Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Integrated Project Portfolio Management as a Tool for Strategic Steering and Business Control

Tutkielman päätavoitteena oli tutkia miten projektisalkun hallinnalla voidaan tukea organisaation strategista ohjausta ja liiketoimintaa. Tämän lisäksi avaintavoitteina oli kuvata projektisalkun hallinnan nykytilanne kohdeyrityksessä, paljastaa erityisiä kehitystarpeita ja lopulta luoda kohdeyrityksen projektisalkunhallinnalle tavoitetila. Kirjallisuuskatsauksessa pohdittiin projektisalkun hallinnan roolia ja tavoitteita, projektisalkun hallinnassa käyttävää prosessia, sekä menetelmiä ja tekniikoita, joilla salkkua hallitaan. Työn empiirisessä osassa syvennyttiin tutkimaan projektinsalkun hallintaan liittyviä erityispiirteitä kohdeyrityksessä. Tutkimustulosten huolellinen analysointi osoitti, että aikaisempi kirjallisuus ei riittävästi huomioi kokonaisvaltaisen, integroidun lähestymistavan tarvetta ja viestinnän tärkeyttä projektisalkun hallinnassa. Tutkimuksen johtopäätöksinä luotiin uusi integroitu projektisalkun hallintamalli ja määriteltiin kohdeyritykselle projektisalkun hallinnan tavoitetila sekä ne kehitysaskeleet, joita yrityksen tulisi lähitulevaisuudessa ottaa.

Population Variation and Genetic Control of Modular Chromatin Architecture in Humans.

Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.

Brief cognitive assessment instruments in schizophrenia and bipolar patients, and healthy control subjects: A comparison study between the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP)

Cognitive impairment in schizophrenia and psychosis is ubiquitous and acknowledged as a core feature of clinical expression, pathophysiology, and prediction of functioning. However, assessment of cognitive functioning is excessively time-consuming in routine practice, and brief cognitive instruments specific to psychosis would be of value. Two screening tools have recently been created to address this issue, i.e., the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP). The aim of this research was to examine the comparative validity of these two brief instruments in relation to a global cognitive score. 161 patients with psychosis (96 patients diagnosed with schizophrenia and 65 patients diagnosed with bipolar disorder) and 76 healthy control subjects were tested with both instruments to examine their concurrent validity relative to a more comprehensive neuropsychological assessment battery. Scores from the B-CATS and the SCIP were highly correlated in the three diagnostic groups, and both scales showed good to excellent concurrent validity relative to a Global Cognitive Composite Score (GCCS) derived from the more comprehensive examination. The SCIP-S showed better predictive value of global cognitive impairment than the B-CATS. Partial and semi-partial correlations showed slightly higher percentages of both shared and unique variance between the SCIP-S and the GCCS than between the B-CATS and the GCCS. Brief instruments for assessing cognition in schizophrenia and bipolar disorders, such as the SCIP-S and B-CATS, seem to be reliable and promising tools for use in routine clinical practice.

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes.

Smoking behaviour, involuntary smoking, attitudes towards smoke-free legislations, and tobacco control activities in the European Union

The six most important cost-effective policies on tobacco control can be measured by the Tobacco Control Scale (TCS). The objective of our study was to describe the correlation between the TCS and smoking prevalence, self-reported exposure to secondhand smoke (SHS) and attitudes towards smoking restrictions in the 27 countries of the European Union (EU27).

Collaborative group membership and access control for JXTA

Peer-reviewed

Position sensorless electrically excited synchronous motor drive for industrial use based on direct flux linkage and torque control

Synchronous machines with an AC converter are used mainly in large drives, for example in ship propulsion drives as well as in rolling mill drives in steel industry. These motors are used because of their high efficiency, high overload capacity and good performance in the field weakening area. Present day drives for electrically excited synchronous motors are equipped with position sensors. Most drives for electrically excited synchronous motors will be equipped with position sensors also in future. This kind of drives with good dynamics are mainly used in metal industry. Drives without a position sensor can be used e.g. in ship propulsion and in large pump and blower drives. Nowadays, these drives are equipped with a position sensor, too. The tendency is to avoid a position sensor if possible, since a sensor reduces the reliability of the drive and increases costs (latter is not very significant for large drives). A new control technique for a synchronous motor drive is a combination of the Direct Flux Linkage Control (DFLC) based on a voltage model and a supervising method (e.g. current model). This combination is called Direct Torque Control method (DTC). In the case of the position sensorless drive, the DTC can be implemented by using other supervising methods that keep the stator flux linkage origin centered. In this thesis, a method for the observation of the drift of the real stator flux linkage in the DTC drive is introduced. It is also shown how this method can be used as a supervising method that keeps the stator flux linkage origin centered in the case of the DTC. In the position sensorless case, a synchronous motor can be started up with the DTC control, when a method for the determination of the initial rotor position presented in this thesis is used. The load characteristics of such a drive are not very good at low rotational speeds. Furthermore, continuous operation at a zero speed and at a low rotational speed is not possible, which is partly due to the problems related to the flux linkage estimate. For operation in a low speed area, a stator current control method based on the DFLC modulator (DMCQ is presented. With the DMCC, it is possible to start up and operate a synchronous motor at a zero speed and at low rotational speeds in general. The DMCC is necessary in situations where high torque (e.g. nominal torque) is required at the starting moment, or if the motor runs several seconds at a zero speed or at a low speed range (up to 2 Hz). The behaviour of the described methods is shown with test results. The test results are presented for the direct flux linkage and torque controlled test drive system with a 14.5 kVA, four pole salient pole synchronous motor with a damper winding and electric excitation. The static accuracy of the drive is verified by measuring the torque in a static load operation, and the dynamics of the drive is proven in load transient tests. The performance of the drive concept presented in this work is sufficient e.g. for ship propulsion and for large pump drives. Furthermore, the developed methods are almost independent of the machine parameters.

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.

Simultaneous determination of gemifloxacin and diuretics in bulk, pharmaceutical dosage forms and human serum by RP-HPLC

An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of gemifloxacin and diuretics (hydrochlorothiazide and furosemide) in bulk, dosage formulations and human serum at 232 nm. Chromatographic separation was achieved on Purospher Start C18 (250 mm x 4.6 mm, 5 µm) column using mobile phase, methanol: water: acetonitrile (70:25:5 v/v/v) adjusted to pH 3.0 via phosphoric acid 85% having flow rate of 0.8 mL min -1 at room temperature. Calibration curves were linear over range of 0.5-10 µg mL -1 with a correlation coefficient ± 0.999. LOD and LOQ were in the ranges of 0.75-2.56 µg mL -1. Intra and inter-run precision and accuracy results were 98.26 to 100.9.

Terrain forms and spatial variability of soil properties in an area cultivatedwith citrus

The technique of precision agriculture and soil-landscape allows delimiting areas for localized management, allowing a localized application of agricultural inputs and thereby may contribute to preservation of natural resources. Therefore, the objective of this work was to characterize the spatial variability of chemical properties and clay content in the context of soil-landscape relationship in a Latosol (Oxisol) under cultivation of citrus. Soil samples were collected at a depth of 0.0-0.2 m in an area of 83.5 ha planted with citrus, as a 50-m intervals grid, with 129 points in concave terrain and 206 points in flat terrain, totaling 335 points. Values for the variables that express the chemical characteristics and clay content of soil properties were analyzed with descriptive statistics and geostatistical modeling of semivariograms for making maps of kriging. The values of range and kriging maps indicated higher variability in the shape of concave topography (top segment) compared with the shape of flat topography (slope and hillside segments below). The identification of different forms of terrain proved to be efficient in understanding the spatial variability of chemical properties and clay content of soil under cultivation of citrus.

The Forms and Functions of Multilingual Practices in Early Modern School Drama from the King‟s School, Canterbury

Käsittelen tutkimuksessani monikielisyyden ilmenemistä Canterburyn katedraalikoulun oppilaiden 1600-luvun loppupuoliskolla esittämissä näytelmissä, jotka löytyvät käsikirjoituksesta Lit.Ms.E41 (Canterburyn katedraalin arkisto). Tämä käsikirjoitus sisältää puheita ja näytelmiä, joiden kielinä ovat englanti, latina ja vähemmissä määrin myös kreikka. Useissa näytelmissä esiintyy koodinvaihtoa näiden kielten välillä, ja tutkielmassani selvitän, millaisia syntaktisia ilmenemismuotoja ja pragmaattisia merkityksiä koodinvaihdolla on. Teoreettinen viitekehykseni on yhdistelmä filologista ja lingvististä lähestymistapaa. Olen sisällyttänyt tutkielmaani aiemman koodinvaihdon tutkimuksen lisäksi Brownin ja Levinsonin kohteliaisuusteorian, jonka avulla erityisesti puhujien välisiin sosiaalisiin suhteisiin liittyviä koodinvaihdon funktioita voidaan luokitella. Koska historiallinen koodinvaihto on tutkimusaiheena vielä melko tuore, käsittelen perusteellisesti erilaisia metodologisia ratkaisuja. Valitsemani metodi yhdistää perinteisen filologisen lähiluvun pragmaattiseen analyysiin, jonka kautta työssäni vaikuttavat muun muassa rationaalisuuden ja empatian käsitteet. Analyysini perusteella kävi ilmi, että erityisen yleinen koodinvaihdon funktio on mahdollistaa intertekstuaalisuus, jolla edelleen voidaan ilmaista esimerkiksi solidaarisuutta eli sosiaalista läheisyyttä tai loukata puhuteltavaa. Solidaarisuus oli myös ilman intertekstuaalisuutta yleinen koodinvaihdon funktio. Näiden lisäksi koodinvaihdon funktioita olivat muun muassa kasvoja uhkaavat teot, eufemismit, stilistiset efektit sekä diskurssin avustaminen. Syntaktisten ilmenemismuotojen osalta keskeisin havainto oli, että koodinvaihdon ja lainaamisen erottaminen ei ole tarpeellista tai edes kannattavaa kaikissa tilanteissa. Lisäksi voitiin todeta, että valittu metodi soveltui hyvin aineiston analysoimiseen, ja sitä tulisi soveltaa mahdollisuuksien mukaan laajempaan materiaaliin sekä muiden pragmaattisten ilmiöiden tutkimiseen.