27 research outputs found
大曆二家詩研究--以盧綸、李益為探討對象
No full text[[abstract]]本篇論文旨在討論唐朝大曆年間二位詩人--盧綸、李益的詩篇風格、特色，同時更進一步探討二家詩篇之異同，及其在文學史上之地位。全文共分六章。第一章﹕緒論。說明大曆十才子的成員，及敘述筆者研究動機、目的和範圍、方法。第二章﹕二家詩的時代背景。分析二家詩人所處的時代背景，和社會政治情勢。第三章﹕盧綸詩篇探究。此章分為三節﹕一為生平，二為內容分析，三為藝術技巧分析，藉由此三節分析說明，以探究盧綸詩篇之思想情意與藝術技巧之特色所在。第四章﹕李益詩篇探究。此章亦分為三﹕一為生平，二為內容分析，三為藝術技巧分析，由此三節分析說明，以探究李益詩篇之思想情意和藝術風格特色。第五章﹕二家詩篇之比較、評述與影響。由三、四章之二家詩篇內容、技巧分析，更進一步探究此二人同處於大曆時期，在詩篇內容、風格、技巧等方面的相同相異處。此外，歷來學者對二家詩篇之評論，及二家詩對後世文學之影響，亦一一闡明。第六章﹕結論，總括前說。
MXD1 regulates the H9N2 and H1N1 influenza A virus–induced chemokine expression and their replications in human macrophage
No full textHuman infection with influenza A/Hong Kong/156/97 (H5N1) avian influenza virus is associated with a high mortality rate of 60%. This virus is originated from influenza A/Quail/Hong Kong/G1/97 (H9N2/G1) avian influenza virus. Since the 1990s, four lineages of H9N2 viruses have been circulating in poultry and cause occasional infection in humans in different countries. Due to its zoonotic and genetic reassortment potential, H9N2/G1 and H5N1 viruses are believed to be the next pandemic candidates. Previous reports, including ours, showed that the virulence of avian virus strains correlates with their ability to dysregulate cytokine expression, including TNF‐α, CXCL10, and related chemokines in the virus‐infected cells. However, the transcriptional factors required for this cytokine dysregulation remains undefined. In light of our previous report showing the unconventional role of MYC, an onco‐transcriptional factor, for regulating the antibacterial responses, we hypothesize that the influenza virus–induced cytokine productions may be governed by MYC/MAX/MXD1 network members. Here, we demonstrated that the influenza A/Hong Kong/54/98 (H1N1)‐ or H9N2/G1 virus–induced CXCL10 expressions can be significantly attenuated by knocking down the MXD1 expression in primary human blood macrophages. Indeed, only the MXD1 expression was up‐regulated by both H1N1 and H9N2/G1 viruses, but not other MYC/MAX/MXD1 members. The MXD1 expression and the CXCL10 hyperinduction were dependent on MEK1/2 activation. By using EMSAs, we revealed that MXD1 directly binds to the CXCL10 promoter–derived oligonucleotides upon infection of both viruses. Furthermore, silencing of MXD1 decreased the replication of H9N2 but not H1N1 viruses. Our results provide a new insight into the role of MXD1 for the pathogenicity of avian influenza viruses.link_to_subscribed_fulltex
Reduced RET expression in gut tissue of individuals carrying risk alleles of Hirschsprung's disease
No full textReceptor tyrosine kinase (RET) single nucleotide polymorphisms (SNPs) are associated with the Hirschsprung's disease (HSCR). We investigated whether the amount of RET expressed in the ganglionic gut of human was dependent on the genotype of three regulatory SNPs (-5G>A rs10900296 and -1A>C rs10900297 in the promoter, and C>T rs2435357 in intron 1). We examined the effects of three regulatory SNPs on the RET gene expression in 67 human ganglionic gut tissues using quantitative real-time PCR. Also, 315 Chinese HSCR patients and 325 ethnically matched controls were genotyped for the three SNPs by polymerase chain reaction (PCR) and direct sequencing. The expression of RET mRNA in human gut tissue did indeed correlate with the genotypes of the individuals. The lowest RET expression was found for those individuals homozygous for the three risk alleles (A-C-T/A-C-T), and the highest for those homozygous for the 'wild-type' counterpart (G-A-C/G-A-C), with expression values ranging from 218.32±125.69 (mean ± SE) in tissues from individuals carrying G-A-C/G-A-C to 31.42±8.42 for individuals carrying A-C-T/A-C-T (P 5 0.018). As expected, alleles -5A, -1C and intron 1 T were associated with HSCR (P 5 5.94 × 10-31, 3.12 3 10-24 and 5.94 × 10-37, respectively) as was the haplotype encompassing the three associated alleles (A-C-T) when compared with the wild-type counterpart G-A-C (χ2 5 155.29, P « 0.0001). To our knowledge, this is the first RET expression genotype-phenotype correlation study conducted on human subjects to indicate common genetic variants in the regulatory region of RET may play a role in mediating susceptibility to HSCR, by conferring a significant reduction of the RET expression. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
A RET founder mutation in Chinese hirschsprung's patients
No full textHirschsprung’s disease (HSCR) is a congenital disorder associated with the lack of intramural ganglion cells in the myenteric and sub-mucosal plexuses along varying segments of the gastrointestinal tract. Rearranged during transfection (RET) gene is implicated in HSCR and is the major gene of this gastrointestinal disease. To date, over 200 low frequency recurrent RET coding sequence (CDS) mutations have been identified in HSCR patients. However, a highly recurrent RET(R114H) mutation has been identified in 10% of the Chinese HSCR patients which has never been found in Caucasians patients or controls nor in 400 Chinese controls. The high frequency of RET(R114H) in our population together with the fact that it is not a “de novo” mutation in the context of the most HSCR-associated RET-haplotype, suggests that it may be a founder HSCR mutation in the Chinese population. Initial investigation involved applying a Bayesian method to 21 single nucleotide polymorphisms (SNPs; across a 62kb region of RET) genotyped in 421 Chinese HSCR patients (of which 24 individuals had the mutation) to predict the approximate age of RET(R114H). The approach allowed the inference of the mutation age based on the observed linkage disequilibrium (LD) at multiple SNPs which predicted the mutation to be between 12 and 13 generations old. Including SNPs from a recently obtained genome-wide 500K dataset for 181 of the above mentioned patients (which now only included 14 patients who had the RET(R114H) mutation), we applied haplotype estimation methods to determine whether there were any segments shared between patients with the RET(R114H) compared to those without the mutation and controls. Data consisted a total of 92 SNPs spanning a 510kb region over the RET gene. Analysis yielded a 256kb (76 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients or controls. This suggests that RET(R114H) is a possible founder effect for Hirschsprung’s disease in the Chinese population.The 59th Annual Meeting of the American Society of Human Genetics (ASHG), Honolulu, HI., 20-24 October 2009
RET mutational spectrum in Hirschsprungs disease: evaluation of 601 Chinese patients
No full textHirschsprung’s disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the lower digestive tract. Aganglionosis is attributed to a disorder of the enteric nervous system (ENS) whereby ganglion cells fail to innervate the lower gastrointestinal tract during embryonic development. There is significant population variation in the incidence of the disease, and it is most often found among Asians (2.8 per 10,000 live births). HSCR most commonly presents sporadically (80% of the cases), with a recurrence risk of 4%, and more males than females affected (4:1). Both rare (<1% in the population) and common germ line variants of the RET gene, acting either alone or in combination, are the main cause of the disease. Yet, while RET common variants are strongly associated with the commonest manifestation of the disease (male, short segment, and sporadic forms), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females, long or total colonic aganglionosis, and familial). Here we present a rare variant (RV) screening of the CDS and intron/exon boundaries of the RET gene in 607 Chinese sporadic HSCR patients, the largest number of patients ever reported. We have found a total of 61 different heterozygous RVs (50 novel) distributed in 100 patients (16.64%). These include 14 silent, 29 missense, 5 nonsense amino-acid changes, 4 frame-shifts, and one in-frame amino-acid deletion in the exonic region and two splice-site deletions, 4 nucleotide substitutions and a 22 bp deletion in intronic or untranslated regions. The exonic variants were mainly clustered in the sequence encoding the extracellular domain of the RET protein. All RVs were predicted to alter the protein function. The highest frequency of rare variants was found among those patients with the most severe form of the disease (24% in long or total vs 15% in short-segment). Phasing of the RVs with the RET risk-haplotype suggested that RET RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants was found in 250 Chinese controls.link_to_OA_fulltextThe 12th International Congress of Human Genetics (ICHG 2011), Montreal, Canada, 11-15 October 2011
Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
No full textBackground: The rearranged during transfection (RET) gene encodes a single-pass receptor whose proper expression and function are essential for the development of enteric nervous system. Mutations in RET regulatory regions are also associated with Hirschsprung disease (HSCR) (aganglionosis of the colon). We previously showed that 2 polymorphisms in RET promoter are associated with the increased risk of HSCR. These single nucleotide polymorphisms overlap with the NK2 homeobox 1 (Nkx2-1) binding motif interrupting the physical interaction of NKX2-1 with the RET promoter and result in reduced RET transcription. In this study, we further delineated Nkx2-1-mediated RET Transcription. Methods and results: First, we demonstrated that PHOX2B, like SOX10 and NKX2-1, is expressed in the mature enteric ganglions of human gut by immunohistochemistry. Second, subsequent dual-luciferase-reporter studies indicated that Nkx2-1 indeed works coordinately with Phox2b and Sox10, but not Pax3, to mediate RET transcription. In addition, identification of Phox2b responsive region in RET promoter further provides solid evidence of the potential functional interaction between Phox2b and RET. Conclusion: In sum, Phox2b and Sox10 act together with Nkx2.1 to modify RET signaling and this interaction may also contribute to HSCR susceptibility. © 2009 Elsevier Inc. All rights reserved.postprin
Functional analyses of RET mutations in Chinese hirschsprung disease patients
No full textBACKGROUND: Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of ganglion cells in various length of distal digestive tract. The rearranged during transfection gene (RET) is considered the major gene in HSCR. Although an increasing number of HSCR-associated RET coding sequence (CDS) mutations have been identified in recent years, not many have been investigated for functional consequence on the RET protein. METHODS AND RESULTS: We examined the functional implications of the de novo RET-CDS mutations V145G, Y483X, V636fsX1, and F961L that we first identified in sporadic Chinese patients with HSCR. The V145G disrupted RET glycosylation and F961L RET phosphorylation. Presumably, the truncation mutations would affect the translocation or the anchoring of the RET protein onto the cellular membrane. CONCLUSION: The study of RET-CDS mutations that appear de novo is essential not only for understanding the mechanistic of the disease but also for penetrance and recurrence risk estimations, being the ultimate goal for the improvement in disease management and counseling. © 2011 Wiley Periodicals, Inc.link_to_subscribed_fulltex
A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma
No full textBackground: The genetic factors that determine the risk of papillary thyroid carcinoma (PTC) among patients with multinodular goiter (MNG) remain undefined. Because thyroid transcription factor-1 (TTF-1) is important to thyroid development, we evaluated whether the gene that encodes it, TITF-1/NKX2.1, is a genetic determinant of MNG/PTC predisposition. Methods: Twenty unrelated PTC patients with a history of MNG (MNG/PTC), 284 PTC patients without a history of MNG (PTC), and 349 healthy control subjects were screened for germline mutation(s) in TITF-1/NKX2.1 by sequencing of amplified DNA from blood. The effects of the mutation on the growth and differentiation of thyroid cells were demonstrated by ectopic expression of wild-type (WT) and mutant proteins in PCCL3 normal rat thyroid cells, followed by tests of cell proliferation, activation of cell growth pathways, and transcription of TTF-1 target genes. All statistical tests were two-sided. Results: A missense mutation (1016C>T) was identified in TITF-1/NKX2.1 that led to a mutant TTF-1 protein (A339V) in four of the 20 MNG/PTC patients (20%). These patients developed substantially more advanced tumors than MNG/PTC or PTC patients without the mutation (P =. 022, Fisher exact test). Notably, this germline mutation was dominantly inherited in two families, with some members bearing the mutation affected with MNG, associated with either PTC or colon cancer. The mutation encoding the A339V substitution was not found among the 349 healthy control subjects nor among the 284 PTC patients who had no history of MNG. Overexpression of A339V TTF-1 in PCCL3 cells, as compared with overexpression of WT TTF-1, was associated with increased cell proliferation including thyrotropin-independent growth (average A339V proliferation rate = 134.27%, WT rate = 104.43%, difference = 34.3%, 95% confidence interval = 12.0% to 47.7%, P =. 010), enhanced STAT3 activation, and impaired transcription of the thyroid-specific genes Tg, TSH-R, and Pax-8. Conclusion: This is the first germline mutation identified in MNG/PTC patients. It could contribute to predisposition for MNG and/or PTC and to the pathogenesis of PTC. © The Author 2009. Published by Oxford University Press. All rights reserved.link_to_subscribed_fulltex
Grand Gavia : Lasisen palkinnon suunnittelu ja toteutus
No full textTämä opinnäytetyö käsittelee lasisen palkinnon suunnittelua ja valmistusta. Palkinto toteutettiin Pohjois-Savon Elinkeino-, liikenne- ja ympäristökeskuksen (ELY) järjestämän Northern Savonia Business Award 2012 -kilpailun voittajalle. ELY- keskus toimi tässä työssä myös asiakkaana. Kilpai-lussa käytettiin Golden Gavia (Kultainen Kuikka) –palvelumallia, jonka graafiseen ilmeeseen ja tyy-liin asiakas halusi palkinnon sointuvan. Palkinto ojennettiin pohjoissavolaiselle voittajayritykselle Savosta Maailmalle –gaalaillassa joulukuussa 2012.
Tekijä keräsi työtä varten aineistoa jo olemassa olevista lasipalkinnoista. Palkintoihin perehtymisen tarkoituksena oli muodostaa käsitys, minkälaisia palkinnot yleensä ovat, mitä yhteisiä ominaisuuk-sia niillä on ja etsiä perinteisistä palkinnoista poikkeavia vaihtoehtoja.
Tekijä suunnitteli ja valmisti kuikan päätä esittävän palkinnon. Tavoitteena oli toteuttaa palkinto, joka vastasi asiakkaan toiveita. Työn tarkoituksena oli perehtyä suunnitteluun, jossa asiakas on vahvasti läsnä sekä kehittää tekijän osaamista lasin työstössä. Palkinnon valmistustekniikaksi valit-tiin lasin uunivalutekniikka teoksen muotojen sekä tekijän oman kiinnostuksen vuoksi. Tekijä kehit-ti kädentaitojaan valumuottien valmistuksessa sekä uunivalutekniikassa tekemällä kokeiluita lasi-murskasta ennen varsinaisen palkinnon toteutusta.
Lopputuloksena opinnäytetyössä valmistui luovanprosessin kautta uniikki, veistosmainen lasipalkin-to, joka vastasi asiakkaan toiveita. Palkinnossa yhdistyivät tekijän oma sekä Golden Gavian tyylit. Opinnäytetyöraportissa kuvataan työn lähtökohdat, keskeisimmät työvaiheet palkinnon suunnitte-lusta ja toteutuksesta, pohditaan työn onnistumista sekä tekijän ammatillista kehittymistä.This final thesis deals with design and manufacture of a glass award. The award was executed for a winner of Northern Savonia Business Award 2012 contest, organized by Centre for Economic Development, Transport and the Environment in North Savo. The organizer of the contest was also a customer of this final thesis. The idea was that the award was match the graphic design of the Golden Gavia service model. The winning company of the competition was awarded the glass award in the Golden Gavia Gala in December 2012.
The award was designed and manufactured to represent a head of a black-throated diver which comes out of water. The goal was to carry out a design which would meet the client’s hopes and suit the competition’s graphic design. The object of the work was to get acquainted with custom-er-based designing and develop the glass processing skills of the author. The glass manufacture technique was kiln casting which was chosen on the basis of the shapes of the award and the au-thor’s interest in the technique. The author developed her glass and mold making skills by making test blocks before the final award.
As a result a unique, sculpture-like glass trophy was executed through a creative process. There in the blue and bright colored glass award is united the author’s own, as well as Golden Gavia’s styles. The main points of designing and manufacturing the award is described in this final thesis report. The author collected information about the existing glass awards as a background for the work
UUDISTETUN VERKKOKAUPAN ASIAKASTYYTYVÄISYYSKYSELY CASE: PORIN VAIHTOKALUSTE OY
No full textTämä opinnäytetyö koostuu teoria- ja tutkimusosuudesta. Teoriaosassa käydään läpi verkkokauppaa, asiakaspalvelua ja asiakastyytyväisyyttä. Tutkimusosassa tutkittiin asiakkaiden tyytyväisyyttä Porin Vaihtokaluste Oy:n verkkokauppaan.
Tämän opinnäytetyön tarkoituksena oli selvittää asiakkaiden tyytyväisyys Porin Vaih-tokalusteen uudistettuun verkkokauppaan. Tutkimuksessa selvitettiin asiakkaiden tyy-tyväisyyttä verkkokaupan toimintaan, ulkonäköön, palveluihin ja tilauksen tekemiseen. Tutkimuksessa selvitettiin myös mitä mieltä asiakkaat ovat Vaihtokalusteen suunnitel-lusta ja jo osittain tehdystä brändiuudistuksesta.
Opinnäytetyön empiirinen aineisto kerättiin opinnäytetyön tekijän laatimalla sähköisellä kyselylomakkeella. Lomakkeessa oli 26 kysymystä, joista kaikki paitsi yksi olivat vaihtoehtokysymyksiä. Linkki kyselyyn jaettiin Porin Vaihtokalusteen Facebook sivuilla ja kyselyyn vastasi lopulta 105 henkilöä.
Tutkimuksen tulosten perusteella vastanneet olivat tyytyväisiä Vaihtokalusteen verkkokauppaan. Vastanneet olivat sitä mieltä, että verkkokauppa on helppo- ja nopeakäyttöinen. Se on selkeä ja he ovat tyytyväisiä sen ulkonäköön. Vastanneiden mielestä tilauksen tekeminen on helppoa ja he olivat tyytyväisiä tarjolla oleviin toimitus- ja maksuvaihtoehtoihin. Brändiuudistus jakoi vastaajat kahtia, mutta pieni enemmistö oli sitä mieltä, että se on positiivinen muutos.
Tutkimus oli onnistunut ja Vaihtokaluste sai tarvitsemaansa asiakaspalautetta, jonka pohjalta he pystyvät edelleen kehittämään verkkokauppaansa.This thesis consists of two parts: theoretical and empirical parts. Theoretical part consists of three main topics: e-commerce, customer service and customer satisfaction. In the empirical part, the author of this thesis, examined and defined the customer satisfaction of Porin Vaihtokaluste Oy’s new online store.
The purpose of this thesis was to define the customer satisfaction for Porin Vaihto-kaluste Oy’s renewed online store. The purpose of the research was to find out what customers thought about the store, how it works and how do they like its looks and services. The purpose was also to find out what the customers thought about their brand renewal and the plans to continue it.
Empirical data for the research was collected with electric questionnaire made by the author of this thesis. The survey included 25 closed-end questions and one open-end question. Link to the survey was shared on Porin Vaihtokaluste Facebook page and 105 people answered to it.
People who answered to the survey, were satisfied with the renewed online store. They thought that the online store was easy and quick to use, and they liked the way it looks. They thought that it’s easy to place orders and they were satisfied with the delivery terms and payment options. The small majority thought that brand renewal was successful and good idea, but it wasn’t a clear-cut opinion.
The thesis was successful and Vaihtokaluste got much needed customer feedback for their renewed online store. With this feedback, they can continue to develop and improve their online store to be even better
