182 research outputs found

    Tom Vroody

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    4-Nitro-N-phthalyl-l-tryptophan

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    The crystal structure of the title compound [systematic name: (2R)-3-(1H-indol-3-yl)-2-(4-nitro-1,3-dioxoisoindolin-2-yl)propanoic acid], C19H13N3O6, an analogue of epigenetic modulator RG108, is constrained by strong hydrogen bonds between the indole N—H group and a carbonyl O atom of the phthalimide ring of a symmetry-related mol­ecule, and between the protonated O atom of the carboxyl group and a carbonyl O atom of the phthalimide ring. π–π stacking inter­actions with centroid–centroid distances of 3.638 (1) and 3.610 (1) Å are also observed between indole and phthalimide rings

    endo-3,3-Dimethyl-4-oxobicyclo­[3.1.0]hexan-2-yl methane­sulfonate

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    The relative configuration of the endo isomer of the title compound, C9H14O4S, has been established and the conformation of the diastereoisomer is discussed. The five-membered ring adopts an envelope conformation. The conformation of the methane­sulfonate substituent is stabilized by inter­molecular C—H⋯O hydrogen bonds. The crystal packing results in alternating layers of polar methane­sulfonates and stacked bicyclo­hexa­nyl rings parallel to ab

    Machine translation of morphologically rich languages using deep neural networks

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    This thesis addresses some of the challenges of translating morphologically rich languages (MRLs). Words in MRLs have more complex structures than those in other languages, so that a word can be viewed as a hierarchical structure with several internal subunits. Accordingly, word-based models in which words are treated as atomic units are not suitable for this set of languages. As a commonly used and eff ective solution, morphological decomposition is applied to segment words into atomic and meaning-preserving units, but this raises other types of problems some of which we study here. We mainly use neural networks (NNs) to perform machine translation (MT) in our research and study their diff erent properties. However, our research is not limited to neural models alone as we also consider some of the difficulties of conventional MT methods. First we try to model morphologically complex words (MCWs) and provide better word-level representations. Words are symbolic concepts which are represented numerically in order to be used in NNs. Our first goal is to tackle this problem and find the best representation for MCWs. In the next step we focus on language modeling (LM) and work at the sentence level. We propose new morpheme-segmentation models by which we finetune existing LMs for MRLs. In this part of our research we try to find the most efficient neural language model for MRLs. After providing word- and sentence-level neural information in the first two steps, we try to use such information to enhance the translation quality in the statistical machine translation (SMT) pipeline using several diff erent models. Accordingly, the main goal in this part is to find methods by which deep neural networks (DNNs) can improve SMT. One of the main interests of the thesis is to study neural machine translation (NMT) engines from diff erent perspectives, and finetune them to work with MRLs. In the last step we target this problem and perform end-to-end sequence modeling via NN-based models. NMT engines have recently improved significantly and perform as well as state-of-the-art systems, but still have serious problems with morphologically complex constituents. This shortcoming of NMT is studied in two separate chapters in the thesis, where in one chapter we investigate the impact of diff erent non-linguistic morpheme-segmentation models on the NMT pipeline, and in the other one we benefit from a linguistically motivated morphological analyzer and propose a novel neural architecture particularly for translating from MRLs. Our overall goal for this part of the research is to find the most suitable neural architecture to translate MRLs. We evaluated our models on diff erent MRLs such as Czech, Farsi, German, Russian, and Turkish, and observed significant improvements. The main goal targeted in this research was to incorporate morphological information into MT and define architectures which are able to model the complex nature of MRLs. The results obtained from our experimental studies confirm that we were able to achieve our goal

    Determination of the Absolute Configuration of Aegelinol by Crystallization of Its Inclusion Complex with β-Cyclodextrin

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    The absolute configuration and structure of aegelinol, a pyranocoumarin isolated from Ferulago asparagifolia Boiss (Apiaceae), has been determined by crystallography. Crystal structure of the inclusion complex of aegelinol in β-cyclodextrin was determined (a = 15.404(1) Å, b = 15.281(1) Å, c = 17.890(1) Å, α = 99.662(1), β = 113.4230(1), γ = 102.481(1)°, P1; R1 = 6.71%) and allowed unambiguous determination of the absolute configuration of the stereogenic center of aegelinol. The pyranocoumarin guest is included within the cylindrical cavity formed by dimeric β-cyclodextrin molecules with a head-to-head arrangement. Crystal structure of aegelinol alone was also determined (a = 6.8921(3) Å, b = 11.4302(9) Å, c = 44.964(3) Å, P212121; R1 = 4.44%) and allowed precise determination of its geometry. Aegelinol crystallizes with three molecules in the asymmetric unit held together by H-bonds and π-stacking interactions

    Phenyl 2,3,4-tri-O-benzyl-1-thio-α-d-mannopyran­oside monohydrate

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    In the title compound, C33H34O5S·H2O, the mannopyran­oside ring adopts a chair conformation with the 2-α-thio­phenyl group occupying an axial position. One of the pendant benzyl groups is disordered over two sets of sites in a 0.5:0.5 ratio. In the crystal, the water mol­ecule makes two O—H⋯O hydrogen bonds to an adjacent sugar mol­ecule with the O atoms of the primary alcohol and ether groups acting as acceptors. At the same time, the OH group of the sugar makes a hydrogen bond to a water mol­ecule

    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
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