cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
title: Circumventing Imatinib Resistance in Chronic Myeloid Leukemia: Novel Telmisartan-based Chemosensitizers with Improved Efficacyand Stability
Creators: name: Gebhart, Maximilian
name: Alilou, Mostafa
name: Gust, Ronald
name: Salcher, Stefan
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the mutation and proliferation of a monoclonal multipotent hematopoietic progenitor cell. Following gene products show a dysregulated tyrosine kinase activity resulting in enhanced proliferation and resistance to apoptosis of CML. Nowadays, targeted therapy of CML with tyrosine kinase inhibitors (TKIs) is available. However, the inability to attain a complete molecular response in most patients due to TKI-resistant cancer cells, has necessitated the exploration of new therapeutic methods to effectively combat these resistances. Previous studies performed by our group indicated that TKI-resistant cells can be efficiently targeted by a combination therapy of Imatinib and derivatives of the angiotensin 2 antagonist Telmisartan. In the present investigation, we continued designing chemosensitizers based on Telmisartan with the intention to improve their efficacy and particularly their stability while maintaining their selectivity. To evaluate the activity and selectivity of our developed compounds we performed a modified MTT assay with wild type K562 CML cells and their respective Imatinib resistant subclone K562-R. With the new compounds, we could increase the cytotoxic activity of Imatinib on resistant CML cells from 10% to >90%. In addition, the compounds were per se non-cytotoxic. The stability of the ester derivatives was investigated in the presence of porcine liver esterase using a validated HPLC method. Crucially, the designed ester derivatives demonstrated markedly enhanced stability against esterase cleavage. These advancements are a significant step towards future in vivo studies, as they promise to enhance the bioavailability and the therapeutic efficacy of these compounds.
title: 02_1291
Creators: name: Wesley Baldwin, John
name: Baldwin, John W.
Publisher: name: NAKALA - https://nakala.fr (Huma-Num - CNRS)
publisherIdentifier: https://ror.org/04ces3204
publisherIdentifierScheme: ROR
Year: 2018
Subjects: subject: LaMOP
subject: Laboratoire de Médiévistique Occidentale de Paris

description: L'ensemble de ces notes ont été crée par John Baldwin lors d'une de ses premières périodes de résidence à Paris. Ces documents comprennent tous les magistri qu’il avait pu rencontrer dans ses sources. Aux XIIème et XIIIème siècles, les universités n'existant pas encore, le titre de magister s'il évoque certainement une compétence n'est pas rattaché de façon systématique au passage par les écoles. De surcroît, les magistris sont le plus souvent désignés par leur seul prénom. La lecture de ces données est donc difficile et suppose un long travail pour tenter d'identifier un individu auquel on pourrait rattacher plusieurs mentions. John Baldwin avait donc renoncé à utiliser ces données pour donner un prolongement à sa magnifique étude sur les gradués d'université et leur emploi par les Capétiens et les Plantagenêts. Néanmoins, il a conservé ces données et elles sont potentiellement très utile dans le cadre de Studium, comme le sont toutes les mentions dans les volumes des Fasti Ecclesiae Gallicanae de chanoines portant ce titre de magister sans autres précisions. L'ampleur des dépouillements rend ces données très utiles et nous devons une grande reconnaissance à John Baldwin pour avoir pris la peine de faire photocopier ses fiches et de nous les avoir transmises amicalement.
Les données ainsi que les images des fiches sont accessibles sur le site Internet à l'adresse suivante : http://studium-baldwin.lamop.fr/.
Les transcriptions des fiches ont été effectuées par des étudiants de Paris 1 Panthéon - Sorbonne mais elles n'ont pas été corrigées par la suite.
description: Relation: https://lamop.hypotheses.org/
Information and energy.pdf
Creators: name: Ising, Hartmut
Publisher: name: figshare
Year: 2018
Subjects: subject: Computer Engineering
subject: 20504 Photonics, Optoelectronics and Optical Communications
subject: FOS: Physical sciences
subject: 29999 Physical Sciences not elsewhere classified
subject: Astrophysics
subject: 89999 Information and Computing Sciences not elsewhere classified
subject: FOS: Computer and information sciences

description:
Information and Energy By Hartmut Ising A photon in a double slit experiment is carrying 1 bit of information. This was demonstrated in a gedankenexperiment by Brukner and Zeilinger. Here it is shown in a modified gedankenexperiment that Planck’s formula for the photon energy can be interpreted as the energy which is equivalent to the flux of information 1 bit/Δt and that Δt is equal to the photon’s period: E = h ν = h (1 bit) c/λ. This result is valid for an isolated photon. Based upon this result an information-energy-hypothesis is introduced for complex information. Experimental tests of the hypothetical equivalence between energy and information flux are suggested. Experimentalists with the necessary equipment are encouraged to perform such experiments as here described. This empirical approach is considered necessary as a first step on the way which could lead – if confirmed – to a quantitative theory of information physics and to experimental evidence of dark energy.
A non-viscous-featured fractograph in metallic glasses
Creators: name: G. N. Yang
name: Y. Shao
name: K. F. Yao
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biophysics
subject: Space Science
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: 111714 Mental Health
subject: FOS: Health sciences

description: A fractograph of non-viscous feature but pure shear-offsets was found in three-point bending samples of a ductile Pd–Cu–Si metallic glass. A sustainable shear band multiplication with large plasticity during notch propagation was observed. Such non-viscous-featured fractograph was formed by a crack propagation manner of continual multiple shear bands formation in front of the crack-tip, instead of the conventional rapid fracture along shear bands. With a 2D model of crack propagation by multiple shear bands, we showed that such fracture process was achieved by a faster stress relaxation than shear-softening effect in the sample. This study confirmed that the viscous fracture along shear bands could be not a necessary process in ductile metallic glasses fracture, and could provide new ways to understand the plasticity in the shear-softened metallic glasses.
European Refugee Crisis - The EU Perspective
Creators: name: Phillip Dennis BA (Hons)
Publisher: name: figshare
Year: 2016
Subjects: subject: 160499 Human Geography not elsewhere classified
subject: FOS: Social and economic geography

description: This article outlines the EU practical priorities for immediate application in an effort to tackle the dilemma between the humanitarian determinates to help refugees, against concern over the practicalities of mass immigration. It highlights the issues raised by the EU in September 2015, and explains the EU funding mechanisms allocated to assistance the relevant appointed agencies for border control, process, and security.
title: Dynamics-based assessment of subtle changes in GPCR ligand recognition and function
Creators: name: Wunsch, Friederike
name: Puls, Kristina
name: Wolber, Gerhard
name: Bermudez, Marcel
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: G protein-coupled receptors (GPCRs) regulate a myriad of physiological processes in the human body, but their complex mechanisms still need to be fully understood. To analyze the dynamic behavior of GPCR-ligand complexes, we use a fully automated combination of MD simulations and 3D pharmacophores (dynophores), which enables the analysis of receptor-ligand interactions throughout a MD simulation in a spatiotemporal manner. Here, we present three applications of the dynophore approach, in which subtle differences in ligand recognition and resulting functional effects could be unveiled. In our first application, we focused on subtype-specific binding site characteristics of the sphingosine-1-phosphate receptor family. We analyzed differences in binding mode dynamics to rationally explain the selectivity profile of marketed drugs including Siponimod, and Ozanimod. In a second application, we provide mechanistic insight into peptide binding to the atypical chemokine receptor 3 (ACKR3). The reported opioid scavenging function renders ACKR3 a potential analgesic target without typical opioid-related side effects. The third application focuses on the possibility of binding mode ensembles as a potential mechanism for partial receptor activation of muscarinic receptors. The dynamic interaction patterns can be correlated with the agonistic efficiency, contributing to the mechanistic understanding of partial agonism. The diversity of the three applications concerning receptor family, ligand type, and studied function demonstrates the broad applicability of the dynophore approach to elucidate complex mechanisms in GPCR functionality.
title: Le Haouz. Zones irrigables
title: Le Haouz. Zones irrigables
Creators: name: :Unkn
Publisher: name: NAKALA - https://nakala.fr (Huma-Num - CNRS)
publisherIdentifier: https://ror.org/04ces3204
publisherIdentifierScheme: ROR
Year: 2023
Subjects: subject: Irrigation

description: Cartographie
description: BESM-carto_1955-64-p602_64-06
description: 602
description: 64
description: Bulletin économique et social du Maroc
description: Source: Maison méditerranéenne des sciences de l'homme, Cité numérique de la Méditerranée (Cinumed), Bibliothèque nationale du Royaume du Maroc (BNRM)
description: Source: Bulletin économique et social du Maroc
description: Source: Bulletin économique et social du Maroc (BESM) > BESM (Cartographie)
description: Relation: https://cinumed.mmsh.univ-aix.fr/idurl/1/81793
description: Coverage: Maroc
description: Coverage: Haouz de Marrakech
description: Coverage: XXe siècle
description: Temporal: XXe siècle
description: Bibliographic citation: « Le Haouz. Zones irrigables », In Bulletin économique et social du Maroc (BESM), n° 64, 1955
description: Provenance: Maison méditerranéenne des sciences de l'homme, Cité numérique de la Méditerranée (Cinumed), Bibliothèque nationale du Royaume du Maroc (BNRM)
description: Provenance: https://cinumed.mmsh.univ-aix.fr/
Sungai Melaka sebagai satu daya tarikan pelancongan baru di Negeri Melaka: Satu ulasan kritis
Creators: name: Hua, Ang Kean
Publisher: name: figshare
Year: 2016
Subjects: subject: Geography
subject: 140216 Tourism Economics
subject: FOS: Economics and business
subject: 50205 Environmental Management
subject: FOS: Earth and related environmental sciences
subject: 50206 Environmental Monitoring
subject: 50209 Natural Resource Management
subject: 50202 Conservation and Biodiversity
subject: FOS: Biological sciences

description: Sektor pelancongan banyak menyumbang kepada pendapatan negara. Kerajaan mempromosikan pelbagai tema dan program bagi menarik perhatian para pelacong. Kesannya, jumlah ketibaan pelancong ke Malaysia meningkat dari setahun ke setahun. Artikel ini mengulas Sungai Melaka sebagai daya tarikan pelancongan. Negeri Melaka merupakan destinasi pelancongan yang bertemakan sejarah namun kini digandingkan dengan pelancongan alamsekitar yang berfokus kepada Sungai Melaka. Fungsi utama Sungai Melaka yang asal adalah sebagai sumber air,makanan, pertanian, penternakan, pengangkutan, dan pekerjaan. Kini kerajaan negeri membangunkan semulaSungai Melaka menjadi seperti ‘Venice of the East’, iaitu sebagai salah satu program pelancongannya. Pembangunan semula secara fizikal telah menjadikan Sungai Melaka lebih menarik. Perubahan fizikal ini juga telah menyebabkan fungsi asal Sungai Melaka berubah. Pembangunan ekonomi moden dan pembandaran di sekitarnya juga telah meningkatkan tahap hubungan manusia-sungai. Pada masa yang sama kelebaran dan kedalaman sungai turut meningkat. Pencemaran sungai juga mula berlaku. Oleh itu, pembangunan, perancangan, dan pengurusan harus dilakukan oleh semua pihak termasuk kerajaan, swasta, penduduk tempatan, dan masyarakat bagi mengekalkankebersihan Sungai Melaka.
title: Deciphering and Predicting the Drug-Bile-Mucus Interplay
Creators: name: Scheller, Lena
name: Hanio, Simon
name: Kehrein, Josef
name: Meinel, Lorenz
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Bile colloids and mucus influence the intestinal absorption of orally administered drugs, but this cannot not yet be predicted well. Bile primarily consists of bile acids, such as Taurocholate, and Lecithin. Taurocholate and Lecithin readily form mixed micelles, within drugs are solubilized and shuttled from the intestinal lumen through the mucus layer to the epithelial surfaces. The mucus layer is formed by the negatively charged glycoprotein Mucin II (MUC2) which consequently plays an important role in its natural barrier function. Numerous studies detail the interaction of molecules with mucus or bile but surprisingly little is known about the interaction of the three components and how knowledge of their interplay could serve as foundation to predict biopharmaceutical characteristics for drug substances. To confirm interaction of drugs with mucus and bile, 1H DOSY NMR and permeation experiments were performed. They demonstrated changes in diffusion kinetics of bile interacting and non-interacting compounds within mucus. 19F-NMR and flux studies using mucus and commercial intestinal porcine MUC2 demonstrated MUC2s capability to depict drug-mucus interaction. Subsequently, 131 drugs were categorized as MUC2 and bile interacting or non-interacting based on 1H NMR signal pattern changes using intestinal porcine MUC2 and simulating intestinal fluids. Their MUC2 interaction profile was further evaluated by HPLC employing a MUC2 based stationary phase. Signal pattern changes were extracted using indirect hard modelling and further correlated with quantitative structure-property relationship (QSPR) models yielding good predictive performance based on a clustering approach. These findings could potentially facilitate pre-screening processes of new drugs substances for their mucus and bile interacting profile and further leverage their rational formulation outcomes.
title: Bio-SAXS of single-stranded DNA-binding proteins: radiation protection by the compatible solute ectoine
Creators: name: Hallier, Dorothea
name: Smales, Glen
name: Seitz, Harald
name: Hahn, Marc
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Biological small-angle X-ray scattering (bio-SAXS) is a versatile experimental technique to obtain structural information of biomolecules in solution. An inherent problem for bio-SAXS is radiation-induced damage to the analyte. Therefore, radiation damage is often the main limiting factor when it comes to maximum exposure time. In this study, a new approach to extend the possible X-ray exposure time of the model protein Gene-V Protein (G5P) was investigated. For this purpose, the scavenger and compatible solute ectoine was utilized during bio-SAXS measurements of the DNA-binding protein. Ectoine was used to protect the G5P protein from radicals generated during radiation exposure and therefore allowing a longer radiation time. The radiation-induced changes in G5P were monitored during the bio-SAXS measurements and the resulting energy-damage relation was determined from microdosimetric calculations using Monte Carlo-based particle scattering simulations. In the presence of ectoine, a threefold increase in energy deposition was required to achieve the same damage level as in pure G5P solutions. This indicates that ectoine increases the potential exposure time by interacting with reactive species in aqueous solution before radiation damage to G5P is observed. In addition, the dominant mode of damage shifted from G5P aggregation in absence of ectoine towards G5P fragmentation for solutions containing ectoine as a cosolute. This could be related to the preferential exclusion of the cosolute from the protein surface. Therefore, it was shown that ectoine offers a possibility to improve the structure determination of proteins via bio-SAXS in future studies and thus can be used as a radiation protection of DNA-binding proteins.
Building a European Media Data Space - Media Data Space Workshop -31st of January 2022
Creators: name: Rabbachin, Alberto
name: Bajart, Anne
Publisher: name: Zenodo
Year: 2022
Subjects: dataspace
media
european
communication

description: On the 31st of January 2022, the Consortium held a Open Stakeholder workshop dedicated to the media sector. Hereby we share the output from the intervention made by the European Commission representatives, specifically form the DG CONNECT. The two speakers addressed the current issues that the industry is facing in light of modern information and social technologies.
title: Design and synthesis of isoform selective c-Jun N-terminal kinase (JNK) inhibitors
Creators: name: Wydra, Valentin
name: Selig, Roland
name: Albrecht, Wolfgang
name: Laufer, Stefan
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: The JNK subfamily of mitogen activated protein kinases (MAPKs) consists of three isoforms and a total of 10 splice variants with highly conserved ATP-binding pockets and great structural similarity towards other MAPKs. A multitude of in vivo mouse studies and siRNA approaches indicate different and sometimes even opposing roles of the individual isoforms in the development and progression of various diseases, such as neurodegenerative disease, inflammatory diseases and cancer. Accordingly, even though the high isoform similarity creates a major challenge, it has been of great interest to both academia and industry in recent years to develop isoform selective small molecule inhibitors for potential clinical use (e.g. CC-90001/ NCT05625412) as well as high quality chemical probes for research purposes. Our research is based on a known class of JNK-inhibitors that showed insufficient selectivity towards the single isoforms. Employing a classical structure based medicinal chemistry approach we were able to further develop this scaffold via iterative optimisation. The resulting large set of designed inhibitors was screened towards JNK 1, 2 and 3 selectivity and the most selective compounds were further tested for their ADME properties. With remarkable isoform selectivity, high metabolic stability in mouse liver microsomes as well as promising pharmacokinetic properties, inhibitors were found which can serve as a toolbox for the further development of JNK inhibitors in vitro and in vivo.
title: Learning to 'belong'
title: an ethnography of urban Aboriginal schooling
titleType: Subtitle
Creators: name: Hudspith, Sandra
Publisher: name: Charles Darwin University
Year: 1996

description: This is a study of urban Aboriginal students' failure in mainstream schooling, a failure evident in their generally low academic achievements, high rates of absenteeism, and behavioural difficulties. It is argued that problems arise from social and cultural misunderstandings between Aboriginal students and their teachers. These students' successes or failures are theorised in terms of a Durkheimian sense of 'belonging' or 'community'; the major question to be answered by the research is 'How might the collective representations of urban Aboriginal students and those of their teachers be reconciled?'. The particular interests of the study prescribed an ethnographic investigation of urban Aboriginal homes and of classrooms where teachers and Aboriginal children attempt to work together. The major part of the research was conducted during a year of field-work in five classrooms (three mainstream and two Aboriginal classes) which were situated in two schools in Darwin. Participant observation was supplemented with analysis of audio- and video-recordings, with the study of documentary and archival material, and with interviews with teachers and Aboriginal students and parents. A pedagogic model, derived from Bernstein's (1975), Bain's (1979, 1992), and Gibson's (1984) structuralist theories, guided the qualitative analysis. The five pedagogies in this study differentially structured children's experience as 'pupils', as Aborigines, and as members of a small social group. They created different kinds of pedagogic 'communities' ('ascribed', neo-tribal, 'organic') for Aboriginal students, and each tended towards one of three ideal types (respectively traditional-authoritarian, personalised-therapeutic, mediated). The mediated praxis of one teacher created an 'organic' pedagogic community which accommodated the social and cultural interests of Aboriginal students and committed them to the instructional and disciplinary imperatives of the school. Qualitative and quantitative data indicated improvements in the pedagogic outcomes of Aboriginal students in this classroom; it will be argued that these were an effect of an exemplary urban Aboriginal pedagogy.
GÉANT Compendium of NRENs Website launch!
Creators: name: Ross, Jennifer
Publisher: name: Zenodo
Year: 2024
Subjects: Compendium
NRENs
GÉANT
website

description: This presentation was delivered at the meeting of the Special Interest Group on Marketing and Communications held in Ljubljana, Slovenia on March 5-6, 2024 hosted by Arnes.

Launch of the new GÉANT Compendium website.
Cuatro métodos para la estimación de la densidad de población humana para el estado Zulia, República Bolivariana de Venezuela
Creators: name: Ferrer-Paris, José R.
Publisher: name: figshare
Year: 2016
Subjects: subject: Geography
subject: 160499 Human Geography not elsewhere classified
subject: FOS: Social and economic geography
subject: 10401 Applied Statistics
subject: FOS: Mathematics
subject: 90903 Geospatial Information Systems
subject: FOS: Environmental engineering
subject: 160399 Demography not elsewhere classified
subject: FOS: Sociology

description: La densidad poblacional o población relativa es una medida del número de habitantes por unidad de área y es un dato útil para la planificación y gestión de recursos, planes de inversión, conservación y manejo de recursos naturales, salud pública, educación, etc.

Este documento considera cuatro métodos que combinan información de censos, uso de la tierra y herramientas de estadística espacial para la estimación de la densidad poblacional (número de habitantes por km2). A manera de ejemplo se aplican estos métodos en el estado Zulia de la República Bolivariana de Venezuela.
The Extraction of Democracy-TRANSNATIONAL INTRUSION AND DEMOCRATIC PERFORMANCE IN COLOMBIA.pdf
Creators: name: Barrera, Santiago Bautista
Publisher: name: figshare
Year: 2016
Subjects: subject: Economics
subject: Sociology
subject: FOS: Sociology
subject: 160699 Political Science not elsewhere classified
subject: FOS: Political science
subject: 160603 Comparative Government and Politics
subject: 160607 International Relations
subject: 160510 Public Policy
subject: 160599 Policy and Administration not elsewhere classified
subject: 140203 Economic History
subject: FOS: Economics and business
subject: History

description: The quality of Democracy on the external measurement tool known as the Democracy Barometer leaves the scores of nation-states to the underpinnings of their own institutions. However, as the world becomes smaller and capital intrudes into every corner of the globe; it implicitly affects the quality of democracy through indicators. Furthermore, extractive industries are targeting war-torn environments challenging business perception that political stability equates profitability. The indicators chosen were based on some of the highest and lowest scores ranked by Colombia as a participant. The correlation was qualitatively attempted by collecting secondary data coupling it with the existing measurements, and inferring the whys of independent scores.
title: Design spaces of Lipid Nanoparticles for effective mRNA therapy
Creators: name: Meiners, Kirstin
name: Sperber, Benedikt
name: Gutmann, Marcus
name: Meinel, Lorenz
name: Lühmann, Tessa
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Lipid Nanoparticles (LNP) are versatile carriers for biomolecules, with a promising focus on the delivery of mRNA for treating and preventing infections. Achieving efficient, safe and tissue-dependent LNP delivery involves the incorporation of specific lipids or the precise adjustment of the LNP’s physicochemical properties, such as size, morphology and zeta potential. The development of novel targeting LNP platforms introduces formulation challenges, as variations in the lipid composition or microfluidic production parameters can significantly impact critical quality attributes (CQA) such as encapsulation efficiency, size or polydispersity index. In response to this challenge, we implemented a Design of Experiment (DoE) to efficiently screen critical process parameters (CPP) during the LNP microfluidic production of two model formulations: Comirnaty™ and Spikevax™. The obtained LNP formulations were investigated for in vitro cell transfection efficiency across various cell lines, facilitating the identification of optimal design space. The resulting correlation of CPPs and CQAs of the LNPs together with the cell transfection knowledge can be used to produce tuneable LNPs with predictable properties, while ensure reproducibility and consistent quality during the production process. Further work will use this acquired knowledge as a foundation for the development of an automated and self-learning Microfluidic system, empowering high-throughput screening of novel lipids, enhancing the versatility and adaptability of the LNP systems.
An electrochemical sensor based on TiO2/activated carbon nanocomposite modified screen printed electrode and its performance for phenolic compounds detection in water samples
Creators: name: Hayat, Akhtar
name: Rhouati, Amina
name: Rupesh K. Mishra
name: Alonso, Gustavo A.
name: Nasir, Muhammad
name: Istamboulie, Georges
name: Marty, Jean Louis
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Space Science
subject: Medicine
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Sociology
subject: FOS: Sociology
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Inorganic Chemistry
subject: Science Policy

description: Herein, we reported a titanium oxide (TiO2) modified activated carbon nanocomposite that showed advantageous characteristics in terms of electro-conductivity, catalytic activity and surface area. The designed nanocomposite was employed to modify the screen printed carbon electrode transducer surface in the construction of an electrochemical sensor. The electrode surface modification was characterised by cyclic voltammetry and impedimetric studies. The modified transducer surface was subsequently used for the detection of four phenolic endocrine disruptors, p-nitrophenol, hydroquinone, catechol and 1-naphtol. Under optimal conditions, TiO2 modified activated carbon sensor was evaluated by differential pulse voltammetry showing a good linearity with correlation coefficients higher than 0.99. It showed, in parallel, a high sensitivity where the detection limits were 348 ng/L, 110.1 ng/L, 3.3 ng/L and 7.2 µg/L for the respective studied compounds (S/N = 3). Finally, we validated the method with river water samples, and good recovery values were obtained showing the potential application of the reported biosensor.
title: Design and Characterization of Imidazole-Based Mutant-Selective ATP-Allosteric Bivalent EGFR Inhibitors
Creators: name: Wittlinger, Florian
name: Ogboo, Blessing
name: Shevchenko, Ekaterina
name: Poso, Antti
name: Laufer, Stefan
name: Heppner, David
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: The epidermal growth factor receptor (EGFR) plays a critical role in the carcinogenesis of non-small cell lung cancer (NSCLC) and investigations for targeted small-molecule kinase inhibitors has led to the discovery of several ATP-competitive inhibitor generations and the approval of front-line drug osimertinib. However, the emergence of the highly prevalent C797S mutation within the kinase domain confers resistance to osimertinib and results in cancer recurrence. Recently, EGFR allosteric inhibitors have been developed to overcome drug-resistance mutations, which bind adjacent to the ATP-binding site and dual targeting of both sites exhibits cooperative binding with synergistic effects in certain inhibitor combinations. Here, we report the design and biological evaluation of ATP-allosteric bivalent inhibitors (AABI) that occupy both pockets simultaneously by fusing allosteric inhibitors with an orthosteric binding trisubstituted imidazole scaffold. We elucidate binding properties of differently linked motifs by crystallographic characterization and demonstrate how these molecules can display picomolar enzymatic activity against the L858R/T790M/C797S osimertinib resistance mutation. Structure activity relationships (SAR) generated in this study, define functionalities within the allosteric pocket responsible for potency and mutant-selectivity and covalently binding examples of AABIs exhibit antiproliferative effects in a variety of NSCLC related cancer cells.
A comparative study of the conducting tissue of evergreen and deciduous trees of the Northern Territory
Creators: name: Hornby, San Kham
Publisher: name: Charles Darwin University
Year: 2006

description: The climate of the top end of the Northern Territory is dominated by alternating wet and dry seasons. Trees of the Northern Territory have developed a variety of responses to this seasonal climate, including a range of leaf phenologies (evergreen, semi-deciduous, brevi-deciduous and deciduous). These phenological groups differ in their anatomical and physiological characteristics. This study investigated the relationship between vessel anatomy and susceptibility to drought induced xylem cavitations. Xylem vessel characteristics were compared among deciduous and evergreen species growing in seasonally dry forests near Darwin. Vessel diameter, vessel length, vessel element length, vessel density and pit membrane pore dimeters were measured in six evergreen and six deciduous species and one coniferous species. This study also examined the linkage between hydraulic conductance, vulnerability to xylem embolism and vessel diameter in deciduous and evergreen species. Deciduous species had a greater proportion of vessels with large diameters than did evergreen species. The mean vessel diameters in (branches, petioles and mid-ribs) were larger in deciduous species (50 μm ±1.7, 28 μm ± 1.56, 28 μm ± 2.1) than evergreen species (32 μm ± 0.6, 18 μm ± 1.2, 18 μm ± 1.1). The mean pit membrane pores diameter in deciduous species (0.49 μm± 0.34) was larger than in evergreen species (0.24.μm ± 0.15). The average hydraulic conductivity in branch of deciduous species (0.03 g m s-1 MPa-1) was larger than in evergreen species (0.01 g m s-1 MPa-1). These results support the conclusion that since deciduous species only have to conduct water during the wet season, their large xylem vessels with large pit membrane pores, which confer relatively larger hydraulic conductivity do not expose the canopy to an unacceptably high risk of xylem cavitation. By contrast, evergreen trees must transport water during more extreme dry season conditions, when they would potentially be more susceptible to xylem embolism. To protect against this, they have developed vessels with generally smaller diameters and with small pit membrane pores or vestured pits.
Résumé. L'effet de la pandémie de COVID-19 sur les réfugiés et leur protection au Ghana, Kenya, Nigeria, en Afrique du Sud, en Ouganda et au Zimbabwe
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: pandemic
subject: refugees
subject: 320 - Politik

description: La pandémie actuelle de COVID-19 affecte toutes les personnes à travers le monde, mais celles qui sont particulièrement vulnérables, y compris les réfugiés et les personnes déplacées, peuvent être exposées à des risques plus importants. Dans une étude récente, nous explorons comment la pandémie de COVID-19 a affecté les réfugiés et la protection des réfugiés dans six pays en Afrique de l'Ouest, Afrique de l'Est et Afrique australe, à savoir le Ghana, le Kenya, le Nigeria, l'Afrique du Sud, l'Ouganda, et le Zimbabwe, pendant la première année de la pandémie jusqu'en février 2021 inclus. À l'aide d'un questionnaire non représentatif, nous cherchons à mieux comprendre les perspectives des réfugiés, des experts, des fonctionnaires du gouvernement et des agents humanitaires travaillant avec et pour les réfugiés. Un total de 90 participants ont rempli le questionnaire.
Executive Summary. Effects of the COVID-19 Pandemic on Refugees and Their Protection in Kenya, Uganda, Ghana, Nigeria, South Africa and Zimbabwe
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: The current COVID-19 pandemic affects all people worldwide but those in particularly vulnerable positions, including refugees and displaced people, may be exposed to greater risks. In a recent study, we explore how the COVID-19 pandemic has affected refugees and refugee protection in six countries in West Africa, East Africa and Southern Africa, namely Ghana, Kenya, Nigeria, South Africa, Uganda and Zimbabwe, during the first year of the pandemic up to and including February 2021. Using a non-representative questionnaire, we seek to gain insights into the perspectives of persons of refugee background, scholars, government officials and aid actors working with and for refugees. A total of 90 respondents filled in the questionnaire.
Refugee Protection in Uganda during COVID-19. Infographic
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: Infographic about the effects ofthe COVID-19 pandemic on refugees and their protection in Uganda.
Nonparametric Estimation of the Leverage Effect: A Trade-Off Between Robustness and Efficiency
Creators: name: Kalnina, Ilze
name: Dacheng Xiu
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biotechnology
subject: Sociology
subject: FOS: Sociology
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy
subject: Plant Biology
subject: FOS: Biological sciences
subject: Computational Biology

description: We consider two new approaches to nonparametric estimation of the leverage effect. The first approach uses stock prices alone. The second approach uses the data on stock prices as well as a certain volatility instrument, such as the Chicago Board Options Exchange (CBOE) volatility index (VIX) or the Black–Scholes implied volatility. The theoretical justification for the instrument-based estimator relies on a certain invariance property, which can be exploited when high-frequency data are available. The price-only estimator is more robust since it is valid under weaker assumptions. However, in the presence of a valid volatility instrument, the price-only estimator is inefficient as the instrument-based estimator has a faster rate of convergence.We consider an empirical application, in which we study the relationship between the leverage effect and the debt-to-equity ratio, credit risk, and illiquidity. Supplementary materials for this article are available online.
title: Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa
Creators: name: Gentile, Rocco
name: Modric, Matea
name: Schott-Verdugo, Stephan
name: Ahmad, Sabahuddin
name: Kovacic, Filip
name: Jaeger, Karl-Erich
name: Gohlke, Holger
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: The Gram-negative Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections by producing numerous virulence factors. Among these factors, type A phospholipases (PLA) can contribute to host membrane damage and modulation of signaling networks in infected cells by modifying the membrane composition. In this context, we focus on PlaF, a phospholipase A1 (PLA1). This enzyme adopts a monomeric active and a dimeric inactive configuration3. A crystal structure of the dimeric PlaF (PDB_ID 6i8w) is available. Computational studies evaluated the dynamics and energetics of the dimerization process. The results reveal that a single PlaF monomer can adopt a tilted configuration, which might facilitate phospholipid substrate access from the membrane. Furthermore, we elucidated the potential channeling mechanisms underlying substrate access and product egress in PlaF in accordance with the enzyme specificity and regioselectivity. Additionally, we revealed that medium-sized free fatty acids (FFAs) can inhibit PlaF activity according to mixed inhibition kinetics. However, the detailed molecular mechanism that governs the inhibition of PlaF by FFAs has remained elusive. Here, we showed by molecular simulations that the presence of FFAs in the membrane affects the dynamics and the energetics of both PlaF dimer dissociation and monomer tilting. Moreover, free energy computations reveal an energetic stabilization of the dimeric inactive configuration, which was correlated to an increased FFA concentration in the membrane. Experimental studies also revealed that FFAs in the periplasmic space can inhibit PlaF activity. We propose a potential FFA-related mechanism of PlaF inhibition using free ligand diffusion simulations. Combined with experimental validations, the identification of FFA binding site(s) involved in the inhibition of PlaF can help design novel drugs against P. aeruginosa.
Refugee Protection in South Africa during COVID-19. Infographic
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: Infographic about the effects ofthe COVID-19 pandemic on refugees and their protection in South Africa.
title: Development of heterobifunctional degraders for RNA and RNA-modifying enzymes
Creators: name: Weldert, Annabelle
name: Frey, Ariane
name: Zimmer, Collin
name: Rodriguez, Laura
name: Krähe, Franziska
name: Kersten, Christian
name: Crews, Craig
name: Schirmeister, Tanja
name: Barthels, Fabian
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Proteolysis targeting chimeras (PROTACs) are novel therapeutic modalities that have emerged in recent years. These heterobifunctional compounds recruit E3 ligases, such as cereblon (CRBN) or Von Hippel Lindau factor (VHL), in close proximity to a protein of interest (POI), leading to targeted degradation of the POI. Since 2019 several PROTACs have entered clinical trials, mainly targeting proteins involved in different types of cancer and autoimmune diseases. We designed and synthesized PROTACs targeting the human METTL3/14 methyltransferase. METTL3/14 is involved in multifaceted biological activities, such as cell cycle, apoptosis, autophagy and differentiation, and has an impact on numerous types of cancers including breast cancer, lung cancer, and acute myeloid leukemia. Additionally we are interested in, ribonuclease-targeting chimeras (RIBOTACs). Similar to PROTACs, RIBOTACs function as targeted degraders, however targeting an RNA of interest (ROI) instead of a POI. RIBOTACs can selectively bind and degrade ROIs by activation of RNase L, part of the innate immune system, an otherwise latent ribonuclease. Choosing the optimal composition of heterobifunctional molecules includes deciding on optimal linker length, type of recruiter, and type of POI/ROI binder. Therefore it is important to characterize the interaction between our molecules and their respective interaction partner. Hence, we employed various biophysical methods such as fluorescence polarization (FP) and Förster resonance energy transfer (FRET) based assays. Moreover, characterization of the ternary complex es is essential for successful degrader development. To achieve this, we developed a homogeneous time resolved fluorescence (HTRF) based method in our PROTAC studies. Additionally, we investigated the permeability of our compounds.
การมีส่วนร่วมของผู้ปกครองในการจัดการศึกษาของบุตร
Creators: name: มูฮัมหมัดอาฟีฟี อัซซอลีฮีย์, นัชชิมา บาเกาะ
Publisher: name: สำนักวิทยบริการ มหาวิทยาลัยสงขลานครินทร์ วิทยาเขตปัตตานี
Year: 2020
Subjects: การเลี้ยงดู, การมีส่วนร่วมของผู้ปกครองในการจัดการศึกษาของบุตร, การให้การศึกษาผู้ปกครอง, parenting, parental involvement in education, parental education

description: วารสารวิทยบริการ มหาวิทยาลัยสงขลานครินทร์, 31, 1, 243-254
Nonparametric Estimation of the Leverage Effect: A Trade-off between Robustness and Efficiency
Creators: name: Kalnina, Ilze
name: Dacheng Xiu
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Space Science
subject: Biotechnology
subject: Sociology
subject: FOS: Sociology
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy
subject: Plant Biology
subject: FOS: Biological sciences
subject: Computational Biology

description: We consider two new approaches to nonparametric estimation of the leverage effect. The first approach uses stock prices alone. The second approach uses the data on stock prices as well as a certain volatility instrument, such as the CBOE volatility index (VIX) or the Black-Scholes implied volatility. The theoretical justification for the instrument-based estimator relies on a certain invariance property, which can be exploited when high frequency data is available. The price-only estimator is more robust since it is valid under weaker assumptions. However, in the presence of a valid volatility instrument, the price-only estimator is inefficient as the instrument-based estimator has a faster rate of convergence. We consider an empirical application, in which we study the relationship between the leverage effect and the debt-to-equity ratio, credit risk, and illiquidity.
Refugee Protection in Zimbabwe during COVID-19. Infographic
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: Infographic about the effects ofthe COVID-19 pandemic on refugees and their protection in Zimbabwe.
Reducing Costs for Meeting Stormwater Regulations for Small to Mid-Size Communities in Massachusetts
Creators: name: Alfred, Daniel
name: Mower, Anthony
name: Rahman, Tasmin
name: Tako, Konstantinos
Publisher: name: QUBES Educational Resources
Year: 2025

description: Stormwater is a major cause of pollution for waterbodies in Massachusetts. The EPA has drafted new regulations with additional requirements to further reduce stormwater pollution. The implementation of these requirements will increase costs associated with stormwater management. The goal of this project was to assist small to mid-size communities in Massachusetts with fulfilling the EPA’s new requirements for stormwater management. To accomplish this goal, we gathered information and conducted case studies to determine resource needs and current stormwater management programs for two Massachusetts towns. We compared these data to the requirements in the new regulations in order to develop a set of recommendations that communities can use as guidelines for reducing costs for implementation.
Refugee Protection in Nigeria During COVID-19. Infographic
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: Infographic about the effects ofthe COVID-19 pandemic on refugees and their protection in Nigeria.
Refugee Protection in Kenya during COVID-19. Infographic
Creators: name: Segadlo, Nadine
name: Krause, Ulrike
name: Zanker, Franzisca
name: Edler, Hannah
Publisher: name: Universität Osnabrück
Year: 2021
Subjects: subject: Covid-19
subject: Pandemic
subject: Refugees
subject: 320 - Politik

description: Infographic about the effects ofthe COVID-19 pandemic on refugees and their protection in Kenya.
title: Chemically Stable Diazopeptides as Cystein Protease Inhibitors Active in Living Cells
Creators: name: Wahl, Juliane
name: Ahsanullah
name: Zupan, Hana
name: Gottschalk, Franziska
name: Mieth, Maren
name: Arkona, Christoph
name: Hocke, Andreas
name: Keller, Bettina
name: Rademann, Jörg
Publisher: name: Fachinformationsdienst für Pharmazie
Year: 2024
Subjects: subject: 615
subject: 610

description: Diazo-compounds show selective reactivity and are therefore intensely investigated for versatile applications in chemical biology. The combination of the diazo reactivity and the selectivity of peptide sequences, tuned to a target, evokes a promising new class of enzyme inhibitors. So far, C- and N-terminal diazo peptides have been reported, but their poor stability towards even mild acidic conditions limits their applicability. We set our aim to the synthesis of internal diazo peptides, stabilized by two adjacent electron withdrawing groups, with higher stability towards challenging conditions. Internal diazo peptides were obtained, as esters or amides, by C-acylation of phosphorane ylides and subsequent cycloaddition-reversion mechanism with electron-deficient azides (a). Starting from polymer supported triphenylphosphine the procedure was compatible with Fmoc-based solid phase peptide synthesis. The formation of both, diazo ester- and amide-peptides, was established in useful yields. The so acquired diazo peptides are stable between pH 1-14 for amides and 1-8 for esters, as well as against thiol nucleophiles. These findings inspired us to explore their potential as cysteine protease inhibitors. A diazo peptide with the well-established sequence of the human Caspase-3 (hC-3) substrate was synthesized and tested for activity against the enzyme, showing IC50-values in the nanomolar range with a time-dependant covalent inhibition mechanism (b). A fluorescent diazo peptide was used to image apoptosis in living cells by labelling of active hC3-protease (c).
ผล O-NET ต่ำในชายแดนใต้: ต้นตอของปัญหาและทางเลือกในการจัดการปัญหา
Creators: name: ศราวุธ สุวรรณวรบุญ, ธีร หฤทัยธนาสันติ์
Publisher: name: สำนักวิทยบริการ มหาวิทยาลัยสงขลานครินทร์ วิทยาเขตปัตตานี
Year: 2020
Subjects: ผล O-NET ตกต่ำ, ต้นตอของปัญหา, ทางเลือกในการจัดการปัญหา, จังหวัดชายแดนภาคใต้, low O-NET scores, origin of the issue, alternative in problem management, southern border provinces

description: วารสารวิทยบริการ มหาวิทยาลัยสงขลานครินทร์, 31, 1, 255-269