jablonkagroup/rise_ai_scientists huggingface dataset:
Authors: Xuan Yang
Source: Mspace (University of Manitoba) (article, 2019-01-01)
Field: Chemistry — Organic Chemistry

Design, synthesis and biological properties of amphiphilic aminoglycosides Antibiotic resistance is a serious threat to human health, as we are facing the emergence of pathogens resistant to all available antibiotics. Amphiphilic aminoglycosides (AAGs) are an emerging source of antibacterials to combat infections caused by antibiotic-resistant bacteria; however, we found that they can also play a role as antibiotic adjuvants in combination therapies. In this study, a new series of amphiphilic aminoglycoside-based (AG-based) adjuvants, tobramycin-based efflux pump inhibitor conjugates, tobramycin-based lysine peptoid conjugates, and nebramine-based conjugates, have been successfully developed. In vitro combination studies indicate the ability of these AG-based conjugates to potentiate multiple classes of legacy antibiotics particularly to tetracyclines, fluoroquinolones, and rifampicin against multidrug-resistant (MDR) Gram-negative bacilli. We also demonstrated in vivo that combinations of selected AG-based conjugates and certain legacy antibiotics (minocycline or rifampicin) protect Galleria mellonella larvae from the lethal effects of MDR Pseudomonas aeruginosa. Mode of action studies indicate that these AG-based conjugates appear to possess intrinsic physicochemical properties that induce multimodal effects including permeabilization of the bacterial outer membrane, depolarization of the inner membrane, and dissipation of the proton motive force (PMF), which energizes efflux pumps. In addition, we discovered AAGs can also boost the innate immune response that may be exploited therapeutically. The amphiphilic tobramycins are capable of inducing the production of the chemokine IL-8, which plays a critical role in the recruitment of immune cells such as neutrophils required for the resolution of infections. Moreover, AAGs can selectively control inflammatory responses induced in the presence of endotoxins. Thus, AAGs represent a promising avenue for the development of multifunctional molecules or antibiotic adjuvants for the prevention or treatment of bacterial infections. Amphiphile ; Chemistry ; Biochemical engineering ; Computer science ; Engineering ; Organic chemistry ; Copolymer Carbohydrate Chemistry and Synthesis ; Glycosylation and Glycoproteins Research ; Click Chemistry and Applications
Authors: Keshav Parashar | Sushil Kumar Starling
Source: Journal of Drug Delivery and Therapeutics (article, 2019-06-15)
Field: Chemistry — Organic Chemistry

Anti-inflammatory and Anti-arrhythmic Activities of 1-(Alkanoylphenoxy/ Thiophenoxy)-3-(N4-Phenylpiperazinyl) Propane Synthesis and pharmacological screening of 1-(o-, m-,p-alkanoyl-, p-benzoyl-, p-cinnamoyl-, p-α-hydroxypropyl- p- α -acetoxypropyl-, p- α-oximainopropyl-, p- α -ureidiminopropyl-phenoxy/ p-propionylthiophenoxy)-3-N4-(phenylpiperazinyl)propanes, 1-(p-propionylphenoxy)-3-substituted aminopropane, 1-(p-propionylphenoxy)-3-N4-(phenylpiperazinyl) ethane and butanes and B-(p-propionylphenoxy)-N1-(N4-phenylpiperazinyl) propionamide are reported. Some of the compounds possess Anti-inflammatory and Anti-arrhythmic activity. Keyword: pharmacological screening, Anti-inflammatory, Anti-arrhythmic activity, anti-depressant activity, IR spectra, etc. Propane ; Chemistry ; Internal medicine ; Medicine ; Pharmacology ; Organic chemistry Synthesis and biological activity ; Analytical Methods in Pharmaceuticals ; Pharmacological Receptor Mechanisms and Effects
Authors: Egor Kraev | Mark Harley
Source: arXiv (Cornell University) (preprint, 2019-06-05)
Field: Materials Science — Materials Chemistry

Probabilistic hypergraph grammars for efficient molecular optimization We present an approach to make molecular optimization more efficient. We infer a hypergraph replacement grammar from the ChEMBL database, count the frequencies of particular rules being used to expand particular nonterminals in other rules, and use these as conditional priors for the policy model. Simulating random molecules from the resulting probabilistic grammar, we show that conditional priors result in a molecular distribution closer to the training set than using equal rule probabilities or unconditional priors. We then treat molecular optimization as a reinforcement learning problem, using a novel modification of the policy gradient algorithm - batch-advantage: using individual rewards minus the batch average reward to weight the log probability loss. The reinforcement learning agent is tasked with building molecules using this grammar, with the goal of maximizing benchmark scores available from the literature. To do so, the agent has policies both to choose the next node in the graph to expand and to select the next grammar rule to apply. The policies are implemented using the Transformer architecture with the partially expanded graph as the input at each step. We show that using the empirical priors as the starting point for a policy eliminates the need for pre-training, and allows us to reach optima faster. We achieve competitive performance on common benchmarks from the literature, such as penalized logP and QED, with only hundreds of training steps on a budget GPU instance. Computer science ; Prior probability ; Hypergraph ; Probabilistic logic ; Reinforcement learning ; Benchmark (surveying) ; Artificial intelligence ; Directed acyclic graph ; Graph ; Rule-based machine translation ; Theoretical computer science ; Machine learning ; Mathematical optimization ; Algorithm ; Mathematics ; Bayesian probability Machine Learning in Materials Science ; Computational Drug Discovery Methods ; Machine Learning and Algorithms
Authors: Harald F. Krug
Source: Arrow@dit (Dublin Institute of Technology) (article, 2019-09-04)
Field: Materials Science — Materials Chemistry

Working Report on the Status Quo of Nanomaterials Impact on Health and Environment Nanotechnology is regarded as one of the key technologies of the future and associated with high expectations by politics, science and economy. Artificially produced nanosized particles and nanoscale system components have new properties which are of importance for the development of new products and applications. Such new properties of materials and substances result from the special properties of surfaces and interfaces and in part, from the geometric shape of the material. In theory nanoparticles (NPs) can be produced from nearly any chemical; however, most NPs that are currently in use today have been made from transition metals, silicon, carbon (single-walled carbon nanotubes; fullerenes), and metal oxides (zinc dioxide and titanium dioxide). Potentially harmful effects of nanotechnology might arise as a result of the nature of the NPs themselves, the characteristics of the products made from them, or aspects of the manufacturing process involved (Borm and Kreyling, 2004). The large surface area, crystalline structure, and reactivity of some NPs may facilitate transport in the environment or lead to harm because of their interactions with cellular material. In the case of nanomaterials, size matters, and could facilitate and exacerbate any harmful effects caused by the composition of the material. The highest risks for humans and the environment are associated with nanomaterials contained in products in the form of free particles. As long as NPs remain firmly embedded in materials, hardly any risk should be expected (Brouwer, 2004). However, it has to be clarified in these cases whether and in which form nanomaterials can be released into the environment during the production process, the use of a product, due to ageing and degradation as well as during disposal and recycling processes. Of course, also in the case of nanomaterials, environmental risk assessment should take into account their entire life cycle. Status quo ; Environmental health ; Business ; Medicine ; Political science Nanoparticles: synthesis and applications ; Graphene and Nanomaterials Applications ; Advanced Nanomaterials in Catalysis
Authors: Daniele Urso
Source: CINECA IRIS Institutial Research Information System (University of Genoa) (article, 2019-03-15)
Field: Materials Science — Biomaterials

Sistemi a base di chitosano per applicazioni farmacologiche This PhD work is about the implementation of innovative chitosan-based Drug Delivery Systems (DDSs) for the cure of periodontal disease. Current treatment of this pathology consists of localized administrations of antibiotic and anti-inflammatory drugs, but repeated therapeutic sessions have negative consequences on the patient?s quality of life. In the present work novel potential drug delivery systems have been investigated with the aim of administering drugs and simultaneously promoting the regeneration of damaged tissues. To this purpose chitosan has been chosen because of its unique properties including biocompatibility, biodegradability, mucoadhesivity, antimicrobial and wound-healing capabilities. Three types of chitosan-based systems have been studied: microbeads with internal sponge-like architecture, obtained by drop-to-drop coagulation of an acetic chitosan solution in a EtOH/ NH3/H2O bath, films obtained by drop-casting, and membranes prepared by electrospinning from an aqueous mixture of chitosan and poly(ethylene oxide). The uptake and release properties of these systems have been tested with the antibiotic drug Doxycycline hydrochloride (DC) and the anti-inflammatory drug Triamcinolone acetonide (TC). Freundlich and pseudo second-order kinetic equations have been applied to describe the processes at varying the drug concentrations. The most relevant results obtained from this PhD work show delayed drug release by microbeads and films, compatible with a controlled DDS behaviour, and highly increased DC uptake by electrospun membranes, likely due to their very porous structure. Base (topology) ; Mathematics Nanocomposite Films for Food Packaging ; Enzyme Catalysis and Immobilization ; Biopolymer Synthesis and Applications
Authors: Di Wang
Source: Gutenberg Open Science (article, 2019-01-01)
Field: Chemistry — Physical and Theoretical Chemistry

Reversible Stimuli Responsive Radicals and Their EPR Spectroscopic Characterization My thesis is about the synthesis of organic radicals with external stimuli-responsive properties, characterization and analysis of spin and magnetic properties with the measurements of electron paramagnetic resonance (EPR) and simulations of density functional calculations (DFT). In this work I discuss different external stimuli factors to interact with the spin systems: e.g. temperature, reduction and or oxidation, and photo stimulation. Different characterizations, especially EPR spectroscopy, were used to detect the transitions or switch of the whole radical systems. Several interesting changes of spin properties were found during the processes, like hyperfine splitting of spin species and the spin coupling interactions between radicals. Some vital transitions of spin species can have bright potentials in the future applications. The introduction of organic radical systems with stimuli responsive properties, their possible applications and the motivations of this thesis are outlined in chapter 1. Then this is followed by a brief description of EPR spectroscopy in 2nd chapter. In chapter 3, I summarized the solvent and temperature effects on flexibly bridged bis(nitronyl nitroxides). Chapter 4 deals with the oxidation of donors like phenothiazine and phenoxazine which are combined with a conjugated nitronyl nitroxide radical unit, which I synthesized. In addition, EPR spectroscopy is successfully used to investigate the mechanism of the whole photo induced reaction by trapping and analysis of the radical intermediate species existing during the whole processes, which is described in chapter 5. In the last chapter, I studied the oxidation and reduction of a spiro bridged bishexabenzocoronene. It turned out that this new molecule cannot be described just by connection of HBCs but new non degenerate HOMOs and LUMOs are formed. Electron paramagnetic resonance ; Radical ; Characterization (materials science) ; Photochemistry ; Chemistry ; Nuclear magnetic resonance ; Materials science ; Nanotechnology ; Physics ; Biochemistry Photochemistry and Electron Transfer Studies ; Photoreceptor and optogenetics research ; Conducting polymers and applications
Authors: Wenzhe Huang
Source: Journal of Drug Delivery and Therapeutics (article, 2019-02-15)
Field: Materials Science — Biomaterials

Peptide-based Drug Delivery for Curing Cancer Peptides have numerous advantages as the chains help treat cancer, tumor and several complex diseases. The review details on the different structures of peptides that can ensure actual and efficient delivery of therapy to tumor and cancer cases. The co-delivery system mainly aims to improve the therapeutic delivery process regarding manufacturing, targeting, and impact.&#x0D; Keywords: Nanotechnology, Peptide-based Drug Delivery, cancer Drug delivery ; Cancer therapy ; Drug ; Cancer ; Medicine ; Cancer drugs ; Targeted drug delivery ; Nanotechnology ; Cancer treatment ; Peptide ; Pharmacology ; Materials science ; Chemistry ; Internal medicine Nanoparticle-Based Drug Delivery ; RNA Interference and Gene Delivery ; Nanoplatforms for cancer theranostics
Authors: Eider Aldalur | José-Ramon Sarasua | Aitor Larrañaga | Jone M. Ugartemendia
Source: EKAIA Euskal Herriko Unibertsitateko Zientzi eta Teknologi Aldizkaria (article, 2019-02-15)
Field: Materials Science — Biomaterials

Mikrotxantiloien fabrikazioa eta hauen aplikazioak biomedikuntzan Azken aldian, biobateragarriak diren eta zelulen itsaspen selektiboa baimentzen duten gainazalak biomedikuntzako zenbait aplikazio ezberdinetarako oso desiragarriak bihurtu dira. Bide horretatik, material biobateragarrietan horrelako gainazalak lortzeko, posible da mikrotxantiloiak (maila mikrometrikoan eginiko gainazaleko formak) erabiltzea; izan ere, horiek substratu zehatz baten gainean zelula-hazkunde kontrolatua eta bideratua baimendu ditzakete. Lan honetan, hain zuzen ere, mikrotxantilioak lortzeko teknikak berrikusten dira, hauek ehun-ingeniaritzan eta biomedikuntzan aurkitzen dituzten aplikazio nagusiak azpimarratuz, hala nola, biosentsoreak, ehun-ingeniaritzarako in vitro eginiko kultibo zelularrak eta inplante gainazal egokiak sortzea. Azkenik, zelulen itsaspen selektiboari dagokionez, gure ikerketa taldean 3D inpresioz sortutako mikrotxantiloi polimerikoen aurre-emaitzak aurkezten dira. Hala, emaitza horietatik ondorioztatu da 3D inpresioa teknika egokia dela mikrotxantiloi zehatzak, errepikakorrak eta egonkorrak fabrikatzeko. Political science Electrospun Nanofibers in Biomedical Applications ; Additive Manufacturing and 3D Printing Technologies ; Bone Tissue Engineering Materials
Authors: Carlos Heras | Daniel Reta | Rosendo Valero | Guillermo Albareda | Nicholas F. Chilton | Alistair J. Fielding | Iberio de P. R Moreira | Josep María Bofill | Francisco Lopez Calahorra
Source: ChemRxiv (preprint, 2019-11-06)
Field: Chemistry — Organic Chemistry

Biradical Formation by Deprotonation in Thiazole-Derivatives: The Hidden Nature of Dasatinib The formation of stable organic biradicals by a deprotonation process is reported for a series of conjugated heterocycles that share a Ph-N(H)-2-thiazole structural motif. We characterise the paramagnetic electronic ground state by means of continuous-wave and pulse EPR. We propose a simple valence bond mechanism for a deprotonation-induced formation of paramagnetic organic molecules, based on the interplay between the electronegativity of heteroatomic groups and the recovery of aromaticity to stabilise the biradical species. The Ph-N(H)-2-thiazole motif is found in a variety of biologically active molecules, exemplified here with the anticancer drug Dasatinib, and our results suggest a radical-based mechanism for the protein kinase inhibition activity of the drug. The existence of this structure-property relationship for an elementary chemical motif suggests that biradical species may be more prevalent than previously thought and have an important role in bioorganic chemistry. Chemistry ; Deprotonation ; Thiazole ; Molecule ; Electronegativity ; Dasatinib ; Stereochemistry ; Valence (chemistry) ; Computational chemistry ; Photochemistry ; Organic chemistry ; Tyrosine kinase ; Signal transduction Synthesis and Characterization of Heterocyclic Compounds ; Synthesis and biological activity ; N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
Authors: Priyanka Panwar | Kepa K. Burusco | Muna Abubaker | Holly Matthews | Andrey Gutnov | Elena Fernández‐Álvaro | Richard A. Bryce | James A. Wilkinson | Niroshini Nirmalan
Source: bioRxiv (Cold Spring Harbor Laboratory) (preprint, 2019-02-01)
Field: Chemistry — Organic Chemistry

Lead optimisation of dehydroemetine for repositioned use in malaria Abstract Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC 50 : 47 nM + 2.1 nM). 2,3-dehydroemetine, a synthetic analogue of emetine dihydrochloride has been claimed to have less cardiotoxic effects than emetine. The structures of two diastereoisomers of 2,3-dehydroemetine were modelled on the reported emetine binding site on cryo-EM structure 3J7A and it was found that (-)-R,S -dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S -dehydroisoemetine. (-)-R,S -dehydroemetine was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S -dehydroisoemetine, which loses its potency due to the change of configuration at C-1’. In addition to its effect on the asexual erythrocytic stages of P. falciparum , the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S -dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S -dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed atovoquone-like activity on the mitochondrial membrane potential. Emetine ; Pharmacology ; Plasmodium falciparum ; Drug ; Artemisinin ; Chloroquine ; Biology ; Efflux ; Malaria ; Biochemistry ; Immunology Synthesis and Biological Evaluation ; Alkaloids: synthesis and pharmacology ; Synthesis and bioactivity of alkaloids
Authors: Hailong Che
Source: Data Archiving and Networked Services (DANS) (article, 2019-09-20)
Field: Chemistry — Organic Chemistry

Self-regulated out-of-equilibrium polymer assemblies Amphiphilic block copolymers can self-assemble into well-defined nanoparticles with various morphologies which have gained much research interest in a great variety of fields ranging from cell mimics to nanomedicine.To facilitate their various emerging applications such as polymersome nanoreactors or nanomotor system, the structural and functional adaption should be taken into account when designing and constructing selfassembled architectures.Introducing an external stimulus to these systems can give rise to relatively large functional outputs based on a physicochemical adjustment of their architectures.In addition, out-of-equilibrium processes are ubiquitous in nature and often characterized by adaptive, transient behavior.Translating this behavior onto functional self-assemblies is an exciting way to create complex, biomimetic systems.In this regard, fuel-driven structural and functional operations under temporal control are thought to play a key role in bridging man-made materials and biology in terms of natural organization and function. Polymer ; Chemistry ; Materials science ; Composite material Advanced Polymer Synthesis and Characterization ; Surface Modification and Superhydrophobicity
Authors: Luc Truong
Source: eScholarship@McGill (McGill) (article, 2019-01-01)
Field: Chemistry — Organic Chemistry

Thermal stabilizers as paradoxical PINK1 activators for the treatment of Parkinson’s disease Parkinson's disease ; PINK1 ; Disease ; Medicine ; Neuroscience ; Parkin ; Psychology ; Internal medicine Click Chemistry and Applications ; Calcium signaling and nucleotide metabolism ; Synthesis of Organic Compounds
Authors: Vanessa M. Eichel
Source: Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) (article, 2019-01-01)
Field: Materials Science — Materials Chemistry

In vivo assessment of hair cell toxicity of gadolinium-based contrast agents in Xenopus embryos Xenopus ; Gadolinium ; In vivo ; Toxicity ; Contrast (vision) ; Embryo ; Chemistry ; Cell biology ; Biology ; Biochemistry ; Computer science ; Genetics Lanthanide and Transition Metal Complexes
Authors: Rebekah P. Nash
Source: Carolina Digital Repository (University of North Carolina at Chapel Hill) (article, 2019-08-13)
Field: Materials Science — Materials Chemistry

The Structure of the Plasmid pCU1 TraI Relaxase and the Role of the pCU1 TraI Relaxase-Helicase during Conjugative Plasmid Transfer Bacteria disseminate genetic material to neighboring cells using conjugative plasmid transfer (CPT). During CPT, a donor bacterium transfers one strand of a double-stranded DNA plasmid to a recipient. Each conjugative plasmid encodes a complex of proteins necessary for its transfer. One of these proteins, the relaxase, initiates plasmid transfer by severing the nic site of the transferred strand (T-strand). A DNA helicase then separates the T-strand from the parent strand, starting at the nic site. The relaxase acts a second time to terminate transfer by resealing the nicked T-strand. The resistance plasmid pCU1 encodes a multi-domain protein, TraI, that supplies both the relaxase and helicase activities required for its transfer. We analyzed the structure and function of pCU1 TraI in order to compare it to similar plasmid-encoded proteins and to identify TraI-mediated activities that could be targeted by inhibitors. Characterization of the pCU1 relaxase revealed unique structural and functional modifications that this enzyme has introduced into the traditional relaxase-mediated DNA nicking mechanism. First, while the overall fold of the pCU1 relaxase is similar to that of homologous relaxases, its conserved DNA nicking residues (Y18,19,26,27) are flipped up to 14 � out of the relaxase active site. Second, the pCU1 relaxase preferentially utilizes Y26 or a combination of Y18+Y19 when nicking DNA. In contrast, homologous relaxases use the first tyrosine in amino acid sequence for DNA nicking. Third, the pCU1 relaxase lacks the sequence-specific DNA binding characteristic of homologous relaxase enzymes. However, it maintains highly sequence specific and metal-dependent DNA nicking. Analysis of the pCU1 helicase established the extent of the minimal helicase domain, the location of the seven conserved helicase motifs, and the substrate requirements of the helicase ATPase activity. The pCU1 helicase harnesses the energy released during ATP hydrolysis to drive DNA strand separation. After optimizing an ATPase assay for use with pCU1 TraI, small molecule libraries were screened for their ability to inhibit pCU1 TraI, and several potential TraI ATPase inhibitors were identified. In summary, this structural and functional characterization of pCU1 TraI identified features unique to this enzyme and revealed particular activities could be targeted by TraI-specific inhibitors. Plasmid ; Genetics ; Helicase ; Bacterial conjugation ; Biology ; Gene Enzyme Structure and Function ; Hemoglobin structure and function ; Protein Structure and Dynamics