Tuning Green Explosives through SNAr Chemistry.

Reactivity and regioselectivity of SNAr-type fluorine substitution with azide in polyfluorosubstituted nitrobenzenes was studied both theoretically and experimentally. The obtained polyazido-substituted nitrobenzene derivatives were extensively characterized by NMR, IR, HPLC, X-ray, and DFT methods. It was found that the substitution with the azide nucleophile occurs first at the para- and the ortho-positions to the NO2-group and that transazidation reactions also occur here. Thermal decomposition of prepared azidonitrobenzenes was studied both in controlled (kinetic decay) and uncontrolled (explosion) modes. In case of the controlled thermal decomposition of ortho-azidonitrobenzenes, benzofuroxans were found as major products of the reaction unless another azido group was adjacent to the furoxan moiety. The bursting power of azidonitrobenzenes was found to rise gradually with the number of the azide substituents in the aromatic ring.

Highly energetic N-cyano-substituted CL-20 analogues: challenging the stability limits of polynitro hexaazaisowurtzitanes.

To design high-energy-density materials of a new level, it is necessary to develop methods for the functionalization of energetic scaffolds, which will make it possible to tune their physicochemical and energetic properties. For this reason, we have elaborated an approach for synthesizing a new series of energetic cage compounds with advanced properties by introducing the N-cyano group into the polynitro hexaazaisowurtzitane framework. The structures of the obtained substances were fully characterized with a combination of methods, including multinuclear (1H, 13C{1H}, 14N, and 15N{1H}) NMR and IR spectroscopy, high-resolution mass spectrometry, X-ray diffraction analysis, electron microscopy and quantum chemical calculations. For the resulting compounds, thermal stability and safety tests were carried out, calorimetric and pycnometric measurements were performed, and the energetic potential was determined by high-temperature chemical equilibrium thermodynamic calculations. The new cyano derivatives have an acceptable density (up to 1.92 g cm-3) and a high enthalpy of formation (up to 2 MJ kg-1), which is 2 times that of the benchmark CL-20. The resistance of the target compounds to friction (up to 220 N) is the highest compared to CL-20 and its known analogues. 4,10-Dicyano-2,6,8,12-tetranitro-2,4,6,8,10,12-hexaazaisowurtzitane of the new series is the most thermally stable (a Tdec of 238 °C) among the known energetic polynitro hexaazaisowurtzitanes and is the first derivative of this family to surpass CL-20 in heat resistance. Moreover, the specific impulse for the novel materials showed an improvement of 6.5-13 s over CL-20.

Postbiotics versus probiotics in early-onset colorectal cancer.

Probiotics and postbiotics mechanisms of action and applications in early-onset colorectal cancer (EOCRC) prevention and treatment have significant importance but are a matter of debate and controversy. Therefore, in this review, we aimed to define the probiotics concept, advantages and limitations in comparison to postbiotics, and proposed mechanisms of anti-tumor action in EOCRC prevention and treatment of postbiotics. Biotics (probiotics, prebiotics, and postbiotics) could confer the health benefit by affecting the host gut microbiota directly and indirectly. The main mechanisms of action of probiotics in exerting anticancer features include immune system regulation, inhibition of cancer cell propagation, gut dysbiosis restoration, anticancer agents' production, gut barrier function renovation, and cancer-promoting agents' reduction. Postbiotics are suggested to have different mechanisms of action to restore eubiosis against EOCRC, including modulation of gut microbiota composition, gut microbial metabolites regulation, and intestinal barrier function improvement via different features such as immunomodulatory, anti-inflammatory, antioxidant, and anti-proliferative properties. A better understanding of postbiotics challenges and mechanism of action in therapeutic applications will allow us to sketch accurate trials in order to use postbiotics as bio-therapeutics in EOCRC.

Expanding the importance of HMERF titinopathy: new mutations and clinical aspects.

OBJECTIVE: Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied. METHODS: Altogether 12 new families with 19 affected patients and diverse nationalities were studied. Most of the patients were investigated using targeted next-generation sequencing; Sanger sequencing was applied in some of the patients and available family members. Histological data and muscle MRI findings were evaluated. RESULTS: Three families had several family members studied while the rest were single patients. Most patients had distal and proximal muscle weakness together with respiratory insufficiency. Five heterozygous TTN A-band mutations were identified of which two were novel. Also with the novel mutations the muscle pathology and imaging findings were compatible with the previous reports of HMERF. CONCLUSIONS: Our collection of 12 new families expands mutational spectrum with two new mutations identified. HMERF is not that rare and can be found worldwide, but maybe underdiagnosed. Diagnostic process seems to be complex as this study shows with mostly single patients without clear dominant family history.

Sustainable Flow Synthesis of Encoded Beads for Combinatorial Chemistry and Chemical Biology.

Monosized beads of polar resins were synthesized for combinatorial chemistry and chemical biology by sustainable microchannel flow synthesis. Regular, biocompatible, and optically encoded beads could be efficiently prepared on large scale and in high yield. In a preparative flow polymerization instrument, taking advantage of a designed T-connector for droplet formation, quality beads were synthesized with accurate size control using a minimal amount of recirculating silicon oil as suspension medium. Bead-size was controlled through shear imposed by the silicon oil flow rate. This process provided 86% yield of ∼500 µm macrobeads beads within a 20 µm size range with no deformities or vacuoles, ideally suited for combinatorial chemistry and protein binding studies. The simple flow equipment consisted of a syringe pump for monomer and initiator delivery, a T-connector, a gear pump for oil recirculation, a long, heated coil of Teflon tubing and a collector syringe. The method was used for preparation of PEGA1900 beads, optically encoded with fluorescent microparticles. The microparticle matrix (MPM) encoded beads were tested in a MPM-decoder showing excellent recognition in bead decoding.

A Flow Procedure for Linearization of Genome Sequence Graphs.

Efforts to incorporate human genetic variation into the reference human genome have converged on the idea of a graph representation of genetic variation within a species, a genome sequence graph. A sequence graph represents a set of individual haploid reference genomes as paths in a single graph. When that set of reference genomes is sufficiently diverse, the sequence graph implicitly contains all frequent human genetic variations, including translocations, inversions, deletions, and insertions. In representing a set of genomes as a sequence graph, one encounters certain challenges. One of the most important is the problem of graph linearization, essential both for efficiency of storage and access, and for natural graph visualization and compatibility with other tools. The goal of graph linearization is to order nodes of the graph in such a way that operations such as access, traversal, and visualization are as efficient and effective as possible. A new algorithm for the linearization of sequence graphs, called the flow procedure (FP), is proposed in this article. Comparative experimental evaluation of the FP against other algorithms shows that it outperforms its rivals in the metrics most relevant to sequence graphs.

A Prospective, Neurophysiologic Comparative Study to Assess the Efficacy and Duration of Effect of IncobotulinumtoxinA and AbobotulinumtoxinA in the Treatment of Crow's Feet.

This randomized, rater-blind, split-face study compared the safety and efficacy of incobotulinumtoxinA and abobotulinumtoxinA for the treatment of crow's feet. Nine units of incobotulinumtoxinA were administered to the lateral periorbital region of one side of the face and 27 units of abobotulinumtoxinA to the other in healthy subjects (aged 35-55 years) with moderate-to-severe crow's feet at rest (2-3 points on the 5-point Merz Aesthetics Scale [MAS]). Investigators assessed efficacy using the MAS, while subjects assessed using a 9-point global assessment scale. Secondary objectives included electromyography to assess muscle activity before injection and at 2 weeks, 4 months, and 6 months afterwards. Twenty women were enrolled and 18 completed the study. At rest and maximum smile, at each time point, the mean wrinkle scores were significantly lower (P ≤ 0.05) than baseline for both treatments. No differences were noted between treatments. Responder (≥ 1-point improvement from baseline) rates for both products were 100% and 83% at 2 weeks and 4 months post-treatment, respectively. At 6 months post-treatment, responder rates were 67% and 61% for incobotulinumtoxinA and abobotulinumtoxinA, respectively. For both, the maximum changes in electromyography parameters were observed 2 weeks post-treatment. A response was maintained for 6 months (P ≤ 0.05 vs baseline). Both treatments were well tolerated; only mild adverse events were reported. In conclusion, for treatment of crow's feet, incobotulinumtoxinA and abobotulinumtoxinA (1:3 dose) demonstrated comparable efficacy in terms of magnitude and longevity of effect. Both products demonstrated a high responder rate, with the response being maintained for 6 months in the majority.

Multiwavelength Resonance Raman Characterization of the Effect of Growth Phase and Culture Medium on Bacteria.

We examine the use of multiwavelength ultraviolet (UV) resonance-Raman signatures to identify the effects of growth phase and growth medium on gram-positive and gram-negative bacteria. Escherichia coli (E. coli), Citrobacter koseri (C. koseri), Citrobacter braakii (C. braakii), and Bacillus cereus (B. cereus) were grown to logarithmic and stationary phases in nutrient broth and brain heart infusion broth. Resonance Raman spectra of bacteria were obtained at multiple wavelengths between 220 and 260 nm; a range that encompasses the resonance frequencies of cellular constituents. We find that spectra of the same bacterial species exhibit differences due to both growth condition and growth phase, but the larger differences reflect changes due to growth phase. The differences in the Raman spectra correlate with genetic differences among the species. Using a Pearson correlation based algorithm, we achieve successful identification of these bacteria in 83% of the cases.

Generation of ultrasound in materials using continuous-wave lasers.

Generating and detecting ultrasound is a standard method of nondestructive evaluation of materials. Pulsed lasers are used to generate ultrasound remotely in situations that prohibit the use of contact transducers. The scanning rate is limited by the repetition rates of the pulsed lasers, ranging between 10 and 100 Hz for lasers with sufficient pulse widths and energies. Alternately, a high-power continuous-wave laser can be scanned across the surface, creating an ultrasonic wavefront. Since generation is continuous, the scanning rate can be as much as 4 orders of magnitude higher than with pulsed lasers. This paper introduces the concept, comparing the theoretical scanning speed with generation by pulsed laser.

Specular integrating tube for scattered-light spectroscopy.

A cylindrical sample cell is adapted to the problem of increasing the scattered-light signal from an optically thin liquid sample. The ends of the cylinder are coated with specularly reflecting aluminum to increase the signal by reflecting the stimulating light beam through the medium multiple times. The circumference of the cylinder is similarly coated to increase the fraction of the emitted light that is collected and sent into the slit of a spectrometer. Such a cell can greatly increase the signal measured by an analysis system without any modifications to the system.

Modified Solc notch filter for deep ultraviolet applications.

We present results of the design and testing of a modified optical Solc notch filter for use in the deep ultraviolet (DUV, 190-300 nm) spectral range. The filter was designed to block a specific wavelength in this region. In addition, a sequence of blocked wavelengths occurs at wavelengths both shorter and longer than the specified wavelength. For Raman applications utilizing tunable lasers, the provision of multiple blocked wavelengths by a single filter may be especially useful. The filter design presented here produces extinction ratios >240 with transmission minima ~1 nm full width at half-maximum. Specific results are shown for the Raman spectra of Teflon excited at 248.4 nm.

Identification of explosives with two-dimensional ultraviolet resonance Raman spectroscopy.

The first two-dimensional (2D) resonance Raman spectra of TNT, RDX, HMX, and PETN are measured with an instrument that sequentially and rapidly switches between laser wavelengths, illuminating these explosives with forty wavelengths between 210 nm and 280 nm. Two-dimensional spectra reflect variations in resonance Raman scatter with illumination wavelength, adding information not available from single or few one-dimensional spectra, thereby increasing the number of variables available for use in identification, which is especially useful in environments with contaminants and interferents. We have recently shown that 2D resonance Raman spectra can identify bacteria. Thus, a single device that identifies the presence of explosives, bacteria, and other chemicals in complex backgrounds may be feasible.

Identification of bacteria from two-dimensional resonant-Raman spectra.

We present the first measurements of two-dimensional resonant-Raman spectra and demonstrate the applicability of the method to the identification of bacteria, including differentiation of genetically similar species. A new device that sequentially illuminates bacteria with different ultraviolet wavelengths and measures a spectrum at each was developed for this purpose. We anticipate that information within such two-dimensional spectra will allow identification of bacteria and chemicals in environments containing multiple organisms and chemicals, leading, for example, to instruments that rapidly identify bacteria in hospital and food plant settings, for screening large populations, and for biochemical-threat warning systems.