Ge-Doped microstructured multicorefiber for customizable supercontinuum generation

Supercontinuum generation in a multicore fiber in which several uncoupled cores were doped with dissimilar concentrations of germanium was studied experimentally. Germanium doping provided control over the separation between the zero-dispersion wavelength and the 1064-nm wavelength of a Q-switched Nd:YAG pump laser. Supercontinua generated independently in each core of the same piece of fiber displayed clear and repeatable differences due to the influence of germanium doping on refractive index and four-wave mixing. The spectral evolution of the subnanosecond pump pulses injected into the different cores was accurately reproduced by numerical simulations

Chromatic confocal setup for displacement measurement using a supercontinuum light source

Chromatic confocal microscopy is a technique to measure distances by analyzing the spectrum of the light reflected by a sample. The key element of the confocal setup is a dispersive lens, which focuses different wavelengths at different distances from the lens. In this paper,a novel setup realized with a supercontinuum light source and a spatial filter composed by reflective elements is described.The supercontinuum source is implemented by injecting high power pulses from a microchip laser into a Ge-doped microstructured optical fiber. The usage of metallic parabolic mirrors, for the focusing and collimation required in the spatial filter, lets the dispersive lens be the only dispersive element of the confocal setup and improves the efficiency of the spatial filter itself. A silicon-based spectrometer is used for the acquisition of the spectra, which are normalized and Gaussian-fitted before extracting the displacement information. A complete calibration is performed, and the set of wavelengths from 500 nm to 900 nm can be mapped into a280 um measuring range. The obtained relativ eaccuracy of 0.36% shows an enhancement of almost one order of magnitude when compared to other supercontinuum-based confocal systems

Incidence of uterine rupture in second-trimester abortion with gemeprost alone compared to mifepristone and gemeprost

OBJECTIVES: To compare uterine rupture rates in women having a medical abortion receiving gemeprost alone to those receiving mifepristone plus gemeprost. STUDY DESIGN: We reviewed the records of women undergoing medical abortion at 13 0/7-23 6/7 weeks from January 2007 to December 2014 at a single center in Italy. Prior to January 2011, we used gemeprost 1 mg vaginally every 3 h up to a maximum of five doses. After January 2011, we added mifepristone 200 mg orally 24 h prior to the same gemeprost protocol. The primary outcome of the study was the incidence of uterine rupture. We compared the outcome between women receiving gemeprost alone with the combination of gemeprost and mifepristone. RESULTS: One thousand and sixty-one (58.5%) and 753 (41.5%) women underwent medical abortion in the gemeprost-alone and the gemeprost/mifepristone groups, respectively. Five (0.47%) uterine ruptures occurred in the gemeprost and four uterine ruptures occurred in the gemeprost/mifepristone groups, respectively (0.53%) (p=.89). All uterine ruptures occurred in women with prior cesarean delivery. CONCLUSIONS: We rep orted no difference in the incidence of uterine rupture between the gemeprost-alone and gemeprost and mifepristone groups. IMPLICATIONS: Uterine rupture is a rare complication of second-trimester medical abortion with gemeprost. Use of mifepristone prior to gemeprost does not affect this risk

Microwave-assisted organic synthesis of nucleoside ProTide analogues

A microwave enhanced synthesis of prodrug nucleotide (ProTide) analogues is presented. Comparison of conventional thermal heating reaction with microwave irradiation exemplifies the potential of the novel methodology herein presented for the selective 5′-phosphoramidate synthesis, without protection of the 3′ position in the ribonucleoside

Seeing the wood through the trees. Combining shape information from different landmark configurations

The geometric morphometric (GM) analysis of complex anatomical structures is an ever more powerful tool to study biological variability, adaptation and evolution. Here, we propose a new method (combinland), developed in R, meant to combine the morphological information contained in different landmark coordinate sets into a single dataset, under a GM context. combinland builds a common ordination space taking into account the entire shape information encoded in the starting configurations. We applied combinland to a Primate case study including 133 skulls belonging to 14 species. On each specimen, we simulated photo acquisitions converting the 3D landmark sets into six 2D configurations along standard anatomical views. The application of combinland shows statistically negligible differences in the ordination space compared to that of the original 3D objects, in contrast to a previous method meant to address the same issue. Hence, we argue combinland allows to correctly retrieve 3D-quality statistical information from 2D landmark configurations. This makes combinland a viable alternative when the extraction of 3D models is not possible, recommended, or too expensive, and to make full use of disparate sources (and views) of morphological information regarding the same specimens. The code and examples for the application of combinland are available in the Arothron R package

Discovery of New Potential Anti-Infective Compounds Based on Carbonic Anhydrase Inhibitors by Rational Target-Focused Repurposing Approaches

In academia, compound recycling represents an alternative drug discovery strategy to identify new pharmaceutical targets from a library of chemical compounds available in house. Herein we report the application of a rational target-based drug-repurposing approach to find diverse applications for our in-house collection of compounds. The carbonic anhydrase (CA, EC 4.2.1.1) metalloenzyme superfamily was identified as a potential target of our compounds. The combination of a thoroughly validated docking screening protocol, together with in vitro assays against various CA families and isoforms, allowed us to identify two unprecedented chemotypes as CA inhibitors. The identified compounds have the capacity to preferentially bind pathogenic (bacterial/protozoan) CAs over human isoforms and represent excellent hits for further optimization in hit-to-lead campaigns

Optical filter based on two coupled PhC GaAs-membranes.

We demonstrate an ultracompact optical filter based on two coupled high-index contrast GaAs photonic crystal (PhC) membranes. The PhC membranes consist of a square lattice of air holes and behave as a Fabry-Perot cavity whose reflectivity and transmissivity depend on the air gap between the two membranes. The normal-incidence reflectance measurements and the numerical simulation of reflection spectra show a high sensitivity to the geometrical parameters, such as the distance between the slabs, whose control would make the device suitable for a new class of tunable optical filters

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand-based drug design.

Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure-Activity Relationship investigation was carried out

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts