Chemistry

La présente contribution se propose de réfléchir aux caractéristiques de la lecture littéraire. Les théories didactiques actuelles s'accordant à construire leurs conceptions de la lecture autour de dichotomies, l'article proposera d'analyser ces différentes conceptions en se basant sur des témoignages de lecteurs réels (cinq étudiantes universitaires). Cette analyse théorique et empirique conduira à proposer une différenciation entre « types » et « modes » de lecture : la première se base sur les représentations des lecteurs, la deuxième sur leurs compétences. Ces reconceptualisations permettront de donner des pistes pour analyser le rôle du plaisir chez les lecteurs en formation.

The method used for removal of brilliant blue dye may have an influence in interpreting the results of spraying deposition studies. The aim of this study was to assess the number of washings and water volumes for brilliant blue dye removal from soybean leaflets and glass slides in fungicide sprayings with and without adjuvants. A completely randomized experimental design was used in a 3 × 3 × 2 × 4 factorial scheme. The factors consisted of number of washings (1st, 2nd, and 3rd), water volume (15, 20, and 30 mL), target type (soybean leaflets and glass slides), and spray solutions (fungicide ProdutorBR ® 0.5 L ha -1 without and with the adjuvants vegetable oil Agr'óleo ® 0.5% v v -1 , mineral oil Nimbus ® 0.5% v v -1 , and surfactant Silwet ® 0.04% v v -1 ). Sprayings were carried out by using the nozzle model TT110015 at a pressure of 300 kPa (medium droplets). After spraying, targets were washed and the amount of brilliant blue dye removed per target area was detected by spectrophotometry. Brilliant blue dye removal is higher in glass slide when compared to soybean leaflets. With a single washing, a higher difficulty in removing the brilliant blue dye was observed for fungicide with vegetable oil. Only the first washing and a water volume of 15 mL are insufficient for brilliant blue dye removal from soybean leaflets and glass slides.

An efficient method for the solution-phase parallel synthesis of 4-substituted-1,4-dihydroisoquinolin-3-ones is developed. The isoquinolinones were constructed employing an intramolecular Heck reaction, providing full regio-and stereoselectivity. Most of the synthesized compounds showed potent antiproliferative activities against tumor cell lines.

The present study was designed to determine the interplay of efflux protein inhibitors on the antibacterial activity and pharmacokinetics of enrofloxacin in chicken. Capsaicin and theobromine were used as efflux protein inhibitors. Birds weighing about 1.5 to 2.0 kg were allocated to 3 groups of six at random. Group I served as enrofloxacin control, whereas Group II and III birds were coad ministered with capsaicin and theobromine along with enrofloxacin. The plasma levels of enrofloxacin was determined by HPLC. The pharmacokinetic parameters were estimated by using Pksolver. Coadministration theobromine improved the bioavailability of enrofloxacin. The antibacterial activity was assessed by using microbroth dilution technique as per CLSI guidelines using MIC as determinant against ATCC strains of E. coli, S. aureus, K. pnemoniae, P. aureginosae. The results obtained in the study reveaed that combination of enrofloxacin with capsaicin and the obrominne enhanced the antibacterial activity of enrofloxacin by reducing the MIC values. The combination may be beneficial in reducing the development of resistance after conducting further studies.

KDM1A (LSD1) is a flavin adenine dinucleotide dependent histone demethylase, responsible for the demethylation of mono and dimethyl lysine 4 on histone H3. As a part of various transcriptional co-repressor complexes, it is known to interact with co-repressor complex CoREST and histone deacetylase 1 and 2. KDM1A is an essential gene, with important roles in different biological relevant processes, including hematopoietic cell lineage differentiation. KDM1A has been reported to be over expressed in a number of hematologic malignancies and lymphoid neoplasm. Specifically in acute myeloid leukemia (AML) KDM1A demonstrated to sustain the in vivo leukemogenic potential of MLL-AF9 expressing leukemia stem cells, thus supporting its determinant role in AML. Here we describe the anti-tumor effect of a novel KDM1A inhibitor (DDP_38003) tested in AML in vitro and in vivo models. DDP_38003 is a potent, selective, oral bioavailable irreversible inhibitor of KDM1A. The cellular activity of the compound, by measuring its ability to inhibit the colony formation of acute myeloid leukemia cells has been investigated. Potent growth inhibition was observed on AML blast colony forming ability of cells lines representative of different AML subtypes. Treatment of AML cells with the compound promoted the induction of myeloid differentiation markers and a differentiated phenotype. The in vivo efficacy of DDP_38003 was determined in mouse models of acute promyelocytic leukemia (APL), MLL-AF9 driven leukemia and on patient derived xenograft (PDX) AML model. Oral administration of DDP_38003 significantly increases the survival of treated mice, both in murine APL and in MLL-AF9 leukemia models. On MLL-AF9 model, the in vivo activity correlated with target inhibition, with a strong and sustained reduction of circulating leukemic blasts, and it was significantly better when compared to standard combined chemotherapy treatment. In addition, an increased survival has also been observed in a PDX (MLL-AF9) disseminated leukemia model. Importantly, in vivo efficacy could be achieved with different dosing regimens of DDP_38003. Collectively, these data support the advancement of DDP-38003 toward preclinical development. No conflict of interest.

The following experimental techniques were used to determine the structure: The reported resolution of this entry is 2.50 Å. Percentile scores (ranging between 0-100) for global validation metrics of the entry are shown in the following graphic. The table shows the number of entries on which the scores are based. Whole archive (#Entries) Similar resolution (#Entries, resolution range(Å)) R f ree 130704 4661 (2.50-2.50) Clashscore 141614 5346 (2.50-2.50) Ramachandran outliers 138981 5231 (2.50-2.50) Sidechain outliers 138945 5233 (2.50-2.50) RSRZ outliers 127900 4559 (2.50-2.50) The table below summarises the geometric issues observed across the polymeric chains and their t to the electron density. The red, orange, yellow and green segments on the lower bar indicate the fraction of residues that contain outliers for >=3, 2, 1 and 0 types of geometric quality criteria respectively. A grey segment represents the fraction of residues that are not modelled. The numeric value for each fraction is indicated below the corresponding segment, with a dot representing fractions <=5% The upper red bar (where present) indicates the fraction of residues that have poor t to the electron density. The numeric value is given above the bar.

Background: Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor sideeffects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, a-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that aflupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, a-flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by a-flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by a-flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, a-flupentixol failed to induce EPS and to alter STN neuronal activity. Our study reports strong evidence to show that hypokinesia and catalepsy induced by a-flupentixol are triggered by dramatic changes occurring in basal ganglia network. We provide new insight into the key role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can be considered as a potential target for the treatment of EPS.

Fast inhibitory synaptic transmission in the brain relies on ionotropic GABAA receptors (GABAAR). Eighteen genes code for GABAAR subunits, but little is known about the ε subunit. Our aim was to identify the synaptic transmission properties displayed by native receptors incorporating ε. Immunogold localization detected ε at synaptic sites on locus coeruleus (LC) neurons. In situ hybridization revealed prominent signals from ε, and θ mRNAs, some low β1 and β3 signals, and no γ signal. Using in vivo extracellular and in vitro patch-clamp recordings in LC, we established that neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics of recombinant receptors including an ε subunit. Surprisingly, LC provided binding sites for benzodiazepines, and GABA-induced currents were potentiated by diazepam (DZP) in the micromolar range. A number of GABAAR ligands significantly potentiated GABA-in...

Amyloid fibrillation is associated with several human maladies, such as Alzheimer&#39;s, Parkinson&#39;s, Huntington&#39;s diseases, prions, amyotrophic lateral sclerosis, and type 2 diabetes diseases. Gaining insights into the mechanism of amyloid fibril formation and exploring novel approaches to fibrillation inhibition are crucial for preventing amyloid diseases. Here, we hypothesized that ligands capable of stabilizing the native state of query proteins might prevent protein unfolding, which, in turn, may reduce the propensity of proteins to form amyloid fibrils. We demonstrated the efficient inhibition of amyloid formation of the human serum albumin (HSA) (up to 85%) and human insulin (up to 80%) by a nonsteroidal anti-inflammatory drug, ibuprofen (IBFN). IBFN significantly increases the conformational stability of both HSA and insulin, as confirmed by differential scanning calorimetry (DSC). Moreover, increasing concentration of IBFN boosts its amyloid inhibitory propensity in...

The authors regret b 1. On page no. 223, in Table , in modulator IV. Transformer II (amyloid-amorphous), the "b. Metal" should be in front of lysozyme, not the Bovine insulin (i.e. one line lower). 2. In same table and modulator, for Bovine insulin the reference no. should be [207] instead of [104] which has been added in "Reference" section. 3. On page no. 25, in section "Drugs", the no. [134] should be deleted. 4. On page no. 25, in section "Dyes", the no. [134] should be inserted in 6th line after completion the sentence "…and unfolding of the protein [134]". 5. On page no. 223, in table 4. (for modulator VI. Inhibitor. l. surfactant, Bovine insulin) and at page no. 226 in section "surfactant": The cited reference no. should be [208] instead of [124] which has been added in "Reference" section. 6. In "Reference" section at page no. 228, the correct reference for [104] has been inserted which is "Q.

Alpha1-acid glycoprotein (AAG) is a major acute phase protein of human plasma. Binding of clofazimine to AAG is investigated using optical spectroscopy and molecular docking tools. We found significant quenching of intrinsic fluorescence of AAG upon the binding of clofazimine, binding mode is static with binding constant of 3.52 × 10at 298 K. The Gibbs free energy change is found to be negative for the interaction of clofazimine with AAG indicating spontaneity of the binding process. Binding of clofazimine induced ordered structure in protein and lead to molecular compaction. Molecular docking results indicate the binding site is located in the central beta barrel, hydrogen bonding and hydrophobic interactions are main bonding forces between AAG-clofazimine.

Protein aggregation and amyloid fibrillation are responsible for several serious pathological conditions (like type II diabetes, Alzheimer&#39;s and Parkinson&#39;s diseases etc.) and protein drugs ineffectiveness. Therefore, a molecule that can inhibit the amyloid fibrillation and potentially clear amyloid fibrils is of great therapeutic value. In this manuscript, we investigated the antiamyloidogenic, fibril disaggregating, as well as cell protective effect of an anti-tuberculosis drug, Capreomycin (CN). Aggregation kinetics data, as monitored by ThT fluorescence, inferred that CN retards the insulin amyloid fibrillation by primarily targeting the fibril elongation step with little effect on lag time. Increasing the dose of CN boosted its inhibitory potency. Strikingly, CN arrested the growth of fibrils when added during the elongation phase, and disaggregated mature insulin fibrils. Our Circular Dichroism (CD) results showed that, although CN is not able to maintain the alpha hel...

Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5-amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T. Premixing of drugs with insulin inhibited the nucleation phase and inhibitory potential was boosted by increasing the concentration of the drug. Moreover, addition of drugs at the studied concentrations attenuated the insulin fibril induced cytotoxicity in breast cancer cell line MDA-MB-231. Our results highlight the amino group of salicylic acid ex...

The newly synthesized unfolded polypeptide attains its functional and unique three-dimensional conformation through the process of protein folding for which several models have been proposed. The protein misfolding diseases include Alzheimer&#39;s, Parkinson&#39;s and Cataract which are result of formation of amyloid or amorphous aggregates, respectively. The distinction in morphology shows relation with the melting temperature (Tm). The temperatures near or slightly higher than Tm induces amyloids while much higher or low temperature mediate amorphous aggregation. The aggregation is not always deleterious rather it also performs several important cellular functions essential for survival wide range of organisms called as functional amyloids. Protein gets modulated by several modulators which mediate the aggregation, acceleration, delay, transformations, inhibition and disaggregation of protein aggregates. The exclusive properties of inhibition and disaggregation displayed by variou...

Numerous phenolic compounds have been reported in the last decade that have a good antioxidant property and interaction affinity towards mammalian serum albumins. In the present study, we have utilized human serum albumins as a model protein to examine their comparative interaction property with polyphenolic compound tannic acid (TA) by using various spectroscopic and calorimetric methods We have also monitored the esterase and antioxidant activity of mammalian serum albumins in the absence and presence of TA. The obtain results recommended that the TA have a good binding affinity (∼10(4) to 10(6)M(-1)) towards mammalian serum albumins and shows double sequential binding sites, which depends on the concentration of TA that induced the conformational alteration which responsible for the thermal stability of proteins. Binding affinity, structural transition and thermodynamic parameters were calculated from spectroscopic and calorimetric method reveals that non-covalent interaction cau...

This review article summarises the possible mechanisms of the protein-ligand interaction, folding, misfolding, aggregation and inhibition of protein aggregates. Under certain stressed condition the folding process deviates from its path and results into misfolding and aggregation of proteins. So aggregates have to be inhibited in order to cure the diseases. In some cases of protein-ligand interaction studies we have seen that the interaction of a protein with more than one ligand may show both type of quenching mechanisms i.e. dynamic as well as static quenching rather than single type of quenching mechanism, that result can be entirely different by the result of binding study utilising single ligand. So, likewise it is hypothesized that if the aggregates are inhibited by using more than one inhibitor may give more fruitful results rather than application of single inhibitor in inhibition and disaggregation of the preformed aggregates. Therefore, we have hypothesized mechanisms for the inhibition of protein aggregates that may assist in curing the neurodegenerative diseases. Thus, besides the mechanism of protein-ligand interaction, folding, misfolding and aggregation; the hypothesized mechanisms for the inhibition of protein aggregates may show new route to researchers either directly or indirectly in treating the diseases.

The aggregation phenomenon (amyloid and amorphous) is associated with several pathological complications in human, such as Alzheimer&#39;s, Parkinson&#39;s, Huntington, Cataract diseases and Diabetes mellitus type 2. In the present study we are offering evidence and breaking the general belief with regard to the polyphenols action as protein aggregate inhibitors. Herein we confirm that tannic acid (TA) is not only an amyloid inducer, but also it switches one type of conformation, ultimately morphology, into another. We ascertain based on our findings that aggregates are not rigid structures and the stability can be challenged under certain conditions. This study also confirms that unfolded and amorphous aggregates can serve as precursors of amyloids and TA interactions with unordered aggregates (amorphous) bringing orderliness in the conformation via amyloidosis. The shifting of unordered conformation towards orderliness is governed by the modulation in surface hydrophobic patches i...

Erucic acid (EA) is one of the key fatty acids usually found in canola oil, mustard oil and rapeseed oil. Consumption of EA in primates was found to cause myocardial lipidosis and cardiac steatosis. To have an insight of the effect of EA in humans, we performed in vitro interaction studies of EA with the primary plasma protein, human serum albumin (HSA). Spectroscopic (UV-vis and fluorescence) analysis of the EA-HSA interaction revealed a static mode of quenching, with binding constant Kb ∼10(4) reflecting high affinity of EA for HSA. The negative value of ΔG° for binding of EA to HSA in the fluorescence studies indicates the process to be spontaneous. Thermodynamic signatures of the EA-HSA interaction in the complex reflect dominance of hydrogen bonds. Despite predominance of hydrogen bonds, hydrophobic interactions in the EA-HSA complex were found acting as a contributing factor in the binding of EA to HSA, observed as structural change in the far-UV CD spectra. Förster&#39;s reso...

Nowadays, understanding of interface between protein and drugs has become an active research area of interest. These types of interactions provide structural guidelines in drug design with greater clinical efficacy. Thus, structural changes in catalase induced by clofazimine were monitored by various biophysical techniques including UV-visible spectrometer, fluorescence spectroscopy, circular dichroism, and dynamic light scattering techniques. Increase in absorption spectra (UV-visible spectrum) confers the complex formation between drug and protein. Fluorescence quenching with a binding constants of 2.47 × 10(4)  M(-1) revealed that clofazimine binds with protein. Using fluorescence resonance energy transfer, the distance (r) between the protein (donor) and drug (acceptor) was found to be 2.89 nm. Negative Gibbs free energy change (ΔG°) revealed that binding process is spontaneous. In addition, an increase in α-helicity was observed by far-UV circular dichroism spectra by adding cl...

 The binding interaction between clofarabine and human serum albumin (HSA) and alpha 1 acid glycoprotein (AAG) was investigated.  Clofarabine caused fluorescence quenching of both HSA and AAG by static mode  UV-visible spectroscopy deciphered the formation of ground state complex between clofarabine and the two studied proteins.  There is stronger interaction of clofarabine with AAG as compared to HSA.  The Gibbs free energy change was found to be negative for the interaction of clofarabine with AAG and HSA indicating the binding process is spontaneous.  Binding of clofarabine with HSA and AAG induced ordered structures in both proteins and leads to molecular compaction.  Hydrogen bonding and hydrophobic interactions are the main bonding forces between HSA-clofarabine and AAG-clofarabine as revealed by docking results.

Under physical or chemical stress, proteins tend to form aggregates either highly ordered (amyloid) or unordered (amorphous) causing many pathological disorders in human and loss of proteins functionality in both laboratory conditions and industries during production and storage at commercial level. We investigated the effect of increasing temperature on Conalbumin (CA) and induced aggregation at 65 • C. The enhanced Thioflavin T (ThT) and ANS (1-anilinonaphtalene 8-sulfonic acid) fluorescence intensity, show no shift on Congo red binding, additionally, transmission and scanning electron microscopy (TEM) (SEM) reveal amorphous morphology of the aggregate. Our investigation clearly demonstrated that polyols namely Glycerol (GL) and Ethylene glycol (EG) are so staunch to inhibit amorphous aggregates via restoring secondary conformation. Addition of polyols (15% GL and 35% EG) significantly decrease the turbidity, Rayleigh scattering ThT and ANS fluorescence intensity. The dynamic light scattering (DLS) data show that hydrodynamic radii (R h ) of the aggregates is ∼20 times higher than native CA while nearly similar for GL and EG protected CA due to condensation of core size with little difference.

Studying amyloid associated neurodegenerative diseases is an active area of research. Cure for these diseases are still to be discovered. In the present study we have performed comprehensive biophysical and computational experiments showing levodopa not only significantly inhibits heat induced fibrillization of human serum albumin but also disaggregates preformed fibrils. Thioflavin T (ThT) binding assay was used to monitor the fibrillation process of human serum albumin (HSA) at 65 • C in the presence and absence of levodopa. Binding of levodopa was studied using isothermal titration calorimetry (ITC), binding constant was found to be 3.6 × 10 3 M -1 . Thermal stabilization effect of levodopa on HSA was studied using differential scanning calorimetry (DSC). Microscopic imaging techniques were employed to analyze the morphology of aggregates and effect of levodopa on aggregation. Further, molecular docking study was also utilized to decipher the amino acid residues involved in the binding interaction of levodopa with HSA. Levodopa interferes in the Fibrillogenesis of HSA by interacting with the amino acid residues near to drug binding site II on the HSA with the binding constant of the order of 10 3 and stabilizes the protein. The results are indicative of the potential use of levodopa as a therapeutic agent for the treatment of amyloid diseases.

Quaternary amine of diethylaminoethyl rosin ester (QRMAE), chemically synthesized by rosin modified biocompatible cationic surfactant, has various biological applications in the field of pharmacy as well as used as food product additive. Here, we report biophysical insights in to the interaction mechanism of thymoquinone (TQ), copper nanoparticles (Cu-NPs) and QRMAE with bovine serum albumin (BSA) individually and also in complexes forms to determine their competitive binding affinity. We have also studied the aggregationinhibition effects of Cu-NPs and TQ individually, as well as in complexes form in the presence of QRMAE surfactants which is responsible for induction of amorphous aggregates in BSA within hours of incubation at 65 ºC and physiological pH. The formation of aggregates was established by using various spectroscopic methods and dye binding assay. The circular dichroism (CD) spectroscopy showed that QRMAE significantly altered the secondary structure of BSA. However, the presence of TQ and Cu-NPs restricted the aggregation process which was observed to be more efficient when TQ and Cu-NPs were present together. This study provides very significant competitive binding results of QRMAE, Cu-NPs, TQ and protein aggregation behavior at higher temperature which was induced by rosin surfactant QRMAE, and this aggregation process was inhibited by Cu-NPs, TQ individually and together. Therefore, our finding suggested that rosin surfactant QRMAE has high propensity to induce amorphous aggregation in BSA which was favored at elevated temperature and higher concentration of the protein. When BSA-QRMAE sample was incubated in the presence Cu-NPs under similar condition, the aggregation propensity reduced, and drastically inhibited by TQ and Cu-NPs together.

Here we have used five non-fluorinated cosolvents (acetonitrile, ethanol, methanol, sec-butanol and terbutanol) at increasing concentrations and analyzed its aggregation inducing behavior on interaction with conalbumin. The aggregates were identified as amorphous by performing spectroscopic experiments like circular dichroic and dye binding assay. The amorphous aggregate contains rich ␤-sheet content, show insignificant increment in thioflavin-T (ThT) fluorescence intensity but strong 1-anilino-8-napthalene sulfonate (ANS) binding with enhanced fluorescence intensity. We also performed transmission electron microscope (TEM) and scanning electron microscope (SEM) imaging of the aggregates which made the result more informative. The morphology appeared on TEM imaging shows aggregates but there is no exhibition of fibril formation, as was observed on amyloid induced by 2,2,2-trifuoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-propan-2-ol (HFIP). SEM imaging also gives the similar results indicating the formation of amorphous aggregates. Web based tools (Waltz and AGGRESCAN) predicted aggregation prone regions in CA which are accountable for the aggregation.

Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4 Â 10 3 M À 1 . The average binding distance between drug and Trp 214 of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV-visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH¼ À26.01 kJ mol À 1 and TΔS¼6.5 kJ mol À 1 ) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations.

In this study we are reporting the conformational modulation as well as the plausible mechanism of structural perturbation in conalbumin (CA). The overall structure of CA is altered by the change in dielectric constant upon addition of fluoroalcohols (TFE and HFIP). We studied the formation of aggregates in CA at pH 7.0 by multiple structural probes in the presence of TFE and HFIP. The protein aggregates maximally in 15% (v/v) TFE and 3% (v/v) HFIP. ANS, ThT binding and transmission electron microscopy data suggest that the aggregates induced by TFE and HFIP have amyloid-like properties. Higher concentrations of TFE and HFIP causes increase in helical propensity. Far-UV circular dichroism, intrinsic fluorescence, ANS and ThT fluorescence data suggests that formation of a partially structured intermediate state precedes the onset of the aggregation process.

Two new series of compounds namely, 3,6-disubstituted-1,2,4-triazolo [3,4-b][1,3,4]thiadizoles (5aej) and 5,6-dihydro-3,6-disubstituted-1,2,4-triazolo[3,4-b][1,3,4]thiadizoles (7aej) were prepared. In continuation of a previously reported study, the first series (5aej) were synthesized by the cyclocondensation of 4-amino-5-(2-bromo-5-methoxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4) with various substituted aromatic carboxylic acids in phosphorus oxychloride and the second series (7aej) by the reaction of (4) with various substituted aromatic aldehydes in the presence of p-Toluene sulfonic acid. Reaction of (4) with the aldehyde (9) afforded the Schiff's base (10) and not the cyclised product (11) on treatment with p-Toluene sulfonic acid. Synthesized compounds were structurally confirmed by spectral analysis and studied for their anti-inflammatory, analgesic, anti-oxidant and antimicrobial activities. Some of the tested compounds showed significant pharmacological activities.

Four new compounds including two new sesquiterpenoid dimers, commiphoroids E (1) and F (2), a new triterpenoid (3), and a new sesquiterpenoid (4), along with three known terpenoids (5−7) were isolated from Resina Commiphora, whose structures were identified by NMR spectra, HRESIMS, and X-ray diffraction analysis. Compounds 1 and 2 both bear an O-bridge ring and feature a plausible [4 + 2] Diels–Alder cycloaddition reaction. Antimycobacterial activities show that all the tested compounds (200 μM) could inhibit the growth of both sensitive and clinically multi-drug resistant (MDR) isolated strains. In addition, cellular toxicity of the isolates against human cancer cells and THP-1 monocyte cells was examined.

One of the most important pathways for exposure to metals is drinking water ingestion. Chronic or acute exposure to metals can endanger the health of the exposed population, and hence, estimation of human health risks is crucial. In the current study for the first time, the concentrations of Mercury (Hg), Arsenic (As), Zinc (Zn), Lead (Pb) and Cobalt (Co) in 120 collected tap water samples (2015, July-November) from Ilam city, Iran were investigated using flame atomic absorption spectrophotometer. Also, the metal-induced carcinogenic and non-carcinogenic risks for consumers exposed to tap drinking water were calculated. The average (range) concentrations of Hg, Zn, As, Pb and Co were defined as 0.40 ± 0.10 μg/L (ND-0.9 μg/L), 5014 ± 5707 μg/L (2900.00-5668.33 μg/L), 21.008 ± 2.876 μg/L (3.5-62 μg/L), 30.38 ± 5.56 μg/L (6-87 μg/L), and 11.34 ± 1.61 μg/L (0.1-50 μg/L), respectively. Average concentrations of all examined metals were significantly higher than WHO and national standard ...

IMS reveals distribution of nitroaromatic compounds and their associations in soil. • Aromatic C plays a key role in sorption of nitroaromatic compounds to soil. • Hydrophobicity affects sorption of nitroaromatic compounds to clay minerals in soil.

Cell membranes are intrinsically heterogeneous, as the local protein and lipid distribution is critical to physiological processes. Even in template systems embedding a single protein type, like purple membranes, there can be a different local response to external stimuli or environmental factors, resulting in heterogeneous conformational changes. Despite the dramatic advances of microspectroscopy techniques, the identification of the conformation heterogeneity is still a challenging task. Tip-enhanced infrared nanospectroscopy is here used to identify conformational changes connected to the hydration state of the transmembrane proteins contained in a 50 nm diameter cell membrane area, without the need for fluorescent labels. In dried purple membrane monolayers, areas with fully hydrated proteins are found among large numbers of molecules with randomly distributed hydration states. Infrared nanospectroscopy results are compared to the spectra obtained with diffraction-limited infrar...

Solute-surface interactions are critical in membrane science and dominate a number of diffusion and selectivity parameters. In water treatment particularly, the charge on the membrane has been shown to affect ion transport selectivity as well as fouling mechanisms. The development of advanced surface technologies that allow for potential customization of the surface charge for specific applications, without compromising the essential performance of the membrane, is therefore desirable. In this paper, a novel plasma polymerization strategy was applied to commercial reverse osmosis membrane in order to tune the surface charge. Two monomers, maleic anhydride and vinylimidazole, were plasma polymerized onto the membrane resulting in a modification of the surface energy with resultant iso-electric points of approx. pH 3 and pH 7 respectively. This required only a short 5 min plasma polymerization treatment in each case. Thus, in addition to enhancing the water permeation by up to 10 %, in comparison to the reference membranes, the overall charge of the membranes was shifted from highly negatively charged upon maleic anhydride polymerization to highly positively charged upon vinylimidazole polymerization. A comprehensive morphological and chemical analysis was performed to correlate the changes to the presence of functional groups and the alteration of the surface texture. Short treatments were found to smooth the surface whilst enriching the surface with either carboxylic or amine/amide groups. This work opens new avenues to engineer advanced membranes with improved performance and selectivity.

The characterization of novel metal reinforced electro-dialysis ion exchange membranes, for water desalination, by attenuated total reflectance Fourier Transform infra-red spectroscopy mapping is presented in this paper. The surface of the porous stainless steel fibre meshes was treated in order to enhance the amount of surface oxide groups and increase the material hydrophilicity. Then, the metal membranes were functionalized through a sol-gel reaction with silane coupling agents to enhance the affinity with the ion exchange resins and avoid premature metal oxidation due to redox reactions at the metalpolymer interface. Polished cross sections of the composite membranes embedded into an epoxy resin revealed interfaces between metallic frameworks and the silane layer at the interface with the ion exchange material. The morphology of the metalpolymer interface was investigated with scanning electron microscopy and Fourier transform infra-red micro-spectroscopy. Fourier transform infra-red mapping of the interfaces was performed using the attenuated total reflectance mode on the polished cross-sections at the Australian Synchrotron. The nature of the interface between the metal framework and the ion exchange resin was shown to be homogeneous and the coating thickness was found to be around 1 μm determined by Fourier transform infra-red micro-spectroscopy mapping. The impact of the coating on the properties of the membranes and their potential for water desalination by electro-dialysis are also discussed.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heter...

In this study, the effects of homogenization pressure (125, 145, and 165 bars) and temperature (45, 60, and 75°C) on the properties of Sesame vegetable cream are investigated. The physical stability of cream was characterized by droplet size and syneresis, and chemical stability of it was evaluated by determining peroxide value and p‐anisidine. The results showed that the cream in the presence of high pressure and temperature treatment exhibits lower stability. At 75°C temperature and 165 bar, the vegetable cream had highest peroxide value (3.61) and p‐anisidine (2.16). However, pressure could protect the droplets against aggregation in the high pressure (165 bar) and greatly increased the physical stability. During increase in process parameters, the syneresis of cream was decreased with a rise of pressure and extension of temperature. The process condition in 145 bar and 60°C led to the high acceptability of vegetable cream.

Background: Due to the adverse effects of artificial preservatives on food and its harmful effects on human health, researchers have been considering replacing these materials with natural substances. In this study, the effect of pomegranate peel extract (PPE) on the stability and antifungal activity of the walnut kernel was studied. Methods: The pomegranate peel was extracted by the solvent and water-solvent method. The extracted sap was evaluated using the antioxidant assay by 2,2-diphenylpicrylhydrazyl (DPPH) assay. The results showed that the extracted sap had 40.11 mg/g dry phenol and 47.27% free radicals scavenging. Four concentrations (0%, 2%, 6%, and 10%) of pomegranate liquid extract were prepared and studied for 90 days for the walnut kernel coating. Walnut kernels were coated on days 1, 15, 30, 60, and 90, and examined for moisture, acidity, peroxide, conjugated diene, and anisidine tests. Data were analyzed using SPSS version 21. Results: By increasing the extract concen...

Introduction: Pesticide poisoning is an important public health problem worldwide. The study aimed to determine the risk of all-cause and cause-specific inpatient mortality and to identify prognostic factors for inpatient mortality associated with unintentional insecticide and herbicide pesticide poisonings. We performed a retrospective cohort study of 3,986 inpatients recruited at hospitalization between 1999 and 2008 in Taiwan. We used the International Classification of Disease, 9th ed., Clinical Modification external causes of injury codes to classify poisoning agents into accidental poisoning by insecticides and herbicides. Comparisons in mortality rates were made between insecticide poisoning patients and herbicide poisoning patients by using the Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: There were 168 deaths during 21,583 person-days of follow-up evaluation (7.8 per 1,000 person-days). The major causes of mortality for insecticide poisonings were the toxic effect of organophosphate and coma, and the major causes of mortality for herbicide poisonings were the toxic effect of other pesticides and the toxic effect of organophosphate. The mortality for herbicide exposure was fourfold higher than that for insecticide exposure. The factors associated with inpatient mortality were herbicide poisonings (HR = 4.58, 95% CI 3.29 to 6.37) and receiving mechanical ventilation treatment (HR = 3.85, 95% CI 2.73 to 5.42). We demonstrated that herbicides stand out as the dominant agent for poisoning-related fatalities. The control of and limiting access to herbicide agents and developing appropriate therapeutic regimens, including emergency care, should be priorities.

Background: There is accumulating epidemiologic evidence that exposure to traffic-related air pollutants, including particulate matter (PM) and polyaromatic hydro carbons (PAHs), plays a role in etiology and prognosis of a large scale of illnesses, although the role of specific causal agents and underlying mechanisms for different health outcomes remains unknown. Objective: Our general objective was to assess the relations between personal exposure to traffic exhausts, in particular ambient PM 2.5 and PAHs, and the occurrence of DNA strand breaks by applying personal monitoring of PM and biomarkers of exposure (urinary 1-hydroxypyrene-glucuronide, 1-OHPG) and effect (urinary 8-hydroxydeoxyguanosine, 8-OHdG and DNA strand breaks). We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei City, Taiwan. We used PM 2.5 personal samplers to collect breathing-zone particulate PAHs samples. Spot urine and blood samples after work shift of 2 consecutive days were analyzed for 1-OHPG, 8-OHdG and DNA strand breaks, respectively. Statistical methods included linear regression and mixed models. Results: Urinary 8-OHdG levels and the occurrence of DNA strand breaks in traffic conductors significantly exceeded those in indoor office workers in mixed models. Particulate PAHs levels showed a positive association with urinary 1-OHPG in the regression model (b = 0.056, p = 0.01). Urinary 1-OHPG levels were significantly associated with urinary 8-OHdG levels in the mixed model (b = 0.101, p = 0.023). Our results provide evidence that exposure to fine particulates causes DNA damage. Further, particulate PAHs could be biologically active constituents of PM 2.5 with reference to the induction of oxidative DNA damages.

New advances in micro and nano scales are being realized and the contributions of micro and nano heat dissipation devices are of high importance in this novel technology development. Past studies showed that microchannel design depends on its thermal resistance and pressure drop. However, entropy generation minimization (EGM) as a new optimization theory stated that the rate of entropy generation should be also optimized. Application of EGM in microchannel heat sink design is reviewed and discussed. Using EGM, majority of the published investigations are conducted based on rectangular cross section microchannel. Latest principles for deriving the entropy generation correlations are discussed to present how this approach can be achieved. The present study involves an optimization procedure using EGM method and derives the entropy generation rate in circular microchannel heat sink based upon thermal resistance and pressure drop simultaneously. The equations are solved using MATLAB and the obtained results are compared to the past studies. The effect of channel diameter and number of channels on the entropy generation rate, Reynolds number, thermal resistance and pressure drop is investigated. Analytical correlations are utilized for heat transfer and friction coefficients. A minimum entropy generation has been observed for N=40 and channel diameter of 90 . It is concluded that for N=40 and channel hydraulic diameter of 90 , the circular microchannel heat sink is on its optimum operating point based on second law of thermodynamics. Penyelidikan pada skala mikro dan nano telah menjadi semakin maju dan sumbangan sistem mikro dan nano sebagai alat penenggelam haba saliran kini menjadi semakin penting. Kajian awal menunjukkan bahawa rekabentuk saliran mikro bergantung kepada rintangan haba dan susutan jumlah tekanan. Walaubagaimanapun, teori terbaru berkaitan penghasilan entropi minimum (EGM) menyatakan bahawa kadar penjanaan entropi juga perlu diambilkira. Aplikasi teori EGM dibincang di sini. Kajian ini merangkumi proses pengoptimuman menggunakan EGM dengan penerbitan kadar penjanaan entropi untuk sistem penenggelam haba saliran mikro berbentuk bulat berdasarkan rintangan haba dan susutan jumlah tekanan. Persamaan berkaitan diselesaikan dengan MATLAB dan perbandingan dilakukan dengan kajian terdahulu. Kesan-kesan garis pusat dan bilangan saluran terhadap penjanaan entropi, angka Reynolds, rintanan haba dan susutan jumlah tekanan telah dikaji. Teori sekaitan telah digunakan untuk pemindahan haba dan pekali geseran. Penjanaan entropi minima dikenal pasti berlaku pada jumlah saliran N = 40 dan garis pusat 90 . Di sini boleh dirumuskan bahawa pada N = 40 dan garis pusat 90 , penenggelam haba saliran mikro berbentuk bulat akan beroperasi pada tahap optima berdasarkan hukum kedua termodinamik.

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In this paper we estimate measurement of uncertainty for determination of Fe, Pb and Zn in natural water samples by solid-phase extraction and i nductively coupled plasma optical emission spectrometry (SPE-ICP-OES). The procedure is based on the retention of analytes in the form of 8-hydroxyquinoline (8-HQ) complexes on a mini column of XAD-4 resin and subsequent elution with nitric acid. The infl uence of various analytical parameters including the amount of solid phase, pH, elution factors (concentration and volume of eluting solution), volume of sample solution, and amount of ligand on the extraction effi ciency of analytes was investigated. To estimate the uncertainty of analytical result obtained, we propose assessing trueness by employing spiked sample. Two kinds of bias (proportional bias and constant bias) estimated. We applied Nested design for calculating proportional bias and Youden method to calculate the constant bias. The results we obtained for proportional bias are calculated from spiked samples. Estimated uncertainty in Karaj water is: (1.0198 ± 0.0075) for Fe, (0.999 ± 0.010) for Pb and (1.0321 ± 0.0137) for Zn.

Spichiger, nach dem Tode von Prof. Simon fortfahren und abschliessen zu dürfen. Prof. Dr. R. Zenobi danke ich für die Übernahme des Korreferats. Zu Dank verpflichtet bin ich der Optik-Gruppe am Paul-Scherrer-Institut Zürich, besonders Dr. R. Kunz, für die wissenschaftliche Begleitung und Unterstützung bei den Messungen in ihren Labors. Ich stehe in der Schuld meiner Freunde und Kollegen für ihre Hilfe, Unterstützung und viele stimulierende Diskussionen. Der gesamten "Simonia" danke ich für die herzliche Aufnahme und Integration in eine lebhafte und anregende Forschungsgruppe. Besonders danken möchte ich Frau Dr. D. Wegmann für ihre sorgfältige Durchsicht des Manuskripts. und in kurzer Zeit an einer grossen Zahl von Menschen durchführbar sein sollten und eindeutige Ergebnisse liefern.

Total ion concentrations of sodium, potassium, calcium and chloride have been measured reversibly by ion-selective optode membranes with comparable selectivity to potentiometric systems. The results of quality-control samples analysed by the selective optode membranes show a good agreement with the assigned values and a reasonable reproducibility, though for quantification of sodium and potassium the unknown concentrations are evaluated in a first trial by a standard addition method. All measurements are referred to a pair of blank membranes in a reference cell to compensate for interferences induced by the diluted plasma sample. The efficiency of the evaluated values with regard to the medical interpretation encompasses the performance standard of the analytical procedure as well as the intra-and interindividual variation of the subjects studied. The required performance characteristics of a sensor are constituted dilhzrently, depending on the mode of application and the medical question to be answered. The type of optodes described may be tailored to a large extent to adapt them to the required performance boundary conditions. This will bc discussed with respect to other optical sensor schemes.

The properties of optode membranes to be used for realizing miniature integrated optical sensors based on refractometry have been investigated theoretically and experimentally. In situ referencing by using optode and reference membranes on the same chip is a powerful means to discriminate against unspecific effects. The plasticized polymer membranes provide the function of selective extraction and chemical recognition of the analyte. In experiments performed for a pair of such membranes, refractive index differences ~3 x 10 3 per decade of molar Ca 2+ concentration in buffered aqueous solutions have been observed. With the characterized type of sensing pad implanted in a miniature integrated optical device, a typical overall resolution of 0.7 to 0.07% in units of Ca 2~ concentration was calculated.

Fluoride (F) as one of the most toxic pollutants affecting the environment severely restricted plant growth and development. The Fluoride toxicity was studied in young olive plants (Olea europaea L. cv Chemlali), which were irrigated for 5 months with increasing NaF concentration: 0 (control), 20, 40, and 80 mM NaF. The NaF application resulted in an increase of the F content in plant tissues with a higher level in roots compared to leaves. Olive plants treated with 20 or 40 mM NaF maintained their mineral status and activated their antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). In fact, lipid peroxidation and electrolyte leakage were not affected in the plant leaves. However, olive plants treated with 80 mM NaF showed (i) the highest reduction of antioxidant enzyme activities and mineral contents, and (ii) an increase of oxidative stress markers such as hydrogen peroxide, thiobarbituric acid reactive substances and electrolyte leakage in both roots and leaves.