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Zeitschriftenartikel zum Thema "ACE100"
1
Shen, Chang-Hui, Benoit P. Leblanc, Jennifer A. Alfieri und David J. Clark. „Remodeling of Yeast CUP1 Chromatin Involves Activator-Dependent Repositioning of Nucleosomes over the Entire Gene and Flanking Sequences“. Molecular and Cellular Biology 21, Nr. 2 (15.01.2001): 534–47. http://dx.doi.org/10.1128/mcb.21.2.534-547.2001.
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ABSTRACT The yeast CUP1 gene is activated by the copper-dependent binding of the transcriptional activator, Ace1p. An episome containing transcriptionally active or inactiveCUP1 was purified in its native chromatin structure from yeast cells. The amount of RNA polymerase II on CUP1 in the purified episomes correlated with its transcriptional activity in vivo. Chromatin structures were examined by using the monomer extension technique to map translational positions of nucleosomes. The chromatin structure of an episome containing inactive CUP1 isolated from ace1Δ cells is organized into clusters of overlapping nucleosome positions separated by linkers. Novel nucleosome positions that include the linkers are occupied in the presence of Ace1p. Repositioning was observed over the entire CUP1 gene and its flanking regions, possibly over the entire episome. Mutation of the TATA boxes to prevent transcription did not prevent repositioning, implicating a chromatin remodeling activity recruited by Ace1p. These observations provide direct evidence in vivo for the nucleosome sliding mechanism proposed for remodeling complexes in vitro and indicate that remodeling is not restricted to the promoter but occurs over a chromatin domain including CUP1 and its flanking sequences.
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Koronyo-Hamaoui, Maya, Julia Sheyn, Eric Y. Hayden, Songlin Li, Dieu-Trang Fuchs, Giovanna C. Regis, Dahabada H. J. Lopes et al. „Peripherally derived angiotensin converting enzyme-enhanced macrophages alleviate Alzheimer-related disease“. Brain 143, Nr. 1 (03.12.2019): 336–58. http://dx.doi.org/10.1093/brain/awz364.
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Abstract Targeted overexpression of angiotensin-converting enzyme (ACE), an amyloid-β protein degrading enzyme, to brain resident microglia and peripheral myelomonocytes (ACE10 model) substantially diminished Alzheimer’s-like disease in double-transgenic APPSWE/PS1ΔE9 (AD+) mice. In this study, we explored the impact of selective and transient angiotensin-converting enzyme overexpression on macrophage behaviour and the relative contribution of bone marrow-derived ACE10 macrophages, but not microglia, in attenuating disease progression. To this end, two in vivo approaches were applied in AD+ mice: (i) ACE10/GFP+ bone marrow transplantation with head shielding; and (ii) adoptive transfer of CD115+-ACE10/GFP+ monocytes to the peripheral blood. Extensive in vitro studies were further undertaken to establish the unique ACE10-macrophage phenotype(s) in response to amyloid-β1-42 fibrils and oligomers. The combined in vivo approaches showed that increased cerebral infiltration of ACE10 as compared to wild-type monocytes (∼3-fold increase; P < 0.05) led to reductions in cerebral soluble amyloid-β1-42, vascular and parenchymal amyloid-β deposits, and astrocytosis (31%, 47–80%, and 33%, respectively; P < 0.05–0.0001). ACE10 macrophages surrounded brain and retinal amyloid-β plaques and expressed 3.2-fold higher insulin-like growth factor-1 (P < 0.01) and ∼60% lower tumour necrosis factor-α (P < 0.05). Importantly, blood enrichment with CD115+-ACE10 monocytes in symptomatic AD+ mice resulted in pronounced synaptic and cognitive preservation (P < 0.05–0.001). In vitro analysis of macrophage response to well-defined amyloid-β1-42 conformers (fibrils, prion rod-like structures, and stabilized soluble oligomers) revealed extensive resistance to amyloid-β1-42 species by ACE10 macrophages. They exhibited 2–5-fold increased surface binding to amyloid-β conformers as well as substantially more effective amyloid-β1-42 uptake, at least 8-fold higher than those of wild-type macrophages (P < 0.0001), which were associated with enhanced expression of surface scavenger receptors (i.e. CD36, scavenger receptor class A member 1, triggering receptor expressed on myeloid cells 2, CD163; P < 0.05–0.0001), endosomal processing (P < 0.05–0.0001), and ∼80% increased extracellular degradation of amyloid-β1-42 (P < 0.001). Beneficial ACE10 phenotype was reversed by the angiotensin-converting enzyme inhibitor (lisinopril) and thus was dependent on angiotensin-converting enzyme catalytic activity. Further, ACE10 macrophages presented distinct anti-inflammatory (low inducible nitric oxide synthase and lower tumour necrosis factor-α), pro-healing immune profiles (high insulin-like growth factor-1, elongated cell morphology), even following exposure to Alzheimer’s-related amyloid-β1-42 oligomers. Overall, we provide the first evidence for therapeutic roles of angiotensin-converting enzyme-overexpressing macrophages in preserving synapses and cognition, attenuating neuropathology and neuroinflammation, and enhancing resistance to defined pathognomonic amyloid-β forms.
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Li, Xiang, Junan Yang, Hui Liu und Pengjiang Hu. „HTLinker: A Head-to-Tail Linker for Nested Named Entity Recognition“. Symmetry 13, Nr. 9 (31.08.2021): 1596. http://dx.doi.org/10.3390/sym13091596.
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Named entity recognition (NER) aims to extract entities from unstructured text, and a nested structure often exists between entities. However, most previous studies paid more attention to flair named entity recognition while ignoring nested entities. The importance of words in the text should vary for different entity categories. In this paper, we propose a head-to-tail linker for nested NER. The proposed model exploits the extracted entity head as conditional information to locate the corresponding entity tails under different entity categories. This strategy takes part of the symmetric boundary information of the entity as a condition and effectively leverages the information from the text to improve the entity boundary recognition effectiveness. The proposed model considers the variability in the semantic correlation between tokens for different entity heads under different entity categories. To verify the effectiveness of the model, numerous experiments were implemented on three datasets: ACE2004, ACE2005, and GENIA, with F1-scores of 80.5%, 79.3%, and 76.4%, respectively. The experimental results show that our model is the most effective of all the methods used for comparison.
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Tan, Chuanqi, Wei Qiu, Mosha Chen, Rui Wang und Fei Huang. „Boundary Enhanced Neural Span Classification for Nested Named Entity Recognition“. Proceedings of the AAAI Conference on Artificial Intelligence 34, Nr. 05 (03.04.2020): 9016–23. http://dx.doi.org/10.1609/aaai.v34i05.6434.
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Named entity recognition (NER) is a well-studied task in natural language processing. However, the widely-used sequence labeling framework is usually difficult to detect entities with nested structures. The span-based method that can easily detect nested entities in different subsequences is naturally suitable for the nested NER problem. However, previous span-based methods have two main issues. First, classifying all subsequences is computationally expensive and very inefficient at inference. Second, the span-based methods mainly focus on learning span representations but lack of explicit boundary supervision. To tackle the above two issues, we propose a boundary enhanced neural span classification model. In addition to classifying the span, we propose incorporating an additional boundary detection task to predict those words that are boundaries of entities. The two tasks are jointly trained under a multitask learning framework, which enhances the span representation with additional boundary supervision. In addition, the boundary detection model has the ability to generate high-quality candidate spans, which greatly reduces the time complexity during inference. Experiments show that our approach outperforms all existing methods and achieves 85.3, 83.9, and 78.3 scores in terms of F1 on the ACE2004, ACE2005, and GENIA datasets, respectively.
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Hartmann, Rudolf, Tjerk Feenstra, Sabine Knappe, Michael Dockal und Friedrich Scheiflinger. „Elucidating the Excessive Pro-Coagulant Effect of a Sequence Identical Analogue to ACE910 in Combination with Bypassing Agents“. Blood 130, Suppl_1 (07.12.2017): 90. http://dx.doi.org/10.1182/blood.v130.suppl_1.90.90.
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Abstract Introduction: Emicizumab (ACE910), an antibody to FIX(a) and FX(a), is currently under investigation for treatment of hemophilia with inhibitors. In a phase III trial, two thromboembolic complications and three cases of microangiopathy were reported in patients on ACE910 prophylaxis [Oldenburg et al. NEJM 2017], whose breakthrough bleeding was treated with activated prothrombin complex concentrate aPCC (FEIBA) or aPCC and rFVIIa. We generated a sequence identical analogue (SIA) to ACE910 and analyzed its synergistic interplay with bypassing agents. Aims: To monitor in vitro the pro-coagulant activity of SIA ACE910 in the presence of FEIBA and rFVIIa, and detect the source of excessive coagulation induced by SIA ACE910 combined with FEIBA. Methods: A sequence identical analogue (SIA) to ACE910 was expressed in HEK293 cells, purified as previously described [Sampei et al. PLoS One 2013], and analyzed in several global hemostatic assays at different concentrations and test conditions using plasma and whole blood assays. In thrombin generation (TG) experiments, platelet-poor plasma (PPP) from hemophilia A inhibitor patients and hemophilia A plasma reconstituted with platelets from 3 healthy donors (PRP) was used. A normal TG range was established in healthy donor plasma. Therapeutic concentrations of SIA ACE910 (20-600 nM) were tested alone and with FEIBA (0.05-1 U/mL) or rFVIIa (0.88-5.25 µg/mL). To measure FEIBA components' contribution to the synergistic effect with SIA ACE910, PPP was spiked with select FEIBA components at concentrations corresponding to 0.5 U/mL FEIBA in combination with the antibody. Thrombus formation was analyzed in FVIII-inhibited blood using rotational thromboelastometry (ROTEM) and Total Thrombus-formation Analysis System (T-TAS). Results: Normal peak thrombin was 47-144 nM for PPP and 88-231 nM for PRP. rFVIIa and FEIBA had an additive effect on TG in combination with SIA ACE910 in both plasma types. Combined with rFVIIa (0.88 µg/mL) or FEIBA (0.5 U/mL), SIA ACE910 (600 nM) induced a ~2- and ~16-fold increase over SIA ACE910 alone. SIA ACE910+rFVIIa did not reach the normal range, while SIA ACE910+FEIBA far exceeded it. Adding individual FEIBA components to PPP showed that FIX was, with a half-maximal effect, the main driver for enhanced TG, followed by FIXa. formation in FVIII-inhibited whole blood using ROTEM and T-TAS confirmed the excessive effect of SIA ACE910+FEIBA. In ROTEM, FEIBA and rFVIIa reduced clotting time to shorter than normal, whereas SIA ACE910 had only little effect. Moreover, adding SIA ACE910 to rFVIIa exerted no effect over rFVIIa alone. Conclusion: Combining SIA ACE910 at plasma concentrations observed in patients [Oldenburg et al. NEJM 2017] with FEIBA induced excessive thrombin generation and faster clot formation. In vitro, this effect is mainly mediated by FEIBA component FIX. ACE910 binds to FIX and FIXa to the same extent, and displays its pro-coagulant effect via an unregulated mechanism. Therefore, careful judgement is needed in treating breakthrough bleeds with FEIBA. Disclosures Hartmann: Shire: Employment. Feenstra: Shire: Employment. Knappe: Shire: Employment. Dockal: Baxalta: Patents & Royalties; Shire: Employment, Equity Ownership; Baxter: Equity Ownership, Patents & Royalties. Scheiflinger: Baxter: Equity Ownership; Shire: Employment, Equity Ownership.
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Li, Hao-Kang, Ching-Wen Hsiao, Sen-Han Yang, Hsiu-Ping Yang, Tai-Sheng Wu, Zih-Fei Cheng, Chia-Yun Lee et al. „772 A potent and off-the-shelf oNK cell therapy product targets HER2+ cancer cells and resists suppressive tumor microenvironment“. Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A821. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0772.
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BackgroundAutologous or allogeneic natural killer (NK) cells possess efficient cytotoxicity against tumor cells without severe side effects such as CRS or graft-versus-host disease (GvHD). In addition to chimeric antigen receptor (CAR) strategy, antibody-cell conjugates (ACC) platform provides more efficient way to arm NK cells with binding specificity and enhanced potency against target cells. In this work, we develop a NK cell therapy product ACE1702, a novel NK cell line oNK conjugated with trastuzumab, and assess its potency against HER2+ solid tumors.Methods oNK cells were covalently conjugated with monoclonal antibody Trastuzumab after sublethal irradiation by our patented antibody-cell conjugates (ACC) platform to become our cryopreserved final product ACE1702 compliant with current good manufacturing practice (cGMP). Function of ACE1702 was validated by real-time xCELLigence analyzer and MTT assay in vitro. Efficacy of intraperitoneally (ip.) delivered ACE1702 was evaluated in tumor-bearing female immune compromised NSG mice. Characterization of ACE1702 was analyzed by flow cytometry.ResultsWe demonstrated that the trastuzumab-armed oNK cells, ACE1702, exerted human epidermal growth factor 2 (HER2) binding specificity and enhanced cytotoxicity against various types of cancer cells with different grade of HER2 expressions compared to control oNK cells in vitro. In vivo results in human ovarian cancer cell line SK-OV-3-bearing xenograft mouse model further supported the in vitro observations. Of note, ACE1702 also displayed a better cytotoxicity against HER2+ cancer cells than trastuzumab and its derived antibody-drug conjugate. ACE1702 also remained cytotoxicity against cancer cells in the suppressive tumor microenvironment. Characterization revealed a preferential expression of NK activation receptors, and conjugation of trastuzumab with cell membrane proteins responsible for NK activity capacitated ACE1702 with enhanced cytotoxicity. These results underscore the potency of ACE1702 in eradication of cancer cells.ConclusionsHere we introduced a novel trastuzumab-modified oNK cell product with enhanced specificity against myriad types of HER2+ cancers. Selective conjugation of trastuzumab with membrane proteins contributing to NK activation conferred ACE1702 with enhanced cytotoxicity even in the suppressive tumor microenvironment.AcknowledgementsNoneTrial RegistrationNoneEthics ApprovalThe animal study was conducted according to protocols approved by the Institutional Animal Care and Use Committee of Muragenics.ConsentNone
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Minami, Hiroaki, Keiji Nogami, Takehisa Kitazawa, Kunihiro Hattori und Midori Shima. „FVIII Heavy Chain Enhances Tenase Activity Induced By FVIIIa Mimicking Bispesific Antibody, ACE910“. Blood 124, Nr. 21 (06.12.2014): 1481. http://dx.doi.org/10.1182/blood.v124.21.1481.1481.
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Abstract Background: ACE910, asymmetric bispecific monoclonal antibodies to activated factor IX (IXa) and factor X, mimics the cofactor function of activated factor VIII (VIIIa) by modulating an optimal position on the tenase assembly. The estimated therapeutic range of ACE910 shows ~30% of thrombin generation in native tenase assembly, supporting that the structure on ACE910-mimicking tenase assembly is different from that on native tenase. Being close to physiological structure consisting from factor IXa, factor X, and factor VIIIa is important for potentiating the clotting function. We examined the effects of factor VIII subunits (light chain, heavy chain, A1 and A2, C2) on ACE910-tenase. Materials/Methods: The factor VIII light chain and heavy chain were isolated from EDTA-treated recombinant factor VIII following chromatography on SP- and Q- Sepharose columns. The A2 and A1 subunits were purified from thrombin-cleaved factor VIII heavy chain by Heparin-, SP- Sepharose columns. Purified factor Xa generation assays was examined with (i) factor VIII subunit (0-40 nM), ACE910 (10 µg/ml), phospholipid (PL) (40 µM), factor IXa (1 nM) and factor X (200 nM), (ii, iii) the A2 or heavy chain (40 nM), ACE910 (10 µg/ml), PL (40 µM), factor IXa and factor X (1 or 0-80 nM, and 0-300 or 200 nM, respectively). These mixtures were reacted for five minutes (i, ii) or one minute (iii). These assays were conducted at 37 °C. Results: (i) The factor Xa generation in ACE910-tenase complex in the absence of factor VIIIa was 10.1±2.2 nM. With the intact heavy chain and A2, amounts of factor Xa were increased dose-dependently, resulting in 1.3- and 1.2-fold increases, respectively. While, the light chain and A1 subunit failed to increase at all. (ii) Vmax for factor X in ACE910-tenase was 173.0±7.0 nM and Km was 31.2±3.9 nM. Vmax obtained with the heavy chain or A2 was 175.9±6.1 or 159.0±6.1 nM, whilst Km was 17.0±2.2 or 31.9±3.5 nM, respectively, indicating that the heavy chain enhanced the binding affinity for factor X in ACE910-tenase. (iii) Vmax for factor IXa in ACE910-tenase was 43.8±2.7 nM and Km was 36.9±4.8 nM. With the heavy chain or A2, Vmax was 46.8±3.0 or 45.0±3.1 nM, and Km was 36.4±3.0 or 32.1±4.9 nM, respectively, indicating that either the heavy chain or A2 did not enhance the catalytic activity and the binding affinity for factor IXa in ACE910-tenase. Conclusion: ACE910-tenase assembly seems to be close to physiological structure by the presence of intact heavy chain interacting with factor X. In addition, ACE910 may substitute the position such as the factor VIII(a) light chain associated with FIXa and FX on ACE910-tenase assembly defecting factor VIII. Disclosures Minami: Chugai Pharmaceutical Co., Ltd.: Research Funding. Nogami:Chugai Pharmaceutical Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kitazawa:Chugai Pharmaceutical Co., Ltd.: Employment, Equity Ownership, Patents & Royalties. Hattori:Chugai Pharmaceutical Co., Ltd.: Employment, Equity Ownership, Patents & Royalties. Shima:Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Yada, Koji, Keiji Nogami, Tomoko Matsumoto, Takehisa Kitazawa, Kunihiro Hattori und Midori Shima. „Activated Protein C-Catalyzed Factor Va Inactivation Predominantly Contributes to the Downregulation of Coagulation Rather Than Factor VIIIa Inactivation“. Blood 124, Nr. 21 (06.12.2014): 4222. http://dx.doi.org/10.1182/blood.v124.21.4222.4222.
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Abstract Activated protein C (APC) directly inactivates factor (F)Va and FVIIIa dependently of protein S (PS), and furthermore inactivates FVIIIa through cofactor function of FV. Any impairment in these inactivation pathways may increase thrombotic risk. A previous report described that the APC resistance (APCR) associated with FV-Leiden was mainly due to the impaired cofactor activity of FV (Castoldi et al. Blood 2004;103, 4173). We have recently reported that FV-Nara carrying W1920R mutation exhibited APCR caused by a loss of FVa susceptibility to APC and APC cofactor activity resulting in more serious thrombotic potential than FV-Leiden (Nogami et al. Blood 2014;123, 2420). The contribution of each inactivation pathway associated with FVIII(a) and/or FV(a) for the hemostatic regulation remains unclear, however. An ACE910, bispecific antibody (Ab) to FIXa and FX mimicking the functions of FVIII, exerts tenase activities without FVIII(a) (Kitazawa et al. Nature Medicine. 2012;18, 1570). In this study, to elucidate the contribution of each pathway, we investigated the regulatory mechanism(s) by APC utilizing ACE910. FXa generation with ACE910 (10μg/ml) or with FVIIIa (0.3 nM) in FVIII-deficient plasma (ΔFVIII) was evaluated by the addition of APC (0-0.5 nM), PS (5 nM), and FV (1 nM). FXa generation with FVIIIa was reduced by ~60% maximally in an APC dose-dependent manner, whilst that with ACE910 was unaffected, indicating that ACE910 itself was not susceptible to inactivation by APC through the cofactor activity of FV. Thrombin generation in ΔFVIII with ACE910 (0-30μg/ml) was enhanced in an ACE910 dose-dependent fashion and ~10-fold of peak thrombin (PeakTh) (442 ± 7.0 nM), equivalent to 77.5% of PeakTh in pool normal plasma (PNP), was observed with ACE910 (30μg/ml) compared to that without ACE910 (44.6 ± 5.0 nM). To investigate the effect of APC upon the hemostatic enhancement by ACE910 in ΔFVIII, thrombin generation in ΔFVIII mixed with ACE910 (30μg/ml) and APC (0-16 nM) was examined. PeakTh showed the APC-dependent reduction to 156 ± 22nM and the %inhibition was 64.7%. Subsequently, we evaluated the effects of APC on thrombin generation in PNP or in PNP with an anti-FVIII Ab (FVIIIAb) (16BU/ml) supplemented by ACE910. Of note, the %inhibition of PeakTh by APC in latter with ACE910 and FVIIIAb (64%) was greater than that in PNP alone (35%) by ~1.9-fold. To elucidate the contribution of APC-catalyzed inactivation of FV(a) to the hemostatic regulation, we evaluated the thrombin generation in FV-diluted plasma (FV-dil) consisting of FV-deficient plasma and FV (8nM) corresponded to ~25% of its physiological concentration mixed with or without ACE910 and FVIIIAb in the presence or absence of APC. The %inhibition of PeakTh by APC in FV-dil with ACE910 and FVIIIAb (46.5%), being reduced in comparison with that of PNP with both Abs, was greater than that in FV-dil alone (18.3%) by ~2.5-fold, indicating that the inhibition of thrombin generation by APC-catalyzed FV(a) inactivation was FV(a) dose-dependent but enhanced in the absence of FVIII(a). Furthermore, the effects on thrombin generation with APC (0-16 nM) in plasmas carrying FV-Leiden without or with FVIIIAb and ACE910 (30μg/ml) were examined. It was of surprise that PeakTh in latter with FVIIIAb and ACE910 reduced exponentially by ~40% in an APC dose-dependent manner, whilst APC showed any little effects upon thrombin generation in FV-Leiden plasma alone indicating APCR. The susceptibility index to APC calculated by the rate of inhibition with FVIIIAb and ACE910 was 0.174, greater than that with FV-Leiden plasma alone (0.085) by ~2-fold. These results strongly suggested that APC could regulate the hemostatic enhancement by inactivation of FV(a) even FV-Leiden in the absence of another substrate, FVIII(a). We conclude that APC potentiates its catalytic activity to FVa more in the absence of FVIII(a) than in the presence of FVIII(a) and this mechanism would play significant roles in the downregulation of coagulation as one of the breaking systems. Disclosures Yada: Chugai Pharmaceutica Co., Ltd: Research Funding. Nogami:Chugai Pharmaceutical Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kitazawa:Chugai Pharmaceutical Co., Ltd.: Employment, Equity Ownership, Patents & Royalties. Hattori:Chugai Pharmaceutical Co., Ltd.: Employment, Equity Ownership, Patents & Royalties. Shima:Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Takeyama, Masahiro, Keiji Nogami, Tomoko Matsumoto, Takehisa Kitazawa, Kunihiro Hattori und Midori Shima. „Anti-Factor IXa/Factor X Antibody (ACE910) Improves the Coagulation Function in Acquired Hemophilia A ex vivo“. Blood 126, Nr. 23 (03.12.2015): 3565. http://dx.doi.org/10.1182/blood.v126.23.3565.3565.
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Abstract <Introduction> Acquired hemophilia A (AHA) is a rare bleeding disorder in which autoantibodies (autoAbs) against coagulation factor (F)VIII impair the coagulation system. Anti-FVIII autoAbs developed in AHA are polyclonal and the majority of these autoAbs bind to the A2, A3, and/or C2 domains in FVIII. Different inhibitory actions of anti-FVIII autoAbs, depending on their epitopes, are well-known. We have recently developed a humanized anti-FIXa/X bispecific antibody, ACE910, which mimics the cofactor function of FVIIIa even in the presence of anti-FVIII alloantibodies. <Aim> In this study, we examined whether ACE910 improved the lower coagulation function in AHA patients using the comprehensive coagulation assays. <Methods> Two representative experiments were performed as follows; 1) In vitro effects of ACE910 on normal pooled plasmas (PNPs) mixed with various anti-FVIII monoclonal Abs (mAbs) as the reconstituted AHA-models. For this experiments, several anti-FVIII mAbs; VIII-9222 (epitope: anti-a1), VIII-2236 (anti-A2), VIII-3776 (anti-A3C1), ESH4 (anti-C2) were prepared. 2) Ex vivo effects of ACE910 on plasmas obtained from nine patients with AHA, whose regions of Abs were A1, A2 and light chain for four patients, A2 and light chain for three patients, A2 for one patient and light chain for one patient. The coagulation functions in obtained samples were evaluated using the comprehensive coagulation assays, clot waveform analysis (CWA) and thrombin generation assays (TGA). In CWA, the minimum value of the first derivative (min1) and the second derivative (min2) were calculated as an index of the maximum acceleration of the reaction and the maximum velocity of coagulation, respectively. In TGA, calibrated automated thrombin generation assays derived the standard parameters; peak thrombin, lagtime, and time to peak. Total thrombin generation at intervals from the beginning to peak level was quantified. These values (nmol/l) were divided by the sample times (min, time to peak - lagtime), and represented the mean velocity of thrombin generation until the reach to peak level, expressed as mean velocity to peak thrombin (MV-peak thrombin). We defined the attenuation of inhibitory effect (% of AIE) represented that ACE910 attenuated the parameters inhibited by mAbs in artificial AHA or by allo-Abs in AHA patients, respectively. Figure 1 represents the % of AIE on thrombin peak in TGA. <Results> PNPs were incubated with various anti-FVIII mAbs (100-500 mcg/ml) at 37 degrees Celsius for 2 hrs, and FVIII activities in these samples were decreased to 2.0-43%. These reactant mixtures were reacted with ACE910 (0-20 mcg/ml) for a further 2 hr-incubation. ACE910 improved the parameters of CWA (|min1|; 40-62%, and |min2|; 49-74% of AIE) and of TGA (thrombin peak; 46-72%, and MV-peak thrombin; 51-70% of AIE, respectively) in all PNPs with mAbs. These data indicated that ACE910 improved the coagulant activity in AHA patients. Therefore, we determined the efficacy of ACE910 for nine AHA patients ex vivo. FVIII activities and FVIII inhibitors were <1.0-7.5 % and 2.2-134 BU/ml, respectively. ACE910 improved the parameters for eight AHA patients in CWA (|min1|; 36-100 %, and |min2|; 52-100 % of AIE, respectively). For one AHA patient whose epitope was A2 and light chain, ACE910 showed the slight improvement in |min1| (12 % of AIE) and in |min2| (31 % of AIE). The reason was that the range of concentration of ACE910 was only from 0 to 5 mcg/dl. On the other hand, ACE910 improved the parameters for all AHA patients in TGA. ACE910 showed effect on thrombin peak (27-77 % of AIE). Furthermore, ACE910 improved MV-peak thrombin (17-73 % of AIE). Figure 2 shows representative TGA curve for the effect of ACE910 on one AHA patient whose allo-Ab was anti-light chain. <Conclusion> Our results indicated that ACE910 could improve the coagulant activities in AHA patients independent of the regions of antibodies and might be useful for the treatment of AHA patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Takeyama: Chugai Pharmaceutical Co., Ltd.: Research Funding. Nogami:Bayer, NovoNordisk, Baxalta, Chugai, Kaketsuken, Pfizer, Biogen: Honoraria; Chugai: Membership on an entity's Board of Directors or advisory committees; Bayer, Novo Nordisk, Baxalta. Biogen: Research Funding. Matsumoto:Chugai Pharmaceutical Co., Ltd: Research Funding. Kitazawa:Chugai Pharmaceutical Co., Ltd: Employment, Equity Ownership, Patents & Royalties. Hattori:Chugai Pharmaceutical Co., Ltd: Employment, Equity Ownership, Patents & Royalties. Shima:Chugai Pharmaceutical Co., Ltd. and F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Muto, Atsushi, Takehisa Kitazawa, Kazutaka Yoshihasi, Minako Takeda, Tetsuhiro Soeda, Tomoyuki Igawa, Zenjiro Sampei et al. „Hemostatic Effect of a Novel Bispecific Antibody (ACE910) Against Activated Factor IX and Factor X in an Acquired Hemophilia A Model“. Blood 120, Nr. 21 (16.11.2012): 42. http://dx.doi.org/10.1182/blood.v120.21.42.42.
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Abstract Abstract 42 Background: Hemophilia A is treated by intravenous replacement therapy with factor VIII (FVIII), either on demand to resolve bleeding or as a prophylactic to prevent bleeding. Recently, routine prophylactic treatment is recommended to effectively prevent bleeding and to reduce bleeding-related chronic joint damage. However, the need for frequent intravenous injections of FVIII negatively affects patients' quality of life and their adherence to the routine prophylactic regimen. More importantly, approximately 30% of severe hemophilia A patients develop inhibitory antibodies toward the injected FVIII, rendering the replacement therapy ineffective. To overcome these drawbacks, we generated a bispecific antibody (termed ACE910) against activated factor IX (FIXa) and factor X (FX), which mimics the cofactor function of FVIII. Objectives: The aims of the present study were to examine the FVIII-mimetic cofactor activity of ACE910 in vitro and its hemostatic activity in vivo. Methods: The FVIII-mimetic cofactor activity of ACE910 was evaluated by a thrombin generation assay in human FVIII-deficient plasma as well as by an enzymatic assay using purified coagulation factors. For in vivo studies, an acquired hemophilia A model was established in cynomolgus monkeys by a single intravenous injection of mouse monoclonal anti-FVIII neutralizing antibody, which was cross-reactive to cynomolgus monkey FVIII but not to porcine FVIII. After artificial bleeding had been induced, ACE910 or porcine FVIII was intravenously administered in a single dose or in twice-daily repeated doses, respectively. Bleeding symptoms, including anemia and skin bruising, were monitored for three days. A pharmacokinetic study of ACE910 was also performed with a single intravenous or subcutaneous administration to cynomolgus monkeys. Results: ACE910 concentration-dependently showed FVIII-mimetic cofactor activity in the enzymatic assay and improved thrombin generation parameters in human FVIII-deficient plasma. Intravenous administration of ACE910 (a single dose of 3 mg/kg) significantly reduced the bleeding symptoms in the acquired hemophilia A model of a non-human primate. This hemostatic effect was comparable to twice-daily intravenous administration of porcine FVIII (repeated doses of 10 U/kg). The half-life of ACE910 was approximately three weeks for both single intravenous and subcutaneous administrations. The subcutaneous bioavailability of ACE910 was nearly 100%. Conclusion: The bispecific antibody against FIXa and FX, ACE910, exerted FVIII-mimetic cofactor activity in vitro. Furthermore, a single dose of ACE910 demonstrated hemostatic activity comparable to twice-daily repeated doses of 10 U/kg porcine FVIII in vivo. Moreover, ACE910 exhibited high subcutaneous bioavailability and approximately three-week half-life in a non-human primate. Our bispecific antibody against FIXa and FX is a subcutaneously injectable, long-acting agent that removes the need to consider the induction or presence of FVIII inhibitors and may establish a novel principle for the prophylactic treatment of hemophilia A patients. Disclosures: Muto: Chugai Pharmaceutical Co., Ltd.: Employment. Kitazawa:Chugai Pharmaceutical Co., Ltd.: Employment. Yoshihasi:Chugai Pharmaceutical Co., Ltd.: Employment. Takeda:Chugai Pharmaceutical Co., Ltd.: Employment. Soeda:Chugai Pharmaceutical Co., Ltd.: Employment. Igawa:Chugai Pharmaceutical Co., Ltd.: Employment. Sampei:Chugai Pharmaceutical Co., Ltd.: Employment. Sakamoto:Chugai Pharmaceutical Co., Ltd.: Employment. Okuyama-Nishida:Chugai Pharmaceutical Co., Ltd.: Employment. Saito:Chugai Pharmaceutical Co., Ltd.: Employment. Kawabe:Chugai Pharmaceutical Co., Ltd.: Employment. Shima:Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding. Hattori:Chugai Pharmaceutical Co., Ltd.: Employment.
Dissertationen zum Thema "ACE100"
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Hubáček, Jan. „Vyšetřování bezpečného únavového života křídla víceúčelového jednomotorového turbovrtulového letounu“. Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2021. http://www.nusl.cz/ntk/nusl-443732.
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Práce se zabývá stanovením bezpečné únavové životnosti křídla. Letadlo, které bylo podrobeno analýze, je vzpěrový hornoplošník celokovové konstrukce. Letadlo je certifikováno na základě předpisu FAR 23 Amendment 23-46. Výpočet bezpečné únavové životnosti musí být proveden v souladu s požadavky předpisu FAR 23 a jeho poradními oběžníky.\\ Teoretická část práce je věnována hlavně přehledu literatury a představení projektu, kde byla stručně shrnuta jeho historie vzniku. Část přehledu projektu také pojednává o podstatě požadavku na posouzení bezpečné únavové životnosti zadavatelem. V další části byl rovněž proveden rozbor literatury týkající se únavy. Jednalo se zejména o rozbor předpisu FAR 23, jeho poradních oběžníků a obecně literatury vztahující se k únavě jak v letectví, tak v obecném strojírenství.\\ Druhá část diplomové práce byla zaměřena zejména na výpočetní analýzu a vývoj specializovaného software. Výpočetní část obsahovala zejména přípravu vstupů, včetně obálek zatížení, stanovení typického letu, výpočet zatížení křídla a napjatostní analýza ve vybraných řezech křídla. Z výstupů prvotní analýzy se následně provedl výpočet poškození a životnosti pro daný typový let.
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Thorne, Nicholas James. „Firmware and gateway for the ACE1 reconfigurable accelerator card“. Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10926.
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This thesis describes the continued work on the in-house designed FPGA based co-processor daughtercard referred to as ACE1. The aim: to create an ecosystem incorporating firmware, bootstrapping code, drivers and a development environment to create a seamless environment. Challenges in setting up and debugging the interface that connects the coprocessor daughtercard to the host server include: problems with the power network, the edge connectors and timing problems with the primary protocol which prevented host-based communications. The options include allowing the daughtercard to function in a stand-alone fashion and we present a gateware solution that allows users to select from a number of alternatives for each of the layers in the Open Systems Interconnect networking model.
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Fudal, Isabelle. „Etude du gène d'avirulence ACE1 de Magnaporthe grisea, agent pathogène du riz : analyse de l'expression du gène ACE1 et évolution dans les populations de Magnaporthe grisea“. Paris 11, 2004. http://www.theses.fr/2004PA112008.
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Les isolats de Magnaporthe grisea possédant le gène d'avirulence ACE1 sont spécifiquement reconnus par les variétés de riz possédant le gène de résistance Pi33. ACE1 code pour une enzyme du métabolisme secondaire (un hybride polycétide synthase/peptide synthétase). L'activité enzymatique d'Ace1 étant nécessaire à l'avirulence, le signal reconnu par les plantes résistantes possédant Pi33 pourrait être le métabolite secondaire dont la biosynthèse dépend d'Ace1. ACE1 est exclusivement exprimé dans les appressoria pendant l'étape de pénétration, aussi bien sur plante que sur certaines membranes artificielles. Aucune expression n'a été détectée dans les appressoria du mutant déficient en mélanine bufl, incapable de développer une pression appressoriale. L'ajout de solutions osmotiques sur des appressoria de bufl rétablit l'expression d'ACE1. Nos résultats suggèrent que l'expression d'ACE1 est dépendante d'un stade de développement atteint juste avant la pénétration et de la pression appressoriale. Des délétions du promoteur d'ACE1 ont révélé une région de 200 bp nécessaire à la transcription dans l' appressorium. L'analyse de l'allèle ACE1 dans le descendant virulent 2/0/3 a révélé l'insertion d'un nouveau retroposon (MINE) dans la POL d'ACE1. La majorité des isolats récoltés dans le monde sont avirulents pour Pi33 et possèdent tous le même allèle ACE1 (ACE1-GUY11. 1). Les isolats virulents ont été majoritairement trouvés en Asie et Amérique du Sud, son génétiquement liés et peuvent être classés en trois groupes en fonction de leur génotype ACE1. Un groupe possède l'allèle virulent (ACE1-GUY11. 2) qui présente 99 % d'identité avec ACEl-GUY11. 1. Le deuxième groupe possède l'allèle virulent (ACE1-CM28) qui présente 88 % d'identité avec ACE1-GUY11. 1. Le troisième groupe possède les allèles virulents ACEl-GUYll. 2 et ACEl-CM28. Ces allèles sont localisés sur des chromosomes différents, indiquant que ces isolats normalement haploi͏̈des sont partiellement diploi͏̈des au locus ACElIsolates of the rice blast fungus Magnaporthe grisea that carry the avirulence gene ACE1 are specifically recognized by rice cultivars carrying the resistance gene Pi33. ACE1 encodes an enzyme of the secondary metabolism (a hybrid polyketide synthase/non-ribosomal peptide synthase). Since Acel enzymatic activity is required for avirulence, the signal recognized by rice cultivars carrying Pi33 should be a secondary metabolite. ACE1 is expressed exclusively in appressoria during the penetration process, either on plant or artificial surfaces. ACE1 was not expressed in appressoria differentiated on Mylar or in appressoria from the melanin-deficient mutant bufl, unable to build up appresorial turgor. Addition of hyper-osmotic solutions to bufl appressoria restored ACE1 expression. Our results suggest that ACE1 expression requires an appressorial developmental stage reached before penetration and turgor. Deletion analysis of ACE1 promoter revealed a 200-bp region required for appressorium specific transcription. Characterization of ACE1 structure in the virulent progeny 2/0/3 revealed an insertion of a new retroposon (MINE) into ACE1 ORF. Most worldwide M grisea isolates were avirulent towards Pi33 and carried the same ACE1 avirulent allele (ACE1-GY11. 1). Isolates virulent towards Pi33 were mostly detected in Asia and South America and classified into three groups according to their ACE1 genotypes. The first group has a virulent allele (ACE1-GY11. 2) that is 99% identical to ACEl-GY11. 1. The second group has a virulent allele (ACE1-CM28) that is 88% identical to ACE1-GY11. 1. The third group has two virulent ACE1 alleles (ACE1-GY11. 1 and ACE1-CM28). These two alleles are localized on different chromosomes, indicating that these normally haploid isolates are partially diploid for ACE1. Typing of isolates from these groups using neutral markers (micro-satellites, SNIPS) revealed that they are genetically related, suggesting that they derive from a single complex event
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Dudek, Débora Nakadomari. „Deleção parcial do fator de transcrição ACE1 para otimização da produção de celulases por trichoderma reesei RUT-C30“. Universidade Estadual do Oeste do Paraná, 2017. http://tede.unioeste.br/handle/tede/2954.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Second generation bioethanol employs lignocellulosic materials in its preparation. One of the steps for these materials degradation utilizes cellulases produced by microorganisms. Among these, Trichoderma reesei fungus is one of the main cellulases producers used in industry. This fungus genetic modification can lead to enzimes production optimization, reducing cost and improving biofuels manufacture. Thus, the present work objective was delete the sequence encoding zinc fingers motifs of cellulase ACE1repressor transcription factor from T. reesei RUT-C30 fungus, seeking enzymatic production optimization. In primers construction for amplification ACE1 regions 5’ and 3' and the hph selection marker, which confers hygromycin B resistance, Joint Genome Institute - JGI site and the BioEdit ® program were used. The deletion cassette with pRS426 vector construction was mediated by Saccharomyces cerevisiae SC9721 yeast. After the cassette construction, T. reesei RUT-C30 transformation was made by protoplast and this transformation confirmation was effected by part of the hph using hphNestF and hphNestR amplification primers. After transformation with mutants obtained, endoglucanase, exoglucanase and total cellulase activity was quantified with carboxymethylcellulose substrates (CMC), microcrystalline cellulose (Avicel®) and Whatman paper filter (PF), respectively. The enzymatic production and biomass hydrolysis efficiency were performed comparing RUT-C30 strain for mutants. After deletion cassette construction, a 3501 bp fragment amplification confirmed the cassette formation. Posteriorly, RUT-C30 strain transformation, a 989 bp amplification was observed, confirming the 3 mutants target sequence deletion. With cellulase activity assay, 3 transformed strain showed higher enzymatic production when compared to RUT-C30 strain. In this comparison, a significant statistical difference was observed of RUT-C30Δace1-1 strain with Avicel® and PF (p <0.001) CMC (p <0.01), RUT-C30Δace1-2 strain with CMC (p<0,01) e PF (p<0,05), and RUT-C30Δace1-3 strain with Avicel (p<0,001), CMC and PF (p<0,01). The mutants also showed greater efficiency in biomass hydrolysis, with release sugar increase between 21 and 42%. Based on this study, mutants are promising for most efficient and viable ethanol production. Nevertheless, additional tests must be carried out to better understand these fungi applicability in the industrial level.
O bioetanol de segunda geração emprega materiais lignocelulósicos na sua elaboração. Uma das etapas para a degradação destes materiais utiliza celulases produzidas por microrganismos. Dentre estes, o fungo Trichoderma reesei é um dos principais produtores de celulases utilizadas na indústria. A modificação genética deste fungo pode levar à otimização da produção de suas enzimas, diminuindo o custo e melhorando a fabricação de biocombustíveis. Desta forma, o objetivo do trabalho foi deletar a região dos motivos dedos de zinco no gene que codifica o fator de transcrição repressor de celulase ACE1 do fungo T. reesei RUT-C30, buscando a otimização na produção enzimática. Na construção dos primers para amplificação das regiões 5’ e 3’ de ace1 e do marcador de seleção hph, que confere resistência à higromicina B, utilizou-se o site Joint Genome Institute – JGI e o programa BioEdit®. A construção do cassete de deleção com o vetor pRS426 foi mediado pela levedura Saccharomyces cerevisiae SC9721. Posteriormente, a construção do cassete, a transformação de T. reesei RUT-C30 foi realizada através de protoplasto e a confirmação desta transformação foi efetuada por amplificação de parte do hph utilizando os primers hphNestF e hphNestR. Após a transformação, com os mutantes obtidos, a atividade de endoglucanase, exoglucanase e celulase total foi quantificada com os substratos carboximetilcelulose (CMC), celulose microcristalina (Avicel®) e papel de filtro Whatman (PF), respectivamente. A produção enzimática e a eficiência na hidrólise da biomassa foram realizadas comparando-se a linhagem RUT-C30 aos mutantes. Após a construção do cassete de deleção, a amplificação de um fragmento de 3501 pb confirmou a formação do cassete. E, posteriormente à transformação da linhagem RUT-C30, o amplificado de 989 pb foi observado, confirmando a deleção da sequência alvo em 3 mutantes. Com o ensaio de atividade de celulases, as 3 linhagens transformadas mostraram maior produção enzimática quando comparadas à linhagem RUT-C30. Nessa comparação, foi observada diferença estatística significativa da linhagem RUT-C30Δace1-1 com Avicel® e PF (p<0,001), da linhagem RUTC30Δace1- 2 com CMC (p<0,01) e PF (p<0,05) e da linhagem RUT-C30Δace1-3 com Avicel (p<0,001), CMC e PF (p<0,01). Os mutantes também apresentaram maior eficiência na hidrólise da biomassa, com aumento na liberação de açúcar entre 21 e 42%. Com base nos dados deste estudo, os mutantes apresentam-se promissores para a produção mais eficiente e viável de etanol. Apesar disso, testes adicionais devem ser realizados para melhor entendimento da aplicabilidade destes fungos a nível industrial.
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Berruyer, Romain Paul Emile. „Etude des interactions riz-Magnaporthe grisea : Caractérisation et clonage du gène de résistance Pi33“. Montpellier, ENSA, 2003. http://www.theses.fr/2003ENSA0003.
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La résistance des plantes aux agents pathogènes suit souvent la théorie gène-pour-gène. Contrairement aux autres gènes d'avirulence, le gène ACE1 de Magnaporthe grisea (responsable de la pyruculariose du riz) code pour une grosse protéine qui n'est pas sécrétée. Au cours de cette thèse, le gène de résistance correspondant à ACE1 a été cartographié sur le bras court du chromosome 8 à l'aide de couples de souches isogéniques. Ce gène de resistance dominant est différent de ceux déjà connus. Il a été nommé Pi33 puis finement cartographié en utilisant une population de 889 lignées et des marqueurs moléculaires. Une cartographie physique a été réalisée sur deux banque BAC, l'une, ordonnée, de la variété Nipponbare (sensible) l'autre, non ordonnée, de la variété IR64 (résistante). L'étude des séquences disponibles dans la zone n'a permis de détecter aucun homologue de gènes de résistance connus. Enfin, le polymorphisme autour de Pi33 et son origine parmi les parents d’IR64 ont été étudiésWe identified the resistance gene corresponding to the avirulence gene ACE1 using pairs of isogenic strains of Magnaporthe grisea differing only by their ACEl allele. This resistance gene was mapped on the rice chromosome 8. Allelism tests permitted us to distinguish this gene from other known resistance genes. This single dominant gene was designated as Pi33. Finally, Pi33 was finely mapped between two molecular markers that are separated by a distance of 1. 6 cM. Using this fine map, we physically mapped Pi33 using the ordered BAC library of the cultivar Nipponbare (susceptible). We then used the markers found during this walk to physically map Pi33 in the IR64 (resistant) unordered BAC library. No resistance gene homologues (RGA) were found in the available sequence data in the area of Pi33. Finally, we studied the polymorphism around Pi33 and the origin of this gene amongst the parents of the IR64 cultivar. Pi33 is probably an ancestral gene that appeared before rice domestication
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Harrison, Jane. „Building mounds : Viking-Late Norse settlement in the North Atlantic, c. AD800-1200“. Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:f5aa50e8-ace0-49fd-9065-c0c94187ffc6.
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The subject of this study is Viking-Late Norse settlement (c. AD800-1200) in the North Atlantic, focusing on Orkney and on longhouse complexes constructed on mounds. For the first time these mound settlements are investigated as a group and as deliberately constructed mounds. Settlement mounds in Orkney are also closely associated with nearly 40 Skaill ON skáli ('hall') place-names, which place-names linked the sites with the social and economic networks of Orkney's peripatetic leaders. This association is examined more closely. The analysis also demonstrates that constructing settlements on mounds required particular building techniques, which relied heavily on the use of midden-type material. Those techniques are examined using new and freshly analysed material from published and grey literature-published excavations and surveys of sites from the Viking-Late Norse period in Orkney and elsewhere. Three core data-sets were established to provide the evidential basis: the first, also drawing on site-visits, looking broadly at mound landscapes and skáli-areas in Orkney; the second at the building techniques and materials used on settlement mounds; and the third, also requiring site-visits, at all the skáli place-name sites. The possible origins of settlement mound living in the settlers' Scandinavian homelands are investigated, then the extent to which mound living was also followed in Shetland, Caithness and the Western Isles, and finally in previously unoccupied lands, using Iceland as a case study. The mound-sites, their archaeology, mound architecture, place-names and landscape setting are also analysed in a new theoretical framework to reach fresh understandings of Viking-Late Norse settlement in Orkney. The analysis thus considers the wider cultural significance of constructing and living on settlement mounds, and what that communicated about Viking-Late Norse society. The thesis argues that Viking-Late Norse groups chose prominently-placed sites for their visual dominance and commanding views, but also that the rebuilding of mound structures in one spot, and building out and up of the mound itself using midden material, set strong cultural messages about stability, continuity and association with the surrounding landscape. The mounds were complex features of culturally meaningful architecture.
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Chilton, Ian James. „Analysis of the sltA (stzA) gene and its orthologues in Aspergillus nidulans and other filamentous fungi“. Thesis, University of Wolverhampton, 2013. http://hdl.handle.net/2436/297439.
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Generation and phenotypic analyses of stzA gene deletion strains of Aspergillus nidulans implies that stzA is allelic to sltA, with the encoded transcription factor regulating tolerance to cations, DNA-damaging agents and high arginine concentrations. The similar severe sensitivity of a sltA1 mutant (GO281) and stzA deletion mutants to these stresses indicated that the premature termination codon in sltA1 represents a total loss-of-function mutation. It was also verified that StzA has no regulatory role in the utilisation of carbon sources. Findings were supported by phenotypic analyses of recombinant progeny resulting from sexual crosses between sltA1 and sltA+ strains. Bioinformatic analysis of genes involved in the osmotic stress response revealed that their promoters were significantly enriched for StzA binding site motifs compared to those of the control group, indicating that StzA may regulate many of these genes that comprise the High Osmolarity Glycerol (HOG) pathway. Although this pathway is activated by fludioxonil, stzA deletants and stzA+ strains showed similar sensitivities to this fungicide. Phenotypic analyses indicate that StzA does not regulate tolerance to sources of oxidative stress, non-ionic osmotic stress or components of the Cell Wall Integrity (CWI) pathway. A. nidulans StzA appears to have no role in cellulase or xylanase expression as revealed by the results of a dinitrosalicylic acid (DNS) assay. Trichoderma reesei ace1 deletant and wild-type strains showed similar sensitivities to cations, DNA-damaging agents, arginine, neomycin, acidic and alkaline pH. These results confirm that A. nidulans StzA and T. reesei Ace1 regulate the distinct phenotypes of abiotic stress tolerance and cellulase and xylanase expression, respectively, despite these two proteins sharing 58% overall amino acid similarity. All twenty-nine StzA orthologues identified are restricted to filamentous ascomycetes of the Pezizomycotina subphylum and may therefore represent specific and novel antifungal drug targets. The C-termini of StzA proteins are highly variable in both length and sequence, with no apparent conservations in amino acids or predicted secondary structure. This region is considered most likely to influence the divergent functions of StzA proteins. Conservations of individual residues in the N-termini correspond to conserved secondary structure (alpha helices) among StzA proteins, implying shared functions for StzA proteins in this region. Regulators of two major nitrogen metabolic pathways (CpcA and AreA) may regulate stzA expression. Statistically significant putative CpcA binding sites were positionally conserved in 26 out of 29 stzA orthologue promoters, indicating an interaction between stzA and CpcA, a transcription factor that mediates the cross pathway control of amino acid biosynthesis. REALALE sequences, likely to be of retrotransposon origin, containing putative overlapping binding sites for StzA and AreA, were found in eleven stzA promoters of the Eurotiomycetes class, indicating an interaction between stzA and the global nitrogen metabolite repressor AreA. Intriguingly, REALALE-containing promoters identified across the genome of A. nidulans were significantly enriched for StzA binding site motifs when compared to a control group of genes. Hence, REALALE may have regulatory significance that extends to other A. nidulans genes.
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Simmons, David Edward. „On the performance of constrained amplify-and-forward networks“. Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:788cdfdd-8a80-4223-ace1-37b6a8095fd7.
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This thesis examines the effects of resource constraints on amplify-and-forward (AF) networks. Chapters 3 and 4 are the first research chapters. Chapter 3 studies the outage probability performance of a two-hop two-way AF peak power constrained orthogonal frequency division multiplexing (OFDM) network. Its performance is then optimized. Chapter 4 focuses on the one-way special case of the system studied in Chapter 3. It begins with an analysis of the network when nonlinear distortion produced by signal clipping dominates the additive noise in the system. To conclude Chapter 4, the theoretical study performed throughout Chapters 3 and 4 is used to optimize the performance of a one-way real world test bed. Chapter 5 studies the n-hop multiple-input multiple-output (MIMO) AF relay network. Novel techniques are developed using random dynamical system (RDS) theory and Lyapunov exponents to establish capacity and power scaling laws for the network as n grows large. One of the main conclusions is that the average transmit power must grow at an exponential rate if capacity decay across the network is to be avoided. Chapter 6 constitutes the final research chapter. In it, the techniques used to study peak-power constrained OFDM-based networks are combined with those developed in Chapter 5, which were used to study capacity and power scaling for multihop AF networks. The conclusion of this is that incorporating OFDM into peak-power constrained multihop AF relay networks will cause the capacity along each of the network's eigenchannels to decay exponentially. Finally, we show that the effects of distortion can be circumvented by ensuring the number of antennas at each node scales at a super-linear rate with the number of hops within the network.
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Chun, Desmond Tan Chia. „Student teachers learning to use 'Assessment for Learning' in schools“. Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:1859713f-79c3-4fe8-ace1-d70fae622bda.
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Assessment for Learning (AfL) has been seen as a key aspect of teaching and learning for almost two decades, since the seminal review by Black and Wiliam (1998a). However, the research has largely been conducted with practising teachers rather than student teachers. This thesis attempts to fill this gap in relation to AfL, and illustrate that understanding how student teachers learn to use conceptual resources, such as AfL, can inform the work of all those who support the learning of teachers in training. The present study investigated how four secondary geography student teachers on a one year post-graduate training programme in England worked with ideas associated with AfL in their teaching during two school placements. The study asked how and why they used AfL or, as became evident, Assessment of Learning (AoL) in their teaching and what their use of AfL might tell us about their learning to teach in schools. The thesis adopted a cultural-historical approach to investigate the actions in activities of the student teachers as they learnt to teach. The four students were followed over two terms in their two placement schools to gather data on their trajectories as learners and beginning teachers. Data collection methods were: (i) semi-structured interviews with the four students; interviews with their teacher mentors and other school staff; and (ii) regular post-lesson interviews with the student teachers, following observations of their teaching. The cultural-historical approach led to examining AfL as a potential tool to be used by the student teachers in their teaching. Engeström's (1990, 1999, 2007) work on tool use and mediating artefacts was deployed to analyse the student teachers' use of AfL and what they saw as its purposes. The attention to purposes of tool use in the study was also informed by Hedegaard's (2012, 2014) work on motives in institutional practices, the activities in the practices and the actions taken by student teachers. This approach pointed to how the institutional motives and demands embedded in school practices influenced their learning. The study also paid attention to the identity work being done by the student teachers. This work was most apparent when the student teachers moved from their first to second placement school and worked with a different set of demands in institutional practices. One early finding was that although school colleagues and student teachers were using the label AfL, closer examination revealed that they were actually using AoL. Key findings from the final analyses were as follows: there was considerable variation in how the geography specialist teacher mentors interpreted and used AfL; some mentors were strongly mediating the AfL/AoL expectations evident in the school inspection system in England; there was evidence of some strong and challenging mentoring, but it was not consistent across the experiences of the students; the students' own sense of the kind of teacher they wanted to become could be tracked in ways which revealed how they coped with the different school demands and what they saw as university expectations; the transition between placement schools was significant for the student teachers in ways that had not been anticipated by the design of the programme. Following the student teachers as learners offered insights into their experiences in the black box of school placements during teacher education. Consequently, the implications for the design of teacher education programmes are a key part of the discussion stimulated by the findings.
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Claiden-Yardley, Kirsten. „Tudor noble commemoration and identity : the Howard family in context, 1485-1572“. Thesis, University of Oxford, 2014. https://ora.ox.ac.uk/objects/uuid:5487809d-9066-4709-ace0-16b5debe825d.
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This thesis examines the relationship between the commemorative strategies of English noblemen in the period 1485-1572 and their identity both as individuals and as a social group. In particular, it will look at the Howard dukes of Norfolk in the context of their peers. The five chapters each address a different aspect of noble identity. The first two chapters deal with the importance of kinship and of status. The importance of kinship is evident across commemorative strategies from burial locations to the heraldry displayed at funerals to the references to ancestry in elegies. Having achieved a particular status, noblemen were defensive of their rank and the dues accorded to it. Funerals were designed to reflect social status and the choice of burial location could also indicate a concern with status. However, there was not always a correlation between the scale of commemoration and status. The third chapter examines the role that service to the Crown played in noble identity. Late medieval ideals of military service and a chivalric culture survived well in to the sixteenth century and traditional commemorative forms remained popular, even amongst noblemen newly ennobled from the ranks of the Tudor administration. Chapter four addresses the importance of local power to the nobility of the period. Burial and commemoration acted as a visible reminder of the social order and were of benefit in maintaining local stability. Noblemen could also use their death as a means of demonstrating good lordship through charity and hospitality. The final chapter examines the importance of religion to a nobleman's identity during a century of turbulent religious change. Studying commemorative strategies allows us to trace noble responses to religious change, the constraints on their public show of belief, and the ways in which they could express individuality.
Bücher zum Thema "ACE100"
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Ace03 Wildcat Pac Doubleday. Osprey, 1997.
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Ace08 Corsair/Ref Doubleday. Osprey, 1997.
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Ace01 Mustang 8th Co-Ed. Osprey, 1997.
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Ace06 Fw190 Russian Front (Coe). Osprey, 1999.
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Ace09 Fw190 Western Front (Coe). Osprey, 1999.
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Ace07 Mustang 9/Ref Doubleday. Osprey, 1997.
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Industry and labor dynamics: The agent-based computational economics approach : proceedings of the Wild@ace2003 workshop, Torino, Italy, 3-4 October 2003. New Jersey: World Scientific, 2004.
Den vollen Inhalt der Quelle findenBuchteile zum Thema "ACE100"
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Sevgen, Selcuk, Eylem Yucel und Sabri Arik. „Cellular Neural Networks Template Training System Using Iterative Annealing Optimization Technique on ACE16k Chip“. In Neural Information Processing, 460–67. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-642-10677-4_52.
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Freiberg, Henning. „Interaktive Computeranimation in Grafik-Design und Kunstpädagogik — Beispiele aus der Lehre an der ACE1 HBK Braunschweig“. In Computer, Software und Vernetzungen für die Lehre, 413–15. Berlin, Heidelberg: Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-84703-5_49.
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„Appendix E Fairchild Specifications for ACE1502“. In Managing Power Electronics, 285–318. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2005. http://dx.doi.org/10.1002/0471776335.app5.
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Lippi, Giuseppe, und Emmanuel J. Favaloro. „Emicizumab (ACE910): Clinical background and laboratory assessment of hemophilia A“. In Advances in Clinical Chemistry, 151–67. Elsevier, 2019. http://dx.doi.org/10.1016/bs.acc.2018.10.003.
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Armstrong, Tyler D., Usa Suwannasual, Conner L. Kennedy, Akshaykumar Thasma, Leah J. Schneider, Danielle Phillippi und Amie K. Lund. „Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice“. In Advances in Alzheimer’s Disease. IOS Press, 2021. http://dx.doi.org/10.3233/aiad210017.
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Background: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer’s disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. Objective: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. Methods: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300 μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. Results: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.
Konferenzberichte zum Thema "ACE100"
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Türkantoz, Halet, Dirk Varnholt und Andreas Tiede. „Monitoring of Emicizumab (ACE910): comparison between clotting and chromogenic assay“. In 49. Hamburger Hämophilie Symposion. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-3400714.
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Carranza, Luis, Francisco Jimenez-Garrido, Gustavo Linan-Cembrano, Elisenda Roca, Servando Espejo Meana und Angel Rodriguez-Vazquez. „ACE16k based stand-alone system for real-time pre-processing tasks“. In Microtechnologies for the New Millennium 2005, herausgegeben von Jose F. Lopez, Francisco V. Fernandez, Jose Maria Lopez-Villegas und Jose M. de la Rosa. SPIE, 2005. http://dx.doi.org/10.1117/12.608220.
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Li, Hao-Kang H., Tai-Sheng E. Wu, Ching-Wen S. Hsiao, Sen-Han S. Yang, Chia-Yun S. Lee, Yan-Liang J. Lin, Zih-Fei Z. Cheng et al. „Abstract 2169: ACE1702: A potent and off-the-shelf oNK cell therapy product“. In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-2169.
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Yang, Zining, Siyu Zhan, Mengshu Hou, Xiaoyang Zeng und Hao Zhu. „Injecting Event Knowledge into Pre-Trained Language Models for Event Extraction“. In 9th International Conference on Natural Language Processing (NLP 2020). AIRCC Publishing Corporation, 2020. http://dx.doi.org/10.5121/csit.2020.101404.
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The recent pre-trained language model has made great success in many NLP tasks. In this paper, we propose an event extraction system based on the novel pre-trained language model BERT to extract both event trigger and argument. As a deep-learningbased method, the size of the training dataset has a crucial impact on performance. To address the lacking training data problem for event extraction, we further train the pretrained language model with a carefully constructed in-domain corpus to inject event knowledge to our event extraction system with minimal efforts. Empirical evaluation on the ACE2005 dataset shows that injecting event knowledge can significantly improve the performance of event extraction.
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Costea, Claudiu Raul, Helga Silaghi, Gabriela Tont und Zoltan Kovendi. „Real Time Determination of Instantaneous Power Flow from Three-phase Electrical Circuits in Nonsymmetric Situations by Using ACE2000“. In 2019 15th International Conference on Engineering of Modern Electric Systems (EMES). IEEE, 2019. http://dx.doi.org/10.1109/emes.2019.8795165.
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Mellenthin, Michelle M., Jennifer L. Mueller, Erick Dario Leon Bueno de Camargo, Fernando Silva de Moura, Sarah J. Hamilton und Raul Gonzalez Lima. „The ACE1 thoracic Electrical Impedance Tomography system for ventilation and perfusion“. In 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2015. http://dx.doi.org/10.1109/embc.2015.7319289.
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Zhu, Xiaoxiang, Mengshu Hou, Xiaoyang Zeng und Hao Zhu. „Cada-Fvae-Gan: Adversarial Training for Few-Shot Event Detection“. In 9th International Conference on Natural Language Processing (NLP 2020). AIRCC Publishing Corporation, 2020. http://dx.doi.org/10.5121/csit.2020.101402.
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Most supervised systems of event detection (ED) task reply heavily on manual annotations and suffer from high-cost human effort when applied to new event types. To tackle this general problem, we turn our attention to few-shot learning (FSL). As a typical solution to FSL, cross-modal feature generation based frameworks achieve promising performance on images classification, which inspires us to advance this approach to ED task. In this work, we propose a model which extracts latent semantic features from event mentions, type structures and type names, then these three modalities are mapped into a shared low-dimension latent space by modality-specific aligned variational autoencoder enhanced by adversarial training. We evaluate the quality of our latent representations by training a CNN classifier to perform ED task. Experiments conducted on ACE2005 dataset show an improvement with 12.67% on F1-score when introducing adversarial training to VAE model, and our method is comparable with existing transfer learning framework for ED.
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Guo, Quan, Hossein Rajaby Faghihi, Yue Zhang, Andrzej Uszok und Parisa Kordjamshidi. „Inference-Masked Loss for Deep Structured Output Learning“. In Twenty-Ninth International Joint Conference on Artificial Intelligence and Seventeenth Pacific Rim International Conference on Artificial Intelligence {IJCAI-PRICAI-20}. California: International Joint Conferences on Artificial Intelligence Organization, 2020. http://dx.doi.org/10.24963/ijcai.2020/382.
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Structured learning algorithms usually involve an inference phase that selects the best global output variables assignments based on the local scores of all possible assignments. We extend deep neural networks with structured learning to combine the power of learning representations and leveraging the use of domain knowledge in the form of output constraints during training. Introducing a non-differentiable inference module to gradient-based training is a critical challenge. Compared to using conventional loss functions that penalize every local error independently, we propose an inference-masked loss that takes into account the effect of inference and does not penalize the local errors that can be corrected by the inference. We empirically show the inference-masked loss combined with the negative log-likelihood loss improves the performance on different tasks, namely entity relation recognition on CoNLL04 and ACE2005 corpora, and spatial role labeling on CLEF 2017 mSpRL dataset. We show the proposed approach helps to achieve better generalizability, particularly in the low-data regime.
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Zhai, Qi, Zhigang Kan, Linhui Feng, Linbo Qiao und Feng Liu. „Glyfn: A Glyph-Aware Fusion Network for Distributed Chinese Event Detection“. In 8th International Conference on Artificial Intelligence and Applications (AIAP 2021). AIRCC Publishing Corporation, 2021. http://dx.doi.org/10.5121/csit.2021.110114.
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Recently, Chinese event detection has attracted more and more attention. As a special kind of hieroglyphics, Chinese glyphs are semantically useful but still unexplored in this task. In this paper, we propose a novel Glyph-Aware Fusion Network, named GlyFN. It introduces the glyphs' information into the pre-trained language model representation. To obtain a better representation, we design a Vector Linear Fusion mechanism to fuse them. Specifically, it first utilizes a max-pooling to capture salient information. Then, we use the linear operation of vectors to retain unique information. Moreover, for large-scale unstructured text, we distribute the data into different clusters parallelly. Finally, we conduct extensive experiments on ACE2005 and large-scale data. Experimental results show that GlyFN obtains increases of 7.48(10.18%) and 6.17(8.7%) in the F1-score for trigger identification and classification over the state-of-the-art methods, respectively. Furthermore, the event detection task for large-scale unstructured text can be efficiently accomplished through distribution.
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MARTINS, Liana Cândido, Carolyne de Castro Barros NOGUEIRA und Manuel Lima SOARES. „UTILIZAÇÃO DOS PARÂMETROS DE ACESSIBILIDADE EM EDIFÍCIOS PÚBLICOS: ESTUDO DE CASO – BIBLIOTECA PÚBLICA GOVERNADOR MENEZES PIMENTEL EM FORTALEZA“. In VI Encontro Nacional de Ergonomia do Ambiente Construído & VII Seminário Brasileiro de Acessibilidade Integral. São Paulo: Editora Edgard Blücher, 2016. http://dx.doi.org/10.5151/despro-eneac2016-ace01-1.
Der volle Inhalt der QuelleBerichte der Organisationen zum Thema "ACE100"
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Musculus, Mark P., und Gurpreet Singh. ACE001: Heavy-Duty Diesel Combustion (Sandia National Laboratories). Office of Scientific and Technical Information (OSTI), Oktober 2018. http://dx.doi.org/10.2172/1637259.
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