Supramolecular drug inclusion complex constructed from cucurbit[7]uril and the hepatitis B drug Adefovir

The interaction between cucuribit[7]uril (Q[7]) and Adefovir (ADV) has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy, Isothermal Titration Calorimetry and mass spectrometry. The results revealed that an inclusion complex was formed via encapsulation of the purine rings of the guest ADV, while the phosphonomethoxyethyl group was prevented from entering the cavity. ITC data revealed that the formation of this 1:1 inclusion complex is mainly driven by favourable enthalpy changes. Studies investigating the release of ADV from the inclusion complex revealed enhanced rates under acidic conditions, although the rates were slower than observed for the free guest under the same conditions. Thermal stability studies indicated that the included form of ADV was more stable that the free form

Amino acid recognition by a fluorescent chemosensor based on cucurbit[8]uril and acridine hydrochloride

A new fluorescent chemosensor comprised of cucurbit[8]uril (Q[8]) and acridine hydrochloride (AC) has been designed and utilized for the recognition of amino acids. The AC was encapsulated by the Q[8] cavity and formed a 1:2 host-guest inclusion complex both in solution (aqueous) and in the solid-state. Whilst free AC is known to be strongly fluorescent, this strong fluorescence was quenched in the inclusion complex Q[8]-AC. This non-fluorescent complex Q[8]-AC was capable of serving as a fluorescence “off-on” probe, and was able to recognize either L-Phe or L-Trp via the competitive interaction between L-Phe or L-Trp. Moreover, the pH responsive nature of the probe allowed for the detection of basic amino acids, namely L-Arg, L-His, or L-Lys). As a result, a fluorescence method for the detection of five amino acids using a single system has been developed

Individual Professional Practice in the Company

Import 23/08/2017Cílem této bakalářské práce je popsat absolvování odborné praxe ve firmě HS Interactive s.r.o. Praxe byla zaměřena na vývoj mobilní aplikace pro operační systém Android. Aplikace je mobilním klientem pro sociální síť MatchToMe. V úvodu popisuji důvody, které vedly k výběru odborné praxe. Dále se věnuji úkolům, které mi byly zadány s jejich implementací a postupem řešení problémů, které se objevily při vývoji. Závěr práce je věnován zhodnocení získaných zkušeností a dosažených výsledků.Purpose of this bachelor thesis is to describe a professional practice in company HS Interactive s.r.o. Practice was focused on the development of mobile application for the operating system Android. The application is a mobile client for social network MatchToMe. In the introduction I describe reasons that led to the selection of professional practice. Then I describe tasks that I have been awarded with their implementations and process of solution issues that have emerged during development. The conclusion of thesis is dedicated to the evaluation of the experience gained and the results achieved.440 - Katedra telekomunikační technikyvýborn

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Substitutional Doping for Aluminosilicate Mineral and Superior Water Splitting Performance

Abstract Substitutional doping is a strategy in which atomic impurities are optionally added to a host material to promote its properties, while the geometric and electronic structure evolution of natural nanoclay mineral upon substitutional metal doping is still ambiguous. This paper first designed an efficient lanthanum (La) doping strategy for nanotubular clay (halloysite nanotube, HNT) through the dynamic equilibrium of a substitutional atom in the presence of saturated AlCl3 solution, and systematic characterization of the samples was performed. Further density functional theory (DFT) calculations were carried out to reveal the geometric and electronic structure evolution upon metal doping, as well as to verify the atom-level effect of the La doping. The CdS loading and its corresponding water splitting performance could demonstrate the effect of La doping. CdS nanoparticles (11 wt.%) were uniformly deposited on the surface of La-doped halloysite nanotube (La-HNT) with the average size of 5 nm, and the notable photocatalytic hydrogen evolution rate of CdS/La-HNT reached up to 47.5 μmol/h. The results could provide a new strategy for metal ion doping and constructive insight into the substitutional doping mechanism

Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2–Inhibitory Activities from Marine-Derived Fungus Aspergillus niger

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC50 > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2–inhibitory activities, with the IC50 values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2–inhibitory activities of BNPs have been reported

Rhodium-Catalyzed Difunctionalization of Alkenes Using Cyclic 1,3-Dicarbonyl-Derived Iodonium Ylides

Herein, we introduce an iodonium ylide strategy to achieve novel α-alkylation of cyclic 1,3-dicarbonyls through harnessing C(sp3)–Rh species generated from 5-exo-trig cyclization to provide rapid access to molecular hybridization of medically important isoindolin-1-ones and cyclic 1,3-dicarbonyls from readily available substrates. This approach features mild conditions, good yield, excellent functional group tolerance, and the simultaneous formation of two new chemical bonds and one stereogenic center. Moreover, the hydroxyl group of resulting product provides a good handle for downstream transformations. Importantly, we also demonstrate this strategy can be achieved in a one-pot manner. A C(sp3)–Rh complex was prepared and proved to be the key intermediate