1,183 research outputs found
A Longitudinal Investigation of Person–Organization Fit, Person–Job Fit, and Contextual Performance: The Mediating Role of Psychological Ownership
No full textIn this study we present new insights into the relationships surrounding employees’ feelings of psychological ownership (PO) at work and the resulting effects on contextual performance. Characterized by a feeling of possession, PO has been theorized to have positive influences on the attitudes and behaviors of employees. To explore PO’s effects, we conducted a three-stage questionnaire survey of employees and their supervisors at a multinational pharmaceutical company in Taiwan. To help attenuate the errors associated with common method variance that trouble most studies using simultaneous data, a longitudinal approach was taken to investigate the relationships between person–organization fit, person–job fit, and PO. During the first stage of data collection, 330 questionnaires were sent to employees, and 168 (51%) valid questionnaires were returned. During the second stage, questionnaires were sent to the 168 employees who had responded to the first-stage survey. There were 134 (80%) valid questionnaires returned. Finally, during the third stage, questionnaires were sent to the supervisors of all 134 employees who had responded to the second-stage survey. There were 88 (66%) valid questionnaires returned. Findings reveal that person–job fit was significantly related to PO, and PO was significantly related to contextual performance. However, contrary to predictions, person–organization fit was positively, but not significantly, related to PO. We conclude by discussing the implications of these findings for both academics and practitioners and make suggestions for future research
Root Contact During Insertion of Miniscrews for Orthodontic Anchorage Increased the Failure Rate—An Animal Study.
No full textThe influence of aging treatments on sulfide stress corrosion cracking of PH 13-8 Mo steel welds
No full textExpression of BCL10 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan.
No full textH.H. Beltman: Natuursteencollecties deel 7
No full textDeel 6 over natuursteencollecties ging over de collectie ir. J.H. Beltman bij het Mineralogisch-Geologisch Museum (MGM) van de TU Delft en hoe deze collectie met 222 marmers terug te voeren valt op de steenhouwerij en machinale fabriek van marmerwerken H.H. Beltman uit Deventer. In deel 7 gaat universitair docent Heritage & Technology en natuursteenspecialist Wido Quist van de TU Delft dieper in op dit bedrijf aan de hand van een in 1907 opgemaakte inventaris van het hele bedrijf en ook op het tweede deel van de inventaris van de collectie.Heritage & Technolog
Higher expressions of p53 and proliferating cell nuclear antigen (PCNA) in atrophic oral lichen planus and patients with areca quid chewing
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Forms a Partnership under the System's Research of Architect office business model \ue2 to H.H. Chang Architect& Partners Co. as the example
No full textAbstract
After joining WTO, the domestic architecture market has been developing freely and internationalizedly. And this is an impact for the environment of architect business office.Hence, facing graduatedly large, complex, and complicated technologically intergrated engineer, architects are little by little accessed that it seemed negative influences on futher business once they did nothing for the demands of rapid changing environment. Finally, they will find the solutions to overcome the hard time through improving, downsizing, emerging with other companies or other ways to change the types of organizations.
Case study was implemented in this thesis to find the key factors of business continuity through understanding the development patterns of the H.H Chang Architect & Partners Co. and propose the practicable suggestions for the futures after the dead of H.H Chang. There are other four partners interviewed, and that took around six hours. The conclusions are as below,
First, they have conventionally stabilized business style. Selection is the first step of shaping the organization indentity. To selection good and proper persons as partners is key to business continuity. They have common personalities of pursuing the stable life and emphasizing the ethics and this had an huge influence on turn over rate of theis company. Besides, the systems which were established by HH Chang are never being questioned and adjusted, and the influence power still exists even he left the TMT (Top Management Team). Excellent systems help them overcome the valley of business recycles.
Second, the business continuity is the core value they own. HH Chang has never been taking the company as his own asset. Instead, one thing he only cares is business continuity, and that is the system of public fund for daily operation expenses. This system has been thoroughly implemented and lasted for 35 years.
Finally, social responsibility is their business goal.The establishment and continuity of public fund is not only kind of bussiness stability and continuity but also can be seen as social responsibility and employee care. Besides, they also provide better offers to emplyees in this field to attract excellent peple to join them.
Key word\uef\ubcHH Chang Architect& Partners Co. Business continuit
Regulation of EGF receptor trafficking by the lysine deacetylase HDAC6
No full textEpidermal growth factor (EGF) receptor belongs to the broad family of enzymatic receptors called receptor tyrosine kinases (RTKs). Generally, the binding of a ligand to these receptors leads to activation of their intracellular kinase activity that sets in motion a cascade of signaling events. In order to ensure appropriate responses to physiological stimuli, the cell is endowed with the ability to regulate signal transduction via numerous mechanisms such as dephosphorylation of the RTK and its substrates as well as downregulation of the RTK. Activation of EGFR is a potent mitogenic (proliferative) and motogenic (cell motility) signal that plays crucial roles during embryonic development and maintenance of adult tissue. EGFR signaling is primarily regulated by ligand-induced receptor internalization with subsequent degradation in lysosomes. While the complex of proteins that are recruited to EGFR after its activation is well understood, proteins that interact with the receptor in the absence of ligand binding are still not systematically studied. With the goal of identifying novel binding partners of non-activated EGFR, a membrane based yeast-two hybrid screen (MYTH) was conducted. MYTH is based on the principle of in vivo reconstitution of the N-terminus (Nub) and C-terminus (Cub) halves of ubiquitin once brought into close proximity. A chimeric protein consisting of EGFR fused to Cub and a transcription factor was used as a bait to screen Nub-tagged cDNA library. Analysis of resultant yeast transformants revealed a total of 87 proteins to interact with EGFR. Of these only 11 were previously shown to bind to EGFR. A majority of the other proteins were shown to interact with the receptor by yeast retransformation. Fifteen were confirmed to bind to EGFR by coimmunoprecipitation assays in mammalian cells. One of the novel EGFR interactors identified in the screen was histone deacetylase 6 (HDAC6). This deacetylase is localized in the cytoplasm and known to deacetylate alpha-tubulin, HSP90 and cortactin. The juxtamembrane region of EGFR binds to the Cterminus of HDAC6. Functionally, overexpression of wild type HDAC6 stabilized ligand-induced degradation of the receptor. On the other hand, deacetylase deficient or EGFR binding compromised mutants of HDAC6 were able to stabilize EGFR only partially. Downmodulation of HDAC6 expression by RNAi markedly accelerated degradation of the receptor. Taken together, HDAC6 is a negative regulator of EGFR downregulation that is dependent on its deacetylase activity and ability to bind to the receptor. Imaging studies revealed that HDAC6 does not affect internalization of EGFR from the plasma membrane but rather influences the post-endocytic trafficking of the receptor-ligand complex to lysosomes. Pulse-chase experiments using fluorophoretagged EGF showed that EGFR is transported faster towards the peri-nuclear region and delivered to late endosomes rapidly in HDAC6 depleted cells. HDAC6 is demonstrated to act, at least partly, by regulating the acetylation of alpha-tubulin. Upon EGFR activation, acetylation of alpha-tubulin on lysine 40 is progressively increased as shown by mass spectrometry and immunoblotting. Forced expression of a dominant negative mutant of alpha-tubulin, but not wild type alpha-tubulin, led to reduced speed and processive movement of early endosomes in GFP-Rab5 expressing cells. In a surprising twist, EGFR is able to phosphorylate HDAC6 on Tyr570. Phosphorylation of Tyr570 and Ser568 leads to inactivation of the deacetylase function of HDAC6 as shown by in vivo and in vitro assays. In summary, HDAC6 diminishes EGFR downregulation by slowing the transport of intracellular vesicles. The inhibitory effect is removed once HDAC6 is phosphorylated on key residues. In line with these findings, two recent reports have shown that hyper-acetylation of alpha-tubulin induced by inhibition of HDAC6 increases the transport of brain derived neurotrophic factor and JNK interacting protein-1 in different cell systems. Acetylated microtubules are more efficient in recruiting motor proteins like kinesin-1 and dynein. These findings indicate that HDAC6 plays an important regulatory role in intracellular trafficking pathways. However, several outstanding issues still remain unresolved. How does acetylation of microtubules influence vesicular trafficking? In this regard, the temporal and spatial dynamics of alpha-tubulin acetylation following EGFR activation should be studied. Furthermore, whether HDAC6 affects the trafficking of other endocytic cargos and additional organelles is an interesting question to address.Der epidermale Wachstumsfaktor-Rezeptor (EGFR) gehört zu der umfassenden Familie enzymatisch aktiver Rezeptoren, die als Rezeptortyrosinkinasen (RTKs) bezeichnet werden. RTKs stellen eine große Gruppe der Zelloberflächenrezeptoren dar, die eine intrinsische Tyrosinkinaseaktivität aufweisen. Sie katalysieren infolge extrazellulärer Stimuli den Transfer der gamma-Phosphatgruppe eines ATP-Moleküls auf Hydroxylgruppen von Tyrosinresten3. Die allgemeine Struktur von RTKs lässt sich in eine extrazelluläre Ligandenbindedomäne, eine einzige Transmembrandomäne und eine zytoplasmatische, katalytisch aktive Region gliedern, auf die der für die Regulation der Signalweiterleitung verantwortliche C-Terminus folgt. Die Bindung eines Liganden an diese Rezeptoren führt im allgemeinen zur Aktivierung ihrer intrazellulären Kinaseaktivität, die eine Kaskade von Signalvorgängen in Gang setzt. Im Fall des EGFR bindet der Ligand (EGF) als Monomer an den Rezeptor in einem Verhältnis von 2:2 und induziert Konformationsänderungen, die zur Dimerisierung des Rezeptors führen. Daraufhin werden Signalwege innerhalb der Zelle eingeleitet, indem Proteine, die eine Phosphotyrosinbindedomäne aufweisen, an phosporylierte Tyrosinreste im Cterminalen Bereich des Rezeptors binden. Die Aktivität des EGFR sowie anderer RTKs ist streng reguliert, um eine angemessene und physiologische Antwort auf einen Stimulus zu generieren. Mehrere Mechanismen wie die Dephosphorylierung des Rezeptors und weiterer Komponenten des Signalweges stellen sicher, dass die Signalweiterleitung entsprechend beendet wird. Der wichtigste Mechanismus, um die Weiterleitung des Signals herunterzuregulieren, besteht jedoch in der schnellen Endozytose und dem anschließendem Abbau sowohl des Rezeptors als auch des Liganden. Die Aktivierung infolge der Bindung eines Liganden führt zur Anhäufung des Rezeptors in von Clathrin überzogenen Einstülpungen (CCPs) auf der Plasmamembran, die sich anschließend durch Bildung von „Clathrin bedeckten Vesikeln“ (CCVs) abschnüren. Der EGFR wird über CCVs, frühe Endosomen und multivesikuläre Körper schließlich zum Abbau ins Lysosom gebracht. Das Schicksal der Fracht entscheidet sich auf der Ebene des frühen Endosoms: entweder kommt es zur Rückführung an die Plasmamembran oder zum Abbau im Lysosom. Welcher Weg eingeschlagen wird, hängt von der Ubiquitinierung der Fracht ab, die von einem Proteinkomplex (endosomal-sorting complex required for transport (ESCRT)) erkannt wird. Mikrotubuli und die an diese assoziierten Motorproteine wie Dynein sind für den Transport früher Endosomen zu späten Endosomen essentiell und somit auch für den Abbau der Fracht. In der vorliegenden Doktorarbeit wurde ein modifizierter membrane yeast two-hybrid screen (MYTH) durchgeführt, um neue Interaktionspartner des Liganden-unbesetzten, inaktiven EGFR zu identifizieren. Das Prinzip des MYTH besteht auf dem splitubiquitin System, wobei ein “quasi natives Ubiquitinmolekül” rekonstituiert wird, wenn die N-terminale und C-terminale Hälfte des Ubiquitinmoleküls (Nub bzw. Cub) in einer Zelle separat exprimiert werden. Ein Transmembranprotein, an das Cub fusioniert ist, kann dabei als Köder benutzt werden, um eine cDNA library, die an Nub gekoppelt vorliegt, auf neue Bindungspartner hin zu untersuchen. Einer der in dem Screen neu identifizierten EGFR-Bindungspartner ist die Histondeacetylase 6 (HDAC6). HDAC6 ist eine einzigartige Deacetylase, die aus zwei katalytischen Domänen und einer Ubiquitin-bindenden Zinkfingerdomäne besteht und fast ausschließlich im Zytoplasma lokalisiert ist. Dadurch, dass sie -Tubulin deacetyliert, spielt HDAC6 u. a. eine wichtige Rolle bei der chemotaktisch induzierten Zellmotilität, der Fusion des HIV-1 Viruspartikels mit der Zellmembran sowie der Bildung von Immunsynapsen. HDAC6 sorgt auch für die Aufrechterhaltung des richtigen Acetylierungsgrades von HSP90, der für die Interaktion mit seinen Ko-Chaperonen und weiteren Assoziationspartnern benötigt wird. Unabhängig von ihrer Deacetylaseaktivität dient HDAC6 durch Bindung an polyubiquitinierte Proteine einerseits und Dynein andererseits als Adaptorprotein. Diese Rolle von HDAC6 ist für die Beseitigung falsch gefalteter Proteine und Aggresomen von Bedeutung. Das Hauptziel dieser Doktorarbeit ist die Identifizierung neuer EGFR Bindungspartner, die an den inaktiven Rezeptor gebunden sind, sowie die funktionelle Charakterisierung putativer Interaktionspartner
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