This paper attempts to quantify the effect of backfilling on pillar strength in highwall mining using numerical modelling.Calibration against the new empirical strength formula for highwall mining ...was conducted to obtain the material parameters used in the numerical modelling.With the obtained coal strength parameters,three sets of backfill properties were investigated.The results reveal that the behavior of pillars varies with the type and amount of backfill as well as the pillar width to mining height ratio(w/h).In case of cohesive backfill,generally 75%backfill shows a significant increase in peak strength,and the increase in peak strength is more pronounced for the pillars having lower w/h ratios.In case of noncohesive backfill,the changes in both the peak and residual strengths with up to 92%backfill are negligible while the residual strength constantly increases after reaching the peak strength only when 100%backfill is placed.Based on the modelling results,different backfilling strategies should be considered on a case by case basis depending on the type of backfill available and desired pillar dimension.
Distal‐less homeobox 3 (Dlx3), a member of the Dlx family of homeobox proteins, is a transcriptional activator of runt‐related transcription factor 2 (Runx2) during osteogenic differentiation. It has ...been demonstrated that forced expression of Runx2 induces an osteogenic program and ectopic calcification in muscles. Therefore, it would be reasonable to predict that Dlx3 also affects myogenic differentiation. The relationship between Dlx3 and myogenesis, however, remains poorly understood. Therefore, in this study, the role and regulation of Dlx3 during myogenic differentiation were investigated. Expression level of Dlx3 was downregulated in human mesenchymal stem cells (MSCs), mouse MSCs, and C2C12 cells cultured in myogenic medium. Dlx3 level was inversely correlated with myogenic differentiation 1 and the muscle‐specific microRNA, microRNA‐133 (miR‐133). The expression level of Runx2 was closely regulated by Dlx3 even under myogenic conditions. Overexpression of Dlx3 markedly downregulated expression levels of myogenic transcription factors and myotube formation in C2C12 cells, whereas Dlx3 knockdown enhanced myogenic differentiation. The Dlx3 3′‐untranslated region (3′‐UTR) has two potential binding sites for miR‐133. Luciferase reporter assays demonstrated that Dlx3 is a direct target of miR‐133a and miR‐133b, and that the two target sites are redundantly active. Taken together, these results suggest that Dlx3 is a negative regulator of myogenic differentiation and that miR‐133a and miR‐133b enhance myogenic differentiation, partly through inhibition of Dlx3 expression via direct targeting of the Dlx3 3′‐UTR.
Dlx3 is a negative regulator of myogenic differentiation. MiR‐133 enhances myogenic differentiation partly through inhibition of Dlx3 expression.
The formation of galactic discs Mo, H. J.; Mao, Shude; White, Simon D. M.
Monthly notices of the Royal Astronomical Society,
04/1998, Letnik:
295, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We study the population of galactic discs expected in current hierarchical clustering models for structure formation. A rotationally supported disc with exponential surface density profile is assumed ...to form with a mass and angular momentum which are fixed fractions of those of its surrounding dark halo. We assume that haloes respond adiabatically to disc formation, and that only stable discs can correspond to real systems. With these assumptions the predicted population can match both present-day discs and the damped Lyα absorbers in QSO spectra. Good agreement is found provided that: (i) the masses of discs are a few per cent of those of their haloes; (ii) the specific angular momenta of discs are similar to those of their haloes; (iii) present-day discs were assembled recently (at z ≤ 1). In particular, the observed scatter in the size—rotation velocity plane is reproduced, as are the slope and scatter of the Tully—Fisher (TF) relation. The zero-point of the TF relation is matched for a stellar mass-to-light ratio of 1 to 2 h in the I-band, consistent with observational values derived from disc dynamics. High-redshift discs are predicted to be small and dense, and could plausibly merge together to form the observed population of elliptical galaxies. In many (but not all) currently popular cosmogonies, discs with rotation velocities exceeding 200 km s−1 can account for a third or more of the observed damped Lyα systems at z ∼ 2.5. Half of the lines of sight to such systems are predicted to intersect the absorber at r ≳ 3 h−1 kpc and about 10 per cent at r > 10 h−1 kpc. The cross-section for absorption is strongly weighted towards discs with large angular momentum and therefore large size for their mass. The galaxy population associated with damped absorbers should thus be biased towards low surface brightness systems.
Summary Background Compared with other countries, patients with chronic hepatitis C infection in Japan tend to be older, have more advanced liver disease, and are more likely to have been previously ...treated for hepatitis C. We aimed to assess the efficacy and safety of an all-oral, fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection. Methods In this randomised, open-label study, we enrolled patients from 19 clinical Japanese centres. Patients were randomly assigned (1:1) to receive either ledipasvir (90 mg) and sofosbuvir (400 mg) or ledipasvir, sofosbuvir, and ribavirin (dosed according to the Japanese Copegus product label—ie, patients ≤60 kg received 600 mg daily, patients >60 kg to ≤80 kg received 800 mg daily, and patients >80 kg received 1000 mg daily) orally once daily for 12 weeks. After completion or early discontinuation of treatment, patients were followed up off-treatment for 24 weeks. Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log10 IU/mL, creatinine clearance of at least 1·0 mL/s, and a platelet count of at least 50 × 109 per L. An interactive web response system was used to manage patient randomisation and treatment assignment. Randomisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category (relapser or breakthrough, non-responder, or interferon-intolerant) for previously treated patients. Within each strata, patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12) assessed in all patients who were randomly assigned and received at least one dose of study drug; safety outcomes were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , number NCT01975675. Findings Between Oct 15, 2013 and Dec 13, 2013, 341 patients were randomly assigned to treatment groups and received at least one dose of study treatment. SVR12 was achieved in all 171 (100%) patients (83 of 83 treatment naive and 88 of 88 treatment experienced) receiving ledipasvir-sofosbuvir (95% CI 98–100) and 167 (98%) of 170 patients (80 of 83 treatment naive and 87 of 87 treatment experienced) receiving ledipasvir-sofosbuvir plus ribavirin (95% CI 95–100). Of the 76 patients with baseline NS5A resistant variants, 75 (99%) achieved SVR12. Two (1·2%) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events. The most common adverse events were nasopharyngitis (50 29·2% of 171), headache (12 7·0% of 171), and malaise (nine 5·3% of 171) in patients receiving ledipasvir-sofosbuvir; and nasopharyngitis (40 23·5% of 170), anaemia (23 13·5% of 170), and headache in those receiving ledipasvir-sofosbuvir and ribavirin (15 8·8% of 170). Interpretation Although existing regimens for the treatment of hepatitis C virus are effective for many patients, medical needs remain unmet, particularly in Japan where the population with hepatitis C virus genotype 1 is generally older and treatment-experienced, with advanced liver disease. The efficacy, tolerability, and absence of drug–drug interactions of ledipasvir-sofosbuvir suggest that it could be an important option for treatment of genotype 1 hepatitis C virus in Japanese patients. Funding Gilead Sciences.
The underutilization of professional care is a perennial problem among Chinese populations. To examine the social-cognitive factors that may affect help-seeking intentions, the present study applied ...and extended Ajzen’s theory of planned behavior (TPB) to understand the intention to seek help from mental health professionals among Chinese. The effect of mental health and perceived barriers to help-seeking were also examined. Nine hundred and forty-one Chinese were recruited using a randomized household design in Hong Kong. Results from structural equation modeling showed that attitude, subjective norm, perceived behavioral control, and perceived barriers significantly predicted help-seeking intention. Mental health showed no significant effect on help-seeking intention. In addition, subjective norm indirectly predicted intention to seek help from mental health professionals through influencing attitude and perceived behavioral control. Results from multi-group analyses revealed that all path coefficients were invariant across gender. Results supported the utilization of TPB in understanding help-seeking intentions and highlighted the importance of subjective norm among Chinese. Implications on the enhancement of mental health awareness and the promotion of mental health services through a social-cognitive approach were highlighted.
This study examined how citizens select science information online based on their preexisting issue attitudes. Voluntary national samples browsed through an online news magazine featuring divergent ...viewpoints about four controversial science topics (stem cell, evolution, genetically modified foods, and global warming). Their online activities, including article selection and the length of exposure, were unobtrusively measured by behavior tracking software. Participants tended to choose science information that challenged rather than supported their views concerning stem cell and genetically modified foods. However, those who perceived that they had sufficient science knowledge and were religious exhibited confirmation-bias, preferring congruent to incongruent information.
T1ρ imaging is a new quantitative MR imaging pulse sequence with the potential to discriminate between malignant and benign tissue. In this study, we evaluated the capability of T1ρ imaging to ...characterize tissue by applying T1ρ imaging to malignant and benign tissue in the nasopharynx and to normal tissue in the head and neck.
Participants with undifferentiated nasopharyngeal carcinoma and benign hyperplasia of the nasopharynx prospectively underwent T1ρ imaging. T1ρ measurements obtained from the histogram analysis for nasopharyngeal carcinoma in 43 participants were compared with those for benign hyperplasia and for normal tissue (brain, muscle, and parotid glands) in 41 participants using the Mann-Whitney
test. The area under the curve of significant T1ρ measurements was calculated and compared using receiver operating characteristic analysis and the Delong test, respectively. A
< .
05 indicated statistical significance.
There were significant differences in T1ρ measurements between nasopharyngeal carcinoma and benign hyperplasia and between nasopharyngeal carcinoma and normal tissue (all,
< .
05). Compared with benign hyperplasia, nasopharyngeal carcinoma showed a lower T1ρ mean (62.14 versus 65.45 × ms), SD (12.60 versus 17.73 × ms), and skewness (0.61 versus 0.76) (all
< .05), but no difference in kurtosis (
= .
18). The T1ρ SD showed the highest area under the curve of 0.95 compared with the T1ρ mean (area under the curve = 0.72) and T1ρ skewness (area under the curve = 0.72) for discriminating nasopharyngeal carcinoma and benign hyperplasia (all,
< .05).
Quantitative T1ρ imaging has the potential to discriminate malignant from benign and normal tissue in the head and neck.
Pelizaeus-Merzbacher disease (PMD) is a rare leukodystrophy caused by mutation of the proteolipid protein 1 gene. Defective oligodendrocytes in PMD fail to myelinate axons, causing global ...neurological dysfunction. Human central nervous system stem cells (HuCNS-SCs) can develop into oligodendrocytes and confer structurally normal myelin when transplanted into a hypomyelinating mouse model. A 1-year, open-label phase-1 study was undertaken to evaluate safety and to detect evidence of myelin formation after HuCNS-SC transplantation. Allogeneic HuCNS-SCs were surgically implanted into the frontal lobe white matter in four male subjects with an early-onset severe form of PMD. Immunosuppression was administered for 9 months. Serial neurological evaluations, developmental assessments, and cranial magnetic resonance imaging (MRI) and MR spectroscopy, including high-angular resolution diffusion tensor imaging (DTI), were performed at baseline and after transplantation. The neurosurgical procedure, immunosuppression regimen, and HuCNS-SC transplantation were well tolerated. Modest gains in neurological function were observed in three of the four subjects. No clinical or radiological adverse effects were directly attributed to the donor cells. Reduced T1 and T2 relaxation times were observed in the regions of transplantation 9 months after the procedure in the three subjects. Normalized DTI showed increasing fractional anisotropy and reduced radial diffusivity, consistent with myelination, in the region of transplantation compared to control white matter regions remote to the transplant sites. These phase 1 findings indicate a favorable safety profile for HuCNS-SCs in subjects with PMD. The MRI results suggest durable cell engraftment and donor-derived myelin in the transplanted host white matter.
Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and ...intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC.
Patients with American Joint Committee on Cancer stage III–IVB NPC were given an initial dose of cetuximab (400 mg/m2) 7–10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m2/week) and cetuximab (250 mg/m2/week).
Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3–4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3–4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months 95% confidence interval (CI) 26.2–32.1 months, the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%).
Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.
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