Does Aliphatic Chain Length Influence Carbocyanines' Orientation in Supported Lipid Multilayers?

UV-Vis linear dichroism was used to study the orientation of 3,3'-dihexyloxacarbocyanine (DiOC6(3)) and 3,3'-dihexadecyloxacarbocyanine (DiOC16(3)) in supported multilayers of dipalmitoylphosphatidylcholine (DPPC) and dilauroylphosphatidylcholine (DLPC). Orientational probability density functions were similar for the two carbocyanines in both lipids. Multimodal distributions were found in all cases. The main peak is at 9 degrees-11 degrees relative to the bilayer normal axis, except for DiOC16(3) in DLPC multilayers (main peaks at 13 degrees and 90 degrees). Quenching studies revealed that the two carbocyanines are localized at the interface region of the membrane regardless of the lipid matrix they are inserted in. Combining these data with linear dichroism results lead to the conclusion that both the aliphatic chain length of carbocyanines and the lipid phase have little influence in the structural organization of these probes in lipidic bilayers. The partition constants of DiOC6 (3), K(p), were determined from fluorescence anisotropy measurements; the values obtained were K(p) (DPPC) = (2.39 +/- 0.05) x 10(3) and K(p) (DLPC) = (5.01 +/- 1.15) x 10(3).     

A one-pot diastereoselective synthesis of cis-3-hexene-1,6-diols via an unusually reactive organozinc intermediate

A highly diastereoselective method for the synthesis of cis-3-hexene-1,6-diols has been developed. This new reaction proceeds with excellent control of diastereoselectivity over four stereocenters and the double bond geometry. The diols are made in a one-pot procedure involving hydroboration of a terminal alkyne and transmetalation to zinc to give a divinylzinc intermediate. This intermediate undergoes reductive elimination, forming a C=C bond. In the absence of a trapping reagent, diene is liberated (70% yield); however, in the presence of ketones or aldehydes, the proposed intermediate metallocyclopentene is trapped via a double insertion of the carbonyl substrate. Workup provides the diols in 47-86% yield.     

Efficient Bayesian Inference for Multivariate Factor Stochastic Volatility Models

We discuss efficient Bayesian estimation of dynamic covariance matrices in multivariate time series through a factor stochastic volatility model. In particular, we propose two interweaving strategies to substantially accelerate convergence and mixing of standard MCMC approaches. Similar to marginal data augmentation techniques, the proposed acceleration procedures exploit nonidentifiability issues which frequently arise in factor models. Our new interweaving strategies are easy to implement and come at almost no extra computational cost; nevertheless, they can boost estimation efficiency by several orders of magnitude as is shown in extensive simulation studies. To conclude, the application of our algorithm to a 26-dimensional exchange rate dataset illustrates the superior performance of the new approach for real-world data. Supplementary materials for this article are available online.     

Development of Electrochemical Platform Based on Molecularly Imprinted Poly(methacrylic acid) Grafted on Iniferter-modified Carbon Nanotubes for 17β-Estradiol Determination in Water Samples

This paper describes the development of a new electrochemical sensor for 17β-estradiol (E2) determination based on glassy carbon electrode (GCE) modified with molecularly imprinted polymer grafted onto iniferter-multiwall carbon nanotubes surface (MIP-MWCNT) and dihexadecyl-hydrogen-phosphate (DHP). The electrochemical method was based on closed-circuit preconcentration of E2 in 0.1 mol L⁻¹ phosphate buffer (pH 7.0) during 500 s. Upon preconcentration, E2 was determined by differential pulse voltammetry (DPV) exhibiting a limit of detection of 0.01 μmol L⁻¹. The sensor exhibited higher selectivity toward E2 and it was applied for E2 determination in natural water samples, with accuracy attested by HPLC-DAD.     

The Endogenous Tryptophan‐derived Photoproduct 6‐formylindolo[3,2‐b]carbazole (FICZ) is a Nanomolar Photosensitizer that Can be Harnessed for the Photodynamic Elimination of Skin Cancer Cells in Vitro and in Vivo

UV‐chromophores contained in human skin may act as endogenous sensitizers of photooxidative stress and can be employed therapeutically for the photodynamic elimination of malignant cells. Here, we report that 6‐formylindolo[3,2‐b]carbazole (FICZ), a tryptophan‐derived photoproduct and endogenous aryl hydrocarbon receptor agonist, displays activity as a nanomolar sensitizer of photooxidative stress, causing the photodynamic elimination of human melanoma and nonmelanoma skin cancer cells in vitro and in vivo. FICZ is an efficient UVA/Visible photosensitizer having absorbance maximum at 390 nm (ε = 9180 L mol^?1 cm^?1), and fluorescence and singlet oxygen quantum yields of 0.15 and 0.5, respectively, in methanol. In a panel of cultured human squamous cell carcinoma and melanoma skin cancer cells (SCC‐25, HaCaT‐ras II‐4, A375, G361, LOX), photodynamic induction of cell death was elicited by the combined action of solar simulated UVA (6.6 J cm^?2) and FICZ (≥10 nm ), preceded by the induction of oxidative stress as substantiated by MitoSOX Red fluorescence microscopy, comet detection of Fpg‐sensitive oxidative genomic lesions and upregulated stress response gene expression (HMOX1, HSPA1A, HSPA6). In SKH1 “high‐risk” mouse skin, an experimental FICZ/UVA photodynamic treatment regimen blocked the progression of UV‐induced tumorigenesis suggesting feasibility of harnessing FICZ for the photooxidative elimination of malignant cells in vivo.     

Deep learning models for inflation forecasting

We propose a hybrid deep learning model that merges Variational Autoencoders and Convolutional LSTM Networks (VAE-ConvLSTM) to forecast inflation. Using a public macroeconomic database that comprises 134 monthly US time series from January 1978 to December 2019, the proposed model is compared against several popular econometric and machine learning benchmarks, including Ridge regression, LASSO regression, Random Forests, Bayesian methods, VECM, and multilayer perceptron. We find that VAE-ConvLSTM outperforms the competing models in terms of consistency and out-of-sample performance. The robustness of such conclusion is ensured via cross-validation and Monte-Carlo simulations using different training, validation, and test samples. Our results suggest that macroeconomic forecasting could take advantage of deep learning models when tackling nonlinearities and nonstationarity, potentially delivering superior performance in comparison to traditional econometric approaches based on linear, stationary models.     

Cytotoxic Mechanism of Sphaerodactylomelol,an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H₂O₂) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC₅₀ range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H₂O₂ production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H₂O₂ levels and downstream apoptosis.     

Assessment of hydrophobic interactions and their contributions through the analysis of the methane dimer

Hydrophobic Interactions (HIs) are important in many phenomena of molecular recognition in chemistry and biology. Still, the relevance of HIs is sometimes difficult to evaluate particularly in large systems and intramolecular interactions. We put forward a method to estimate the magnitude and the different contributions of a given HI of the C···C, H? C···H, and H···H type through (i) the analysis of the electron density in the intermolecular region for eleven relative orientations of the methane dimer and (ii) the subsequent decomposition of the corresponding interaction energy in physically significant contributions using Symmetry Adapted Perturbation Theory (SAPT). Strong correlations were found between the topological properties of calculated at intermolecular bond critical points and plus its different contributions with the C···C distance of the considered orientations of (CH₄)₂. These correlations were used to construct Mollier‐like diagrams of and its components as a function of the separation between two carbons and the orientation of the groups bonded to these atoms. The ethane dimer and tert‐butylcyclohexane are used as representative examples of this new approach. Overall, we anticipate that this new method might prove useful in the study of both intramolecular and intermolecular HIs particularly of those within large systems wherein SAPT or electronic structure calculations are computationally expensive or even prohibitive. © 2014 Wiley Periodicals, Inc.     

A disposable laser print-cut-laminate polyester microchip for multiplexed PCR via infra-red-mediated thermal control

Infrared (IR)-mediated thermal cycling system, a method proven to be a effective for sub-μL scale polymerase chain reaction (PCR) on microchips, has been integrated with DNA extraction and separation on a glass microchip in a fully integrated micro Total Analysis System by Easley et al., in 2006. IR-PCR has been demonstrated on both glass and PMMA microdevices where the fabrication (bonding) is not trivial. Polyester-toner (PeT) microfluidic devices have significant potential as cost-effective, disposable microdevices as a result of the ease of fabrication (∼$0.25 USD and <10 min per device) and availability of commercial substrates. For the first time, we demonstrate here the thermal cycling in PeT microchips on the IR-PCR system. Undesirable IR absorption by the black-toner bonding layer was eliminated with a spatial filter in the form of an aluminum foil mask. The solution heating rate for a black PeT microchip using a tungsten lamp was 10.1 ± 0.7 °C s⁻¹ with a cooling rate of roughly −12 ± 0.9 °C s⁻¹ assisted by forced air cooling. Dynamic surface passivation strategies allowed the successful amplification of a 520 bp fragment of the λ-phage genome (in 11 min) and a 1500 bp region of Azospirillum brasilense. Using a centrosymmetric chamber configuration in a multichamber PeT microchip, homogenous temperature distribution over all chambers was achieved with inter-chamber temperature differences at annealing, extension and denaturing steps of less than ±2 °C. The effectiveness of the multichamber system was demonstrated with the simultaneous amplification of a 390 bp amplicon of human β-globin gene in five PeT PCR microchambers. The relative PCR amplification efficiency with a human β-globin DNA fragment ranged from 70% to 90%, in comparison to conventional thermal cyclers, with an inter-chamber standard deviation of ∼10%. Development of PeT microchips for IR-PCR has the potential to provide rapid, low-volume amplification while also integrating PCR with extraction upstream and separation/detection downstream.     

High Final Energy of Low‐Level Gallium Arsenide Laser Therapy Enhances Skeletal Muscle Recovery without a Positive Effect on Collagen Remodeling

The aim of this study was to evaluate the effects of a Gallium Arsenide (GaAs) laser, using a high final energy of 4.8 J, during muscle regeneration after cryoinjury. Thirty Wistar rats were divided into three groups: Control (C, n = 10); Injured (I, n = 10) and Injured and laser treated (Injured/LLLT, n = 10). The cryoinjury was induced in the central region of the tibialis anterior muscle (TA). The applications of the laser (904 nm, 50 mW average power) were initiated 24 h after injury, at energy density of 69 J cm^?1 for 48 s, for 5 days, to two points of the lesion. Twenty‐four hours after the final application, the TA muscle was removed and frozen in liquid nitrogen to assess the general muscle morphology and the gene expression of TNF‐α, TGF‐β, MyoD, and Myogenin. The Injured/LLLT group presented a higher number of regenerating fibers and fewer degenerating fibers (P < 0.05) without changes in the collagen remodeling. In addition, the Injured/LLLT group presented a significant decrease in the expression of TNF‐α and myogenin compared to the injured group (P < 0.05). The results suggest that the GaAs laser, using a high final energy after cryoinjury, promotes muscle recovery without changing the collagen remodeling in the muscle extracellular matrix.