Democratized image analytics by visual programming through integration of deep models and small-scale machine learning

Analysis of biomedical images requires computational expertize that are uncommon among biomedical scientists. Deep learning approaches for image analysis provide an opportunity to develop user-friendly tools for exploratory data analysis. Here, we use the visual programming toolbox Orange (http://orange.biolab.si) to simplify image analysis by integrating deep-learning embedding, machine learning procedures, and data visualization. Orange supports the construction of data analysis workflows by assembling components for data preprocessing, visualization, and modeling. We equipped Orange with components that use pre-trained deep convolutional networks to profile images with vectors of features. These vectors are used in image clustering and classification in a framework that enables mining of image sets for both novel and experienced users. We demonstrate the utility of the tool in image analysis of progenitor cells in mouse bone healing, identification of developmental competence in mouse oocytes, subcellular protein localization in yeast, and developmental morphology of social amoebae

Positioning colloids at the surfaces of cholesteric liquid crystal droplets

We report on the internal configurations of aqueous dispersions of droplets of cholesteric liquid crystals (LCs; 5-50 mu m-in-diameter; comprised of 4-cyano-4'-pentylbiphenyl and 4-(1-methylheptyloxycarbonyl)-phenyl-4-hexyloxybenzoate) and their influence on the positioning of surface-adsorbed colloids (0.2 or 1 mm-in-diameter polystyrene (PS)). When N = 2D/P was less than 4, where D is the droplet diameter and P is the cholesteric pitch, the droplets adopted a twisted bipolar structure (TBS) and colloids were observed to assume positions at either the poles or equator of the droplets. A statistical analysis of the distribution of locations of the colloids revealed a potential well of depth 2.7 k(B)T near the equator, a conclusion that was supported by computer simulations performed via the minimization of the Landau-de Gennes free energy (well depth of 7 k(B)T from simulation). In contrast, for N > 4, a majority of the droplets exhibited a radial spherical structure (RSS) characterized by a pair of closely spaced surface defects (angle of separation with respect to the center of the droplet theta < 5 degrees) connected by a disclination winding to/from the droplet center, which led to the positioning of pairs of colloids with well-defined spacing at these surface defects. The separation of the pairs of surface-adsorbed colloids was colloid size-dependent, ranging from 1.11 +/- 0.04 mu m for 1 mu m-in-diameter colloids to 1.7 +/- 0.2 mu m for 200 nm-in-diameter colloids. We also observed long-lived metastable configurations in which the two surface point defects were separated by much larger distances (corresponding to populations with angles of theta = 20 +/- 10 degrees and 85 +/- 101 with respect to the center), and observed these pairs of defects to also position pairs of colloids. A third configuration, the diametrical spherical structure (DSS) was also observed. Consistent with the predictions of computer simulations, we found experimentally that the DSS is indeed composed of disconnected defect rings positioned along the diameter of the droplet. Overall, these results reveal that the rich palette of defects exhibited by confined cholesteric LC systems (equilibrium and metastable) provide the basis of a versatile class of templates that enable the surface positioning of colloids in ways that are not possible with achiral LC droplets

Chelated Assisted Metal-Mediated N–H Bond Activation of β‑Lactams: Preparation of Irida‑, Rhoda‑, Osma‑, and Ruthenatrinems

2-Azetidinones substituted with pyridine (<b>2a</b>), quinoline (<b>2b</b>), isoquinoline (<b>2c</b>), imidazole (<b>2d</b>), and benzimidazole (<b>2e</b>) at the 4-position of the four-membered ring have been prepared in order to synthesize tribactams containing a transition metal and its associated ligands, L_<i>n</i>M, at the 2-position of the tricyclic skeleton. The developed procedure is compatible with a wide range of transition-metal starting complexes. Thus, the iridium and rhodium dimers [M­(η⁵-C₅Me₅)­Cl₂]₂ react with <b>2a</b>–<b>e</b>, in the presence of sodium acetate, to afford irida- and rhodatrinems (<b>1a</b>–<b>j</b>) containing the half-sandwich d⁶ metal fragments M­(η⁵-C₅Me₅)Cl (M = Ir, Rh). The reactions of [M­(μ-OMe)­(η⁴-COD)]₂ (M = Ir, Rh) with <b>2a</b> lead to irida- and rhodatrinems (<b>1k</b>,<b>l</b>) with the d⁸ moieties M­(η⁴-COD). The coordination sphere and oxidation state of the metal center in these compounds can be modified, without affecting the 2-azetidinone backbone, by means of substitution and oxidative addition reactions. As a proof of concept, metallatrinems with the M­(CO)₂ (M = Ir (<b>1m</b>), Rh (<b>1n</b>)) and Ir­(Me)­I­(CO)₂ (<b>1o</b>) units are also reported. Osmatrinems <b>1p</b>,<b>q</b> containing the d⁴ metal fragment OsH₃(PⁱPr₃)₂ have been obtained starting from the d² hexahydride OsH₆(PⁱPr₃)₂, by reaction with <b>2a</b>,<b>b</b>, whereas the treatment of the tetrahydroborate complexes MH­(η²-H₂BH₂)­(CO)­(PⁱPr₃)₂ (M = Os, Ru) with <b>2a</b> yields osma- and ruthenatrinems (<b>1r</b>,<b>s</b>) containing six-coordinate bis­(phosphine) d⁶ metal fragments. The IR stretching frequency of the lactamic carbonyl, the bent angle between the five- and four-membered rings of the tricycle, and the N–CO bond length in the lactamic ring are clearly infuenced by the L_<i>n</i>M fragment

Carbapenems: Past, Present, and Future ▿

In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as “slow substrates” or inhibitors of β-lactamases, and still target penicillin binding proteins. This “value-added feature” of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades