Crystal Structure of the Complex between Calyculin A and the Catalytic Subunit of Protein Phosphatase 1

AbstractThe crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1γ, in complex with a marine toxin, calyculin A, was determined at 2.0 Å resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseudocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1γ, which is consistent with findings from the studies of dose-inhibition analysis

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

<p>Abstract</p> <p>Background</p> <p>Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.</p> <p>Methods</p> <p>Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.</p> <p>Results</p> <p>Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.</p> <p>Conclusions</p> <p>These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.</p

Generaattorin saarekekäyttö ja suojausten testaus

Työn aiheena oli sähkövoimatekniikan laboratorion oppimisympäristön generaattorin saarekekäyttö ja sen suojausten testaus. Opinnäytetyön tavoitteena oli testata ja käyttää generaattoria saarekekäytössä ja tehdä sille kytkentäohjelma, jonka avulla voidaan myöhemmin käyttää generaattoria saarekekäytön opetuk-sessa. Tavoitteena oli tehdä myös generaattorin relesuojauksille toiminnalliset testit. Opinnäytetyön teoriaosuudessa käsiteltiin generaattoreita ja niiden relesuojauksia. Generaattoreissa keskityttiin enemmän tahtigeneraattoreihin, koska opinnäytetyössä käytettiin sellaista. Työssä esiteltiin myös laiteympäristö, johon tätä opinnäytetyötä tehtiin. Opinnäytetyössä käytiin läpi myös ohjelmistot, joita tässä ympäristössä on mahdollista käyttää. Lähdemateriaaleina käytettiin alan kirjallisuutta sekä laitevalmistajien manuaaleja sekä nettisivuja. Työssä asetetut tavoitteet täyttyivät ja tulokseksi saatiin kytkentäohjelma gene-raattorin saarekekäyttöön ja tieto siitä, kuinka sitä kuormitettiin. Myös generaat-torin suojauksien toiminnallisille testeille tehtiin ohjeistus, jonka avulla voidaan tulevaisuudessa tehdä toiminnallisia testejä. Myös REG630- releelle tehtiin ohjeistuksia, joiden avulla sitä voidaan myöhemmin käyttää.The subject of the thesis was electric power engineering laboratory learning environment for testing a generator in island operation and testing its protec-tion. The aim of the thesis was to test and use the generator in island operation and to make a switch program, which can later be used in education of using the generator in island operation. The other aim was to test a generator´s relay protection. The theoretical part of the thesis was concerned with generator´s and their relay protection. The focus was more on a synchronous generators were more focused, because synchronous generator was used in this thesis. The presentation of the thesis section presents a platform, where this thesis was made. Softwares, that are possible to use in this platform, were also presented in this thesis. The source materials were based on the field of the literature, as well as in the manufacturer`s Internet websites and manuals. The aim of the thesis was met and the results were that the switch program for using the generator in island operation was made and how it was loaded. Generator´s protections were also tested and the instructions were made, which helps in doing these tests in the future. Instructions were also made for the REG630 relay. These instructions help to use it

Properties of Composite Electrodes for All-solid-state Fluoride-ion Secondary Batteries Processed by High-pressure Torsion

All-solid-state fluoride-ion batteries (FIBs) using metal/metal fluorides are expected to be the next generation of storage batteries because they exhibit high volumetric energy densities by utilizing multielectron reactions, compared to the current lithium-ion batteries. However, method of fabricating a composite electrode for all-solid-state fluoride-ion batteries has not yet been established. A fabrication method for a composite electrode that disperses the active material and solid electrolyte is required. To approach this problem, in this study, we employed a high-pressure torsion (HPT) method, in which an active material, solid electrolyte, and conductive agent can be mixed with size reduction, as a new process and prepared Cu (active material)/PbSnF₄ (solid electrolyte)/acetylene black (conductive agent) cathode composites. The crystalline sizes of Cu and PbSnF₄ were significantly reduced. The apparent grain boundary resistance was also reduced owing to the more homogeneous distribution in the cathode composites after HPT processing. These structural and morphological changes led to high electrochemical performances, compared to a cathode composite without HPT

Time-Dependent Interaction between Differentiated Embryo Chondrocyte-2 and CCAAT/Enhancer-Binding Protein ␣ Underlies the Circadian Expression of CYP2D6 in Serum- Shocked HepG2 Cells

ABSTRACT Differentiated embryo chondrocyte-2 (DEC2), also known as bHLHE41 or Sharp1, is a pleiotropic transcription repressor that controls the expression of genes involved in cellular differentiation, hypoxia responses, apoptosis, and circadian rhythm regulation. Although a previous study demonstrated that DEC2 participates in the circadian control of hepatic metabolism by regulating the expression of cytochrome P450, the molecular mechanism is not fully understood. We reported previously that brief exposure of HepG2 cells to 50% serum resulted in 24-h oscillation in the expression of CYP3A4 as well as circadian clock genes. In this study, we found that the expression of CYP2D6, a major drug-metabolizing enzyme in humans, also exhibited a significant oscillation in serum-shocked HepG2 cells. DEC2 interacted with CCAAT/enhancer-binding protein (C/EBP␣), accompanied by formation of a complex with histone deacetylase-1, which suppressed the transcriptional activity of C/EBP␣ to induce the expression of CYP2D6. The oscillation in the protein levels of DEC2 in serum-shocked HepG2 cells was nearly antiphase to that in the mRNA levels of CYP2D6. Transfection of cells with small interfering RNA against DEC2 decreased the amplitude of CYP2D6 mRNA oscillation in serumshocked cells. These results suggest that DEC2 periodically represses the promoter activity of CYP2D6, resulting in its circadian expression in serum-shocked cells. DEC2 seems to constitute a molecular link through which output components from the circadian clock are associated with the time-dependent expression of hepatic drug-metabolizing enzyme