Sigmoidal Profile Research Articles

Thioacyl-Transfer Ring-Expansion Polymerization of Thiiranes Based on a Cyclic Dithiocarbamate Initiator

We report the novel thioacyl-transfer ring-expansion polymerization (REP) of thiiranes, using 3H-benzothiazol-2-thione (BTT) as the cyclic dithiocarbamate initiator and tetrabutylammonium chloride (TBAC) as the catalyst. REP proceeded in a controlled manner to produce cyclic polysulfides with a narrow Mw/Mn of 1.1 and whose cyclic structures were confirmed by MALDI-TOF mass spectrometry. Time-course studies revealed unique sigmoidal profiles due to the stable five-membered cyclic structure of the BTT initiator. The GPC curves were analyzed by the Gaussian fitting method, which revealed that the cyclic polymers are accompanied by another fraction with nearly twice the molecular weight of the main product due to ring-crossover reactions between cyclic polysulfides during REP. The BTT-initiated cyclic polysulfides produced in this manner act as macroinitiators for the REP of thiiranes, highlighting the living characteristics of the BTT-initiated REP developed herein. Post-polymerization further enabled the preparation of cyclic block copolymers with different combinations of thiiranes.

Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity.

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-β-CD - MβCD and (2-hydroxy)propyl-β-CD - HPβCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhibitor lopinavir (LPV) as model drug, LPV loaded CD polymers (pHPβCD and pMβCD) were prepared and fully characterized. The physicochemical characterization and in vitro drug release confirmed the successful synthesis of pHPβCD and pMβCD, the formation of sub-micron sized particles and a 12-14 fold increase in LPV solubility. Cytotoxicity assays indicated that both pHPβCD and pMβCD were able to improve the safety profile of LPV while the viral infectivity assay revealed a concentration independent anti-HIV-1 effect for both pHPβCD and pMβCD with a maximum percentage inhibition (MPI) of 79 and 91% respectively. After LPV loading, the antiviral profile of pHPβCD was reversed to the sigmoidal dose-response profile of LPV, while pMβCD maintained its dose-independent profile followed by a LPV mediated increase in viral inhibition. Overall, both pHPβCD and pMβCD demonstrated anti-HIV-1 activity, while drug loaded pMβCD indicated its potential as functional sub-micron sized drug delivery polymers for achieving synergistic anti-HIV activity.

Composite nanocellulose-based hydrogels with spatially oriented degradation and retarded release of macromolecules.

The oral delivery of macromolecular therapeutics to the intestinal tract requires novel, robust, and controlled formulations. Here, we report on fabrication by molding of composite hydrogel cylinders made of cellulose nanocrystals (CNCs) and chitosan (Cht) and their performance as delivery vehicles. CNCs provide excellent mechanical and chemical stress resistance, whereas Cht allows scaffold degradation by enzyme digestion. The release of a representative medium size protein (bovine serum albumin) dispersed in the hydrogel is slow and shows a sigmoidal profile; meanwhile, the hydrogel scaffold degrades according to a preferred route, that is the cylinder is eroded along the vertical axis. The cup-like, scarcely interconnected porous network, with a gradient of hardness along the cylinder axis, and the compact skin-like layer covering the lateral wall which stayed in contact with the mold during gelification, explain the preferred erosion direction and the long-term protein release. The possible effect of the molding process on hydrogel structure suggests that molding could be a simple and cheap way to favor surface compaction and directional scaffold degradation.

Cell Morphology and Substrate Ligand Density Determines Adhesion Strength and Remodelling Under Dynamic Shear

Cells adhere to substrates through dynamic mechanosensitive focal adhesion complexes. These complexes are connected mechanically and through biochemical signalling pathways to the underlying cytoskeleton. Adhesion strength of cells to substrates depends on the cellular shape and area, distribution and integrin density, and the focal adhesion composition. Fluid shear-based experiments to quantify the critical shear stress required for cell detachment provide a quantitative measure of cell-substrate interactions. We used a custom microscope-mountable fluid shear device to quantify the adhesion strength of NIH3T3 cells when exposed to increasing shear stress at different rates (1, 5, and 10 minutes) ranging from 0-8 Pa. Cells were allowed to attach to glass petri-dishes coated with either fibronectin (10, 20, 40, 80, 200 μm/ ml) or collagen-1 (10, 20, 40, 80, 200 μm/ ml) prior to the experiment. The number of cells adhered to the petri-dish decreased with increasing shear stress in a sigmoidal profile. The critical shear stress for 50% cell attachment increased with ligand density and with higher shear exposure duration for both fibronectin and collagen-1 coated substrates. The mean spread area increased linearly (p<0.05) from 1371.6±516.9 for 10 μg/ml fibronectin coated substrates by ∼1.8 times as compared to the corresponding 200μg/ml group. Collagen-1 treated substrates showed a similar response with two-fold increase. There were no differences in cell areas between the two ligand groups at low concentrations; the differences were apparent at higher concentrations alone. These results will be correlated with in changes to actin and vinculin remodelling and organization at. The mean tractions will be quantified using regularized-FTTC following shear-induced cytoskeletal remodelling. A better understanding of cell adhesion strength under mechanical cues may help identify highly metastatic cells which may aid in faster diagnosis and cell sorting.

Transport properties at a sigmoidal graded heterojunction

A sigmoidal grading profile is proposed for the efficient study of the influence of material parameters and effective mass mismatch on the properties of graded heterojunctions. For the interest of accessing bound and scattering states, we have shown the exact solvability of the model on the entire real line. Focussing on transport across a compositionally graded heterojunction, we have discussed the effect of interface width and effective mass mismatch on the transmission probability.

Sorption isotherms of tobacco (Nicotiana tabacumL.) seeds

The moisture sorption capacity of tobacco seeds is decisive for their safe long-term storage; therefore, the analysis of the sorption isotherms, in a wide temperature and water activity range, is essential for seed quality maintenance in storage. In this study, the equilibrium sorption isotherms of tobacco (N. tabacumL.) seeds, “Kroumovgrad 90” variety of Oriental tobacco, were determined. The experimental data were obtained by the static gravimetric method at different temperatures and water activities. Sorption isotherms showed a typical Type II sigmoidal profile, with a significant hysteresis effect and a decrease of seed sorption capacity with the increase of temperature. The best fitting with tobacco seed sorption isotherms were the modified Chung-Pfost (desorption) and Oswin (adsorption) models. The monolayer moisture content, important for the safe storage of tobacco seeds, was also determined. The outcomes from the study might be of practical use in tobacco seed conditioning and storage design.

Fibroblast Growth Factor 2 Protein Stability Provides Decreased Dependence on Heparin for Induction of FGFR Signaling and Alters ERK Signaling Dynamics.

Fibroblast growth factor 2 (FGF2) plays important roles in tissue development and repair. Using heparan sulfates (HS)/heparin as a cofactor, FGF2 binds to FGF receptor (FGFR) and induces downstream signaling pathways, such as ERK pathway, that regulate cellular behavior. In most cell lines, FGF2 signaling displays biphasic dose-response profile, reaching maximal response to intermediate concentrations, but weak response to high levels of FGF2. Recent reports demonstrated that the biphasic cellular response results from competition between binding of FGF2 to HS and FGFR that impinge upon ERK signaling dynamics. However, the role of HS/heparin in FGF signaling has been controversial. Several studies suggested that heparin is not required for FGF-FGFR complex formation and that the main role of heparin is to protect FGF from degradation. In this study, we investigated the relationship between FGF2 stability, heparin dependence and ERK signaling dynamics using FGF2 variants with increased thermal stability (FGF2-STABs). FGF2-STABs showed higher efficiency in induction of FGFR-mediated proliferation, lower affinity to heparin and were less dependent on heparin than wild-type FGF2 (FGF2-wt) for induction of FGFR-mediated mitogenic response. Interestingly, in primary mammary fibroblasts, FGF2-wt displayed a sigmoidal dose-response profile, while FGF2-STABs showed a biphasic response. Moreover, at low concentrations, FGF2-STABs induced ERK signaling more potently and displayed a faster dynamics of full ERK activation and higher amplitudes of ERK signaling than FGF2-wt. Our results suggest that FGF2 stability and heparin dependence are important factors in FGF-FGFR signaling complex assembly and ERK signaling dynamics.

Real-Time In-Situ Monitoring of a Tunable Pentapeptide Gel-Crystal Transition.

Supramolecular gels often become destabilized by the transition of the gelator into a more stable crystalline phase, but often the long timescale and sporadic localization of the crystalline phase preclude a persistent observation of this process. We present a pentapeptide gel-crystal phase transition amenable for continuous visualization and quantification by common microscopic methods, allowing the extraction of kinetics and visualization of the dynamics of the transition. Using optical microscopy and microrheology, we show that the transition is a sporadic event in which gel dissolution is associated with microcrystalline growth that follows a sigmoidal rate profile. The two phases are based on β-sheets of similar yet distinct configuration. We also demonstrate that the transition kinetics and crystal morphology can be modulated by extrinsic factors, including temperature, solvent composition, and mechanical perturbation. This work introduces an accessible model system and methodology for studying phase transitions in supramolecular gels.

Real‐Time In‐Situ Monitoring of a Tunable Pentapeptide Gel–Crystal Transition

AbstractSupramolecular gels often become destabilized by the transition of the gelator into a more stable crystalline phase, but often the long timescale and sporadic localization of the crystalline phase preclude a persistent observation of this process. We present a pentapeptide gel–crystal phase transition amenable for continuous visualization and quantification by common microscopic methods, allowing the extraction of kinetics and visualization of the dynamics of the transition. Using optical microscopy and microrheology, we show that the transition is a sporadic event in which gel dissolution is associated with microcrystalline growth that follows a sigmoidal rate profile. The two phases are based on β‐sheets of similar yet distinct configuration. We also demonstrate that the transition kinetics and crystal morphology can be modulated by extrinsic factors, including temperature, solvent composition, and mechanical perturbation. This work introduces an accessible model system and methodology for studying phase transitions in supramolecular gels.

Morphology and sedimentology of the shelf-upper slope transition in the Abrolhos continental shelf (east Brazilian margin)

In mixed terrigenous-carbonate shelves, terrigenous sediment input may influence changes in slope morphology and sedimentation. Moreover, sea level changes and antecedent geology can also play an important role in defining depositional patterns for the shelf-slope system. This work investigates contrasting depositional and geomorphological patterns in the Abrolhos shelf-slope system, eastern Brazilian margin, South Atlantic. We have combined existing bathymetric datasets with bottom imagery and samples collected at the Johnson-Sea-Link manned submersible along two Abrolhos slope sites, which are separated by almost 2° of latitude. Our dataset includes seafloor sediments, single-beam echosounder, and 20 h of video recording. Dives ranged from 90 to 620 m water depth. Results showed that the north and south Abrolhos shelf-slope systems are distinct in terms of their morphology and sedimentology. The depositional pattern in the northern upper slope is typically carbonate dominated, with the occurrence of carbonate mounds around 500 m deep, small biogenic structures around 200 m deep, interspersed with wackstones and packstones. The upper slope is characterized by a steep limestone wall at 120 m deep that resembles a shelf-edge reef, followed by extensive rhodolith beds at the shelf edge and outer shelf. The southern upper slope shows a sigmoidal profile with a gentle gradient. Mixed siliciclastic–carbonate fine sedimentation dominates from 300 to 700 m deep. On the upper slope, fine carbonate sedimentation predominates, and a biogenic reef structure is observed in a water depth around 120–130 m. The shelf edge and outer shelf are also characterized by extensive rhodolith beds. Main findings indicate that a volcanic rock complex is an important antecedent geology that may influence the setting up of distinct sedimentary regimes and sediment input to the slope. The geometry of the antecedent geology controls the paleotopography forming a gradient towards the south. This, combined with sea-level changes and Rio Doce riverine sediment input, can explain the contrasts between the northern and southern shelf-upper slope depositional settings. Here, for the first time, the presence of possible Last Glacial Maximum or early deglaciation stage shelf-edge reef systems is reported for the Abrolhos Bank.

Mathematical Modelling of the Growth of Burkholderia sp. on Glyphosate

Glyphosate is an agricultural herbicide with usage in the amounts of thousands of tonnes per year in Malaysia. In certain soils, glyphosate can persist for months and its removal through bioremediation is the most economical and practical. A glyphosate-degrading bacterium has been isolated from contaminated soil. The growth of the bacterium on glyphosate as the sole phosphorous source shows classical sigmoidal profile. Important growth constants can be reliably obtained through nonlinear regression modelling using growth models such as logistic, Gompertz, Richards, Schnute, Baranyi-Roberts, Von Bertalanffy, Buchanan three-phase and the Huang models. The modified Gompertz model was chosen as the best model based on statistical tests such as root-mean-square error (RMSE), adjusted coefficient of determination (adjR2), bias factor (BF), accuracy factor (AF) and corrected AICc (Akaike Information Criterion). Novel constants obtained from the modelling exercise would be useful for further secondary modelling implicating the effect of media conditions and other factors on the growth of this bacterium on glyphosate. The fitted value of maximal growth rate showed a decline when the concentration of glyphosate was increased indicating substrate inhibition. The results from this work can be further used in secondary modelling exercises.

Design of Aqueous-Liquid Crystal Interfaces To Monitor Protein Aggregation at Nanomolar Concentrations

Amyloids are proteinaceous aggregates, the deposition of which is associated with neurodegenerative diseases, such as Alzheimer’s disease. In vitro protein aggregation requires high protein concentration, which is generally far from physiological concentration. Here, we utilize the interfacial properties of liquid crystals (LCs) to monitor the membrane-induced aggregation of a bacterial functional amyloid, curli, at nanomolar concentration. The binding event triggers an orientational transition of the LC, which is accompanied by the appearance of dynamic spatial patterns enabling sensitive detection of lipopolysaccharide (LPS)-mediated protein aggregation. Quantification of LC response shows a sigmoidal time profile, typical of a protein fibrillation assay. Curli is composed of two subunits (CsgA and CsgB) and is expressed on the outer membrane of Gram-negative bacteria containing LPSs endotoxin. CsgA forms the major subunit of curli, which is nucleated by the membrane-tethered minor subunit CsgB. Using a...

Bibliometric Analysis of Global Research on Clavulanic Acid.

Clavulanic acid (CA), a potent inhibitor of the β-lactam, ase enzyme, is frequently co-formulated with a broad spectrum of antibiotics to treat infections caused by β-lactamase-producing pathogens. In order to evaluate the impact and the progress of CA studies in the last four decades, a bibliometric analysis of the global scientific production of CA was carried out. A total of 39,758 records in the field of CA were indexed in the Scopus database for a 43-year period of study (1975–2017). The results indicated that CA studies have grown, showing three phases (1975–1999, 2000–2003 and 2004–2017) based on records of publications; the results showed a sigmoidal profile. Medicine was the main subject area for CA studies, whereas biochemistry, genetics and molecular biology were areas of research for CA production by Streptomyces clavuligerus (S. clavuligerus). Nevertheless, chemical engineering (as a subject area) had the highest increase in the percentage of publications related to CA production by S. clavuligerus. The United States, France, the United Kingdom, Spain and Brazil were the leading countries in the scientific production of studies on both CA and CA related to S. clavuligerus. This analysis allowed the identification of the area of knowledge with the highest impact on CA studies, the top researchers and their geographic distribution, and also helped to highlight the existence of antibiotic-resistant bacteria as an emergent area in CA research.

Mathematical Modelling of the Growth Curve of Vibrio sp. Isolate MZ Grown in Seawater Medium

Pollution in the environment is deteriorating the ecology due to human activities in a large array of industrial and agricultural sectors. Bioassay of polluted waters using bioluminescent bacterium has been touted as one of the most economical, rapid and sensitive tests. The growth of the bacterium on seawater medium exhibited a typical sigmoidal profile. To extract important growth parameters useful for further modelling exercise, various primary growth models were utilized in this study such as Modified Logistic, modified Gompertz, modified Richards, modified Schnute, Baranyi-Roberts, von Bertalanffy, Huang and the Buchanan three-phase model. The best performance was Huang model with the lowest value for RMSE, AICc and the highest value for adjusted R2. The AF and BF values were also excellent for the model with their values were the closest to 1.0. The Huang parameters, which include A or Y0 (bacterial growth lower asymptote), m (maximum specific bacterial growth rate),  (lag time) and Ymax (bacterial growth upper asymptote) were 7.866 (95% confidence interval of 7.850 to 7.883), 0.329 (95% confidence interval of 0.299 to 0.359), 1.543 (95% confidence interval of 1.303 to 1.784) and 8.511 (95% confidence interval of 0.299 to 0.359).

Optimal design of aging systems: A-frame coolers design under fouling

This work presents a parametric programming framework for the optimal design and operation of systems with performance loss over time. A two-stage procedure is proposed. The unit is designed for the operating conditions just before maintenance. In a second stage, a multiperiod problem is solved for the optimal the operation of the unit over time including cleaning costs. The minimum operating cost as a function of the cycle length determines the operating cycle and the unit design. The methodology is applied to A-frame cooling systems under fouling conditions, where fouling affects the pressure drop and the global heat transfer coefficient. The sigmoidal deposition profile results in an optimal cycle time of 8 years. This design allows reducing the energy required to around 4% of the energy produced by the concentrated solar power plant. It is a promising result that can be affected by plant layout and ground availability.

Mechanics of population aging and survival.

In this paper we extend the previous work of Witten and her team on defining a classical physics-driven model of survival in aging populations (Eakin, Bull Math Biol 56(6):1121-1141, 1994; Eakin and Witten, Mech Aging Dev 78(2):85-101,1995; Witten and Eakin, Exp Gerontol 32(2):259-285, 1997) by revisiting the concept of a force of aging and introducing the concepts of a momentum of aging, a kinetic energy and a potential energy of an aging population. We further extend the analysis beyond the deterministic Newtonian mechanics of a macroscopic population as a whole by considering the probabilistic nature of survival of individual population cohort members, thus producing new statistical physics-based concepts of entropy and of a gerontological "temperature". These new concepts are then illustrated with application to the classic parametric Gompertz survival model, which is a commonly used empirical descriptor for survival dynamics of mammalian species, human populations in particular. As a function of chronological age the Gompertz Model force, momentum, and power are seen to have an asymmetric unimodal peak profile, while the potential energy has a descending sigmoidal profile similar to that of the survival fraction. The "temperature" is an exponential function of age and the entropy for a future age at a current census age can be represented as a topological surface with an asymmetric unimodal hump.

In Situ and Real-Time Studies, via Synchrotron X-ray Scattering, of the Orientational Order of Cellulose Nanocrystals during Solution Shearing.

In this manuscript, we report on the ordering of the cellulose nanocrystals (CNCs) as they experience shear forces during the casting process. To achieve these measurements, in situ and in real time, we used synchrotron-based grazing incidence wide-angle X-ray scattering (GIWAX). We believe that the GIWAX technique, although not commonly used to probe these types of phenomena, can open new avenues to gain deeper insights into film formation processes and surface-driven phenomena. In particular, we investigated the influence of solution concentration, shear-cast velocity, and drying temperature on the ordering of cellulose nanocrystals (CNCs) using GIWAXS. The films were prepared from aqueous suspensions of cellulose nanocrystals at two concentration values (7 and 9 wt %). As the films were cast, the X-ray beam was focused on a fixed position and GIWAXS patterns were recorded at regular time intervals. Structural characterization of the dry films was carried out via polarized optical microscopy and scanning electron microscopy. In addition, a rheological study of the CNC suspensions was performed. Our results show that the morphology of the CNC films was significantly influenced by shear velocity, concentration of the precursor suspension, and evaporation temperature. In contrast, we observed that the orientation parameter of the films was not significantly affected. The scattering intensity of the peak (200) was analyzed as a function of time, following a sigmoidal profile, hence indicating short- and long-range interactions within the anisotropic domains as they reached their final orientation state. A model capable of describing the resulting film morphologies is also proposed. The results and analysis presented in this manuscript provide new insights into the controlled alignment of cellulose nanocrystals under shear. This controlled alignment has significant implications in the development of advanced coatings and films currently used in a myriad of applications, such as catalysis, optics, electronics, and biomedicine.

Unraveling the sigmoidal profiles in Fenton catalysis: Toward mechanistic elucidation

Fenton reactions are widely known and have been employed to degrade different pollutants in various environmental matrices. However, some controversies related to the Fenton mechanism remain unresolved. Although not comprehensively understood, kinetic sigmoidal profiles with an initial induction period have frequently been reported for Fenton systems. A thorough kinetic study was carried out at different temperatures involving Fenton reactions promoted by Fe3+ and Fe2+ and under the influence of radical scavengers. Catalysis supported by Fe2+ displayed the usual pseudo-first-order profile, while Fe3+ catalysis showed a sigmoidal pattern. The sigmoidal profiles were correlated to a pseudo-elementary autocatalytic mechanism developed by Finke and Watzky (F–W). The use of the F–W equation indicates that a certain amount of oxidative species must be generated to promote the substrate degradation. This correlation is a breakthrough in the understanding of Fenton catalysis.

Critical analysis of the relationship between imposex and butyltin body burden in Nassarius reticulatus and Nucella lapillus

Imposex is a disorder caused by organotins, mainly tributyltin, which results in the appearance of male sexual characteristics in females of gastropod mollusks. The main objective of this work was to make a critical analysis of the relationship between imposex and butyltin body burdens in Nucella lapillus and Nassarius reticulatus. Specifically, this study evaluates possible additive effects among butyltins, proposes scales of effects based on robust statistical criteria as alternatives to existing ones and defines the body burdens of TBT in N. lapillus and N. reticulatus corresponding to the assessment classes (ACs) of the Vas Deferens Sequence Index (VDSI) established by OSPAR. Data of organotin body burdens and biological effects was retrieved from the ICES Dataset and from scientific literature. All responses, except the percentage of females displaying Imposex (IMPF) in Nucella lapillus, showed a sigmoidal profile regarding to the body burden of mono- (MBT), di- (DBT) and tributyltin and sum of butyltins (SumBTs). TBT and the SumBTs were better indicators of the VDSI or Relative Penis Size Index/Relative Penis Length Index (RPSI/RPLI) responses than MBT or DBT in most cases. From a statistical point of view, RPSI/RPLI and VDSI were better indicators of contamination by TBT than IMPF, although both RPSI and RPLI showed lower sensitivity than VDSI. The model used for describing the joint effect of butyltins provided a statistically significant fitting to the data assuming a null effect for both MBT and DBT for N. lapillus, and a lower toxic contribution of MBT and DBT with respect to TBT for N. reticulatus. RPSI or RPLI values, equivalent to the ACs for VDSI, were proposed as alternative criteria when measuring moderate to high levels of imposex. TBT concentrations in N. reticulatus and N. lapillus tissues, corresponding to the ACs were calculated and provided valuable information for cross-species comparisons.

The role of sucrose concentration in self-assembly kinetics of high methoxyl pectin

Several natural and synthetic polysaccharides are able to form, under appropriate conditions, supramolecular structures, typically physical hydrogels, and, together with their biocompatibility, this explains their wide use in food, pharmaceutical and biomedical sectors. In the case of high methoxyl pectins (HMP) the gel formation is promoted by the presence of cosolutes (sugars or polyols) and low pH. The present investigation mainly regards the structuring kinetics of aqueous HMP solutions at acid pH (3.1) with the same pectin concentration (0.2% w/w) and different sucrose concentrations (from 56 to 65% w/w). Preliminary viscosity tests were performed to individuate the threshold of the sol region.A sequence of consecutive frequency sweeps was applied to each sample immediately after its preparation. The time evolution of the linear viscoelastic behavior is described by the sigmoidal profiles of both moduli at each applied frequency and more thoroughly defined through the change of the mechanical spectrum, i.e. the variation of the parameters of the generalized Maxwell model or the Friedrich-Braun model which are both suitable to provide a satisfactory data fitting. In particular, the equilibrium modulus Ge offers a significant description of the gelation kinetics and its sucrose dependence.