694 results on '"Daniel Jun"'
Search Results
102. SPECT/CT to quantify early small airway disease and its relationship to clinical symptoms in smokers with normal lung function: a pilot study
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Daniel Juneau, Antoine Leblond, Rami Chatta, Valérie Lévesque, Annabelle Lussier, and Bruno-Pierre Dubé
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small airway ,ventilatory distributions ,SPECTCT ,tobacco ,pulmonary function test ,Physiology ,QP1-981 - Abstract
IntroductionSmokers frequently display respiratory symptoms despite the fact that their pulmonary function tests (PFTs) can be normal. Quantitative lung ventilation single-photon emission computed tomography (SPECT/CT) can provide a quantification of lung ventilatory homogeneity and could prove useful as an early marker of airway disease in smokers. We measured the effects of smoking on regional ventilation distribution in subjects with normal lung function and evaluated whether ventilation distribution in these subjects is related to lung function tests results and clinical symptoms.MethodsSubjects without any history of respiratory disease were prospectively recruited and separated in two groups: active smokers (AS: ≥10 cigarettes/day and history of ≥15 pack-years) and never smokers (NS: lifetime exposure of 40%, (AUC-CV40%) was used as the measure of ventilation heterogeneity.Results30 subjects were recruited (15 per group). Subjects in the AS group displayed higher dyspnea levels (1 [1–2] vs. 0 [0–1] units on mMRC scale, p < 0.001). AUC- CV40% was significantly higher in the AS group (0.386 ± 0.106 vs. 0.293 ± 0.069, p = 0.004). AUC-CV40% was significantly correlated to FEV1 (rho = −0.47, p = 0.009), DLCO (rho = −0.49, p = 0.006), CAT score (rho = 0.55, p = 0.002) and mMRC score (rho = 0.54, p = 0.002). Subjects with mMRC >0 had higher AUC-CV40% values than those without dyspnea (0.289 ± 0.071 vs. 0.378 ± 0.102, p = 0.006), while FEV1 and DLCO were not different between those groups. ROC analyses showed that the AUC for AUC-CV40% in identifying subjects with mMRC score >0 was 0.78 (95%CI 0.61–0.95, p = 0.009), which was significantly higher than that of FEV1 and DLCO.DiscussionIn smokers with normal lung function, ventilatory inhomogeneities can be quantified using SPECT/CT. AUC-CV40% values are related to lung function decline and to respiratory symptomatology, suggesting a potential role for this marker in the evaluation of symptomatic smokers.
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- 2024
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103. OPCW BIOMEDICAL PROFICIENCY TEST IN THE LABORATORY OF ANALYTICAL CHEMISTRY AT THE DEPARTMENT OF TOXICOLOGY AND MILITARY PHARMACY
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Rafael Doležal, David Herman, Petr Bzonek, Lukáš Prchal, Marie Vajrychová, Nela Váňová, Alžběta Dlabková, and Daniel Jun
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Emergency Medical Services ,Immunology and Microbiology (miscellaneous) ,Veterinary (miscellaneous) ,Public Health, Environmental and Occupational Health ,Emergency Medicine ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Abstract
S ohledem na udalosti poslednich let neni riziko vojenskeho ci teroristickeho zneužiti vysoce toxických latek vcetně zakazaných bojových otravných latek zanedbatelne. Katedra toxikologie a vojenske farmacie Fakulty vojenskeho zdravotnictvi Univerzity obrany tudiž zavedla analyticke metody a postupy uprav biologických vzorků (plasma, moc) pro stanoveni identifikacnich znaků (biomarkerů) vystaveni nervově paralytickým latkam (sarinu, cyklosarinu, somanu, tabunu a V-latkam) a yperitu, cimž přinasi do Armady Ceske republiky schopnost potvrdit jejich zneužiti vůci žive sile. Metody popsane v clanku jsou založeny na průkazu metabolitů (O-alkyl methylfosfonových kyselin pro nervově paralyticke latky a thiodiglykolu pro yperit) a produktů jejich reakci s přitomnými biomolekulami (tyrosinových aduktů nervově paralytických latek a peptidových aduktů sirneho yperitu) pomoci kapalinove a plynove chromatografie spojene s hmotnostni spektrometrii. Funkcnost těchto metod je ověřovana a diskutovana v ramci testu odborne způsobilosti pro biomedicinskou analýzu s mezinarodni ucasti, který každorocně pořada Organizace pro zakaz chemických zbrani. Katedra se těchto testů ucastni od roku 2016, kdy se konal prvni rocnik.
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- 2020
104. DEFINITION OF THE TARGET POPULATION FOR EXTERNAL PACEMAKER AS A KEY ASPECT IN SUCCESSFUL MEDICAL DEVICE HTA PROCESS
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Jan Honegr, Petra Maresova, Kamil Kuca, and Daniel Jun
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Emergency Medical Services ,Medical device ,Process management ,business.industry ,Process (engineering) ,Veterinary (miscellaneous) ,Public Health, Environmental and Occupational Health ,Target population ,Immunology and Microbiology (miscellaneous) ,Emergency Medicine ,Key (cryptography) ,Medicine ,business ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Published
- 2020
105. Introduction of the Menaquinone Biosynthetic Pathway into Rhodobacter sphaeroides and de Novo Synthesis of Menaquinone for Incorporation into Heterologously Expressed Integral Membrane Proteins
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Amita Mahey, Tomas Richardson-Sanchez, Rachel C. Fernandez, Daniel Jun, J. Thomas Beatty, and Michael E. P. Murphy
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0106 biological sciences ,Photosynthetic reaction centre ,0303 health sciences ,biology ,Operon ,Chemistry ,Chloroflexus aurantiacus ,Biomedical Engineering ,General Medicine ,biology.organism_classification ,medicine.disease_cause ,Photosynthesis ,7. Clean energy ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Metabolic engineering ,03 medical and health sciences ,Rhodobacter sphaeroides ,Biochemistry ,010608 biotechnology ,medicine ,Escherichia coli ,Integral membrane protein ,030304 developmental biology - Abstract
Quinones are redox-active molecules that transport electrons and protons in organelles and cell membranes during respiration and photosynthesis. In addition to the fundamental importance of these processes in supporting life, there has been considerable interest in exploiting their mechanisms for diverse applications ranging from medical advances to innovative biotechnologies. Such applications include novel treatments to target pathogenic bacterial infections and fabricating biohybrid solar cells as an alternative renewable energy source. Ubiquinone (UQ) is the predominant charge-transfer mediator in both respiration and photosynthesis. Other quinones, such as menaquinone (MK), are additional or alternative redox mediators, for example in bacterial photosynthesis of species such as Thermochromatium tepidum and Chloroflexus aurantiacus. Rhodobacter sphaeroides has been used extensively to study electron transfer processes, and recently as a platform to produce integral membrane proteins from other species. To expand the diversity of redox mediators in R. sphaeroides, nine Escherichia coli genes encoding the synthesis of MK from chorismate and polyprenyl diphosphate were assembled into a synthetic operon in a newly designed expression plasmid. We show that the menFDHBCE, menI, menA, and ubiE genes are sufficient for MK synthesis when expressed in R. sphaeroides cells, on the basis of high performance liquid chromatography and mass spectrometry. The T. tepidum and C. aurantiacus photosynthetic reaction centers produced in R. sphaeroides were found to contain MK. We also measured in vitro charge recombination kinetics of the T. tepidum reaction center to demonstrate that the MK is redox-active and incorporated into the QA pocket of this heterologously expressed reaction center.
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- 2020
106. Simple validated method of LC–MS/MS determination of BZ agent in rat plasma samples
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Jana Zdarova Karasova, Alzbeta Dlabkova, Daniel Jun, Lenka Cechova, Jan Misik, David Herman, and Nela Vanova
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Male ,Spectrometry, Mass, Electrospray Ionization ,3-Quinuclidinyl benzilate ,Electrospray ionization ,Pharmaceutical Science ,Mass spectrometry ,01 natural sciences ,High-performance liquid chromatography ,Cholinergic Antagonists ,Analytical Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Limit of Detection ,Tandem Mass Spectrometry ,Lc ms ms ,medicine ,Animals ,Environmental Chemistry ,Sample preparation ,030216 legal & forensic medicine ,Rats, Wistar ,Chromatography, High Pressure Liquid ,Spectroscopy ,Detection limit ,Chromatography ,Chemistry ,010401 analytical chemistry ,Extraction (chemistry) ,Rats ,0104 chemical sciences ,Quinuclidinyl Benzilate ,medicine.drug - Abstract
Agent BZ (3-quinuclidinyl benzilate) is a centrally acting synthetic anticholinergic agent, considered as a potential military incapacitating chemical warfare agent. Despite its significance as a model compound in pharmacological research and its potential misuse in chemical attacks, few modern analytical methods for BZ determination in biological samples have been published. The goal of the present work is to develop and validate a sensitive and rapid LC-MS/MS method for the determination of agent BZ in rat plasma. The sample preparation was based on solid-phase extraction on C-18 cartridges. The reversed-phase HPLC coupled with the mass spectrometer with electrospray ionization in the positive ion-selective reaction monitoring mode was employed in the BZ analysis. Atropine was used as an internal standard. The presented method is selective, accurate, precise, and linear (r2 = 0.9947) in a concentration range from 0.5 ng/mL to 1 000 ng/mL and sensitive enough (limit of detection 0.2 ng/mL; limit of quantification 0.5 ng/mL) to determine the BZ plasma levels in rats exposed to 2 mg/kg and 10 mg/kg of BZ. The highest level of BZ in plasma was observed 5 minutes after intramuscular administration (154.6 ± 22.3 ng/mL in rats exposed to 2 mg/kg of BZ and 1024 ± 269 ng/mL in rats exposed to 10 mg/kg). After 48 h, no BZ was observed at detectable levels. This new method allows the detection and quantification of BZ in biological samples after exposure of an observed organism and it will be further optimized for other tissues to observe the distribution of BZ in organs.
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- 2020
107. Synthesis, in vitro screening and molecular docking of isoquinolinium-5-carbaldoximes as acetylcholinesterase and butyrylcholinesterase reactivators
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Daniel Jun, Eva Mezeiova, Rudolf Andrys, Jan Korabecny, Lukas Gorecki, Kamil Musilek, David Malinak, Miroslava Hozova, Veronika Racakova, Petr Bzonek, Kamil Kuca, Miroslav Psotka, Vendula Hepnarova, and Rafael Dolezal
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Cholinesterase Reactivators ,Stereochemistry ,organophosphate ,RM1-950 ,01 natural sciences ,oxime ,chemistry.chemical_compound ,Drug Discovery ,Humans ,Butyrylcholinesterase ,Cholinesterase ,Pharmacology ,biology ,010405 organic chemistry ,Organophosphate ,General Medicine ,Oxime ,Isoquinolines ,Acetylcholinesterase ,In vitro ,0104 chemical sciences ,reactivator ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,chemistry ,biology.protein ,Therapeutics. Pharmacology ,Cholinesterase Inhibitors ,Research Paper - Abstract
The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators., GRAPHICAL ABSTRACT
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- 2020
108. A Singular Value Approach to Robustify Deep Convolutional Neural Network
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Yeli Feng, Daniel Jun Xian Ng, and Arvind Easwaran
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- 2022
109. Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury
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Jina Yun, Daniel Jun-Kit Hu, Justin Elstrott, and Heinrich Jasper
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Cell division ,Science ,Enteroendocrine Cells ,General Physics and Astronomy ,Enteroendocrine cell ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Movement ,medicine ,Regeneration ,Animals ,Drosophila Proteins ,Cell migration ,Intestinal Mucosa ,Wnt Signaling Pathway ,Adult stem cells ,Multidisciplinary ,Regeneration (biology) ,Time-lapse imaging ,Stem Cells ,Wnt signaling pathway ,Receptor Protein-Tyrosine Kinases ,General Chemistry ,Intestinal epithelium ,Epithelium ,Cell biology ,Intestines ,Wnt Proteins ,medicine.anatomical_structure ,Wounds and Injuries ,Drosophila ,PTK7 ,Stem cell ,Cell signalling - Abstract
Tissue regeneration after injury requires coordinated regulation of stem cell activation, division, and daughter cell differentiation, processes that are increasingly well understood in many regenerating tissues. How accurate stem cell positioning and localized integration of new cells into the damaged epithelium are achieved, however, remains unclear. Here, we show that enteroendocrine cells coordinate stem cell migration towards a wound in the Drosophila intestinal epithelium. In response to injury, enteroendocrine cells release the N-terminal domain of the PTK7 orthologue, Otk, which activates non-canonical Wnt signaling in intestinal stem cells, promoting actin-based protrusion formation and stem cell migration towards a wound. We find that this migratory behavior is closely linked to proliferation, and that it is required for efficient tissue repair during injury. Our findings highlight the role of non-canonical Wnt signaling in regeneration of the intestinal epithelium, and identify enteroendocrine cell-released ligands as critical coordinators of intestinal stem cell migration., Stem cell migration is critical during adult tissue regeneration. Here, the authors demonstrate that enteroendocrine cells coordinate stem cell migration towards sites of injury in the Drosophila intestine by activating non-canonical Wnt signaling.
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- 2021
110. Non-covalent acetylcholinesterase inhibitors: In vitro screening and molecular modeling for novel selective insecticides
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Vendula Hepnarova, Martina Hrabinova, Lubica Muckova, Tomas Kucera, Monika Schmidt, Rafael Dolezal, Lukas Gorecki, Veronika Hrabcova, Jan Korabecny, Eva Mezeiova, Daniel Jun, and Jaroslav Pejchal
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Insecticides ,Mosquito Vectors ,General Medicine ,Toxicology ,Organophosphates ,Carbofuran ,Butyrylcholinesterase ,Anopheles ,Acetylcholinesterase ,Tacrine ,Animals ,Humans ,Cholinesterase Inhibitors ,Carbamates - Abstract
Insecticides represent the most crucial element in the integrated management approach to malaria and other vector-borne diseases. The evolution of insect resistance to long-used substances and the toxicity of organophosphates (OPs) and carbamates are the main factors contributing to the development of new, environmentally safe pesticides. In our work, fourteen compounds of 7-methoxytacrine-tacrine heterodimers were tested for their insecticidal effect. Compounds were evaluated in vitro on insect acetylcholinesterase from Anopheles gambiae (AgAChE) and Musca domestica (MdAChE). The evaluation was executed in parallel with testing on human erythrocyte acetylcholinesterase (HssAChE) and human butyrylcholinesterase (HssBChE) using a modified Ellman's method. Compound efficacy was determined as IC
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- 2022
111. A Singular Value Approach to Robustify Deep Convolutional Neural Network
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Feng, Yeli, primary, Ng, Daniel Jun Xian, additional, and Easwaran, Arvind, additional
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- 2022
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112. Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): Identification of new structural scaffold for treatment of Alzheimer's disease
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Rudolf, Vrabec, Jana, Maříková, Miroslav, Ločárek, Jan, Korábečný, Daniela, Hulcová, Anna, Hošťálková, Jiří, Kuneš, Jakub, Chlebek, Tomáš, Kučera, Martina, Hrabinová, Daniel, Jun, Ondřej, Soukup, Vincenza, Andrisano, Jaroslav, Jenčo, Marcela, Šafratová, Lucie, Nováková, Lubomír, Opletal, and Lucie, Cahlíková
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Glycogen Synthase Kinase 3 beta ,Alzheimer Disease ,Butyrylcholinesterase ,Phytochemicals ,Acetylcholinesterase ,Monoterpenes ,Plant Components, Aerial ,Vinca ,Indole Alkaloids - Abstract
One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. The NMR data of several alkaloids have been revised, corrected, and missing data have been supplemented. Alkaloids isolated in sufficient quantity were screened for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibitory activity. Selected compounds were also evaluated for prolyl oligopeptidase (POP; E.C. 3.4.21.26), and glycogen synthase 3β-kinase (GSK-3β; E.C. 2.7.11.26) inhibition potential. Significant hBuChE inhibition activity has been shown by (-)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole with an IC
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- 2021
113. Synthesis and Decontamination Effect on Chemical and Biological Agents of Benzoxonium-Like Salts
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Ondrej Soukup, Marketa Benkova, Aneta Markova, Lenka Pulkrabkova, Radek Sleha, Daniel Jun, Michaela Hympanova, Lukas Prchal, Marek Matula, Jan Marek, and Zuzana Krocova
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quaternary ammonium salts ,benzoxonium ,decontamination ,organophosphates ,disinfection ,micellar catalysis ,Chemical Health and Safety ,biology ,Low toxicity ,Chemistry ,Health, Toxicology and Mutagenesis ,Chemical technology ,Biofilm ,Dual effect ,Human decontamination ,TP1-1185 ,Toxicology ,biology.organism_classification ,Combinatorial chemistry ,Article ,BENZOXONIUM ,Biological decontamination ,Biological warfare ,Francisella tularensis - Abstract
Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C10-C18 set of benzoxonium-like salts to evaluate the effect of their chemical and biological decontamination capabilities. In particular, biocidal activity against a panel of bacterial strains including Staphylococcus aureus in biofilm form was screened. In addition, the most promising compounds were successfully tested against Francisella tularensis as a representative of potential biological warfare agents. From a point of view of chemical warfare protection, the efficiency of BOC-like compounds to degrade the organophosphate simulant fenitrothion was examined. Notwithstanding that no single compound with universal effectiveness was identified, a mixture of only two compounds from this group would be able to satisfactorily cover the proposed decontamination spectrum. In addition, the compounds were evaluated for their cytotoxicity as a basic safety parameter for potential use in practice. In summary, the dual effect on chemical and biological agents of benzoxonium-like salts offer attractive potential as active components of decontamination mixtures in the case of a terrorist threat or chemical or biological accidents.
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- 2021
114. A note on O6 intersections in AdS flux vacua
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Daniel Junghans
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Flux Compactifications ,Superstring Vacua ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract The DGKT-CFI construction of AdS flux vacua in type IIA string theory has interesting features such as classical moduli stabilization and a parametric scale separation between the Hubble scale and the Kaluza-Klein scale. A possible worry regarding the consistency of these vacua is that pathologies could arise due to intersections of the O6-planes, which are not well understood in the 10D solution. In this note, we show in explicit examples that such intersections are absent if one compactifies on smooth Calabi-Yau manifolds instead of toroidal orbifolds. In particular, we show that the blow-up of the T 6 /ℤ3 orbifold yields a single O6-plane which wraps a smooth submanifold without any (self-)intersections. On the other hand, blowing up the T 6 / ℤ 3 2 $$ {\mathbb{Z}}_3^2 $$ orbifold seems to yield an O6-plane which self-intersects. However, we show that this is due to an inconsistent orientifold involution in the original DGKT model. Imposing a consistent involution again yields a single smooth O6-plane without self-intersections on the blown-up manifold.
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- 2024
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115. Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease
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Jaroslav Jenčo, Abdullah Al Mamun, Vincenza Andrisano, Jana Markova, Jana Maříková, Daniela Hulcová, Negar Maafi, Tomas Kucera, Angela De Simone, Marcela Šafratová, Rozálie Peřinová, Lucie Cahlíková, Jiří Kuneš, Ana Martínez, Daniel Jun, Lucie Nováková, Jan Korábečný, Eliška Kohelová, Rozálie Peřinová, Negar Maafi, Jan Korábečný, Eliška Kohelová, Angela De Simone, Abdullah Al Mamun, Daniela Hulcová, Jana Marková, Tomáš Kučera, Daniel Jun, Marcela Šafratová, Jana Maříková, Vincenza Andrisano, Jaroslav Jenčo, Jiří Kuneš, Ana Martinez, Lucie Nováková, Lucie Cahlíková, Charles University (Czech Republic), University Hospital Hradec Králové, Ministerio de Ciencia, Innovación y Universidades (España), Czech Science Foundation, Peřinová, Rozálie [0000-0002-3919-5082], Maafi, Negar [0000-0002-4227-7855], Korábečný, Jan [0000-0001-6977-7596], Kohelová, Eliška [0000-0003-1365-0283], De Simone, Angela [0000-0003-1915-458X], Hulcová, Daniela [0000-0003-2414-3551], Jun, Daniel [0000-0002-0882-6304], Safratova, Marcela [0000-0003-4690-5107], Maříková, Jana [0000-0001-9758-2067], Andrisano, Vincenza [0000-0003-4396-1904], Jenco, Jaroslav [0000-0001-8667-8303], Kuneš, Jiří [0000-0001-7257-0641], Martínez, Ana [0000-0002-2707-8110], Nováková, Lucie [0000-0003-3570-5871], Cahlíková, Lucie [0000-0002-1555-8870], Peřinová, Rozálie, Maafi, Negar, Korábečný, Jan, Kohelová, Eliška, De Simone, Angela, Hulcová, Daniela, Jun, Daniel, Safratova, Marcela, Maříková, Jana, Andrisano, Vincenza, Jenco, Jaroslav, Kuneš, Jiří, Martínez, Ana, Nováková, Lucie, and Cahlíková, Lucie
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Haemanthamine ,In silico ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Alzheimer Disease ,Acetylcholinesterase Alzheimer’s disease Amaryllidaceae Butyrylcholinesterase Docking studies Haemanthamine ,Drug Discovery ,Humans ,Docking studies ,Molecular Biology ,IC50 ,Butyrylcholinesterase ,chemistry.chemical_classification ,Binding Sites ,010405 organic chemistry ,Alkaloid ,Organic Chemistry ,Amaryllidaceae ,Biological activity ,Esters ,Alzheimer's disease ,Acetylcholinesterase ,In vitro ,0104 chemical sciences ,Phenanthridines ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Kinetics ,Enzyme ,chemistry ,Blood-Brain Barrier ,Amaryllidaceae Alkaloids ,Cholinesterase Inhibitors ,Alzheimer’s disease - Abstract
23 p.-6 fig.-1 tab., A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC50value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood–brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds., This project was supported by Charles University grants (GA UK Nr. 178518, SVV UK 260412, 260 401; Progres/UK Q40 and Q42), by MH CZ - DRO (University Hospital Hradec Kralove, Nr. 00179906), by Long-term development plan (Faculty of Military Health Sciences), and by EFSA-CDN (Nr.CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by ERDF, by MICU (grant Nr. SAF2016-76693-R to A.M.), and by Czech Science Foundation (Nr. 20-29633 J). Computational resources were provided by the CESNET LM2015042 and the CERIT Scientific Cloud LM2015085, provided under the program “Projects of Large Research,Development, and Innovations Infrastructures”., preprint
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- 2020
116. Improving Variational Autoencoder based Out-of-Distribution Detection for Embedded Real-time Applications
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Arvind Easwaran, Daniel Jun Xian Ng, and Yeli Feng
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FOS: Computer and information sciences ,Computer Science - Machine Learning ,business.industry ,Computer science ,Computer Vision and Pattern Recognition (cs.CV) ,Computer Science - Computer Vision and Pattern Recognition ,Inference ,Machine learning ,computer.software_genre ,Autoencoder ,Machine Learning (cs.LG) ,Task (project management) ,Generative model ,Hardware and Architecture ,Robustness (computer science) ,Artificial intelligence ,Scenario testing ,business ,Focus (optics) ,computer ,Software ,Integer (computer science) - Abstract
Uncertainties in machine learning are a significant roadblock for its application in safety-critical cyber-physical systems (CPS). One source of uncertainty arises from distribution shifts in the input data between training and test scenarios. Detecting such distribution shifts in real-time is an emerging approach to address the challenge. The high dimensional input space in CPS applications involving imaging adds extra difficulty to the task. Generative learning models are widely adopted for the task, namely out-of-distribution (OoD) detection. To improve the state-of-the-art, we studied existing proposals from both machine learning and CPS fields. In the latter, safety monitoring in real-time for autonomous driving agents has been a focus. Exploiting the spatiotemporal correlation of motion in videos, we can robustly detect hazardous motion around autonomous driving agents. Inspired by the latest advances in the Variational Autoencoder (VAE) theory and practice, we tapped into the prior knowledge in data to further boost OoD detection's robustness. Comparison studies over nuScenes and Synthia data sets show our methods significantly improve detection capabilities of OoD factors unique to driving scenarios, 42% better than state-of-the-art approaches. Our model also generalized near-perfectly, 97% better than the state-of-the-art across the real-world and simulation driving data sets experimented. Finally, we customized one proposed method into a twin-encoder model that can be deployed to resource limited embedded devices for real-time OoD detection. Its execution time was reduced over four times in low-precision 8-bit integer inference, while detection capability is comparable to its corresponding floating-point model., This article appears as part of the ESWEEK-TECS special issue and will be presented in the International Conference on Embedded Software (EMSOFT), 2021
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- 2021
117. Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies
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Ondřej Soukup, Filip Pidaný, Rozálie Peřinová, Lubica Muckova, Jiří Kuneš, Tomas Kucera, Abdullah Al Mamun, Negar Maafi, Jan Korábečný, Rudolf Andrýs, Monika Schmidt, Jiří Janoušek, Martina Hrabinova, Jana Maříková, Lucie Cahlíková, Daniela Hulcová, Daniel Jun, Lucie Nováková, and Maria Carmen Catapano
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Pharmacology ,01 natural sciences ,chemistry.chemical_compound ,Neuroblastoma ,Tumor Cells, Cultured ,Biology (General) ,Spectroscopy ,Butyrylcholinesterase ,0303 health sciences ,biology ,Biological activity ,General Medicine ,Receptor antagonist ,Acetylcholinesterase ,Computer Science Applications ,Molecular Docking Simulation ,Chemistry ,Alzheimer’s disease ,medicine.drug_class ,QH301-705.5 ,Tyramine ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Structure-Activity Relationship ,medicine ,Humans ,Computer Simulation ,Physical and Theoretical Chemistry ,Amaryllidaceae Alkaloids ,norbelladine-type ,Molecular Biology ,IC50 ,QD1-999 ,amaryllidaceae alkaloid ,030304 developmental biology ,Cholinesterase ,Cell Proliferation ,010405 organic chemistry ,Organic Chemistry ,docking studies ,0104 chemical sciences ,chemistry ,Docking (molecular) ,biology.protein ,Cholinesterase Inhibitors - Abstract
Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1–20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 µM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.
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- 2021
118. Population-level management of Type 1 diabetes via continuous glucose monitoring and algorithm-enabled patient prioritization: Precision health meets population health
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Dianelys P. Morales, Ming Yeh Lee, Johannes O. Ferstad, David M. Maahs, Christos Vasilakis, Ramesh Johari, Priya Prahalad, Esli Osmanlliu, Jacqueline Vallon, Anastasiya Vitko, Brianna Leverenz, Daniel Jun, David Scheinker, Jeannine Leverenz, and Angela Gu
- Subjects
Prioritization ,Research design ,Blood Glucose ,Male ,Telemedicine ,medicine.medical_specialty ,Time Factors ,Population level ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Dashboard (business) ,Population health ,Article ,Cohort Studies ,SDG 3 - Good Health and Well-being ,medicine ,Internal Medicine ,Humans ,Pediatrics, Perinatology, and Child Health ,Precision Medicine ,Child ,remote monitoring ,Retrospective Studies ,Type 1 diabetes ,Population Health ,Continuous glucose monitoring ,business.industry ,Blood Glucose Self-Monitoring ,medicine.disease ,Hospitals, Pediatric ,Diabetes Mellitus, Type 1 ,population management ,Pediatrics, Perinatology and Child Health ,Emergency medicine ,continuous glucose monitoring ,Female ,business ,Algorithms - Abstract
Objective To develop and scale algorithm-enabled patient prioritization to improve population-level management of type 1 diabetes (T1D) in a pediatric clinic with fixed resources, using telemedicine and remote monitoring of patients via continuous glucose monitor (CGM) data review. Research design and methods We adapted consensus glucose targets for T1D patients using CGM to identify interpretable clinical criteria to prioritize patients for weekly provider review. The criteria were constructed to manage the number of patients reviewed weekly and identify patients who most needed provider contact. We developed an interactive dashboard to display CGM data relevant for the patients prioritized for review. Results The introduction of the new criteria and interactive dashboard was associated with a 60% reduction in the mean time spent by diabetes team members who remotely and asynchronously reviewed patient data and contacted patients, from 3.2 ± 0.20 to 1.3 ± 0.24 minutes per patient per week. Given fixed resources for review, this corresponded to an estimated 147% increase in weekly clinic capacity. Patients who qualified for and received remote review (n = 58) have associated 8.8 percentage points (pp) (95% CI = 0.6-16.9 pp) greater time-in-range (70-180 mg/dL) glucoses compared to 25 control patients who did not qualify at twelve months after T1D onset. Conclusions An algorithm-enabled prioritization of T1D patients with CGM for asynchronous remote review reduced provider time spent per patient and was associated with improved time-in-range. This article is protected by copyright. All rights reserved.
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- 2021
119. Population-level management of Type 1 diabetes via continuous glucose monitoring and algorithm-enabled patient prioritization: Precision health meets population health
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Brianna Leverenz, Ming Yeh Lee, David M. Maahs, Priya Prahalad, Jeannine Leverenz, Anastasiya Vitko, Esli Osmanlliu, David Scheinker, Dianelys P. Morales, Ramesh Johari, Christos Vasilakis, Angela Gu, Daniel Jun, Jacqueline Vallon, and Johannes O. Ferstad
- Subjects
Research design ,Prioritization ,Type 1 diabetes ,Telemedicine ,medicine.medical_specialty ,Population level ,Continuous glucose monitoring ,business.industry ,Dashboard (business) ,Population health ,medicine.disease ,Emergency medicine ,medicine ,business - Abstract
ObjectiveTo develop and scale algorithm-enabled patient prioritization to improve population-level management of type 1 diabetes (T1D) in a pediatric clinic with fixed resources, using telemedicine and remote monitoring of patients via continuous glucose monitor (CGM) data review.Research Design and MethodsWe adapted consensus glucose targets for T1D patients using CGM to identify interpretable clinical criteria to prioritize patients for weekly provider review. The criteria were constructed to manage the number of patients reviewed weekly and identify patients who most needed provider contact. We developed an interactive dashboard to display CGM data relevant for the patients prioritized for review.ResultsThe introduction of the new criteria and interactive dashboard was associated with a 60% reduction in the mean time spent by diabetes team members who remotely and asynchronously reviewed patient data and contacted patients, from 3.2±0.20 to 1.3±0.24 minutes per patient per week. Given fixed resources for review, this corresponded to an estimated 147% increase in weekly clinic capacity. Patients who qualified for and received remote review (n=58) have associated 8.8 percentage points (pp) (95% CI = 0.6–16.9pp) greater time-in-range (70-180 mg/dL) glucoses compared to 25 control patients who did not qualify at twelve months after T1D onset.ConclusionsAn algorithm-enabled prioritization of T1D patients with CGM for asynchronous remote review reduced provider time spent per patient and was associated with improved time-in-range.
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- 2021
120. Correlating structural assemblies of photosynthetic reaction centers on a gold electrode and the photocurrent - potential response
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J. Thomas Beatty, Adrian Jan Grzędowski, Dan Bizzotto, Amita Mahey, Daniel Jun, and Sylvester Zhang
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0301 basic medicine ,Photosynthetic reaction centre ,Materials science ,Science ,02 engineering and technology ,Electrolyte ,Electrochemistry ,7. Clean energy ,Article ,03 medical and health sciences ,Electron transfer ,Monolayer ,Photocurrent ,Multidisciplinary ,Biophotovoltaic ,business.industry ,021001 nanoscience & nanotechnology ,Surface chemistry ,3. Good health ,Chemistry ,Surface science ,030104 developmental biology ,Electrode ,Optoelectronics ,0210 nano-technology ,business - Abstract
Summary The use of biomacromolecules is a nascent development in clean alternative energies. In applications of biosensors and biophotovoltaic devices, the bacterial photosynthetic reaction center (RC) is a protein-pigment complex that has been commonly interfaced with electrodes, in large part to take advantage of the long-lived and high efficiency of charge separation. We investigated assemblies of RCs on an electrode that range from monolayer to multilayers by measuring the photocurrent produced when illuminated by an intensity-modulated excitation light source. In addition, atomic force microscopy and modeling of the photocurrent with the Marcus-Hush-Chidsey theory detailed the reorganization energy for the electron transfer process, which also revealed changes in the RC local environment due to the adsorbed conformations. The local environment in which the RCs are embedded significantly influenced photocurrent generation, which has implications for electron transfer of other biomacromolecules deposited on a surface in sensor and photovoltaic applications employing a redox electrolyte., Graphical abstract, Highlights • Controlled the formation of monolayer or multilayers of RCs on a gold electrode • Correlated electrochemical and photocurrent responses to the RC adsorbed conformations measured using AFM • Adsorbed RC conformations affect photocurrent generation • Photocurrent-potential response influenced by local redox mediator concentration and pH environment experienced by the adsorbed RCs, Chemistry; Electrochemistry; Surface chemistry; Surface science
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- 2021
121. Improving Variational Autoencoder based Out-of-Distribution Detection for Embedded Real-time Applications
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Feng, Yeli, primary, Ng, Daniel Jun Xian, additional, and Easwaran, Arvind, additional
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- 2021
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122. Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury
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Hu, Daniel Jun-Kit, primary, Yun, Jina, additional, Elstrott, Justin, additional, and Jasper, Heinrich, additional
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- 2021
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123. Highly Sensitive Method to Isolate Photocurrent Signals from Large Background Redox Currents on Protein‐Modified Electrodes
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Dan Bizzotto, J. Thomas Beatty, and Daniel Jun
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Photocurrent ,Photosynthetic reaction centre ,Electron transfer ,Chemistry ,Electrode ,Electrochemistry ,Photochemistry ,Redox ,Catalysis ,Highly sensitive - Published
- 2019
124. Photosynthetic Reaction Centres Assembled on a Gold Electrode and the Photocurrent - Potential Response
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Daniel Jun, Adrian Grzedowski, J. Thomas Beatty, and Dan Bizzotto
- Abstract
The photosynthetic reaction centre (RC) from Rhodobacter sphaeroides has been studied for use in biohybrid solar cells. Much of the previous work has focussed on improving photocurrent generation by loading the electrode surface with many copies of the protein resulting in multilayers. The primary disadvantage with this approach is the random orientation of proteins, with some supposedly oriented properly. We used RCs with Cys for covalent attachment to a gold electrode and for proper orientation. Areas of bare electrode surface and RCs bound non-specifically (i.e. not bound via the Cys) were competitively displaced by an insulating, non-redox layer of mercaptohexanol (MCH). The adsorbed monolayer of RCs was imaged using atomic force microscopy to detail the distribution of RCs on the gold surface for surfaces prepared with different RC deposition concentrations. Photocurrents were measured for all RC modified surfaces using a LED modulation method which enabled measurement of photocurrent in the presence of large faradaic currents from the sacrificial reactant (hydroquinone) at a variety of applied potentials.[1] The photocurrents generated from a monolayer composed of RCs and MCH resulted in consistent photocurrent currents. which enabled modeling of the photocurrent generation using the Marcus-Hush-Chidsey theory to extract a reorganization energy for this process. Multilayers of adsorbed RCs were distinctly different and revealed that the local environment in which the RCs are embedded significantly influenced photocurrent generation. [1] Jun, D.; Beatty, J. T.; Bizzotto, D. Highly Sensitive Method to Isolate Photocurrent Signals From Large Background Redox Currents on Protein‐Modified Electrodes. ChemElectroChem 2019, 6 (11), 2870–2875.
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- 2022
125. Contract-Based Hierarchical Resilience Management for Cyber-Physical Systems
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Karthikeyan Thangamariappan, Daniel Jun Xian Ng, Mohammad Shihabul Haque, Arvind Easwaran, and School of Computer Science and Engineering
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FOS: Computer and information sciences ,0209 industrial biotechnology ,General Computer Science ,Computer science ,Software Reliability ,media_common.quotation_subject ,02 engineering and technology ,User requirements document ,Fault detection and isolation ,Computer Science - Software Engineering ,D.2.4.g ,D.2.4.f ,020901 industrial engineering & automation ,Software ,D.2.15 ,Component (UML) ,0202 electrical engineering, electronic engineering, information engineering ,Resilience (network) ,media_common ,Flexibility (engineering) ,Resilience ,business.industry ,Cyber-physical system ,020202 computer hardware & architecture ,Software Engineering (cs.SE) ,Risk analysis (engineering) ,Computer science and engineering [Engineering] ,Psychological resilience ,business - Abstract
Orchestrated collaborative effort of physical and cyber components to satisfy given requirements is the central concept behind Cyber-Physical Systems (CPS). To duly ensure the performance of components, a software-based resilience manager is a flexible choice to detect and recover from faults quickly. However, a single resilience manager, placed at the centre of the system to deal with every fault, suffers from decision-making overburden; and therefore, is out of the question for distributed large-scale CPS. On the other hand, prompt detection of failures and efficient recovery from them are challenging for decentralised resilience managers. In this regard, we present a novel resilience management framework that utilises the concept of management hierarchy. System design contracts play a key role in this framework for prompt fault-detection and recovery. Besides the details of the framework, an Industry 4.0 related test case is presented in this article to provide further insights., Comment: \copyright 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works
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- 2018
126. Synthesis of New Biscoumarin Derivatives, In Vitro Cholinesterase Inhibition, Molecular Modelling and Antiproliferative Effect in A549 Human Lung Carcinoma Cells
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Daniel Jun, Monika Hudáčová, Juraj Ševc, Jana Vargová, Jana Janockova, Mária Kožurková, Veronika Ihnatova, Jan Korábečný, Petr Bzonek, Lucie Junova, Nikola Novakova, Eva Konkoľová, Kamil Kuca, Ondrej Soukup, Rastislav Jendželovský, Slávka Hamuľaková, Peter Fedoročko, and Tomas Kucera
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0301 basic medicine ,Models, Molecular ,Chemistry Techniques, Synthetic ,Pharmacology ,blood–brain barrier ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,A549 ,Coumarins ,lcsh:QH301-705.5 ,Spectroscopy ,Butyrylcholinesterase ,Molecular Structure ,Cell Cycle ,General Medicine ,Cell cycle ,Acetylcholinesterase ,Computer Science Applications ,Blood-Brain Barrier ,030220 oncology & carcinogenesis ,Alzheimer’s disease ,antiproliferative activity ,cholinesterase ,Cell Survival ,Antineoplastic Agents ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Structure-Activity Relationship ,Alzheimer Disease ,Humans ,MTT assay ,Physical and Theoretical Chemistry ,Molecular Biology ,A549 cell ,biscoumarin ,Dose-Response Relationship, Drug ,Cell growth ,Organic Chemistry ,In vitro ,Enzyme Activation ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,A549 Cells ,Cancer cell ,Cholinesterase Inhibitors - Abstract
A series of novel C4-C7-tethered biscoumarin derivatives (12a–e) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC50 = 6.30 µM) and butyrylcholinesterase (BChE, IC50 = 49 µM). Detailed molecular modelling studies compared the accommodation of ensaculin (well-established coumarin derivative tested in phase I of clinical trials) and 12d in the human recombinant AChE (hAChE) active site. The ability of novel compounds to cross the blood–brain barrier (BBB) was predicted with a positive outcome for compound 12e. The antiproliferative effects of newly synthesized biscoumarin derivatives were tested in vitro on human lung carcinoma cell line (A549) and normal colon fibroblast cell line (CCD-18Co). The effect of derivatives on cell proliferation was evaluated by MTT assay, quantification of cell numbers and viability, colony-forming assay, analysis of cell cycle distribution and mitotic activity. Intracellular localization of used derivatives in A549 cells was confirmed by confocal microscopy. Derivatives 12d and 12e showed significant antiproliferative activity in A549 cancer cells without a significant effect on normal CCD-18Co cells. The inhibition of hAChE/human recombinant BChE (hBChE), the antiproliferative activity on cancer cells, and the ability to cross the BBB suggest the high potential of biscoumarin derivatives. Beside the treatment of cancer, 12e might be applicable against disorders such as schizophrenia, and 12d could serve future development as therapeutic agents in the prevention and/or treatment of Alzheimer’s disease.
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- 2021
127. Curcumin and carvacrol co-loaded zein nanoparticles: Comprehensive preparation and assessment of biological activities in pest control
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Patricia Luiza de Freitas Proença, Estefânia Vangelie Ramos Campos, Tais Germano Costa, Renata de Lima, Ana Cristina Preisler, Halley Caixeta de Oliveira, Claudiane Martins da Rocha, Daniel Junior de Andrade, Kelly Cristina Goncalves, Ricardo Antonio Polanczyk, and Leonardo Fernandes Fraceto
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Crop protection ,Nanotechnology ,Nature-base solutions ,Acaricidal effect ,Insecticides activity ,Botany ,QK1-989 - Abstract
To address the escalating global demand for food production, it is imperative to minimize agricultural losses caused by pests, accounting for up to 40 % of the substantial worldwide losses of 70 billion USD. While conventional pesticides raise environmental concerns, environmentally friendly alternatives like curcumin and carvacrol face low biological activity due to their low solubility and premature degradation in environmental conditions, that is, degradation can occur due to solar radiation, high temperature, etc., before the active ingredients can exert its full potential. This study introduces zein-based nanocarriers encapsulating curcumin and carvacrol, exhibiting favorable characteristics. Cytotoxicity tests indicate approximately 60% viability for fibroblast cell lines compared to 20% for keratinocyte cell lines. The nanoencapsulated compounds exhibit promising biological activity against soybean pests, mites, and caterpillars, without causing phytotoxicity. Tetranychus urticae mortality rates reach 77.1 ± 11.5 %, and nanoencapsulated ingredients demonstrate higher repellency (61.1 ± 8.8%) than emulsified ones (51.1 ± 5.4 %). Nanoencapsulated ingredients exhibit significantly higher mortality rates for Spodoptera cosmioides and Spodoptera eridania, underscoring the potential of nanoencapsulation in bolstering bioactivity against specific pests and promoting sustainable agricultural practices.
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- 2024
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128. Effect of Module Elevation Height on Incident Solar Irradiance and Plant Growth in a Tropical Photovoltaic-Green Roof (PV-GR) system
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Rahmaniah, Faizatuzzahrah, primary, Zhang, Wen, additional, Hii, Daniel Jun Chung, additional, Hien, Wong Nyuk, additional, and Tay, Stephen En Rong, additional
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- 2021
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129. Embedded out-of-distribution detection on an autonomous robot platform
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Yuhas, Michael, primary, Feng, Yeli, additional, Ng, Daniel Jun Xian, additional, Rahiminasab, Zahra, additional, and Easwaran, Arvind, additional
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- 2021
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130. Monitoring Cumulative Cost Properties
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Al-Bataineh, Omar, primary, Ng, Daniel Jun Xian, additional, and Easwaran, Arvind, additional
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- 2021
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131. (±)- BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channel Antagonism and Antiaggregating Properties for Alzheimer's Disease
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Vendula Hepnarova, Kamil Musilek, Aurélie Baguet, Daniel Jun, José Marco-Contelles, Lhassane Ismaili, Emmanuel Haffen, Tomas Kucera, Jan Korabecny, Jana Janockova, Angela De Simone, Eva M. García-Frutos, Vincenza Andrisano, Manuela Bartolini, B. Refouvelet, Lucía Viejo, Cristóbal de los Ríos, Adeline Etievant, Ondrej Soukup, Rudolf Andrys, Julie Monnin, Raquel L Arribas, Conseil régional of Franche-Comté, Czech Science Foundation, Ministry of Education, Youth and Sports (Czech Republic), Ismaili L., Monnin J., Etievant A., Arribas R.L., Viejo L., Refouvelet B., Soukup O., Janockova J., Hepnarova V., Korabecny J., Kucera T., Jun D., Andrys R., Musilek K., Baguet A., Garcia-Frutos E.M., De Simone A., Andrisano V., Bartolini M., De Los Rios C., Marco-Contelles J., and Haffen E.
- Subjects
cholinesterase ,Physiology ,Monoamine oxidase ,Cognitive Neuroscience ,Ligand ,Pharmacology ,Ligands ,Calcium Channel ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,In vivo ,GSK-3 ,Humans ,Cholinesterases ,Cholinesterase Inhibitor ,Biginelli reaction ,Alzheimer's disease ,calcium channel ,cholinesterases ,GSK 3β ,MAO ,Calcium Channel Blockers ,Calcium Channels ,Cholinesterase Inhibitors ,Glycogen Synthase Kinase 3 beta ,Monoamine Oxidase ,GSK3B ,030304 developmental biology ,Cholinesterase ,0303 health sciences ,Voltage-dependent calcium channel ,biology ,Chemistry ,Calcium channel ,Cell Biology ,General Medicine ,Calcium channel, GSK 3β, MAO ,biology.protein ,Monoamine oxidase A ,Calcium Channel Blocker ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Human - Abstract
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified as a promising new hit compound showing in vitro balanced activities toward the aforementioned recognized AD targets. Additional in vitro studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein and β-amyloid peptide. The in vivo studies have shown that (±)-BIGI-3h (10 mg/kg intraperitoneally) significantly reduces scopolamine-induced cognitive deficits., L.I. thanks the Regional Council of Franche-Comté (2016YC- 04540 and 04560) for financial support, Mrs. M.-J. Henriot (PHV Pharma) for her support in the HPLC analyses, and Vincent Luzet for preliminary results in synthesis. O.S., J.J., and J.K. acknowledge the support from the grant by Czech Science Foundation no. 20-29633J. T.K., D.J., and V.H. acknowledge support from the Long-term Development Plan (Faculty of Military Health Sciences). R.A. and K.M. thank the Ministry of Education, Youth and Sports of the Czech Republic (ERDF no. CZ.02.1.01/0.0/0.0/16_025/0007444).
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- 2021
132. Cooling the urban environment
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Steve Kardinal Jusuf, Tong Shanshan, Daniel Jun Chung Hii, Tan Puay Yok, Tan Chun Liang, and Wong Nyuk Hein
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Environmental science ,Environmental planning ,Urban environment - Published
- 2020
133. Molecular characterization of Fusarium venenatum-based microbial protein in animal models of obesity using multi-omics analysis
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Daniel Junpyo Lee, An Na Kang, Junbeom Lee, Min-Jin Kwak, Daye Mun, Daseul Lee, Sangnam Oh, and Younghoon Kim
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Biology (General) ,QH301-705.5 - Abstract
Abstract Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement.
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- 2024
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134. de Sitter-eating O-planes in supercritical string theory
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Daniel Junghans
- Subjects
Flux Compactifications ,String and Brane Phenomenology ,Superstring Vacua ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract It has been proposed that flux compactifications of supercritical string theories (i.e., with spacetime dimension D > 10) have dS vacua, with large D acting as a control parameter for corrections to the classical spacetime effective action. In this paper, we provide a detailed analysis of the self-consistency of such models, focussing on α ′ and backreaction corrections. We first show that all supercritical AdS, Minkowski and dS vacua in this setting have ≳ O 1 $$ \gtrsim \mathcal{O}(1) $$ curvature and/or field strengths in the string frame. This may be in tension with suppressing α ′ corrections unless the coefficients of the higher-derivative terms have a sufficiently strong large-D suppression. We then argue that an additional and more severe problem arises in the dS case due to the backreaction of O-planes. In particular, we argue using a combination of geometric bounds and string-theory constraints that the O-plane backreaction is large in supercritical dS models. This implies that a large part of the naive classical geometry is eaten up by singular holes and thus indicates a breakdown of the classical description. Our finding resonates with several other recent results suggesting that string theory does not admit dS vacua in regimes where string and backreaction corrections are under control. As byproducts of our analysis, we derive a number of technical results that are useful beyond the specific applications in this paper. In particular, we compute the leading backreaction corrections to the smeared solution in a general flux compactification from D to d dimensions for an arbitrary distribution of O-planes and D-branes. We further argue for a general estimate for Green’s functions on compact manifolds (and therefore for the backreaction corrections) in terms of their diameter, volume and dimension.
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- 2023
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135. Chest Pain Evaluation: Diagnostic Testing
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Benjamin J.W. Chow, MD, PhD, FRCPC, FACC, FESC, FASNC, MSCCT, Paul Galiwango, MD, FRCPC, Anthony Poulin, MD, Paolo Raggi, MD, FACC, FAHA, FACP, FASNC, FSCCT, Gary Small, MBChB, PhD, MRCP, Daniel Juneau, MD, FRCPC, Mustapha Kazmi, MD, FRCPC, Bilal Ayach, MC, MSc, PhD, FRCPC, Rob S. Beanlands, MD, FRCPC, Anthony J. Sanfilippo, MD, FRCPC, FACC, Chi-Ming Chow, MDCM, MSc, FRCPC, FCCS, D. Ian Paterson, MD, FRCPC, Michael Chetrit, MD, FRCPC, FACC, Davinder S. Jassal, MD, FACC, FCCS, FRCPC, Kim Connelly, MBBS, PhD, FSCMR, FCCS, Eric Larose, DVM, MD, FRCPC, FCCS, FAHA, Helen Bishop, MD, FRCPC, Malek Kass, MD, Todd J. Anderson, MD, Haissam Haddad, MD, John Mancini, MD, FRCPC, FACP, FACC, Katie Doucet, MD, FRCPR, Jean-Sebastien Daigle, MD, FRCPC, Amir Ahmadi, MD, FRCPC, FACC, FSCCT, Jonathan Leipsic, MD, FRCPC, Siok Ping Lim, MRCP(UK), FRCR(UK), FRCPC, Andrew McRae, MD, PhD, FRCPC, and Annie Y. Chou, MD, FRCPC
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice. Résumé: La douleur ou la gêne thoracique sont des symptômes fréquents qui peuvent poser un dilemme diagnostique pour de nombreux médecins. Les erreurs de diagnostic d’une cause aiguë ou chronique progressive d’origine cardiaque peuvent d'ailleurs entraîner un risque considérable de morbidité et de mortalité. La présente synthèse porte sur les différentes options et modalités d’établissement du diagnostic et de la gravité d’une coronaropathie. Un algorithme efficace pour le choix des tests doit être adapté à chaque patient afin de maximiser l’exactitude diagnostique dans les plus brefs délais, de déterminer le pronostic à court et à long terme, et de permettre une mise en œuvre de traitements fondés sur des données probantes tout en tenant compte des coûts. Un algorithme décisionnel a donc été conjointement mis au point (www.chowmd.ca/cadtesting) et pourrait être largement adopté dans la pratique clinique.
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- 2023
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136. Achieving resilience for cyber-physical systems with 4DIAC IEC 61499 through parametric contracts
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Daniel Jun Xian Ng
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Risk analysis (engineering) ,Computer science ,Cyber-physical system ,Resilience (network) ,Parametric statistics - Published
- 2020
137. Development of versatile and potent monoquaternary reactivators of acetylcholinesterase
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José A. Dias, Tereza Kobrlova, Vendula Hepnarova, Tomas Kucera, Daniel Jun, Lubica Muckova, Florian Nachon, David Malinak, Jan Korabecny, Kamil Musilek, Franz Worek, Martina Hrabinova, Lukas Gorecki, Ondrej Soukup, Charlotte Courageux, Jana Zdarova Karasova, and Lukas Prchal
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0301 basic medicine ,Male ,Cholinesterase Reactivators ,Health, Toxicology and Mutagenesis ,Antidotes ,010501 environmental sciences ,Pharmacology ,Molecular Dynamics Simulation ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,In vivo ,Oximes ,medicine ,Animals ,Butyrylcholinesterase ,0105 earth and related environmental sciences ,Tabun ,Nerve agent ,Mice, Inbred BALB C ,General Medicine ,Acetylcholinesterase ,In vitro ,Acute toxicity ,030104 developmental biology ,chemistry ,Toxicity ,Female ,medicine.drug - Abstract
To date, the only treatments developed for poisoning by organophosphorus compounds, the most toxic chemical weapons of mass destruction, have exhibited limited efficacy and versatility. The available causal antidotes are based on reactivation of the enzyme acetylcholinesterase (AChE), which is rapidly and pseudo-irreversibly inhibited by these agents. In this study, we developed a novel series of monoquaternary reactivators combining permanently charged moieties tethered to position 6- of 3-hydroxypyridine-2-aldoxime reactivating subunit. Highlighted representatives (21, 24, and 27; also coded as K1371, K1374, and K1375, respectively) that contained 1-phenylisoquinolinium, 7-amino-1-phenylisoquinolinium and 4-carbamoylpyridinium moieties as peripheral anionic site ligands, respectively, showed efficacy superior or comparable to that of the clinically used standards. More importantly, these reactivators exhibited wide-spectrum efficacy and were minutely investigated via determination of their reactivation kinetics in parallel with molecular dynamics simulations to study their mechanisms of reactivation of the tabun-inhibited AChE conjugate. To further confirm the potential applicability of these candidates, a mouse in vivo assay was conducted. While K1375 had the lowest acute toxicity and the most suitable pharmacokinetic profile, the oxime K1374 with delayed elimination half-life was the most effective in ameliorating the signs of tabun toxicity. Moreover, both in vitro and in vivo, the versatility of the agents was substantially superior to that of clinically used standards. Their high efficacy and broad-spectrum capability make K1374 and K1375 promising candidates that should be further investigated for their potential as nerve agents and insecticide antidotes.
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- 2020
138. Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimeŕs drugs dealing with cholinergic, amyloid and mitochondrial systems
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Jana Janockova, Jana Kubackova, Karel Vales, Petr Jost, João Pina, Zuzana Bednarikova, Jan Korabecny, Katarina Motykova, Eugenie Nepovimova, Luísa Cortes, Zofia Chrienova, Kamil Musilek, Carlos Serpa, Rafael Dolezal, Lucie Svobodova, Lucie Junova, Laura Aitken, Vendula Hepnarova, Martin Vališ, Katarina Chalupova, Ondrej Soukup, Danijela Rostohar, Marketa Chvojkova, Daniel Jun, Lubica Muckova, Catarina S. H. Jesus, Zuzana Gazova, Kamil Kuca, Rebecca E. Hughes, and Tomas Kucera
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Amyloid ,Cholinergic Agents ,Pharmacology ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Protein Aggregates ,Structure-Activity Relationship ,In vivo ,Alzheimer Disease ,Drug Discovery ,medicine ,Humans ,Benzothiazoles ,Enzyme Inhibitors ,Molecular Biology ,IC50 ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,3-Hydroxyacyl CoA Dehydrogenases ,Acetylcholinesterase ,In vitro ,0104 chemical sciences ,Mitochondria ,010404 medicinal & biomolecular chemistry ,Neuroprotective Agents ,Benzothiazole ,chemistry ,Tacrine ,Cholinergic ,medicine.drug - Abstract
A series of tacrine – benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. The best derivative of the series could be considered 10w that was found to be highly potent and selective towards AChE with the IC50 value in nanomolar range. Moreover, the same drug candidate exerted absolutely the best results of the series against ABAD, decreasing its activity by 23% at 100 µM concentration. Regarding the cytotoxicity profile of highlighted compound, it roughly matched that of its parent compound – 6-chlorotacrine. Finally, 10w was forwarded for in vivo scopolamine-induced amnesia experiment consisting of Morris Water Maze test, where it demonstrated mild procognitive effect. Taking into account all in vitro and in vivo data, highlighted derivative 10w could be considered as the lead structure worthy of further investigation.
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- 2020
139. Bio-Phototransistors with Immobilized Photosynthetic Proteins
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J. Thomas Beatty, Arash Takshi, Daniel Jun, and Houman Yaghoubi
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Photosynthetic reaction centre ,Absorption spectroscopy ,Computer Networks and Communications ,Photodetector ,lcsh:TK7800-8360 ,Electron donor ,02 engineering and technology ,010402 general chemistry ,Photosynthesis ,Photochemistry ,01 natural sciences ,bio-phototransistor ,Rhodobacter sphaeroides ,chemistry.chemical_compound ,rhodobacter sphaeroides ,Electrical and Electronic Engineering ,biology ,Chemistry ,reaction center ,lcsh:Electronics ,021001 nanoscience & nanotechnology ,biology.organism_classification ,0104 chemical sciences ,Hardware and Architecture ,Control and Systems Engineering ,Signal Processing ,Photosynthetic bacteria ,ISFET ,0210 nano-technology - Abstract
The efficient mechanism of light capture by photosynthetic proteins allows for energy transfer and conversion to electrochemical energy at very low light intensities. In this work, reaction center (RC) proteins, or a core complex consisting of the RC encircled by light harvesting (LH1) proteins (RC-LH1) from photosynthetic bacteria, were immobilized on an insulating layer of an ion-sensitive field-effect transistor (ISFET) to build bio-photodetectors. The orientation of the RC proteins was controlled via application of a hybrid linker made of 10-carboxydecylphosphonic acid and cytochrome c that anchored the RCs to their electron donor side. Bio-phototransistors consisting of either the core RC or the RC-LH1 core complex were tested under white and monochromic light. The difference between the dark and light currents at different wavelengths are well-matched with the absorption spectrum of the photosynthetic proteins. The results show potential for the use of photosynthetic proteins in photodetectors.
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- 2020
140. Introduction of the Menaquinone Biosynthetic Pathway into
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Daniel, Jun, Tomas, Richardson-Sanchez, Amita, Mahey, Michael E P, Murphy, Rachel C, Fernandez, and J Thomas, Beatty
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Electron Transport ,Kinetics ,Spectrometry, Mass, Electrospray Ionization ,Photobleaching ,Bacterial Proteins ,Metabolic Engineering ,Ubiquinone ,Photosynthetic Reaction Center Complex Proteins ,Membrane Proteins ,Vitamin K 2 ,Rhodobacter sphaeroides ,Chromatography, High Pressure Liquid ,Plasmids - Abstract
Quinones are redox-active molecules that transport electrons and protons in organelles and cell membranes during respiration and photosynthesis. In addition to the fundamental importance of these processes in supporting life, there has been considerable interest in exploiting their mechanisms for diverse applications ranging from medical advances to innovative biotechnologies. Such applications include novel treatments to target pathogenic bacterial infections and fabricating biohybrid solar cells as an alternative renewable energy source. Ubiquinone (UQ) is the predominant charge-transfer mediator in both respiration and photosynthesis. Other quinones, such as menaquinone (MK), are additional or alternative redox mediators, for example in bacterial photosynthesis of species such as
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- 2020
141. Is It the Twilight of BACE1 Inhibitors?
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Martina Hrabinova, Daniel Jun, Ondrej Soukup, Jaroslav Pejchal, Monika Schmidt, and Tomas Kucera
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Amyloid beta ,Skin rashes ,Disease ,Bioinformatics ,Placebo ,Weight loss ,Alzheimer Disease ,Aricle ,mental disorders ,inhibitors ,Medicine ,Aspartic Acid Endopeptidases ,Humans ,β-secretase ,Pharmacology (medical) ,Prospective Studies ,Adverse effect ,substrates ,Pharmacology ,clinical trials ,Amyloid beta-Peptides ,biology ,business.industry ,General Medicine ,Clinical trial ,amyloid beta ,Psychiatry and Mental health ,Neurology ,β secretase ,biology.protein ,Neurology (clinical) ,medicine.symptom ,Amyloid Precursor Protein Secretases ,business ,Alzheimer’s disease - Abstract
β-secretase (BACE1) has been regarded as a prime target for the development of amyloid beta (Aβ) lowering drugs in the therapy of Alzheimer´s disease (AD). Although the enzyme was discovered in 1991 and helped to formulate the Aβ hypothesis as one of the very important features of AD etiopathogenesis, progress in AD treatment utilizing BACE1 inhibitors has remained limited. Moreover, in the last years, major pharmaceutical companies have discontinued clinical trials of five BACE1 inhibitors that had been strongly perceived as prospective. In our review, the Aβ hypothesis, the enzyme, its functions, and selected substrates are described. BACE1 inhibitors are classified into four generations. Those that underwent clinical trials displayed adverse effects, including weight loss, skin rashes, worsening of neuropsychiatric symptoms, etc. Some inhibitors could not establish a statistically significant risk-benefit ratio, or even scored worse than placebo. We still believe that drugs targeting BACE1 may still hide some potential, but a different approach to BACE1 inhibition or a shift of focus to modulation of its trafficking and/or post-translational modification should now be followed.
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- 2020
142. List of contributors
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Arturo Anadón, Rudolf Andrys, Pavel Avdonin, Jiri Bajgar, Mahdi Balali-Mood, Frank Balszuweit, Atrayee Banerjee, Cheryl B. Bast, Daria Belinskaia, Vijay K. Bharti, Claire E. Bollinger, Robert P. Casillas, Ryan Clark, Edward D. Clarkson, Toby B. Cole, Rhian B. Cope, Robert W. Coppock, Lucio G. Costa, Wolf-D. Dettbarn, Alzbeta Dlabkova, Robin B. Doss, Margitta M. Dziwenka, Jorge Estevez, Tim J. Evans, John K. Fink, Swaran J.S. Flora, Clement E. Furlong, Josef Fusek, Jacqueline Garrick, Jeffery M. Gearhart, Donald R. Gerecke, Dana F. Glass-Mattie, Saryu Goel, Nikolay Goncharov, Richard K. Gordon, Joshua P. Gray, Zoran Grubic, Kavita Gulati, Ramesh C. Gupta, Sharon M. Gwaltney-Brant, Tracey A. Hamilton, Kenneth J. Harris, Darryl B. Hood, Edward M. Jakubowski, Richard Jenkins, David A. Jett, Yuqin Jiao, Harald John, Nathan H. Johnson, Milan Jokanović, Daniel Jun, Georgy Karakashev, Jiri Kassa, Maja Katalinic, Kai Kehe, Natalia Khlebnikova, Urmila P. Kodavanti, Ekaterina Korf, Nadezhda Koryagina, Bojan Kovač, Gopala Krishna, Mayur Krishna, Kamil Kuca, Dinesh Kumar, Yukio Kuroiwa, Sergey Kuznetsov, Kamil Kuča, Joseph C. Larsen, Mikhail Leninskiy, Jing Liu, Heather Lochotzki, Oksana Lockridge, Jordana Lockwich, Bommanna G. Loganathan, Dragana Lončar-Stojiljković, Sofya V. Lushchekina, Megan E. Lyman, Mark Maguire, Galina F. Makhaeva, Jitendra K. Malik, David Malinak, Tomaz Mars, Judit Marsillach, María-Rosa Martínez-Larrañaga, Patrick Masson, Shigeki Masunaga, Monique McCallister, Linda A. McCauley, Roger O. McClellan, Patrick M. McNutt, Edward C. Meek, Elaine Merrill, Sylvia Milanez, Igor Mindukshev, Katarina Mis, Jan Misik, Michael J. Murphy, Kamil Musilek, Tamie Nakajima, Marian R. Nelson, Eugenie Nepovimova, Tetsu Okumura, Jiri Patocka, Katarina Pegan, Jaroslav Pejchal, Sergej Pirkmajer, René Pita, Jason Pitt, Yiuka Pitt, Gennady E. Platoff, Carey N. Pope, Andrey Radilov, Anu Rahal, Aramandla Ramesh, Arunabha Ray, Vladimir Rembovskiy, Raina Rhoades, Rudy J. Richardson, Dragana Ristić, Peter J. Robinson, Alejandro Romero, Chris Ruark, Harry Salem, Natalia Samchenko, Tetsuo Satoh, Russell E. Savage, Elena Savelieva, Lawrence M. Schopfer, Alfred M. Sciuto, Yasuo Seto, Michael P. Shakarjian, Vladimir Shmurak, Adam Skarka, Ranko Škrbić, Miguel Sogorb, Shardell M. Spriggs, Sakshi Srivastava, Dirk Steinritz, Miloš P. Stojiljković, Neera Tewari-Singh, Horst Thiermann, Suresh Kumar Thokchom, Larry J. Thompson, Anton Ukolov, Luis G. Valerio, M.J. van der Schans, Daya R. Varma, Eugenio Vilanova, Annetta Watson, Sanjeeva J. Wijeyesakere, Tina Wismer, R. Mark Worden, Franz Worek, Linzzi K. Wright, Hidenori Yamasue, Takemi Yoshida, Toshiharu Yoshioka, Robert A. Young, Snjezana Zaja-Milatovic, Valeriy Zinchenko, and Csaba K. Zoltani
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- 2020
143. Pharmacological prophylaxis against nerve agent poisoning: experimental studies and practical implications
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Josef Fusek, Daniel Jun, Kamil Kuca, Jiri Bajgar, and Jiri Kassa
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Benactyzine ,Chemistry ,medicine.medical_treatment ,Organophosphate ,Pharmacology ,Acetylcholinesterase ,chemistry.chemical_compound ,Pyridostigmine ,Detoxification ,medicine ,Antidote ,Butyrylcholinesterase ,medicine.drug ,Nerve agent - Abstract
Prophylaxis against intoxication with organophosphate (OP) nerve agents is based on various approaches. Protection of acetylcholinesterase (AChE), the target enzyme for toxic action of OP nerve agents, is a basic requirement for effective prophylaxis. This can be achieved by using reversible AChE inhibitors, preferably carbamates (CMs). AChE inhibited by CMs is resistant to the action of an OP nerve agent for a transient period. After spontaneous recovery of the activity, normal AChE serves as a source of the active enzyme. Detoxification is carried out by the administration of enzymes hydrolyzing the OPs or evaluating specific enzymes (cholinesterases). The OP nerve agent is bound to the exogenously administered enzyme, and thus the OP level in the organism is decreased (“scavenger” effect). The administration of enzymes, such as AChE and butyrylcholinesterase, as scavengers seems to be very promising, as the enzyme acts at the very beginning of the toxic action, and without interaction with target tissues and without side effects. The antidotes currently used for the treatment of OP poisoning can be tested as prophylactics. This principle can be considered as a treatment in advance. Standard antidotes were studied in this respect; that is, anticholinergics, enzyme reactivators, anticonvulsants, and others. The problem with their use is the timing, duration, and achievement of sufficient levels of these antidotes after administration. At present, pyridostigmine seems to be a common prophylactic antidote, while PANPAL (tablets with pyridostigmine, trihexyphenidyle, and benactyzine) and TRANSANT (a transdermal patch containing HI-6) are the prophylactics. Future drug development will be focused on scavengers (cholinesterases and other enzymes) acting prior to the binding of the nerve agent to the target sites, and to other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, physostigmine, acridine derivatives, etc.) or other compounds.
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- 2020
144. CLAIR: A Contract-based Framework for Developing Resilient CPS Architectures
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Arvind Easwaran, Sidharta Andalam, Daniel Jun Xian Ng, and Karthikeyan Thangamariappan
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FOS: Computer and information sciences ,Computer science ,media_common.quotation_subject ,Multitier architecture ,Distributed computing ,020208 electrical & electronic engineering ,020207 software engineering ,02 engineering and technology ,Transparency (human–computer interaction) ,Decoupling (cosmology) ,Automaton ,Software Engineering (cs.SE) ,Computer Science - Software Engineering ,Multilayered architecture ,0202 electrical engineering, electronic engineering, information engineering ,Code (cryptography) ,Psychological resilience ,Code maintenance ,media_common - Abstract
Industrial cyber-infrastructure is normally a multilayered architecture. The purpose of the layered architecture is to hide complexity and allow independent evolution of the layers. In this paper, we argue that this traditional strict layering results in poor transparency across layers affecting the ability to significantly improve resiliency. We propose a contract-based methodology where components across and within the layers of the cyber-infrastructure are associated with contracts and a light-weight resilience manager. This allows the system to detect faults (contract violation monitored using observers) and react (change contracts dynamically) effectively. It results in (1) improving transparency across layers; helps resiliency, (2) decoupling fault-handling code from application code; helps code maintenance, (3) systematically generate error-free fault handling code; reduces development time. Using an industrial case study, we demonstrate the proposed methodology., Comment: \copyright 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works
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- 2020
- Full Text
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145. ATLAS: Software for analysing the relationship between urban microclimate and urban morphology in a tropical city
- Author
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Nyuk Hien Wong, Daniel Jun Chung Hii, Zhongqi Yu, Yang He, Shisheng Chen, Marcel Ignatius, and Wen Zhang
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Environmental Engineering ,media_common.quotation_subject ,Geography, Planning and Development ,Microclimate ,Urban morphology ,Regression analysis ,Building and Construction ,Solar irradiance ,Atmospheric sciences ,Quartile ,Sky ,Principal component analysis ,Tropical climate ,Environmental science ,Civil and Structural Engineering ,media_common - Abstract
This research applied clustering to unsupervised learning of meteorological data and evaluated the impact of urban morphology on temperature in different weather. Air Temperature Learning Algorithms (ATLAS) was developed for the cluster analysis of urban meteorological data and regression analysis of urban morphology and outdoor air temperature. The case study experiment was conducted on the university campus. Based on principal component analysis (PCA) reduced K-means clustering, this study evaluated the characteristics of reference meteorological data, and local solar irradiance and air temperature. Three weather conditions were identified for the given reference meteorological data. Revised selection criteria for clear, hot, and calm weather in tropical climate were proposed. The mean R a i n t o t shall be less than 0.01 mm, with 25th, 50th and 75th quartile to be 0 mm, respectively. The mean W a v g and its quartiles shall be less than 3 m/s. The mean, 50th and 75th quartile of S t o t , S m a x , and S a v g shall be higher than 5000 Wh/m2, 800 W/m2 and 200 W/m2, respectively. The mean, 50th and 75th quartile of T a v g , T m a x and T m i n shall be higher than 29 °C , 32 °C and 26 °C , respectively. The hourly ground level air temperature models were established in different weather. The results indicate the ground level air temperature in rainy and cool weather conditions are more predictable than hot and dry weather conditions. The sky view factor, exterior wall area, and green plot ratio have a greater impact on air temperature in sunny days than rainy days.
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- 2022
146. Sustainable laboratory evaluations: Optimized fume-hood- intensive ventilation and energy efficiency without compromising occupational safety and comfort
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Yueyang He, Daniel Jun Chung Hii, Nyuk Hien Wong, and Thian-Guan Peck
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Renewable Energy, Sustainability and the Environment ,Strategy and Management ,Building and Construction ,Industrial and Manufacturing Engineering ,General Environmental Science - Published
- 2022
147. Oxime K033-Reactivation Activity of Cholinesterases Inhibited by Various Nerve Agents and Organophosphorus Pesticides
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Kamil Musilek, Ondrej Krejcar, Ondrej Soukup, Qinghua Wu, Daniel Jun, Teodorico C. Ramalho, Raquel O. Lopes, Jaroslav Pejchal, Tanos C. C. França, Marek Penhaker, Eugenie Nepovimova, and Kamil Kuca
- Subjects
biology ,Chemistry ,medicine.medical_treatment ,010401 analytical chemistry ,Pharmaceutical Science ,04 agricultural and veterinary sciences ,Pharmacology ,Pesticide ,Oxime ,040401 food science ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Drug Discovery ,medicine ,biology.protein ,Molecular Medicine ,Antidote ,Organophosphorus pesticides ,Nerve agent ,medicine.drug ,Cholinesterase - Published
- 2018
148. ANÁLISE DO METABOLISMO OXIDATIVOS E SUA CORRELAÇÃO COM O DESEMPENHO OCUPACIONAL DE PACIENTES COM DOENÇA DE PARKINSON SOB PARÂMETROS DA CLASSIFICAÇÃO INTERNACIONAL DE FUNCIONALIDADE, INCAPACIDADE E SAÚDE
- Author
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Esther Samara da Costa Santos, Daniel Jun Hayashi, and Guilherme Henrique Siqueira Oeiras
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- 2019
149. Inhalation of molecular hydrogen prevents ischemia-reperfusion liver damage during major liver resection
- Author
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Zdeněk Turek, Aleš Kohout, Jiří Kotek, Věra Radochová, Nela Váňová, David Astapenko, Jiří Páral, Ondřej Malý, Radomír Hyšpler, Ján Zajak, and Daniel Jun
- Subjects
medicine.medical_specialty ,Antioxidant ,medicine.medical_treatment ,Ischemia ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Lactate dehydrogenase ,medicine ,Tourniquet ,Inhalation ,business.industry ,General Medicine ,medicine.disease ,Editorial ,chemistry ,030220 oncology & carcinogenesis ,Alkaline phosphatase ,030211 gastroenterology & hepatology ,Original Article ,Hepatic portal vein ,business ,Oxidative stress - Abstract
Background: Liver resection is a surgical procedure associated with a high risk of hepatic failure that can be fatal. One of the key mechanisms involves ischemia-reperfusion damage. Building on the well- known positive effects of hydrogen at mitigating this damage, the goal of this work was to demonstrate the antioxidant, anti-inflammatory, and anti-apoptotic effects of inhaled hydrogen in domestic pigs during major liver resection. Methods: The study used a total of 12 domestic pigs, 6 animals underwent resection with inhaled hydrogen during general anesthesia, and 6 animals underwent the same procedure using conventional, unsupplemented, general anesthesia. Intraoperative preparation of the left branch of the hepatic portal vein and the left hepatic artery was performed, and a tourniquet was applied. Warm ischemia was induced for 120 minutes and then followed by liver reperfusion for another 120 minutes. Samples from the ischemic and non-ischemic halves of the liver were then removed for histological and biochemical examinations. Results: An evaluation of histological changes was based on a numerical expression of damage based on the Suzuki score. Liver samples in the group with inhaled hydrogen showed a statistically significant reduction in histological changes compared to the control group. Biochemical test scores showed no statistically significant difference in hepatic transaminases, alkaline phosphatase (ALP), lactate dehydrogenase (LD), and lactate. However, a surprising result was a statistically significant difference in gamma-glutamyl-transferase (GMT). Marker levels of oxidative damage varied noticeably in plasma samples. Conclusions: In this experimental study, we showed that inhaled hydrogen during major liver resection unquestionably reduced the level of oxidative stress associated with ischemia-reperfusion damage. We confirmed this phenomenon both histologically and by direct measurement of oxidative stress in the organism.
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- 2019
150. Outcomes of underweight, overweight, and obese pediatric kidney transplant recipients
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Ernesto P. Molmenti, Lulette Infante, Elliot Grodstein, Christine B. Sethna, Rachel M. Frank, Laura Castellanos, Daniel Jun, Pamela Singer, Kiranjot Kaur, Lewis W. Teperman, and Ahmed Fahmy
- Subjects
Adult ,Graft Rejection ,Male ,Nephrology ,medicine.medical_specialty ,Adolescent ,030232 urology & nephrology ,Delayed Graft Function ,030204 cardiovascular system & hematology ,Overweight ,Lower risk ,Body Mass Index ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Thinness ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Obesity ,Registries ,Risk factor ,Child ,Kidney transplantation ,Retrospective Studies ,business.industry ,Graft Survival ,Age Factors ,Length of Stay ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Transplantation ,Child, Preschool ,Preoperative Period ,Pediatrics, Perinatology and Child Health ,Kidney Failure, Chronic ,Female ,medicine.symptom ,Underweight ,business ,Body mass index - Abstract
Obesity is a risk factor for poor transplant outcomes in the adult population. The effect of pre-transplant weight on pediatric kidney transplantation is conflicting in the existing literature. Data was collected from the Organ Procurement and Transplantation Network (OPTN) database on recipients aged 2–21 years who received a kidney-only transplant from 1987 to 2017. Recipients were categorized into underweight, normal, overweight, and obese cohorts. Using adjusted regression models, the relationship between recipient weight and various graft outcomes (delayed graft function [DGF], acute rejection, prolonged hospitalization, graft failure, mortality) was examined. 18,261 transplant recipients (mean age 14.1 ± 5.5 years) were included, of which 8.7% were underweight, 14.8% were overweight, and 15% were obese. Obesity was associated with greater odds of DGF (OR 1.3 95% CI 1.13–1.49, p
- Published
- 2018
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