Corrective control: stability analysis of Unified Controller combining frequency control and congestion management

This paper analyses stability of the Unified Controller (UC) that combines frequency control and congestion management and therefore makes it possible to move from preventive to corrective power system control. Earlier work by the authors of UC proved asymptotic stability of the methodology but the proof was based on a simplified first-order model of the turbine and turbine governor. We show that a higher order model of the turbine governor leads to eigenvalues with small but positive real parts. Consequently, we develop a modification of the methodology that decouples the physical and control systems and therefore results in all the eigenvalues having negative real parts. We illustrate the effectiveness of the modification on a realistic model of 39-bus model of New England power system implemented in Power System Toolbox (PST)

The changes of standard DXA measurements and TBS depending on outcomes of neurosurgical treatment in patients with Cushing's disease

BACKGROUND:Patients with endogenous hypercortisolism have reduced bone mineral density (BMD) and trabecular bone score (TBS) that are the causes of secondary osteoporosis and low-traumatic fractures. It is well known that radical treatment (neurosurgery or radiosurgery) of Cushings disease leads to a decline of cortisol levels in all body fluids to normal values. However, it is still uncertain whether bone tissue structure, and particularly its microarchitecture, does recover in remission of the disease. AIMS:To evaluate an influence of hormone activity (presence or absence of remission) in patients with Cushing's disease on changes of bone structure measurements in accordance with DXA values (TBS, BMD, T- and Z-scores), as well as significance of such changes in 12 and 24 months after neurosurgical treatment. MATERIALS AND METHODS:In patients with confirmed active Cushing's disease (ACTH-producing pituitary adenoma) (n = 44) and in control group of healthy volunteers (n = 40), BMD in lumbar spine (L1-L4) and simultaneously TBS, in cut-off points before neurosurgical treatment (in both groups) and in 12 and 24 months after it (only in patients), were assessed. We diagnosed presence or absence of disease remission at cut-offs. All measurements were performed using a GE iDXA device (GE Healthcare Lunar, Madison, Wisconsin, USA). The TBS was calculated simultaneously from taken BMD scans, blinded to clinical outcome using TBS iNsight software v2.1 (Medimaps, Merignac, France). The activity of Cushings disease was evaluated using late-night salivary cortisol (LNSC, at 23:00). To determine the differences in DXA and TBS values before and after neurosurgical intervention depending on remission occurrence, covariate analysis (ANCOVA) was applied. RESULTS:There were found significant changes in TBS, BMD and T-score values in 12 months after neurosurgical treatment associated with presence or absence of disease remission (p = 0.039, 0.046 and 0.048, respectively). No differences in Z-score as well as in all measurements in 24 months, that might be associated with remission occurrence, were revealed. The gain in all DXA measurements (including TBS) during 24 months of observation period was statistically significant when analyzing data using Students paired t-test. However, the values corresponding to the age references had not been achieved for the specified time interval. CONCLUSIONS:Patients with Cushings disease have lower TBS values. In remission conditions TBS is getting significantly higher. The increase in BMD and TBS occurs during 24 months after achieving remission of Cushings disease but doesnt lead to a full restoration of normal bone mass and microstructure throughout observation period of 24 months

The assessment of Trabecular bone score to improve the sensitivity of FRAX in patients with type 2 diabetes mellitus

Aim. To estimate the trabecular bone score (TBS) for evaluation of fracture probability in order to make decisions about starting osteoporosis treatment in patients with type 2 diabetes mellitus (T2DM). Materials and methods. We obtained the bone mineral density (BMD) and trabecular bone score (TBS) using dual energy X-ray absorptiometry (iDXA) in patients with T2DM (with and without a history of osteoporotic fractures) versus the control group. Before and after TBS measurements we assessed the ten-year probability of fracture using the Fracture Risk Assessment Tool (FRAX). Results. We enrolled 48 patients with T2DM, including 17 with a history of low-traumatic fracture, 31 patients without fractures and 29 subjects of a control group. BMD was higher in patients with T2DM compared to the control group at L1–L4 (mean T-score 0.44, 95% CI -3.2 – 4.9 vs mean T-score 0.33, 95% CI -2.9 – 3.0 in a control group p=0.052) and Total Hip (mean T-score 0.51, 95% CI -2.1 – 3.0 vs mean T-score -0.03, 95% CI -1.4 – 1.2 in a control group p=0,025). The TBS and 10-year probability of fracture (FRAX) was not different in patients with T2DM versus the control group. However, when the TBS was entered as an additional risk factor, the 10-year probability of fracture became higher in patients with T2DM (10-year probability of fracture in T2DM- 8.68, 95% CI 0.3-25.0 versus 6.68, 95% CI 0.4–15.0 in control group, p=0.04). Among patients with diabetes with and without fractures the FRAX score was higher in subjects with fractures, but no difference was found in regards to BMD or TBS. Entering BMD and TBS values into the FRAX tool in subjects with diabetes and fractures decreased the FRAX score. However, patients with low-traumatic fractures should be treated for osteoporosis without a BMD, TBS or FRAX assessment. Conclusion. TBS improves the results of FRAX assessment in patients with T2DM and should be entered while evaluating FRAX in patients with T2DM. However, additional research is needed to develop a more sensitive tool to evaluate fracture risk in patients with T2DM

Hsp70 Chaperones as Modulators of Prion Life Cycle: Novel Effects of Ssa and Ssb on the Saccharomyces cerevisiae Prion [PSI(+)]

[PSI(+)] is a prion isoform of the yeast release factor Sup35. In some assays, the cytosolic chaperones Ssa1 and Ssb1/2 of the Hsp70 family were previously shown to exhibit “pro-[PSI(+)]” and “anti-[PSI(+)]” effects, respectively. Here, it is demonstrated for the first time that excess Ssa1 increases de novo formation of [PSI(+)] and that pro-[PSI(+)] effects of Ssa1 are shared by all other Ssa proteins. Experiments with chimeric constructs show that the peptide-binding domain is a major determinant of differences in the effects of Ssa and Ssb proteins on [PSI(+)]. Surprisingly, overproduction of either chaperone increases loss of [PSI(+)] when Sup35 is simultaneously overproduced. Excess Ssa increases both the average size of prion polymers and the proportion of monomeric Sup35 protein. Both in vivo and in vitro experiments uncover direct physical interactions between Sup35 and Hsp70 proteins. The proposed model postulates that Ssa stimulates prion formation and polymer growth by stabilizing misfolded proteins, which serve as substrates for prion conversion. In the case of very large prion aggregates, further increase in size may lead to the loss of prion activity. In contrast, Ssb either stimulates refolding into nonprion conformation or targets misfolded proteins for degradation, in this way counteracting prion formation and propagation

Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress

Self-perpetuating ordered protein aggregates (amyloids and prions) are associated with a variety of neurodegenerative disorders. Although environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. We have employed endogenous yeast prions as a model system to study environmental control of amyloid formation. A short-lived actin-associated yeast protein Lsb2 can trigger prion formation by other proteins in a mode regulated by the cytoskeleton and ubiquitin-dependent processes. Here, we show that such a heterologous prion induction is due to the ability of Lsb2 to form a transient prion state, generated in response to thermal stress. Evolutionary acquisition of prion-inducing activity by Lsb2 is traced to a single amino acid change, coinciding with the acquisition of thermotolerance in the Saccharomyces yeast lineage. This raises the intriguing possibility that the transient prion formation could aid in functioning of Lsb2 at higher temperatures

Profiling and Verifying the Substrates of E3 Ubiquitin Ligase Rsp5 in Yeast Cells

Yeast is an essential model organism for studying protein ubiquitination pathways; however, identifying the direct substrates of E3 in the cell presents a challenge. Here, we present a protocol for using the orthogonal ubiquitin transfer (OUT) cascade to profile the substrate specificity of yeast E3 Rsp5. We describe steps for OUT profiling, proteomics analysis, in vitro and in cell ubiquitination, and stability assay. The protocol can be adapted for identifying and verifying the ubiquitination targets of other E3s in yeast. For complete details on the use and execution of this protocol, please refer to Wang et al