958 resultados para Hansen, Collin: The winning helix
Resumo:
Process development will be largely driven by the main equipment suppliers. The reason for this development is their ambition to supply complete plants or process systems instead of single pieces of equipment. The pulp and paper companies' interest lies in product development, as their main goal is to create winning brands and effective brand management. Design engineering companies will find their niche in detail engineering based on approved process solutions. Their development work will focus on increasing the efficiency of engineering work. Process design is a content-producing profession, which requires certain special characteristics: creativity, carefulness, the ability to work as a member of a design team according to time schedules and fluency in oral as well as written presentation. In the future, process engineers will increasingly need knowledge of chemistry as well as information and automation technology. Process engineering tools are developing rapidly. At the moment, these tools are good enough for static sizing and balancing, but dynamic simulation tools are not yet good enough for the complicated chemical reactions of pulp and paper chemistry. Dynamic simulation and virtual mill models are used as tools for training the operators. Computational fluid dynamics will certainlygain ground in process design.
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Calcineurin is a key protein phosphatase required for hyphal growth and virulence in Aspergillus fumigatus, making it an attractive antifungal target. However, currently available calcineurin inhibitors, FK506 and cyclosporine A, are immunosuppressive, limiting usage in the treatment of patients with invasive aspergillosis. Therefore, the identification of endogenous inhibitors of calcineurin belonging to the calcipressin family is an important parallel strategy. We previously identified the gene cbpA as the A. fumigatus calcipressin member and showed its involvement in hyphal growth and calcium homeostasis. However, the mechanism of its activation/inhibition through phosphorylation and its interaction with calcineurin remains unknown. Here we show that A. fumigatus CbpA is phosphorylated at three distinct domains, including the conserved SP repeat motif (phosphorylated domain-I; PD-I), a filamentous fungal-specific domain (PD-II), and the C-terminal CIC motif (Calcipressin Inhibitor of Calcineurin; PD-III). While mutation of three phosphorylated residues (Ser208, Ser217, Ser223) in the PD-II did not affect CbpA function in vivo, mutation of the two phosphorylated serines (Ser156, Ser160) in the SP repeat motif caused reduced hyphal growth and sensitivity to oxidative stress. Mutational analysis in the key domains in calcineurin A (CnaA) and proteomic interaction studies confirmed the requirement of PxIxIT motif-binding residues (352-NIR-354) and the calcineurin B (CnaB)-binding helix residue (V371) for the binding of CbpA to CnaA. Additionally, while the calmodulin-binding residues (442-RVF-444) did not affect CbpA binding to CnaA, three mutations (T359P, H361L, and L365S) clustered between the CnaA catalytic and the CnaB-binding helix were also required for CbpA binding. This is the first study to analyze the phosphorylation status of calcipressin in filamentous fungi and identify the domains required for binding to calcineurin.
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The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed and surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis.
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Replication of human immunodeficiency virus (HIV) requires base pairing of the reverse transcriptase primer, human tRNA(Lys3), to the viral RNA. Although the major complementary base pairing occurs between the HIV primer binding sequence (PBS) and the tRNA's 3'-terminus, an important discriminatory, secondary contact occurs between the viral A-rich Loop I, 5'-adjacent to the PBS, and the modified, U-rich anticodon domain of tRNA(Lys3). The importance of individual and combined anticodon modifications to the tRNA/HIV-1 Loop I RNA's interaction was determined. The thermal stabilities of variously modified tRNA anticodon region sequences bound to the Loop I of viral sub(sero)types G and B were analyzed and the structure of one duplex containing two modified nucleosides was determined using NMR spectroscopy and restrained molecular dynamics. The modifications 2-thiouridine, s(2)U(34), and pseudouridine, Psi(39), appreciably stabilized the interaction of the anticodon region with the viral subtype G and B RNAs. The structure of the duplex results in two coaxially stacked A-form RNA stems separated by two mismatched base pairs, U(162)*Psi(39) and G(163)*A(38), that maintained a reasonable A-form helix diameter. The tRNA's s(2)U(34) stabilized the interaction between the A-rich HIV Loop I sequence and the U-rich anticodon, whereas the tRNA's Psi(39) stabilized the adjacent mismatched pairs.
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Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
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Neutral and selective processes c an drive repeated patterns of evolu tion in dif ferent groups of populationsexp eriencing similar ecol ogica l gradients. In this paper, we used a combinat ion of nucl ear and mitochondrialDNA markers, as well as geometric morphometrics, to investigate repeated patterns of morphological andgenetic divergence of E uropean minnows in two mountain ranges : the Pyrenees and the Al ps. Europeanminnows (Phoxinus phoxinus) are cyprinid fish i nha bitin g most freshwater bodies in Europe, including those indifferent mountain r anges that could act as major geographical barriers to gene flow. We explored patterns ofP. phoxinus phenotypic and genetic di versi fication along a gradi ent of alti tude common to the two mountainranges, and tested for isolation by distance (IBD), isolation by environment (IBE) and isolation by adaptation(IBA). The results indicated that populations from the Pyr enees a nd the Alps bel ong to two well differentiated,reciprocally monophyletic mt DNA lineages. Substantial genetic differentiation due to geographical isolationwithin and between populations from the Pyrenees and the Alps was also found using rapidly evolving AFLPsmarkers (isolation by distance or IBD), as well as morphological differences between mountain ranges. Als o,morphology varied strong ly with elevation and so did genetic differentiation to a lower extent. Despitemoderate evidence for IBE and IBA, and therefore of repeated evolution, substantial population heterogeneitywas found at the genetic level, suggesting that selection and population specific genetic drift act in concert toaffect genetic divergence.
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Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.
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This work evaluated the use of the Hildebrand/Hansen solubility parameters for selection of solvents for extraction of the organochlorine pesticides pp' DDT, pp' DDE, Aldrin and a-Endossulfan from soil using columns packed with Al2O3. The mixtures hexane:dichloromethane (7:3; v/v), hexane:acetonitrile (1:1; v/v), hexane:acetone (1:1; v/v) and pure hexane were chosen as extracting solutions. In the addition and recovery tests, different extraction solutions provided high recoveries percentages (>75%) with coefficients of variation below 15%. The recoveries are in agreement with the Hildebrand/Hansen parameters, demonstrating its applicability in the selection of extracting solution and in the replacement of toxic solvents, as dichloromethane
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Military conscription and peacetime military service were the subjects of heated political, social and cultural controversies during the early years of national independence in Finland. Both the critics and the supporters of the existing military system described it as strongly formative of young men’s physical and moral development into adult men and male citizens. The conflicts over conscription prompted the contemporaries to express their notions about what Finnish men were like, at their best and at their worst, and what should and could be done about it. This thesis studies military conscription as an arena for the “making of manhood” in peacetime Finnish society, 1918–1939. It examines a range of public images of conscripted soldiering, asking how soldiering was depicted and given gendered meanings in parliamentary debates, war hero myths, texts concerned with the military and civic education of conscripts, as well as in works of fiction and reminiscences about military training as a personal experience. Studying conscription with a focus on masculinity, the thesis explores the different cultural images of manliness, soldiering and male citizenship on offer in Finnish society. It investigates how political parties, officers, educators, journalists, writers and “ordinary” conscripts used and developed, embraced or rejected these notions, according to their political purposes or personal needs. The period between the two world wars can be described as a fast-forward into military modernity in Finland. In the process, European middle class gender ideologies clashed with Finnish agrarian masculinities. Nationalistic agendas for the militarisation of Finnish manhood stumbled against intense class conflicts and ideological resistance. Military propaganda used images of military heroism, civic virtue and individual success to persuade the conscripts into ways of thinking and acting that were shaped by bourgeois mentality, nationalistic ideology and religious morality. These images are further analysed as expressive of the personal experiences and emotions of their middle-aged, male authors. The efforts of these military educators were, however, actively resisted on many fronts, ranging from rural working class masculinities among the conscripted young men to ideological critiques of the standing army system in parliament. In narratives about military training, masculinity was depicted as both strengthened and contradicted by the harsh and even brutal practices of interwar Finnish military training. The study represents a combination of new military history and the historical study of men and masculinities. It approaches masculinity as a contested and highly political form of social and cultural knowledge that is actively and selectively used by historic actors. Instead of trying to identify a dominant or “hegemonic” form of masculinity within a pre-determined theoretical structure, this study examines how the meanings ascribed to manhood varied according to class, age, political ideology and social situation. The interwar period in Finland can be understood as a period of contest between different notions of militarised masculinity, yet to judge by the materials studied, there was no clear winning party in that contest. A gradual movement from an atmosphere of conflict surrounding conscription towards political and cultural compromises can be discerned, yet this convergence was incomplete and many division lines remained.
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Pro gradu -tutkielmassani tarkastelen, miten amerikkalainen unelma on Yhdysvaltain historian saatossa kehittynyt yhteiskunnallisen kontrollin välineeksi. Amerikkalaisen unelman yksilölliset ja kollektiiviset kokemukset ovat ristiriidassa unelman sisäisten rakenteiden kanssa, jotka kätkeytyvät sen vahvan retoriikan taakse. Täten unelmasta muodostuu ideologia ja ideologinen valtakoneisto marxilaisen yhteiskuntateoreetikon Louis Althusserin määritelmien mukaisesti. Tutkielmassani tarkastelen amerikkalaisen unelman ilmenemistä amerikkalaisessa populaarikulttuurissa. Populaarikulttuuri tavoittaa laajan yleisön, ja sen arkipäiväiset aiheet välittävät ja uusintavat amerikkalaista unelmaa tehden siitä luonnollisen ja sisäistetyn osan amerikkalaisia toiminta- ja ajattelumalleja. Populaarikirjallisuutta esimerkkinä käyttäen pyrin selvittämään, miten amerikkalainen unelma ideologisena valtakoneistona käyttää hyväksi yksilön subjektiviteetin rakenteita taatakseen oman jatkuvuutensa. Teoreettisen viitekehyksen subjektiviteetin tarkastelulle luo ranskalaisen semiotiikantutkijan Julia Kristevan psykoanalyyttinen teoria, jonka mukaan subjektiviteetti rakentuu yksilön piilotajunnan ja tietoisuuden vuorovaikutuksesta. Amerikkalainen unelma hyödyntää tätä vuorovaikutusta peilaamalla yksilön piilotajuisia pelkoja ja haluja. Kristeva käsittelee piilotajuisia haluja käyttäen apunaan ranskankielistä termiä jouissance, joka viittaa sellaiseen tiedostamattomaan haluun tai tarpeeseen, joka toimii elämän elinehtona ja selviytymisviettinä. Pelkoja Kristeva puolestaan tarkastelee abjektion käsitteen kautta. Abjekti tarkoittaa sellaista tunnistamatonta pelkoa, joka purkautuu tietoisuuteen piilotajunnan ja tietoisuuden vuorovaikutuksen ansiosta. Sekä abjekti että jouissance ilmenevät tietoisuudessa ahdistuksen kokemuksena, johon amerikkalainen unelma tarjoaa ratkaisun asettamalla abstrakteja ja konkreettisia tavoitteita, jotka yksilön tulisi saavuttaa. Amerikkalainen unelma ei kuitenkaan koskaan toteudu. Se perustuu liikkeeseen jonka keskiössä on jatkuva muutos ja kehitys.
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Strategic partnerships have become a key to competitive advantage and success in a dynamic, global business environment. Partnering provides a strategic response to complex offerings that need multiple sources of technology and knowledge, allowing companies to offer a wider range of services and solutions to meet their customers’ needs. Companies that collaborate with strategic partners in sales channels may significantly grow their business and improve their prospects of winning major contracts. As a consequence, companies are increasingly transforming their go-to-market strategies and sales channel structures to align with the need to create added value to customers together with a business partner. The research objective of this case study is to review and assess the success of an established sales channel partnership in IT services industry and to find ways how to develop it towards a strategic collaboration. The research consists of two main parts. The first part reviews the literature, concluding with the identification of the critical success factors for partnering. The second part sets out for the case findings, focusing on how the success of the established sales channel partnership is perceived by key executives within the partner organizations, and further what actions are required to make the sales channel partnership and joint go-to-market more strategic.
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The important role of entrepreneurship in countries’ economic development and overall society well-being is widely recognized by researchers, experts as well as policy makers. Every phase of the process of starting a new business is related to the interaction with at least one player of country innovation system and therefore the efficiency of this interaction may have an influence on the success of whole entrepreneurial process and consequently on the willingness of potential entrepreneurs to engage into this process. The study proposes a System Dynamics model for studying the impact of National Innovation System (NIS) on the entrepreneurial venture creation process. The developed model also takes country population aspect into account and provides results for estimation the effect various demographic tendencies on the process performance. The special impact is made on possible ways to facilitate the development of entrepreneurial framework conditions. Business incubators are seen as one of the effective tool for accomplishing such task. The study also provides the result for estimation of possible impact arising from properly functioned Business Incubators.
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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014
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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014
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Previous studies have examined the arrangement of regulatory elements along the apolipoprotein B (apoB) promoter region (-3067 to +940) and a promoter fragment extending from nucleotides -150 to +124 has been demonstrated to be essential for transcriptional activation of the apoB gene in hepatic and intestinal cells. It has also been shown that transcriptional activation of apoB requires a synergistic interaction between hepatic nuclear factor-4 (HNF-4) and CCAAT/enhancer-binding protein a (C/EBPa) transcription factors. Here, we have examined the hypothesis that HNF-4 factor binding to DNA may induce a DNA helix bend, thus facilitating the communication with a C/EBPa factor located one helix turn from this HNF-4 factor in the apoB promoter. A gel electrophoretic mobility shift assay using wild type double-stranded oligonucleotides or modified wild type duplex oligonucleotides with 10 nucleotides inserted between HNF-4 and C/EBPa factor motifs showed similar retarded complexes, indicating that HNF-4 and C/EBPa factors interact independently of the distance between binding sites. However, when only one base, a thymidine, was inserted at the -71 position of the apoB promoter, the complex shift was completely abolished. In conclusion, these results regarding the study of the mechanisms involving the interaction between HNF-4 and C/EBPa factors in the apoB promoter suggest that the perfect 5'-CCCTTTGGA-3' motif is needed in order to facilitate the interaction between the two factors.