In Vivo Longitudinal (1)H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T.

In vivo (1)H MR spectroscopy allows the non invasive characterization of brain metabolites and it has been used for studying brain metabolic changes in a wide range of neurodegenerative diseases. The prion diseases form a group of fatal neurodegenerative diseases, also described as transmissible spongiform encephalopathies. The mechanism by which prions elicit brain damage remains unclear and therefore different transgenic mouse models of prion disease were created. We performed an in vivo longitudinal (1)H MR spectroscopy study at 14.1 T with the aim to measure the neurochemical profile of Prnp -/- and PrPΔ32-121 mice in the hippocampus and cerebellum. Using high-field MR spectroscopy we were able to analyze in details the in vivo brain metabolites in Prnp -/- and PrPΔ32-121 mice. An increase of myo-inositol, glutamate and lactate concentrations with a decrease of N-acetylaspartate concentrations were observed providing additional information to the previous measurements.

Etelä-Pohjanmaan kartta 1550-60 [Kartta-aineisto] : kokoilemia muinaistutkinnon alalta / julkaissut J. R. Aspelin.

Liittyy julkaisuun Kokoilemia muinaistutkinnon alalta / J. R. Aspelin.

Long term dietary deficiency in steers: vital functions and T3 and IGF-1 relationships

To evaluate the influence of diets with different degrees of energy deficiency on the hormonal profile and vital functions, 12 steers were randomly distributed into 3 groups of 4 animals. For 140 days, each group received (G1) a diet to promote a weight gain of 900gr/day (17.7 Mcal/d DE and 13% CP), (G2) 80% of the maintenance requirements (5.8 Mcal/d DE and 7% CP), or (G3) 60% of the maintenance requirements (4.7 Mcal/d DE and 5% CP). In G2 and G3, the energy deficit caused a marked decrease in the heart rate and respiratory rate and a reduction in the blood levels of Insulin like growth factor-1 (IGF-1) and triiodothyronine (T3). The decrease in heart rate, respiratory movement and, to a lesser extent, reduction of the rectal temperature, reflected the low status of energy and was negatively impacted by the low levels of T3. There was a strong correlation between the hormones T3 and IGF-1 (r=0.833). There were also strong correlations between T3 and HR (r=0.701), T3 and RR (r=0.632), IGF-1 and HR (r=0.731), and IGF-1 and RR (r=0.679). There were intermediate correlations between T3 and TºC (r=0.484), T3 and insulin (r=0.506), IGF-1 and insulin (r=0.517), and IGF-1 and TºC (r=0.548). This study showed the influence of a long period of providing an energy-deficient diet on animal performance, correlating hormonal status and vital functions in growing cattle. The results indicated that the evaluated parameters represent an important tool for the early detection of dietary deficiency.

Two variants of HIV-1 B serotype are transmitted heterosexually in São Paulo, Brazil

HIV-1 variability may have an important impact on transmission and pathogenicity. Better characterization of the HIV epidemic in Brazil is necessary for the development of vaccine trials in this country. We analyzed sera from 108 HIV-1-infected volunteers from São Paulo City to determine serotype and reactivity for V3 motifs of HIV in this population, and the relationship to transmission mode. We concluded that the HIV-1 B serotype is frequent among heterosexually infected women, even in the absence of anal sex, and that two major V3 motifs, GPGR and GWGR, had similar prevalence among women (48% and 52%, respectively) and men (56% and 44%, respectively). We also observed an equal distribution of these strains regardless of their CD4+ T cell counts, clinical status, and mode of transmission. Even though V3 serology for HIV-1 subtyping is an inexpensive tool for use in developing countries, additional methods, such as heteroduplex mobility assay and direct DNA sequencing, should be included to determine HIV-1 genetic diversity.

Iridium(I) complexes of phenanthroline-derived benzimidazolylidenes : synthetic, structural and catalytic studies

N-heterocyclic carbenes (NHCs) have undergone rapid development in recent years. Due to their strong a-electron donation and structural variability properties, NHCs are becoming a major class of ligands in organometallic chemistry. Compared with the other two types of NHCs (imidazolylidenes and imidazolinylidenes), benzimidazolylidenes have not been well represented. Limited synthetic approaches may impede the development ofbenzimidazolylidenes. This thesis is focused on the synthesis of phenanthroline-derived benzimidazolylidene ligands and their metal complexes. A series of benzimidazolylidene-iridium complexes were synthesized and characterized spectroscopically and crystallographic ally. All of the new complexes showed varying degrees of catalytic activity and enantioselectivity toward transfer hydrogenation and asymmetric hydrogenation. The best results were achieved in hydrogenation of methyl-2-acetamidoacrylate, which afforded (-)-(R)-methyl-2-acetamidopropanoate in 97% yield and 81 % ee.

El Madrid de los Austrias.

Es un material didáctico, destinado a profesores, basado en recorridos urbanísticos por Madrid. Describe la estructura urbana de la ciudad en los siglos XVI y XVII y algunas calles y edificios singulares. Incluye varios itinerarios, lecturas, recursos y actividades pedagógicas.

Synthesis and properties of new trinuclear Mo(II) complexes containing imidazole and benzimidazole ferrocene units

The reaction of FcCOC1 (Fc = (C5H5) Fe(C5H4)) with benzimidazole or imidazole in 1: 1 ratio gives the ferrocenyl derivatives FcCO(benzim) (L1) or FcCO(im) (L2), respectively. Two molecules of L1 or L2 can replace two nitrile ligands in [Mo(eta(3)-C3H5)( CO)(2)(CH3CN)(2)Br] or [Mo(eta(3)-C5H5O)(CO)(2)(CH3CN)(2)Br] leading to the new trinuclear complexes [Mo(eta(3)-C3H5)(CO)(2)(L)(2)Br] (C1 for L = L1; C3 for L = L2) and [Mo(eta(3)-C5H5O)(CO)(2)(L)(2)Br] (C-2 for L = L1; C4 for L = L2) with L1 and L2 acting as N-monodentade ligands. L1, L2 and C2 were characterized by X-ray diffraction studies. [Mo(eta(3)-C5H5O)(CO) 2(L1)(2)Br] was shown to be a trinuclear species, with the two L1 molecules occupying one equatorial and one axial position in the coordination sphere of Mo(II). Cyclic voltammetric studies were performed for the two ligands L1 and L2, as well as for their molybdenum complexes, and kinetic and thermodynamic data for the corresponding redox processes obtained. In agreement with the nature of the frontier orbitals obtained from DFT calculations, L1 and L2 exhibit one oxidation process at the Fe(II) center, while C1, C3, and C4 display another oxidation wave at lower potentials, associated with the oxidation of Mo(II). (C) 2007 Elsevier B. V. All rights reserved.

The synthesis, structure, and reactions of some simple unsaturated σ-hydrocarbylplatinum(II) complexes

Trimethyltin compounds Me3SnR(R = CHCH2, CFCF2, or CCPh) are selective reagents for the synthesis of unsaturated hydrocarbyl derivatives such as trans-PtCl(R)(PPhEt2)2, by R/Cl exchange or oxidative addition (e.g., to Pt(PPh3)3); single crystal X-ray analyses of two such compounds (R = CHCH2 or CCPh) show that the trans-influence of R has only a low sensitivity to hybridisation at carbon, with sp3 > sp ⩾ sp2.

Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3 beta/mTOR signaling pathway

Several studies have implicated the renin angiotensin system in the cardiac hypertrophy induced by thyroid hormone. However, whether Angiotensin type 1 receptor (AT(1)R) is critically required to the development of T(3)-induced cardiomyocyte hypertrophy as well as whether the intracellular mechanisms that are triggered by AT(1)R are able to contribute to this hypertrophy model is unknown. To address these questions, we employed a selective small interfering RNA (siRNA, 50 nM) or an AT(1)R blocker (Losartan, 1 mu M) to evaluate the specific role of this receptor in primary cultures of neonatal cardiomyocytes submitted to T(3) (10 nM) treatment. The cardiomyocytes transfected with the AT(1)R siRNA presented reduced mRNA (90%, P < 0.001) and protein (70%, P < 0.001) expression of AT(1)R. The AT(1)R silencing and the AT(1)R blockade totally prevented the T(3)-induced cardiomyocyte hypertrophy, as evidenced by lower mRNA expression of atrial natriuretic factor (66%, P < 0.01) and skeletal alpha-actin (170%, P < 0.01) as well as by reduction in protein synthesis (85%, P < 0.001). The cardiomyocytes treated with T(3) demonstrated a rapid activation of Akt/GSK-3 beta/mTOR signaling pathway, which was completely inhibited by the use of PI3K inhibitors (LY294002, 10 mu M and Wortmannin, 200 nM). In addition, we demonstrated that the AT(1)R mediated the T(3)-induced activation of Akt/GSK-3 beta/mTOR signaling pathway, since the AT(1)R silencing and the AT(1)R blockade attenuated or totally prevented the activation of this signaling pathway. We also reported that local Angiotensin I/II (Ang I/II) levels (120%, P < 0.05) and the AT(1)R expression (180%, P < 0.05) were rapidly increased by T(3) treatment. These data demonstrate for the first time that the AT(1)R is a critical mediator to the T(3)-induced cardiomyocyte hypertrophy as well as to the activation of Akt/GSK-3 beta/mTOR signaling pathway. These results represent a new insight into the mechanism of T(3)-induced cardiomyocyte hypertrophy, indicating that the Ang I/II-AT(1)R-Akt/GSK-3 beta/mTOR pathway corresponds to a potential mediator of the trophic effect exerted by T(3) in cardiomyocytes.

Classical and hologram QSAR studies on a series of inhibitors of trypanosomatid Glyceraldehyde-3-Phosphate Dehydrogenase

Leishmaniasis and trypanosomiasis are major causes of morbidity and mortality in both tropical and subtropical regions of the world. The current available drugs are limited, ineffective, and require long treatment regimens. Due to the high dependence of trypanosomatids on glycolysis as a source of energy, some glycolytic enzymes have been identified as attractive targets for drug design. In the present work, classical Two-Dimensional Quantitative Structure -Activity Relationships (2D QSAR) and Hologram QSAR (HQSAR) studies were performed on a series of adenosine derivatives as inhibitors of Leishmania mexicana Glyceraldehyde-3-Phosphate Dehydrogenase (LmGAPDH). Significant correlation coefficients (classical QSAR, r(2)=0.83 and q(2) =0.81; HQSAR, r(2)=0.91 and q(2) =0.86) were obtained for the 56 training set compounds, indicating the potential of the models for untested compounds. The models were then externally validated using a test set of 14 structurally related compounds and the predicted values were in good agreement with the experimental results (classical QSAR, r(pred)(2) = 0.94; HQSAR, r(pred)(2) = 0.92).

Approximation algorithms and hardness results for the clique packing problem

For a fixed family F of graphs, an F-packing in a graph G is a set of pairwise vertex-disjoint subgraphs of G, each isomorphic to an element of F. Finding an F-packing that maximizes the number of covered edges is a natural generalization of the maximum matching problem, which is just F = {K(2)}. In this paper we provide new approximation algorithms and hardness results for the K(r)-packing problem where K(r) = {K(2), K(3,) . . . , K(r)}. We show that already for r = 3 the K(r)-packing problem is APX-complete, and, in fact, we show that it remains so even for graphs with maximum degree 4. On the positive side, we give an approximation algorithm with approximation ratio at most 2 for every fixed r. For r = 3, 4, 5 we obtain better approximations. For r = 3 we obtain a simple 3/2-approximation, achieving a known ratio that follows from a more involved algorithm of Halldorsson. For r = 4, we obtain a (3/2 + epsilon)-approximation, and for r = 5 we obtain a (25/14 + epsilon)-approximation. (C) 2008 Elsevier B.V. All rights reserved.

Involutions of RA Loops

Let L be an RA loop, that is, a loop whose loop ring over any coefficient ring R is an alternative, but not associative, ring. Let l bar right arrow l(theta) denote an involution on L and extend it linearly to the loop ring RL. An element alpha is an element of RL is symmetric if alpha(theta) = alpha and skew-symmetric if alpha(theta) = -alpha. In this paper, we show that there exists an involution making the symmetric elements of RL commute if and only if the characteristic of R is 2 or theta is the canonical involution on L, and an involution making the skew-symmetric elements of RL commute if and only if the characteristic of R is 2 or 4.

Trätorn : Kan det vara något för svensk vindkraft i skogsmiljö?

Inom ramen för projektet Energi- och miljökompetenscentrum vid Högskolan Dalarna haren kortare förstudie kring tekniken som används av Timber Tower GmbH för högavindkrafttorn i trä gjorts. Huvudsyftet med studien har varit att titta närmare på teknikenoch dess potential för svensk landbaserad vindkraft samt utreda vad detta kan innebära förregionen.Trenden för landbaserad vindkraft i skogsmiljö går mot allt högre torn. Skogsmiljön gör attden marknära turbulensen och vindgradienten blir större än över t.ex. hav vilket gör detmer föredelaktigt att använda högre torn.Tekniken som Timber Tower GmbH använder är att bygga tornet på plats med en koniskhålstomme av plana paneler av korslimmat limträ (som annars främst används vidbyggnation av höga hus med massivträstomme). Tekniken är skyddad av ett flertalpatentansökningar varav minst en är beviljad.Vid en jämförelse mellan trätorn och svetsade ståltorn (som är den dominerandetorntekniken idag) kan det konstateras att trätornstekniken är ekonomiskt intressant.Framförallt blir trätornen mer intressanta i jämförelse med ståltornen vi ökande höjder (>100 m) pga. dess transportfördelar. Vidare bör det nämnas att de torntekniker somanvänds idag vid höjder runt 140 m och högre främst är fackverkstorn i stål ochhybridtorn med en hög bas av förspänd betong och övre delen i stål.Då ett typgodkännande av ett vindkraftverk gäller torn och turbin är det i praktiken alltidturbintillverkaren som prissätter och levererar ett komplett vindkraftverk. Medutgångspunkt i regeringens planeringsram för svensk vindkraftutbyggnad (20 TWh/årlandbaserad vindkraft 2020) kan dock marknadsvärdet för torn uppskattas till 2-3 miljarderkr/år fram till 2020. För trätorn motsvarar detta en årlig potentiell volym på ca 190 000 m3.Slutsatsen i denna korta studie är att det är tekniskt möjligt att designa ett trätorn i rimligadimensioner för en 2-3 MW turbin med navhöjd ca 140 m och att detta sannolikt även ärekonomiskt intressant. Då ett trätorn blir något lättare än motsvarande ståltorn går det åtmindre energi för att göra ett trätorn. Hur mycket mindre är dock osäkert pga. den storaspridningen i siffror för energiåtgång för stålproduktion och i praktiken blir skillnadenäven leverantörsberoende. Eftersom andelen förnyelsebar energi är betydligt större vidtillverkningen av materialet för trätornen kommer trätornet att ge en betydande sänkningpå utsläppt CO2e/kWhel jämfört med motsvarande verk med ståltorn. Ett annat argumentför trätorn är förenklade transporter jämfört med t.ex. svetsade ståltorn eller hybridtornmed prefabricerade betongelement.Om tekniken etableras kan det i förlängningen leda till en regional påverkan i form av ökatlokalt innehåll i vindkraftprojekten t.ex. genom ökade råvaruleveranser (eg. sågat ochtorkat virke), lokal produktion av korslimmat limträ eller exempelvis bildande avspecialiserade montagefirmor. Det största hindret för tekniken just nu är dessmarknadsintroduktion och acceptans samt typgodkännande tillsammans med en för svenskmarknad intressant turbinleverantör. För att få acceptans för tekniken krävs byggande ochutvärdering av minst ett verk med trätorn. En intressant storlek för marknaden är en 2-3MW turbin med navhöjd ca 140 m. Ett sådant verk skulle i så fall få det högstavindkrafttornet i Sverige och sannolikt det högsta vindkrafttornet i trä i världen. Byggandetav ett första verk med trätorn skulle sannolikt även kräva ett behov av stödfinansiering föratt täcka en projektörs ökade risk. Då flera vindkraftetableringar i regionen uppvisar godaproduktionsresultat (med Tavelberget som gott exempel) visar det att regionen ärintressant för introduktion och utvärdering av ny teknologi.

Projektet: W7 DALARNA - Ett regionalt resurscentrum för kvinnligt entreprenörskap, jämställdhet och integration

De flesta kvinnor är enmansföretagare och driver en enskild firma, medan männen driver ett aktiebolag. I Dalarna gick det år 2006 2,7 manliga företagare på en kvinnlig, samtidigt som allt fler kvinnorna startar eget företag. I några av de kommuner som deltar i projektet W7 Dalarna har en hög andel kvinnliga företagare bland de företag som startas.Det övergripande syftet för W7 DALARNA formulerades som: ”att bygga upp en stark organisation med lokal närvaro och samordnad verksamhet.” Verksamhetens innehåll skulle inriktas på opinionsbildning, inspiration, utbildning, erfarenhetsutbyte, metodutveckling och att tillvarata synergieffekter inom projektets tre verksamhetsteman. Projektet syftadeockså till att utveckla kompetens- och kvalitetssäkring inom området affärsrådgivningoch att etablera och upprätthålla en lokal fysisk närvaro. Därutöver skulle projektet: ”verka för att Resurscentra för kvinnor skall accepteras som en aktör för lokal och regional utveckling, och fungera som en jämbördig partner i tillväxtarbetet.”