35 research outputs found

    Characterization and application of novel chemical tools to control folding and amyloid formation

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    SSVLaboratory of Molecular Neurobiology and Functional Neuroproteomics, EPFL. - Supervision: Awad Loay. - External Expert : Catherine Servis, PhD Department of Biochemistry, Unil, Lausanne, EPF

    Synthesis of a C-linked disaccharide analogue of the Thomsen Friedenreich (TF)-epitope a-O-conjugated to L-serine and formation of a cluster as potential anticancer vaccine

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    Cell surface glycoproteins and glycolipids are responsible for cellular recognition processes. Vaccination is the procedure whereby the immune system is induced to create antibodies against a foreign molecule involved in disease or viral infection. In many disease states, the oligosaccharide chains presented on cell surface glycoprotein are altered. In some tumors, the glycan chains of glycoproteins are attenuated to only a few sugar residues. In the case of the TF-antigen, the polysaccharide chains have been shortened to a galactose-β-(1–>3)-N-acetyl-galactosamine disaccharide structure α-linked to a serine or threonine. Immunogenicity of this epitope in synthetic vaccines has been demonstrated. However, this disaccharide conjugate is relatively short-lived in the blood stream because of its hydrolysis catalysed by ubiquitous glycosidases in vivo. C-disaccharides are sugar mimetics whose interglycosidic linkage is non-hydrolysable as required for a disaccharide-based vaccine. In the first part of the work, we report the first synthesis of TF-antigen analogues applying the methodology developed by our group for the synthesis of C(1–>3)-disaccharides. Conjugate addition of diethylaluminium iodide (Et2AlI) to isolevoglucosenone leads to an aluminium enolate, which reacts with the sugar derived carbaldehyde, 2,6-anhydro-3,4,5,7-tetrakis-O-[(tert-butyldimethyl)silyl]-D-glycero-L-manno-heptose, to give an aldol. The convergent and stereoselective synthesis of this adduct allows us to obtain C(1–>3)-disaccharides. Reduction of the moiety derived from isolevoglucosenone with lithium borohydride, followed by cleavage of the 1,6-anhydro bridge produces C-disaccharides with D-galacto configuration. Königs-Knorr glycosidation of N-Fmoc-serine tert-butylester, followed by reduction of azide moiety to the corresponding acetamido group allows us to obtain TF-antigen analogues linked either by hydroxymethano (-CH(OH)-) or methano (-CH2-) group. In a second part we report the synthesis of a fully deprotected thio-glycotripeptide based on the TFantigen -C-analogues linked by hydroxymethano - N-acetyl-O-{α-D-glyco}-D-seryl-O-{α-D-glyco}-D-seryl-rac-N-(3-[(acetylthio)amino]propyl)-O-{α-D-glyco}-D-serinamide, which was covalently conjugated to the KLH protein carrier via Michael addition reaction. Biological trials with the TF (analogues)-KLH are in progress. We report also the synthesis of fully deprotected TF-antigen -C-analogues linked by hydroxymethano (-CH(OH) and methano (-CH2-) group. their conformational analysis is currently in progress

    Synthesis of C-linked and glycopeptide towards non-hydrozable T epitopes and artificial Anticancer Vaccines

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    SCGCDIPLOMES; GR - 53 333; ICO; . Consultable sur demande à la Bibliothèque de l'EPFL / Offered in consultation at the EPFL library

    Synthesis of chemical tools to improve water solubility and promote the delivery of salinomycin to cancer cells

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    Chemotherapy and radiation are unable to eliminate all cancer cells, particularly apoptosis-resistant cancer cells, despite their ability to kill cancer cluster cells. Thus, it is important to identify methods that eliminate all cancer cells in order to prevent relapse. Salinomycin has the ability to control and eradicate different types of cancer, including breast cancer; however, its molecular mechanism remains unclear. The main difficulty in testing salinomycin activity and understanding the governing mechanisms is its low solubility in water (17 mg/l), which can hinder convenient delivery of salinomycin to the protein receptor at the cell surface of stem cells. In the present study, salinomycin was conjugated to the trans-activator of transcription-protein in order to facilitate its delivery to the cancer cells. Conjugated salinomycin demonstrated improved solubility in both in vitro. Salinomycin was tested in breast cancer cells (MCF7 and JIMT-1) by the cleavage of the linker through photolysis at l >= 365 nm during in vitro analysis, in the present study.LMN

    The game changer. Hur AI förändrar undervisning i biologi.

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    Sammanfattning Syftet med detta arbete har varit att analysera hur implementering av AI i gymnasieskolan har påverkat biologiundervisningen utifrån lärarens samt elevens perspektiv. Studien har undersökt hur AI:s ökade närvaro i undervisningen påverkar elevers lärandeförmåga samt på vilket sätt AI kan assistera läraren i biologiundervisningen. Relevant litteratur har samlats in från olika sökmotorer och databaser utifrån blocksökningar samt osystematiska sökningar. Litteraturen som användes i arbetet har varit kopplat till biologiundervisningen men även berört andra naturvetenskapliga ämnen till följd av brist på forskning. De senare har sedan härletts till specifikt biologiundervisningen. Inledningsvis presenteras en definition av AI samt dess historiska bakgrund. Därefter presenteras den svenska skolan strategi för att implementera digitala verktyg i undervisningen utifrån gymnasieskolans styrdokument. I resultatet presenteras olika AI-redskap som kan påverka både lärare och elever positivt. Utifrån lärarens perspektiv presenteras litteratur som visar på hur AI kan fungera som ett effektiviserande redskap och kan avlasta lärare från vissa arbetsuppgifter. AI kan även individanpassa undervisningen för varje elev. Dock presenteras även risker med användandet av AI som exempelvis mer belastningen för läraren beroende på implementering samt hämmande av elevernas kreativitet och ökad risk för fusk. I slutsatsen görs flera kopplingar till biologiundervisningen. Det poängteras även att AI med största sannolikhet kommer att finnas kvar inom biologiundervisningen i framtiden och utvecklas ytterligare. Den viktigaste aspekten för en lyckad implementering av AI i undervisningen är att lärare har rätt och tillräcklig kompetens om AI samt har rätt inställning och ett intresse för det. Slutligen poängterar studien att vidare forskning inom området biologi och AI i undervisning behöver utföras för att öka kunskapen om ämnet.The purpose of this work has been to analyze how the implementation of AI in high school has affected biology education from the perspectives of both teachers and students. The study has examined how the increased presence of AI in education affects students' learning ability and how AI can assist the teacher in biology education. Relevant literature has been gathered from various search engines and databases through both block searches and unsystematic searches. The literature used in the work has been related to biology education but has also touched on other natural science subjects due to a lack of research. The latter has then been extrapolated to specifically focus on biology education. Initially, a definition of AI and its historical background is presented. Then, the Swedish school's strategy for implementing digital tools in education is presented based on the high school's official documents. The results present various AI tools that can positively impact both teachers and students. From the teacher's perspective, literature is presented that shows how AI can function as an efficiency tool and can relieve teachers from certain tasks. AI can also personalize education for each student. However, risks of using AI are also presented, such as increased workload for the teacher depending on the implementation and inhibiting students' creativity, as well as an increased risk of cheating. In the conclusion, several connections to biology education are made. It is emphasized that AI is likely to remain in biology education in the future and continue to evolve. The most important aspect for a successful implementation of AI in education is that teachers have the right and sufficient competence in AI and have the right attitude and interest in it. Finally, the study emphasizes the need for further research in the field of biology and AI in education to increase knowledge on the subject. And one last thing. This text has been translated with chatGPT

    Evaluating economic and environmental aspects of using solar panels on multi-angled facades of office buildings

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    This paper is concerned with using solar panels as high-tech cladding materials on multi-angled facades for office buildings. The energy produced by the solar panels will be consumed inside the office rooms by cooling compressors, ventilation, lighting and office equipment. Each multi-angled facade unit is directed into two different orientations on a vertical axis (right and left), but not tilted up and down. The different facade orientations will optimize the use of solar radiation to produce the needed energy from the solar panels when placing them on the parapets of these facades. In this regard, four scenarios with different facade configurations and orientations are evaluated and discussed. The method for the simulations and calculations depends on two main programs: first, IDA ICE program to calculate the energy consumption and evaluate the indoor climate of the building; and second, PVBAT to calculate the cost of the electricity produced by the solar panels and evaluate the total amount of energy produced from these panels along with the ratio to the energy bought directly from the electricity grid. There is also an environmental evaluation for the system by calculating the CO2 emissions in the different scenarios

    THMs Precursor Removal Efficiency from Different Wastewater Treatment Technologies Effluents

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    Treated wastewater is one of the critical practices of sustainable water management. In Palestinian authority region different wastewater technologies are used to produce variety of effluents that are potentially suitable for different purposes. In this study, these different treated wastewater effluents were characterized chemically, biologically, and physically. Results showed that some of these effluents neither comply with Palestinian nor with other global effluent discharge guidelines. Chemical reactivity of five different treated wastewater effluents with chlorine was measured by determining their chlorine demand and total trihalomethane formation potential (TTHMFP). Results showed that different wastewater effluents chemical reactivity with chlorine and TTHMFP is not only dependent on wastewater treatment technology but also is affected by original water source from which was the water emerged. In all cases, measured THMs superseded acceptable drinking water limits. This would indicate responsibility of high percentage of cancer, hepatic and renal diseases among the local people.Authors will like to thanks Al-Quds University for helping in implementation this work
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