2,988 research outputs found
Properties of Laminated Veneer Lumber Manufactured from Acacia Mangium Thinnings and Rubberwood (Hevea Brasiliensis)
This study attempts to assess the properties of
structural laminated veneer lumber (LVL) made from low
grade raw materials and produced on commercial plywood
and LVL lines. Ten-year old Acacia mangium (Mangium)
thinnings and old-growth Hevea brasiliensis (Rubberwood)
were peeled to 3.6 mm thick veneers and processed into
IS-ply LVL. Two different veneer configurations were
used in the LVL fabrication, with melamine urea
formaldehyde (MUF), phenol formaldehyde (PF) and urea
formaldehyde (UF) as binders. The LVL were subsequently
finger-jointed and the bending strength evaluated. The
properties of LVL with different proportions of Mangium
and Rubberwood were also evaluated. Total green veneer
recoveries of about 70% were recorded for both Mangium
and Rubberwood, using a 4-ft Meinan Aristo-lathe. In general, Rubberwood demonstrated good compatibility with
UF resin, whilst MUF performed better than PF
Gamified mathematics practice: Designing with e-commerce and computational concepts.
learning Mathematics: first, students who face difficulty
understanding and are too shy to participate in discussions
and subsequently do not manage to resolve their doubts,
and second, dull e-learning websites. The many rules in
Mathematics compounds the problem further. We thus aim
to address these problems through a gamified-commerce oriented Mathematics learning practice system, Alzebra,
for informal learning. Focusing on principles of
Information Systems Analysis and Design, e-commerceoriented
computational concepts are embedded in the game
to motivate online practice. The system concept, design
methodology and user testing outcomes are presented.
Significance lies in deriving perception towards
gamification and components which users liked or disliked
and the efficacy of our hybrid approach in systems
development
The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation
Biological processes are often regulated by signal transduction pathway via transcription factor through protein-protein interactions (PPIs). Aberrant activation of transcription factor deregulates the cell signaling pathway which contributes to disease progression. Cancer is well characterized as a result of over activation of transcription factor and/or loss of an essential protein-protein interaction. Therefore, transcription factor have become attractive molecular target for drug development. Protein-templated fragment ligations have been established as a powerful method for the assembly and detection of optimized protein ligands. Initially developed for reversible ligations, the method has been expanded to irreversible reactions enabling the formation of super-additive fragment combinations. In this thesis, protein-induced Mannich ligations are introduced and discovered as a biocatalytic reaction furnishing inhibitors of the transcription factor STAT5. STAT5 protein was employed to catalyze multicomponent reactions of a phosphate mimetic, formaldehyde, and 1H-tetrazoles yielding protein ligands with greatly increased binding affinity and ligand efficiency. Reactions are induced under physiological conditions selectively by native STAT5 but not by other proteins. Formation of ligation products and (auto-) inhibition of the reaction are quantified and the mechanism is investigated. Inhibitors assembled by STAT5 were further validated using functional biochemical assay and were proven to block specifically the phosphorylation of this protein in a cellular model of acute myeloid leukemia (AML), DNA-binding of STAT5 dimers, expression of downstream targets of the transcription factor, and the proliferation of cancer cells in mice. In addition, STAT5 inhibitors also exert strong synergistic effect with tyrosine kinase inhibitor, PKC412 in targeting leukemic cells.
Throughout our effort in establishing highly selective STAT5 inhibitor, a first class of inhibitors that assembled through protein induced Mannich ligation reported to date have been successfully identified. STAT5 assembled inhibitors have proven to exhibit favorable potency and selectivity profile against STAT5 and possess the potential to become candidate for combination therapy with tyrosine kinase inhibitor for pre-clinical trials as STAT5 targeted therapeutic. Last but not least, these small molecules STAT5 inhibitors well served as a research tool to study the effect of knocking down of STAT5 function at the protein level on cancer prognosis and progression.Biologische Prozesse werden häufig über Signaltransduktionswege durch Transkriptionsfaktoren gesteuert und werden durch Protein-Protein-Interaktion (PPIs) vermittelt. Die abweichende Aktivierung eines Transkriptionsfaktors verändert den zellulären Signalweg, was zur Entwicklung oder zum Fortschreiten von Krankheiten beitragen kann. Krebs ist gut charakterisiert als das Ergebnis einer Überaktivierung von Transkriptionsfaktoren und/oder des Verlustes von essentiellen Protein-Protein-Interaktionen. Daher sind Transkriptionsfaktoren ein attraktives molekulares Ziel für die Arzneimittelentwicklung. Protein-templierte Fragment-Ligationen wurden als leistungsfähiges Verfahren zur Gewinnung und zur Erkennung von optimierten Protein-Liganden eingeführt. Ursprünglich entwickelt für reversible Ligationen wurde die Methode auf irreversible Reaktionen ausgeweitet und ermöglicht die Bildung von super-additiven Fragmentkombinationen. In dieser Arbeit werden protein-induzierte Mannich-Ligationen als eine biokatalytische Reaktion entdeckt, die Inhibitoren für den Transkriptionsfaktor STAT5 liefern. STAT5-Protein katalysiert Multikomponenten-Reaktionen eines Phosphat-Mimetikums, von Formaldehyd und von 1H-Tetrazolen, die Proteinliganden mit stark erhöhter Bindungsaffinität und Ligandeneffizienz liefern. Reaktionen werden unter physiologischen Bedingungen selektiv durch natives STAT5, aber nicht durch andere Proteine ausgelöst. Die Bildung von Ligationsprodukten und die (Auto-)Inhibition der Reaktion werden gemessen und der Mechanismus wird erforscht. Durch STAT5 gebildeten Inhibitoren werden weiter in funktionellen biochemischen Assays validiert und es wird gezeigt, dass sie spezifisch die Phosphorylierung dieses Proteins in einem zellulären Modell der akuten myeloischen Leukämie (AML), die DNA-Bindung von STAT5-Dimern, die Expression von Zielproteinen des Transkriptionsfaktors und die Proliferation von Krebszellen in Mäusen blockieren. Zusätzlich haben STAT5-Inhibitoren zusammen mit dem Tyrosinkinase-Inhibitor PKC412 eine starke synergistische Wirkung auf Leukämiezellen. Wir haben die erste bisher bekannte Klasse von Inhibitoren identifiziert, die durch eine Protein-induzierte Mannich-Ligation gebildet wurden. Die durch STAT5 entstandenen Inhibitoren zeigen günstige Wirkungen und ein vorteilhaftes Selektivitätsprofil gegenüber STAT5 und besitzen das Potential, Kandidaten für eine Kombinationstherapie mit Tyrosinkinase-Inhibitoren für vorklinische Versuche als gezielte STAT5-Therapien zu werden. Zu guter Letzt dienten diese kleinen STAT5 Inhibitor-Moleküle als geeignete Forschungswerkzeuge, um die Effekte der Ausschaltung von STAT5-Funktionen auf die Prognose und den Verlauf von Krebserkrankungen zu untersuchen
Aryl Phosphoramidates of 5-Phospho Erythronohydroxamic Acid, A New Class of Potent Trypanocidal Compounds
RNAi and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-PGDH) in Trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human African trypanosomiasis. 2,3-O-Isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite Trypanosoma brucei 6-phosphogluconate dehydrogenase (6-PGDH), the third enzyme of the pentose phosphate pathway. However, this compound does not have trypanocidal activity due to its poor membrane permeability. Consequently, we have previously reported a prodrug approach to improve the antiparasitic activity of this inhibitor by converting the phosphate group into a less charged phosphate prodrug. The activity of prodrugs appeared to be dependent on their stability in phosphate buffer. Here we have successfully further extended the development of the aryl phosphoramidate prodrugs of 2,3-O-isopropylidene-4-erythrono hydroxamate by synthesizing a small library of phosphoramidates and evaluating their biological activity and stability in a variety of assays. Some of the compounds showed high trypanocidal activity and good correlation of activity with their stability in fresh mouse blood
Crack analysis using extended finite element method with virtual crack closure technique
Dalam kajian ini, XFEM bersempena dengan VCCT diperkenalkan untuk mengira parameter SERR dan SIF. Dalam kombinasi tersebut, VCCT dinyatakan sebagai kriteria kegagalan untuk mengira SERR di hujung retakan. Selain itu, analisis tiada perambatan retakan dibentangkan di plat retakan pinggir dan plat retakan condong. Sementara itu, analisis perambatan retakan ditunjukkan oleh rasuk dua julur (DCB). Keputusan simulasi dibandingkan dengan keputusan teori di mana ia sebagai rujukan. Dalam analisis penumpuan, analisis jejaring berstruktur menggunakan XFEM-VCCT telah terbukti secara stabil dalam analisis apabila retakan terletak di muka elemen dan juga di pinggir elemen. Dalam analisis retakan pinggir, purata perbezaan diperolehi oleh XFEM-VCCT adalah kira-kira 0.5% manakala ralat purata dikira dengan FEM konvensional adalah lebih daripada 1% berbanding dengan penyelesaian teori.
In this study, XFEM in conjunction with VCCT was utilized to calculate the parameters of SERR and SIF. In the combination, the VCCT was specified as the fracture criterion to calculate the SERR at the crack tip. As case studies, non-crack propagation analysis was presented in edge-crack plate and inclined-crack plate. For crack propagation analysis, the double cantilever beam (DCB) problem was used as case study. The simulation results were compared to the theoretical results as the reference point. In the convergence analysis, the structured mesh analysis using XFEM-VCCT was proven to be stable for analysis when the crack lied on the face of element and also on the edge of element. In the edge-crack analysis, the average error obtained by XFEM-VCCT was approximately 0.5% whereas the average error computed by conventional FEM in conjunction with J-integral was more than 1% compared to theoretical results. Furthermore, in the different inclined-crack angle analysis, the average error produced by XFEM-VCCT was 1.06% and 1.45% for KI and KII, respectively
Effects of face to core particle size ratios on properties of particleboard manufactured from Ethiopian highland bamboo - Yushania alpina.
A study was conducted to evaluate the effects of face to core proportion of particles on the mechanical and physical properties of oriented particleboard produced from Ethiopian highland bamboo (Yushania alpina). Three-layered oriented particleboards were manufactured from 4 face to core particle proportions at 750 kg/m3 target density. Urea formaldehyde resin (10%) was used as a binder. Strength and dimensional stability performances of all boards were assessed based on ISO standards. The results showed that the Modulus of rupture (MOR) and Modulus of elasticity (MOE) increased by 23 to 34 per cent and 9 to 20 per cent respectively, with an increase of fine particles at face layer from 20 per cent to 25 per cent and 30 per cent. A further increase of the ratio beyond 30 percent at face layer could not improve MOR and MOE. Decreasing core layer ratios below 50 per cent resulted in the improvement of internal bond (IB) strength. Higher surface screw withdrawal resistances were obtained for boards made with 25 per cent and 30 per cent fine particles at face layers. On the other hand, edge screw withdrawal resistance showed an increasing trend with increase of IB strength. Increase in fine particles proportion from 20 per cent to 25 per cent and to 30 per cent reduced thickness swelling by 11 and 21 per cent, respectively. However, further increase to 40 per cent increased the thickness swelling significantly. According to the results, bamboo boards made with the ratio efface to core particle being 30:40:30 have highly improved properties than others. Generally, Y. alpina culms are suitable raw material for the production of high performance regular purpose particleboards
FingerReader: A Wearable Device to Explore Printed Text on the Go
Accessing printed text in a mobile context is a major challenge for the blind. A preliminary study with blind people reveals numerous difficulties with existing state-of-the-art technologies including problems with alignment, focus, accuracy, mobility and efficiency. In this paper, we present a finger-worn device, FingerReader, that assists blind users with reading printed text on the go. We introduce a novel computer vision algorithm for local-sequential text scanning that enables reading single lines, blocks of text or skimming the text with complementary, multimodal feedback. This system is implemented in a small finger-worn form factor, that enables a more manageable eyes-free operation with trivial setup. We offer findings from three studies performed to determine the usability of the FingerReader.SUTD-MIT International Design Centr
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