Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Androgen receptor (AR) belongs to the nuclear receptor superfamily and mediates the biological actions of male sex steroids. In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro. The catalytic kinase domain of ANPK shares considerable sequence similarity with the minibrain gene product, a protein kinase suggested to contribute to learning defects associated with Down syndrome. However, the rest of ANPK sequence, including the AR-interacting interface, exhibits no apparent homology with other proteins. ANPK is a nuclear protein that is widely expressed in mammalian tissues. Its overexpression enhances AR-dependent transcription in various cell lines. In addition to the zinc finger region, ligand-binding domain and activation function AF1 of AR are needed, as the activity of AR mutants devoid of these domains was not influenced by ANPK. The receptor protein does not appear to be a substrate for ANPK in vitro, and overexpression of ANPK does not increase the extent of AR phosphorylation in vivo. In view of this, it is likely that ANPK-mediated activation of AR function is exerted through modification of AR-associated proteins, such as coregulatory factors, and/or through stabilization of the receptor protein against degradation.

Phosphorylated Human Keratinocyte Ornithine Decarboxylase Is Preferentially Associated with Insoluble Cellular Proteins

Ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, is highly regulated by many trophic stimuli, and changes in its levels and organization correlate with cytoskeletal changes in normal human epidermal keratinocytes (NHEK). NHEK ODC exhibits a filamentous perinuclear/nuclear localization that becomes more diffuse under conditions that alter actin architecture. We have thus asked whether ODC colocalizes with a component of the NHEK cytoskeleton. Confocal immunofluorescence showed that ODC distribution in NHEK was primarily perinuclear; upon disruption of the actin cytoskeleton with cytochalasin D, ODC distribution was diffuse. The ODC distribution in untreated NHEK overlapped with that of keratin in the perinuclear but not cytoplasmic area; after treatment with cytochalasin D, overlap between staining for ODC and for keratin was extensive. No significant overlap with actin and minimal overlap with tubulin filament systems were observed. Subcellular fractionation by sequential homogenizations and centrifugations of NHEK lysates or detergent and salt extractions of NHEK in situ revealed that ODC protein and activity were detectable in both soluble and insoluble fractions, with mechanical disruption causing additional solubilization of ODC activity (three- to sevenfold above controls). Fractionation and ODC immunoprecipitation from [32P]orthophosphate-labeled NHEK lysates showed that a phosphorylated form of ODC was present in the insoluble fractions. Taken together, these data suggest that two pools of ODC exist in NHEK. The first is the previously described soluble pool, and the second is enriched in phospho-ODC and associated with insoluble cellular material that by immunohistochemistry appears to be organized in conjunction with the keratin cytoskeleton.

Cortical processing of change detection: Dissociation between natural vowels and two-frequency complex tones

We compared magnetoencephalographic responses for natural vowels and for sounds consisting of two pure tones that represent the two lowest formant frequencies of these vowels. Our aim was to determine whether spectral changes in successive stimuli are detected differently for speech and nonspeech sounds. The stimuli were presented in four blocks applying an oddball paradigm (20% deviants, 80% standards): (i) /α/ tokens as deviants vs. /i/ tokens as standards; (ii) /e/ vs. /i/; (iii) complex tones representing /α/ formants vs. /i/ formants; and (iv) complex tones representing /e/ formants vs. /i/ formants. Mismatch fields (MMFs) were calculated by subtracting the source waveform produced by standards from that produced by deviants. As expected, MMF amplitudes for the complex tones reflected acoustic deviation: the amplitudes were stronger for the complex tones representing /α/ than /e/ formants, i.e., when the spectral difference between standards and deviants was larger. In contrast, MMF amplitudes for the vowels were similar despite their different spectral composition, whereas the MMF onset time was longer for /e/ than for /α/. Thus the degree of spectral difference between standards and deviants was reflected by the MMF amplitude for the nonspeech sounds and by the MMF latency for the vowels.

ANX7, a candidate tumor suppressor gene for prostate cancer

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome

THE AIM OF THE STUDY There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. RESULTS Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. CONCLUSIONS Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.

Multivariate monitoring of a biological wastewater treatment process: a case study at Melbourne Water's Western Treatment Plant

Biological wastewater treatment is a complex, multivariate process, in which a number of physical and biological processes occur simultaneously. In this study, principal component analysis (PCA) and parallel factor analysis (PARAFAC) were used to profile and characterise Lagoon 115E, a multistage biological lagoon treatment system at Melbourne Water's Western Treatment Plant (WTP) in Melbourne, Australia. In this study, the objective was to increase our understanding of the multivariate processes taking place in the lagoon. The data used in the study span a 7-year period during which samples were collected as often as weekly from the ponds of Lagoon 115E and subjected to analysis. The resulting database, involving 19 chemical and physical variables, was studied using the multivariate data analysis methods PCA and PARAFAC. With these methods, alterations in the state of the wastewater due to intrinsic and extrinsic factors could be discerned. The methods were effective in illustrating and visually representing the complex purification stages and cyclic changes occurring along the lagoon system. The two methods proved complementary, with each having its own beneficial features. (C) 2003 Elsevier B.V. All rights reserved.

Projecting the fate of fish populations using ecological-economic modeling

Four marine fish species are among the most important on the world market: cod, salmon, tuna, and sea bass. While the supply of North American and European markets for two of these species - Atlantic salmon and European sea bass - mainly comes from fish farming, Atlantic cod and tunas are mainly caught from wild stocks. We address the question what will be the status of these wild stocks in the midterm future, in the year 2048, to be specific. Whereas the effects of climate change and ecological driving forces on fish stocks have already gained much attention, our prime interest is in studying the effects of changing economic drivers, as well as the impact of variable management effectiveness. Using a process-based ecological-economic multispecies optimization model, we assess the future stock status under different scenarios of change. We simulate (i) technological progress in fishing, (ii) increasing demand for fish, and (iii) increasing supply of farmed fish, as well as the interplay of these driving forces under different sce- narios of (limited) fishery management effectiveness. We find that economic change has a substantial effect on fish populations. Increasing aquaculture production can dampen the fishing pressure on wild stocks, but this effect is likely to be overwhelmed by increasing demand and technological progress, both increasing fishing pressure. The only solution to avoid collapse of the majority of stocks is institutional change to improve management effectiveness significantly above the current state. We conclude that full recognition of economic drivers of change will be needed to successfully develop an integrated ecosystem management and to sustain the wild fish stocks until 2048 and beyond.

Suomenlahden alueen alusöljy- ja aluskemikaalivahinkojen torjunnan yhteistoimintasuunnitelma

Suomenlahden alueen alusöljy- ja aluskemikaalivahinkojen torjunnan yhteistoimintasuunnitelma on laadittu Uudenmaan ELYkeskuksen johdolla eri viranomaisten yhteistyönä. Suunnitelma perustuu öljyvahinkojen torjuntalain 13. §:ään. Suunnitelman tarkoituksena on varmistaa torjuntatöiden nopea käynnistyminen ja laadukas toteuttaminen viranomaisten yhteistoimin kaikissa toiminta-alueen vahinkotilanteissa. Suunnitelmassa on esitetty Suomenlahden alueen erityispiirteitä sekä eri viranomaisten ja muiden torjuntaan osallistuvien tehtäviä ja resursseja. Suunnitelmassa kuvataan torjuntatyön eri vaiheita ja toimenpiteitä. Torjuntajärjestelyt perustuvat ensisijaisesti pelastustoimen, muiden torjuntaviranomaisten sekä virka-apuviranomaisten yhteistoimintaan. Suurten merialueella tapahtuvien vahinkojen torjunnassa tarvitaan aina resursseja yhteistoiminta-alueen ulkopuolelta. Yhteistyötä ja koordinaatiota yhteistoiminta-alueiden välillä ja valtakunnallisella tasolla tulee kehittää. Kokonaisuus muun muassa päivitettyine uhkakuvineen tulee laatia valtakunnallisen torjuntastrategian muotoon. Suunnitelman laatimisen aikana kirjattujen kehittämistarpeiden toimenpanoa pyritään edistämään lähivuosina.

Privity of Contract and Third Party Rights in European Construction Projects

Privity of contract has lately been criticized in several European jurisdictions, particu-larly due to the onerous consequences it gives rise to in arrangements typical for the modern exchange such as chains of contracts. Privity of contract is a classical premise of contract law, which prohibits a third party to acquire or enforce rights under a contract to which he is not a party. Such a premise is usually seen to be manifested in the doctrine of privity of contract developed under common law, however, the jurisdictions of continental Europe do recognize a corresponding starting point in contract law. One of the traditional industry sectors affected by this premise is the construction industry. A typical large construction project includes a contractual chain comprised of an employer, a main contractor and a subcontractor. The employer is usually dependent on the subcontractor's performance, however, no contractual nexus exists between the two. Accordingly, the employer might want to circumvent the privity of contract in order to reach the subcontractor and to mitigate any risks imposed by such a chain of contracts. From this starting point, the study endeavors to examine the concept of privity of con-tract in European jurisdictions and particularly the methods used to circumvent the rule in the construction industry practice. For this purpose, the study employs both a com-parative and a legal dogmatic method. The principal aim is to discover general principles not just from a theoretical perspective, but from a practical angle as well. Consequently, a considerable amount of legal praxis as well as international industry forms have been used as references. The most important include inter alia the model forms produced by FIDIC as well as Olli Norros' doctoral thesis "Vastuu sopimusketjussa". According to the conclusions of this study, the four principal ways to circumvent privity of contract in European construction projects include liability in a chain of contracts, collateral contracts, assignment of rights as well as security instruments. The contempo-rary European jurisdictions recognize these concepts and the references suggest that they are an integral part of the current market practice. Despite the fact that such means of circumventing privity of contract raise a number of legal questions and affect the risk position of particularly a subcontractor considerably, it seems that the impairment of the premise of privity of contract is an increasing trend in the construction industry.

A series of trials in the UK as part of the Ofcom TV white spaces pilot

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A tentative argument for regional quality targets in assimilating schwa

Amerikanenglannin redusoitunut švaa-vokaali tuotetaan puheessa laadultaan huomattavan monimuotoisena. Kirjallisuudessa ei kuitenkaan vallitse selkeää käsitystä siitä, mitkä tekijät ehdollistavat tätä švaan laatuvaihtelua, ja etenkin sen mahdollinen sosiaalinen ulottuvuus on jäänyt aiemmissa tutkimuksissa varsin vähälle huomiolle. Tässä tutkielmassa pyritäänkin selvittämään, millainen vaikutus puhujan alueellisella murteella on hänen tuottamansa švaan akustiikkaan. Tutkimukseen valittiin 21 informanttia muutamista Yhdysvaltain eteläisistä ja läntisistä osavaltioista. Informanttien haastattelunauhoitteista poimittiin analyysiin yhteensä 433 švaan F1- ja F2-formanttiarvot siten kuin ne esiintyivät sanassa the. Analyysissä havaittiin, että eteläisten puhujien švaat keskittyivät vokaalien [u,U] tuntumaan, kun taas läntisten informanttien švaat asettuivat vokaalien [i,u] väliin. Tulokset antoivat aihetta kysyä, onko eteläinen švaa sulautunut takavokaaleihin [u,U]. Kysymystä varten suoritettiin jatkotutkimus, johon valittiin yksi ensimmäisen tutkimuksen eteläisistä puhujista. Puhujalta mitattiin 66 švaan ja 45 [U]:n formantit. Näitä tarkastellessa löydettiin tilastollista viitettä siitä, että puhujan švaa oli saattanut sulautua vokaaliin [U]. Tulostensa pohjalta tutkielma ehdottaa, että the-sanassa esiintyvässä amerikanenglannin švaassa saattaa toteutua puhujan alueellista murretta mukaileva tavoitevaihe siitä huolimatta, että tämä vokaali on samanaikaisesti huomattavasti kontekstiinsa assimiloitunut. Tavoitevaihe näyttäisi lähtökohtaisesti sijoittuvan F2:ssa vokaalialueen keskelle, ollen kuitenkin eteläisten puhujien kohdalla altis siirtymään taaemmas kohti vokaalilaatuja [u,U].

Kissa ihmisen peilinä. Muutos, sukupuoli ja vuorovaikutus taiteessa

Tutkielman aiheena on kissa ja sen representaatiot visuaalisessa taiteessa. Tutkielmassa tarkastellaan 12 eri tekniikoilla valmistettua taideteosta, jotka ovat valmistuneet vuosien 1974 ja 2015 välisenä aikana. Tutkielmaan valitut taiteilijat, teokset ja valmistusvuodet ovat seuraavat: Jan Harrison, Chuff and Roll Over 1997; Jan Harrison, Cat with Raw Nose 2006; Sampsa Indrén, Hello Kitty 2012; Nanna Susi, Maliblue 2013; Olli Lyytikäinen, Kolme pyramidia ja sfinksi 1974, Kari Soinio, Sankarin koti nr 9 2009; elokuvasta Yön ritarin paluu Kissanainen/Selena Kyle (Anne Hathaway) 2012; Stiina Saaristo, Turengin Tuhkimo 2012; sarjakuvasta Simpsonit Matt Groening (piirt.), Crazy Cat Lady/Eleanor Abernathy 1998; sarjakuvahahmo, Jim Davis (hahmotelma ja käsikirj.), Karvinen 1989; Carolee Schneemann, Infinity Kisses (1988) ja Katinka Simonse, alias Tinkebell, My dearest cat Pinkeltje. (2009). Tutkielman tarkoituksena on ollut selvittää, mikä tarkoitus kissan olemassaololla on valituissa teoksissa ja mitä sen avulla on haluttu kertoa. Tutkielman käsittelyaineisto on jaettu kolmeen pääryhmään, 1) kissa ihmisen sisäisen ja tiedostamattoman tulkkina, 2) kissa sukupuoliroolien ja stereotypioiden symbolina, 3) kissa lemmikkinä. Tarkastelussa on käytetty muun muassa psykoanalyyttistä, filosofista, sukupuolentutkinnallista ja fenomenologista lähestymistapaa. Tutkielman psykoanalyyttinen tarkastelutapa perustuu pääasiassa freudilaisiin ja filosofinen näkökulma deleuzelais-guattarilaisiin näkemyksiin. Tutkimuksella on pyritty tulkitsemaan ja kartoittamaan tapoja, joilla taiteilija on kissaa apunaan käyttäen lähestynyt ihmisen henkistä muutosta piilotajunnasta nousevien halujen ja yhteiskunnallisten stereotypioiden puristuksessa. Tuleminen joksikin, muodonmuutos sekä ihmisen ja eläimen yhteys ovat tutkielman tärkeimpiä tulkinnan kohteita.