Nonperturbative estimate of the heavy quark momentum diffusion coefficient

We estimate the momentum diffusion coefficient of a heavy quark within a pure SU(3) plasma at a temperature of about 1.5Tc. Large-scale Monte Carlo simulations on a series of lattices extending up to 1923×48 permit us to carry out a continuum extrapolation of the so-called color-electric imaginary-time correlator. The extrapolated correlator is analyzed with the help of theoretically motivated models for the corresponding spectral function. Evidence for a nonzero transport coefficient is found and, incorporating systematic uncertainties reflecting model assumptions, we obtain κ=(1.8–3.4)T3. This implies that the “drag coefficient,” characterizing the time scale at which heavy quarks adjust to hydrodynamic flow, is η−1D=(1.8–3.4)(Tc/T)2(M/1.5  GeV)  fm/c, where M is the heavy quark kinetic mass. The results apply to bottom and, with somewhat larger systematic uncertainties, to charm quarks.

Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun

Interactions among transcription factors that bind to separate sequence elements require bending of the intervening DNA and juxtaposition of interacting molecular surfaces in an appropriate orientation. Here, we examine the effects of single amino acid substitutions adjacent to the basic regions of Fos and Jun as well as changes in sequences flanking the AP-1 site on DNA bending. Substitution of charged amino acid residues at positions adjacent to the basic DNA-binding domains of Fos and Jun altered DNA bending. The change in DNA bending was directly proportional to the change in net charge for all heterodimeric combinations between these proteins. Fos and Jun induced distinct DNA bends at different binding sites. Exchange of a single base pair outside of the region contacted in the x-ray crystal structure altered DNA bending. Substitution of base pairs flanking the AP-1 site had converse effects on the opposite directions of DNA bending induced by homodimers and heterodimers. These results suggest that Fos and Jun induce DNA bending in part through electrostatic interactions between amino acid residues adjacent to the basic region and base pairs flanking the AP-1 site. DNA bending by Fos and Jun at inverted binding sites indicated that heterodimers bind to the AP-1 site in a preferred orientation. Mutation of a conserved arginine within the basic regions of Fos and transversion of the central C:G base pair in the AP-1 site to G:C had complementary effects on the orientation of heterodimer binding and DNA bending. The conformational variability of the Fos–Jun–AP-1 complex may contribute to its functional versatility at different promoters.

Activation of p53 in cervical carcinoma cells by small molecules

In over 90% of cervical cancers and cancer-derived cell lines, the p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 and thus inhibits the stabilization and activation of p53 that would normally occur in response to HPV E7 oncogene expression. Restoration of p53 function in these cells by blocking this pathway should promote a selective therapeutic affect. Here we show that treatment with the small molecule nuclear export inhibitor, leptomycin B, and actinomycin D leads to the accumulation of transcriptionally active p53 in the nucleus of HeLa, CaSki, and SiHa cells. Northern blot analyses showed that both actinomycin D and leptomycin B reduced the amount of HPV E6-E7 mRNA whereas combined treatment with the drugs showed almost complete disappearance of the viral mRNA. The combined treatment activated p53-dependant transcription, and increases in both p21WAF1/CIP1 and Hdm2 mRNA were seen. The combined treatment resulted in apoptotic death in the cells, as evidenced by nuclear fragmentation and PARP-cleavage indicative of caspase 3 activity. These effects were greatly reduced by expressing a dominant negative p53 protein. The present study shows that small molecules can reactivate p53 in cervical carcinoma cells, and this reactivation is associated with an extensive biological response, including the induction of the apoptotic death of the cells.

Dynamics of Fos-Jun-NFAT1 complexes

Transcription initiation in eukaryotes is controlled by nucleoprotein complexes formed through cooperative interactions among multiple transcription regulatory proteins. These complexes may be assembled via stochastic collisions or defined pathways. We investigated the dynamics of Fos-Jun-NFAT1 complexes by using a multicolor fluorescence resonance energy transfer assay. Fos-Jun heterodimers can bind to AP-1 sites in two opposite orientations, only one of which is populated in mature Fos-Jun-NFAT1 complexes. We studied the reversal of Fos-Jun binding orientation in response to NFAT1 by measuring the efficiencies of energy transfer from donor fluorophores linked to opposite ends of an oligonucleotide to an acceptor fluorophore linked to one subunit of the heterodimer. The reorientation of Fos-Jun by NFAT1 was not inhibited by competitor oligonucleotides or heterodimers. The rate of Fos-Jun reorientation was faster than the rate of heterodimer dissociation at some binding sites. The facilitated reorientation of Fos-Jun heterodimers therefore can enhance the efficiency of Fos-Jun-NFAT1 complex formation. We also examined the influence of the preferred orientation of Fos-Jun binding on the stability and transcriptional activity of Fos-Jun-NFAT1 complexes. Complexes formed at sites where Fos-Jun favored the same binding orientation in the presence and absence of NFAT1 exhibited an 8-fold slower dissociation rate than complexes formed at sites where Fos-Jun favored the opposite binding orientation. Fos-Jun-NFAT1 complexes also exhibited greater transcription activation at promoter elements that favored the same orientation of Fos-Jun binding in the presence and absence of NFAT1. Thus, the orientation of heterodimer binding can influence both the dynamics and promoter selectivity of multiprotein transcription regulatory complexes.

Fos and Jun bend the AP-1 site: effects of probe geometry on the detection of protein-induced DNA bending.

The effect of Fos and Jun binding on the structure of the AP-1 recognition site is controversial. Results from phasing analysis and phase-sensitive detection studies of DNA bending by Fos and Jun have led to opposite conclusions. The differences between these assays, the length of the spacer between two bends and the length of the sequences flanking the bends, are investigated here using intrinsic DNA bend standards. Both an increase in the spacer length as well as a decrease in the length of flanking sequences resulted in a reduction in the phase-dependent variation in electrophoretic mobilities. Probes with a wide separation between the bends and short flanking sequences, such as those used in the phase-sensitive detection studies, displayed no phase-dependent mobility variation. This shape-dependent variation in electrophoretic mobilities was reproduced by complexes formed by truncated Fos and Jun. Results from ligase-catalyzed cyclization experiments have been interpreted to indicate the absence of DNA bending in the Fos-Jun-AP-1 complex. However, truncated Fos and Jun can alter the relative rates of inter- and intramolecular ligation through mechanisms unrelated to DNA bending, confounding the interpretation of cyclization data. The analogous phase- and shape-dependence of the electrophoretic mobilities of the Fos-Jun-AP-1 complex and an intrinsic DNA bend confirm that Fos and Jun bend DNA, which may contribute to their functions in transcription regulation.

Fos and Jun do not bend the AP-1 recognition site.

We have used a solution-based DNA cyclization assay and a gel-phasing method to show that contrary to previous reports [Kerppola, T. K. & Curran, T. (1991) Cell 66, 317-326], basic region leucine zipper proteins Fos and Jun do not significantly bend their AP-1 recognition site. We have constructed two sets of DNA constructs that contain the 7-bp 5'-TGACTCA-3' AP-1 binding site, from either the yeast or the human collagenase gene, which is well separated from and phased by 3-4 helical turns against an A tract-directed bend. The cyclization probabilities of DNAs with altered phasings are not significantly affected by Fos-Jun binding. Similarly, Fos-Jun and Jun-Jun bound to differently phased DNA constructs show insignificant variations in gel mobilities. Both these methods independently indicate that Fos and Jun bend their AP-1 target site by <5 degrees, an observation that has important implications in understanding their mechanism of transcriptional regulation.

(Table 1) Radiocarbon ages of samples taken from five sites in north-eastern European Russia

Aim: Concepts about patterns and rates of post-glacial tree population migration are changing as a result of the increasing amount of palaeobotanical information being provided by macroscopic plant remains. Here we combine macrofossil, pollen and stomata records from five sites in north-eastern European Russia and summarize the results for the late-glacial-early Holocene transition. The late-glacial-early Holocene transition encompasses the first indications of trees (tree-type Betula, Picea abies, Abies sibirica and Larix sibirica) and subsequent forest development. Considerable time-lags between the first macrobotanical and/or stomata finds of spruce (Picea abies) and the establishment of a closed forest are reconsidered. Location: Pechora basin, north-eastern European Russia. Methods: We used plant macrofossil, stomata, pollen and radiocarbon analyses to reconstruct late-glacial and early Holocene tree establishment and forest development. The data were derived from lake sediment and peat archives. Results: Palaeobotanical data reveal an early Holocene presence (11,500-10,000 cal. yr bp) of arboreal taxa at all five sites. One site presently located in the northernmost taiga zone, shows the presence of spruce and reproducing tree birch during the late-glacial. Given the current view of post-glacial population dynamics and migration rates, it seems likely that the source area of these early tree populations in north-eastern European Russia was not located in southern Europe but that these populations had local origins. Results thus support the emerging view that the first post-glacial population expansions in non-glaciated regions at high latitudes do not reflect migration from the south but were a result of an increase in the size and density of small persisting outlying tree populations. Main conclusions: Results suggest that the area east of the margin of the Scandinavian ice sheet to the Ural Mountains had isolated patches of trees during the late-glacial and early Holocene and that these small populations acted as initial nuclei for population expansion and forest development in the early Holocene.

Vierasvelkapantinsaajan asema konkurssissa

Tutkielmani tarkoituksena on selvittää voimassa olevan oikeuden perusteella, millaiseksi vierasvelkapantinsaajan asema muodostuu velallisen ja pantinantajan konkurssissa. Panttausta koskevaa yleistä lainsäädäntöä on melko vähän, mutta vierasvelkapanttauksen osalta keskeisimmät säännökset ovat kodifioitu lakiin takauksesta ja vierasvelkapanttauksesta. Takauksesta ja vierasvelkapanttauksesta annettu laki ei kuitenkaan sääntele esimerkiksi tehokkaan panttioikeuden perustamista eikä pantin realisointiin liittyviä tilanteita. Soveltamisohjeita näihin tilanteisiin tulee hakea panttausta koskevasta muusta, varsin hajanaisesta lainsäädännöstä. Tutkimuksen tarkoituksena onkin selvittää tämän pohjaltaan hajanaisen lainsäädännön, lainvalmistelutöiden sekä oikeuskirjallisuuden perusteella, minkälaista suojaa vierasvelkapantinsaaja saa konkurssissa ja millä edellytyksin. Selvitän tutkielman alussa vierasvelkapanttauksen tehokkaalle perustamiselle asetettuja edellytyksiä sekä niiden merkitystä konkurssitilanteessa. Tämän jälkeen tutkin panttioikeuden voimassapysymistä konkurssissa sekä pantinsaajalle tähän liittyen asetettuja velvoitteita. Lisäksi tutkin pantinsaajalla olevia realisointioikeuksia ja niiden rajoituksia sekä pantinsaajan mahdollisuuksia suojautua konkurssitakaisinsaannilta. Tutkielmani kannalta tärkeimpiä lähdeteoksia ovat Erkki Havansi: Esinevakuusoikeudet 1992; Risto Koulu: Konkurssioikeus 2009; Jarno Tepora – Janne Kaisto – Esa Hakkola: Esinevakuudet 2009; Sakari Wuolijoki – Mika Hemmo: Pankkioikeus 2013; Jarmo Tuomisto: Saatavan panttaus 2015 sekä Vierasvelkavakuus ja velallisen insolvenssista johtuva takaisinsaantiriski oikeuskäytännön valossa 2004. Vierasvelkapantinsaajalla on edelleen vahva asema sekä päävelallisen että pantinantajan konkurssissa. Vahvan suojan saaminen edellyttää kuitenkin, että panttioikeus on tehokkaasti perustettu noudattaen muun muassa julkivarmistukselle asetettuja vaatimuksia. Lisäksi nykyiset luotonantajan tiedonantovelvollisuutta koskevat säännökset asettavat luotoantajalle velvollisuuksia, joiden laiminlyöminen tarkoittaa luotonantajan saaman panttihyödyn vähenemistä. Edes vuoden 2004 konkurssilakiin otetuilla säännöksillä, joilla heikennettiin pantinsaajan etuoikeuksia entisestä, ei ole ollut merkittäviä negatiivisia vaikutuksia pantinsaajan oikeuksiin konkurssissa. Pantinsaajan tärkeimpiä taloudellisia etuoikeuksia ei ole tarkoituksenmukaista kaventaa. Lähinnä vain menettelyllisiin etuoikeuksiin voidaan lainsäädännöllä puuttua.

Evaluation of the GPS Accuracy of Tablets

Augmented Reality (AR) applications often require knowledge of the user’s position in some global coordinate system in order to draw the augmented content to its correct position on the screen. The most common method for coarse positioning is the Global Positioning System (GPS). One of the advantages of GPS is that GPS receivers can be found in almost every modern mobile device. This research was conducted in order to determine the accuracies of different GPS receivers. The tests included seven consumer-grade tablets, three external GPS modules and one professional-grade GPS receiver. All of the devices were tested with both static and mobile measurements. It was concluded that even the cheaper external GPS receivers were notably more accurate than the GPS receivers of the tested tablets. The absolute accuracy of the tablets is difficult to determine from the test results, since the results vary by a large margin between different measurements. The accuracy of the tested tablets in static measurements were between 0.30 meters and 13.75 meters.