatigue is analyzed. Hard mask is used to reduce the size of the capacitors and damage caused in etching process. In our process, Al2O3 is developed as hard mask, which simplifies the FeRAM backend integration process.
Eu(DBM)3phen-doped poly(methyl methacryate) (PMMA) with different doping concentration were prepared. The highest doping concentration sample (10000 ppm) was examined by near-field scanning optical microscopy (NSOM) with a resolution of 50 nm; and the result showed that there were no aggregates larger than 50 nm in the doped polymer. This result was further confirmed by optical properties of the doping material. Concentration quenching was not detected by metastable-state lifetime measurements, indicating that no aggregates existed. According to the fluorescence spectra analysis, the relative intensity ratio (R) of 5D0→7F2 to 5D0→7F1 transition was not shown to be significantly changed with the increasing of Eu3+ content. The analysis reflected that the local structure and asymmetry in the vicinity of europium ions were not changed, and that the Eu3+ ions in PMMA were homogeneously dispersed.
Eu(DBM)3Phen-doped poly(methyl methacrylate) (PMMA) with different doping concentrations was prepared. Judd–Ofelt parameters Ω2 and Ω4 and the fluorescence intensity ratio R were computed from the fluorescence emission spectra and were analyzed. The radiative properties, such as transition probabilities, emission cross section (46.47 × 10−22 cm2), fluorescence branching ratios (90.34%), and radiative lifetime (1.704 ms), reveal that Eu(DBM)3 Phen-doped PMMA has potential use as a laser material.
The present work proposes a Dugdale type model to theoretically predict the multiple cracks of a residually tensile stressed thin film on a ductile substrate. The results show that there exists a critical value, Rc, of the cracking resistance number, R. When R < R, the film > c cracks and the normalized crack spacing is determined by cracking resistance number and the stress ratio of the residual stress to the yield strength of the substrate.
Vickers indentation tests were carried out at room temperature with a microhardness tester on ZnO thin films deposited on (100) Si wafers. The films with thicknesses ranging from 0.202 to 1.535 νm were tested under indentation loads varying from 50 mN to 2.0 N. The experiments exhibited a film thickness dependent deformation behavior. When the film thickness is smaller than a critical value, only indentation-induced radical cracking occurred and for a given load, the radical crack size decreased with film thickness. On the other hand, indentation-induced delamination was observed if the film thickness was larger than the critical value. In this case, the radial crack, if induced, had a size smaller than the size of delamination or even smaller than the size of indentation impression. Under a same indentation load, the delamination size increased with the film thickness.
With regard to substrate deformation, this work analyzed the microcantilever beam-bending test and provided a closed formula of deflection versus load. The substrate deformation was formulated using two coupled springs; the spring compliances were related to the elastic compliances of the substrate, the support angle between the substrate and the microcantilever beam, and the beam thickness. Finite element analysis was conducted to calculate the spring compliances and verify the analytic formula. The results showed that the proportionality factor of the load to the deflection was a third-order polynomial of the length from the loading point to the fixed beam end. Examples are also given to indicate the relative error of Young's modulus when evaluated with the beam-bending theory without considering the substrate deformation.
In this paper, the wall-following problem of an AGV is characterized by keeping a constant distance from a wall. Four Polaroid ultrasonic range sensors (sonar) are used to obtain information of the distance between the AGV and the wall. Four sonars are divided into two groups being placed at the front and back end on the right side of the AGV, respectively. A digital filter is used to get rid of disturbance and wrong readings. The former results mainly from the door and the latter from the specular reflection and accidental scattering. To obtain good dynamic and steady performances, a new compound fuzzy-I control algorithm is presented. Our methods have been verified by following a 15-meter-long wall with one door by using our TIT-1 AGV (TIT: Tianjin Institute of Technology). The results show a good performance with an error of ±2 cm from the desired distance to the wall.
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