RNA Levels and Activity of \u3cem\u3eFLOWERING LOCUS C\u3c/em\u3e are Modified in Mixed Genetic Backgrounds of \u3cem\u3eArabidopsis Thaliana\u3c/em\u3e

Flowering time and FLOWERING LOCUS C (FLC) RNA levels were analyzed in different accessions of Arabidopsis thaliana and in mixed genetic backgrounds resulting from crosses between accessions. Dominant alleles of FRIGIDA (FRI) promote accumulation of FLC RNA, which in turn promotes late flowering. Although the coding regions of sequenced FLC alleles are identical, some accessions have genetically weak alleles that do not promote late flowering in the presence of FRI. In this study, a new weak allele of FLC with open reading frame identity to previously sequenced alleles was isolated from a Niederzenz (Nd) accession. The FLC‐Nd allele accumulated less RNA in the presence of FRI than did the strong Columbia (Col) allele. The weak FLC‐Nd allele was semidominant in the mixed Nd/Col genetic background containing FRI, and a linear correlation between the level of FLC RNA and lateness of flowering was observed. However, late‐flowering transgressions with elevated levels of FLC RNA in the absence of FRI were also obtained from crosses between early‐flowering accessions Col and Nd. Moreover, compared to Nd, the weak Landsberg erecta (Ler) allele of FLC was recessive and not semidominant in the mixed Ler/Col genetic background. However, very early‐flowering transgressions lacking detectable FLC RNA were also obtained from crosses between FRI containing Col and Ler. The results indicate that modifier genes other than FRI influence the level and genetic activity of FLC RNA in different genetic backgrounds resulting from crosses between naturally occurring accessions of A. thaliana

\u3cem\u3eFRIGIDA LIKE 2\u3c/em\u3e Is a Functional Allele in Landsberg \u3cem\u3eerecta\u3c/em\u3e and Compensates for a Nonsense Allele of \u3cem\u3eFRIGIDA LIKE 1\u3c/em\u3e

The Landsberg erecta (Ler) accession of Arabidopsis (Arabidopsis thaliana) has a weak allele of the floral inhibitor FLOWERING LOCUS C (FLC). FLC-Ler is weakly up-regulated by the active San Feliu-2 (Sf2) allele of FRIGIDA (FRI-Sf2), resulting in a moderately late-flowering phenotype. By contrast, the Columbia (Col) allele of FLC is strongly up-regulated by FRI-Sf2, resulting in a very late-flowering phenotype. In Col, the FRI-related gene FRI LIKE 1 (FRL1) is required for FRI-mediated upregulation of FLC. It is shown here that in Ler, the FRL1-related gene FRI LIKE 2 (FRL2), but not FRL1, is required for FRI-mediated up-regulation of FLC. FRL1-Ler is shown to be a nonsense allele of FRL1 due to a naturally occurring premature stop codon in the middle of the conceptual protein sequence, suggesting that FRL1-Ler is nonfunctional. Compared to FRL2-Col, FRL2-Ler has two amino acid changes in the conceptual protein sequence. Plants homozygous for FRI-Sf2, FLC-Ler, FRL1-Ler, and FRL2-Col have no detectable FLC expression, resulting in an extremely early flowering phenotype. Transformation of a genomic fragment of FRL2-Ler, but not of FRL2-Col, into a recombinant inbred line derived from these plants restores both FRI-mediated up-regulation of FLC expression and a late-flowering phenotype, indicating that FRL2-Ler is the functional allele of FRL2. Taken together, these results suggest that in the two different Arabidopsis accessions Col and Ler, either FRL1 or FRL2, but not both, is functional and required for FRI-mediated up-regulation of FLC

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans. METHODS: A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization. RESULTS: Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance. CONCLUSION: Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy. FUNDING: This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship

Multiple FLC haplotypes defined by independent cis-regulatory variation underpin life history diversity in Arabidopsis thaliana

Relating molecular variation to phenotypic diversity is a central goal in evolutionary biology. In Arabidopsis thaliana, FLOWERING LOCUS C (FLC) is a major determinant of variation in vernalization—the acceleration of flowering by prolonged cold. Here, through analysis of 1307 A. thaliana accessions, we identify five predominant FLC haplotypes defined by noncoding sequence variation. Genetic and transgenic experiments show that they are functionally distinct, varying in FLC expression level and rate of epigenetic silencing. Allelic heterogeneity at this single locus accounts for a large proportion of natural variation in vernalization that contributes to adaptation of A. thaliana

Simulation for position control of DC motor using fuzzy logic controller

The purpose of this project is to control the position of DC Motor by using Fuzzy Logic Controller (FLC) with MATLAB application. The scopes includes the simulation and modelling of DC motor, fuzzy controller and conventional PID controller as benchmark to the performance of fuzzy system. The position control is an adaptation of Closed Circuit Television (CCTV) system. Fuzzy Logic control can play important role because knowledge based design rules can be easily implemented in the system with unknown structure and it is going to be popular since the control design strategy is simple and practical. This make FLC an alternative method to the conventional PID control method used in nonlinear industrial system. The results obtained from FLC are compared with PID control for the dynamic response of the closed loop system. Parameters such as peak position in degree, settling time in second and maximum overshoot in percent will be part of the simulation result. Overall performance show that FLC perform better than PID controller

Serum Free Light Chains Removal by HFR Hemodiafiltration in Patients with Multiple Myeloma and Acute Kidney Injury. a Case Series

Background/Aims: Multiple myeloma (MM) represents 10% of all haematologic malignancies. Renal involvement occurs in 50% of MM patients; of them, 12-20% have acute kidney injury (AKI), with 10% needing dialysis at presentation. While hemodialysis (HD) has no effect upon circulating and tissue levels of monoclonal proteins, novel apheretic techniques aim at removing the paraproteins responsible for glomerular / tubular deposition disease. High cut-off HD (HCO-HD) combined with chemotherapy affords a sustained reduction of serum free light chains (FLC) levels. One alternative technology is haemodiafiltration with ultrafiltrate regeneration by adsorption on resin (HFR–SUPRA), employing a “super high-flux” membrane (polyphenylene S-HF, with a nominal cut-off of 42 kD). Aim of our pilot study was to analyze the effectiveness of HFR-SUPRA in reducing the burden of FLC, while minimizing albumin loss and hastening recovery of renal function in 6 subjects with MM complicated by AKI. Methods: Six HD-dependent patients with MM were treated with 5 consecutive sessions of HFR-SUPRA on a Bellco® monitor, while simultaneously initiating chemotherapy. Levels of albumin and FLC were assessed, calculating the rates of reduction. Renal outcome, HD withdrawal and clinical follow-up or death were recorded. Results: All patients showed a significant reduction of FLC, whereas serum albumin concentration remained unchanged. In three, HD was withdrawn, switching to a chemotherapy alone regimen. The other patients remained HD-dependent and died shortly thereafter for cardiovascular complications. Conclusion: Our study suggests that HFR-SUPRA provides a rapid and effective reduction in serum FLC in patients with MM and AKI

Dynamic Response of a fast near infra-red Mueller matrix ellipsometer

The dynamic response of a near infrared Ferroelectric Liquid Crystal based Mueller matrix ellipsometer (NIR FLC-MME) is presented. A time dependent simulation model, using the measured time response of the individual FLCs, is used to describe the measured temporal response. Furthermore, the impulse response of the detector and the pre-amplifier is characterized and included in the simulation model. The measured time-dependent intensity response of the MME is reproduced in simulations, and it is concluded that the switching time of the FLCs is the limiting factor for the Mueller matrix measurement time of the FLC-based MME. Based on measurements and simulations our FLC based NIR-MME system is estimated to operate at the maximum speed of approximately 16 ms per Mueller matrix measurement. The FLC-MME may be operated several times faster, since the switching time of the crystals depends on the individual crystal being switched, and to what state it is switched. As a demonstration, the measured temporal response of the Mueller matrix and the retardance of a thick liquid crystal variable retarder upon changing state is demonstrated.Comment: to be published in Journal of Modern Optics 20 pages, 6 figure

Induction motor controller using fuzzy logic

Induction Motor is widely used in general industry applications focusing on production area. Induction motor speed control is becoming very important due to increase the profit to the industries with increase efficiency, reliability and performance of induction motor. Due to the problem facing in induction motor that require complex mathematical model and varying parameters, Fuzzy Logic Controller (FLC) is applied to overcome this problem. The FLC based on the concepts of an artificial intelligence and attractive alternatives method to tackle the problem of controller design for complex mathematical model of system. This project used FLC Sugeno types. The purpose used FLC is to control speed and increase the efficiency of IM. While, the conventional controller only works well for linear system and their performances will decrease for nonlinear system. To make an induction motor operates such as Direct Current (DC) motor, Field Oriented Control (FOC) drives is applied for Induction Motor drive. FOC also offering a fast dynamic response and a high precision ability for IM drive. This project is implemented using Simulink Matlab. Based on the test results show the response of the speed curve takes less time to settle and reach the desired value

The influence of curvature on FLC’s of mild steel, (A)HSS and aluminium

In literature the influence of curvature on formability has been reported. This\ud paper shows results for four materials when an FLC is measured with increasing curvature. It shows the FLC increases for sharper curvature most notably with 20 [mm] tool diameter. The increase is negligible on the left hand side, moderate on the right hand side and large on the plane strain axis. It is thought that contact pressure plays a role here and preliminary simulations indicate that this is quite possible