Blockchain for Collaborative Businesses

Mobile Networks and Applications - Blockchain applications have continuously improved ever since its first debut on cryptocurrency. From then on, its uses have branched out from the financial...     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Dynamical modelling of an activated sludge system of a petrochemical plant operating at high temperatures.

The Mexican petrochemical industry, Morelos S.A. de C.V., is one of the biggest and more important petroleum industries in Mexico and Latin America. It has an activated sludge system to treat its wastewater flow, which is approximately 7,000 m3/d. The wastewater contains volatile organic carbon substances classified as toxics. The old surface aeration system was changed for fine bubble diffusers; however, one major drawback of the new aeration system is that the temperature in the bioreactor has increased due to the compression of the air, which at the compressor exit reaches 85 degrees C. This effect results in the temperature in the bioreactor attaining 32 degrees C during the fall, whereas in the spring and summer, the bioreactor temperature reaches higher values than 40 degrees C. The high temperatures reduce the microorganism activity and cause a higher volatilisation rate of volatile compounds, among other effects, which affect the performance of the biological treatment. This work was performed to obtain a better modelling of the wastewater treatment from the petrochemical industry. The model describes the effect of the temperature on the performance of the biological treatment. The model was obtained from tests that were carried out in laboratory reactors with 14 L capacity, which were operated at different temperatures (from 30 to 45 degrees C), with the same wastewater and conditions as the actual system.     

Potential use of phenolic antioxidants on peanut to control growth and aflatoxin B1 accumulation by Aspergillus flavus and Aspergillus parasiticus

Food‐grade antioxidants: butylated hydroxyanisole (BHA), propyl paraben (PP) and butylated hydroxytoluene (BHT) (10 and 20 mmol g^?1) and all the mixtures of these chemicals were tested for inhibitory activity on the growth of and aflatoxin B₁ (AFB₁) accumulation by Aspergillus parasiticus and A. flavus on irradiated (7 kGy) peanut grains. Also, the influence of these treatments was evaluated in different water conditions (0.982, 0.955, 0.937a_w) at 11 and 35 days of incubation at 28 °C. Water activity (a_w) affected the fungal growth, no fungal development was observed at the highest stress water condition (0.937a_w). Butylated hydroxyanisole at 10 mmol g^?1 level and all the mixtures with PP and/or BHT were significantly effective (P = 0.05) in increasing lag phase and reducing growth rate and colony forming units per gram of peanut of both Aspergillus section Flavi strains and AFB₁ accumulation. The application of BHA at concentrations of 20 mmol g^?1 alone or with PP and/or BHT totally inhibited fungal growth at 11 and 35 days of incubation. The results suggest that the addition of these chemical mixtures on peanut grains at low levels has potential to impact synergically on the control of Aspergillus section Flavi. Copyright © 2007 Society of Chemical Industry     

Retaining maximum antioxidative potency of wheat germ oil refined by molecular distillation

A process of physical refining wheat germ oil using the technique of molecular distillation (MD) is presented in this work. Wheat germ oil was obtained from the germ by solvent extraction using hexane and also by cold pressing. The oil extracted with hexane was degummed and bleached before deacidification in order to modify the parameters of phosphorus and color. The goal in carrying out the stage of physical refining by MD was to preserve the maximum amount of original antioxidative potential obtained from extraction of the crude oil. The effect of evaporation temperature of one‐stage MD on the efficiency of free fatty acid elimination was studied. The antioxidant portion was followed by means of analytic determination of tocopherols by high‐performance liquid chromatography. Tocopherol retention up to 98% was achieved in the oil extracted by pressing, and yields of up to 96% were achieved in the oil extracted with hexane. Copyright © 2007 Society of Chemical Industry     

Drugs, memory, and metamemory: A dose-effect study with lorazepam and scopolamine.

This experiment was designed to use the graded dose-related amnesia produced by the benzodiazepine lorazepam (1.0, 2.0 mg/70 kg, oral) and the anticholinergic scopolamine (0.3, 0.6 mg/70 kg, subcutaneous) as a tool to explore the cognitive and neurochemical mechanisms underlying metamemory in the judgment of learning paradigm, with a placebo-controlled independent groups design in healthy volunteers (n=12/group). Results provide evidence for a pharmacological dissociation between effects on memory versus metamemory (relative accuracy of item-by-item monitoring) across a range of levels of memory performance and suggest that the drugs selectively impair those aspects of metamnemonic monitoring that require participants' awareness of their overall current state of functioning (absolute accuracy of prospective item-by-item monitoring, prospective global monitoring) but not those that rely solely on assessment of individual item characteristics (relative accuracy of item-by-item monitoring). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microfluidic motion for a direct investigation of solvent interactions with PDMS microchannels

Solid surface/liquid interactions play an important role in microfluidics and particularly in manipulation of films, drops and bubbles, a basic requirement for a number of lab-on-chip applications. The behavior of solvents in coated microchannels is difficult to be predicted considering theories; therefore, experimental methods able to estimate the properties at the interface in real time and during the operational regime are amenable. Here, we propose to use an experimental setup to evaluate the effective dynamics of solvents inside PDMS microchannels. The influence of the solvent properties as well as of the channel wall’s wettability on the fluid movements was evaluated. Modification of the channel properties was achieved by introducing Teflon coatings that allow producing stable hydrophobic microchannel walls. The results were fitted according to Washburn-type power-law and compared with theoretical calculations of the parameter β that expresses the dependence of capillary dynamics on surface tension γ, liquid viscosity η, contact angles θ and the hydraulic radius R _H. A comparison between the calculated and the experimental values reveled that parameters other than the contemplated ones influenced the measurements. The main parameter that affects the flow of solvents such as water, methanol ethanol, dimethylformamide, acetonitrile and acetone was found to be the γ/η ratio. Considering these results, the investigation tool described here is believed to be promising to predict the dynamics of common organic solvents inside integrated functional fluidic devices and to accurately control solvent flow, particularly in capillary-driven pumpless systems, a basic requirement for widening the application range of PDMS lab-on-chip devices.     

Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.     

Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis

Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate limited efficacies. Advancing our understanding of the pathogenic mechanisms of lung fibrosis will provide a future path for the cure. Cellular senescence has gained substantial interest in recent decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence-targeted signaling molecules and specific therapies to target senescent cells, known collectively as “senolytic” or “senotherapeutic” agents.