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To study differences in SRB1 gene expression between Candida albicans fluconazole-resistant strains and fluconazole-sensitive strains, and to identify new antifungal drug treatment targets. We studied 30 fluconazole-resistant and 47 fluconazole-sensitive C. albicans strains. The strains were routinely cultured, and total RNA was extracted, reverse transcribed into cDNA and analyzed with real-time PCR amplification with 18S rRNA used as an internal reference gene. The expression levels of the two groups were analyzed in Light Cycler system software version 3.0, and independent Student’s t test was performed in SPSS 19.0 statistical software. P  less then  0.05 was considered to indicate a statistical difference. DNAMAN multiple sequence alignment analysis was used to randomly analyze SBR1 related sequences of four resistant strains and four sensitive strains. An evolutionary tree was constructed with the maximum likelihood method in Mega6.0 software. The mean SRB1 gene expression in the drug-resistant group was 0.75138 × 10-3, and that in the sensitive group was 1.6664 × 10-3. Independent Student’s t test indicated a statistically significant difference (T = -3.972, P = 0.000, P  less then  0.05). DNAMAN multiple sequence alignment analysis showed that the sequence identity of the CDS in the eight strains was 75.17%, and that of sequences 1000 bp upstream of the CDS was 96.35%. Cluster analysis showed that the CDS and sequences 1000 bp upstream of the CDS showed no significant differences between groups. At the mRNA level, the SRB1 gene expression in fluconazole-resistant C. albicans was lower than that in fluconazole-sensitive strains, thus suggesting that the gene may be associated with drug resistance and that the regulatory mechanism leading to this difference is complex.The effects of epigenetic modulation on secondary metabolite biosynthesis were investigated with five Aspergillus species cultured in the presence of either the DNA methyltransferase inhibitor 5-azacitidine or the histone deacetylase inhibitor vorinostat. With Aspergillus calidoustus and Aspergillus westerdijkiae, fermentation in the presence of vorinostat (100 μM) induced significant changes in secondary metabolite profile with examples of both induction and repression. We identified putative biosynthetic gene clusters for emericellamide in A. calidoustus and ochratoxin in A. westerdijkiae. A substantial induction in production levels was observed for two secondary metabolites the diketopiperazine alkaloid phenylahistin in A. calidoustus and the polyketide penicillic acid in A. westerdijkiae, indicating the potential of epigenetic regulation for the activation of silent fungal biosynthetic pathways.We apply adaptive feedback for the partial refrigeration of a mechanical resonator, i.e. with the aim to simultaneously cool the classical thermal motion of more than one vibrational degree of freedom. The feedback is obtained from a neural network parametrized policy trained via a reinforcement learning strategy to choose the correct sequence of actions from a finite set in order to simultaneously reduce the energy of many modes of vibration. The actions are realized either as optical modulations of the spring constants in the so-called quadratic optomechanical coupling regime or as radiation pressure induced momentum kicks in the linear coupling regime. As a proof of principle we numerically illustrate efficient simultaneous cooling of four independent modes with an overall strong reduction of the total system temperature.Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. see more Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells.Introduction There has been speculation about early exfoliation of carious primary molar teeth treated with the Hall Technique (HT).Aim To investigate the hypothesis that there is a difference in exfoliation times between teeth treated with the HT and contralateral teeth not treated with the HT.Methods Split-mouth retrospective cohort study of children treated in Dundee Dental Hospital and School (DDH&S). Radiographs and clinical records were assessed to compare children’s ages at exfoliation for HT-treated primary molars and their contralateral teeth not treated with the HT. Primary molars’ root resorption was also evaluated to assess whether the HT influenced the rate of root resorption.Results Using DDH&S’s clinical systems, children’s records (n = 13,160) were screened for children’s ages and sequential radiographs, with 192 children potentially eligible. After assessing radiographs and clinical records, 39 children met the inclusion criteria. Their mean age at time of HT treatment was 7.2 years (range = 4.0 to 11.0; SD = 1.5). There was no evidence of a difference (p = 0.41) between children’s ages at exfoliation of HT teeth (10.7; SD = 1.2 years) and contralateral teeth (11.0; SD = 1.4 years).Conclusion There is no evidence that use of the Hall Technique is associated with early exfoliation of primary molars.